This document is a term paper on liver transplantation submitted by Aswathi P. to her lecturer Mrs. Resmi G. at Al-Shifa College of Nursing. It begins with an introduction that describes liver transplantation as replacing a diseased liver with a healthy liver from a donor. It then discusses the anatomy and physiology of the liver, including its structure, lobes, blood supply from the hepatic artery and portal vein, and internal lobule structure composed of hepatocytes and sinusoids. The functions of the liver are also summarized, such as protein synthesis, carbohydrate and lipid metabolism, and detoxification.

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TERM PAPER
ON
LIVER TRANSPLANTATION
Submitted by, Submitted to,
Aswathi. P Mrs. Resmi. G
1st yr Msc Nursing Lecturer
Al-shifa college of Nursing Al-shifa college of Nursing
Perinthalmanna Perinthalmanna
Submitted on: 17 -08-2015

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INDEX
Sl No Content Page No
1 Introduction
2 Anatomy and physiology of liver

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INTRODUCTION
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with
some or all of a healthy liver from another person (allograft). The most commonly used
technique is orthotopic transplantation, in which the native liver is removed and replaced by the
donor organ in the same anatomic location as the original liver. Liver transplantation is a viable
treatment option for end-stage liver disease and acute liver failure. Typically three surgeons and
two anesthesiologists are involved, with up to four supporting nurses. The surgical procedure is
very demanding and ranges from 4 to 18 hours depending on outcome. Numerous anastomoses
and sutures, and many disconnections and reconnections of abdominal and hepatic tissue, must
be made for the transplant to succeed, requiring an eligible recipient and a well-calibrated live or
cadaveric donor match
ANATOMY AND PHYSIOLOGY OF LIVER

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The liver is the largest solid organ in the body. In adults, the liver can weigh up to 1.5 kilograms
(kg). It is in the upper-right abdomen, just under the rib cage and below the diaphragm (the thin
muscle below the lungs and heart that separates the chest cavity from the abdomen). The liver is
part of the digestive system.
Structure
LOBES
External Structure
The liver is the largest gland in the body weighing about 1.4 kg in an adult. It is situated under
the diaphragm in the upper abdominal cavity and is held in place by several ligaments.
It is a reddish-brown colour and comprises of four anatomical lobes. When viewed from the
front, the dominant left and right lobes can be seen which are separated by the falciform
ligament.
Situated in a depression on the posterior surface of the liver is the gall bladder, a pear-shaped sac
which stores bile synthesised by the liver. The liver performs many vital metabolic functions. It
has the ability to store and metabolise useful substances such as nutrients, but it breaks down or
detoxifying harmful substances to render them inert and less harmful.
The liver has 2 main lobes: the larger right lobe and the smaller left lobe. Each lobe is divided
into segments.

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The lobes are separated by a band of tissue called the falciform ligament (also called the broad
ligament), which helps attach the liver to the diaphragm.
A layer of connective tissue, called Glisson’s capsule or the capsule, covers the liver.
Blood Supply
The liver receives a blood supply from two sources. The first is the hepatic artery which delivers
oxygenated blood from the general circulation. The second is the hepatic portal vein delivering
deoxygenated blood from the small intestine containing nutrients.
The blood flows through the liver tissue to the hepatic cells where many metabolic functions take
place. The blood drains out of the liver via the hepatic vein.
The liver tissue is not vascularised with a capillary network as with most other organs, but
consists of blood filled sinusoids surrounding the hepatic cells.
Unlike most other organs, the liver has 2 major sources of blood:
 portal vein – carries blood from the digestive system to the liver
o Approximately 75% of the liver’s blood supply comes from the portal vein.
 hepatic artery – supplies the liver with oxygen-rich blood from the heart

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Most of the blood is removed from the liver through 3 hepatic veins (the right, middle and left
hepatic veins) found inside the liver.
Hepatic portal vein
.
"Portal vein" redirects here. For a vein that connects two systems of capillary beds, see portal
venous system.
The hepatic portal vein is a blood vessel that conducts blood from the gastrointestinal tract and
spleen to the liver. This blood is rich in nutrients that have been extracted from food, and the
liver processes these nutrients; it also filters toxins that may have been ingested with the food.
The liver receives about 75% of its blood through the hepatic portal vein, with the remainder
coming from the hepatic artery proper. The blood leaves the liver to the heart in the hepatic
veins.

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The hepatic portal vein is not a true vein, because it conducts blood to capillary beds in the liver
and not directly to the heart. It is a major component of the hepatic portal system, one of only
two portal venous systems in the body – with the hypophyseal portal system being the other.
The hepatic portal vein is usually formed by the confluence of the superior mesenteric and
splenic veins and also receives blood from the inferior mesenteric, gastric, and cystic veins.
Conditions involving the hepatic portal vein cause considerable illness and death. An important
example of such a condition is elevated blood pressure in the hepatic portal vein. This condition,
called portal hypertension, is a major complication of cirrhosis
Structure
Tributaries of the hepatic portal vein[1]
 Splenic vein
 Superior mesenteric vein
 Inferior mesenteric vein
 Gastric veins
 Cystic vein
Measuring approximately 8 cm (3 inches) in adults, the hepatic portal vein is located in the right
upper quadrant of the abdomen, originating behind the neck of the pancreas.
In most individuals, the hepatic portal vein is formed by the union of the superior mesenteric
vein and the splenic vein. For this reason, the hepatic portal vein is occasionally called the
splenic-mesenteric confluence. Occasionally, the hepatic portal vein also directly communicates
with the inferior mesenteric vein, although this is highly variable. Other tributaries of the hepatic
portal vein include the cystic and gastric veins. Immediately before reaching the liver, the portal
vein divides into right and left. It ramifies further, forming smaller venous branches and
ultimately portal venules. Each portal venule courses alongside a hepatic arteriole and the two

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vessels form the vascular components of the portal triad. These vessels ultimately empty into the
hepatic sinusoids to supply blood to the liver.
Portacaval anastomoses
The portal venous system has several anastomoses with the systemic venous system. In cases of
portal hypertension these anastamoses may become engorged, dilated, or varicosed and
subsequently rupture. new
Accessory hepatic portal veins
Accessory hepatic portal veins are those veins that drain directly into the liver without joining
the hepatic portal vein. These include the paraumbilical veins as well as veins of the lesser
omentum, falciform ligament, and those draining the gallbladder wall.
Function
The hepatic portal vein and hepatic arteries form the liver's dual blood supply. Approximately
75% of hepatic blood flow is derived from the hepatic portal vein, while the remainder is from
the hepatic arteries. Unlike most veins, the hepatic portal vein does not drain into the heart.
Rather, it is part of a portal venous system that delivers venous blood into another capillary
system, namely the hepatic sinusoids of the liver. In carrying venous blood from the
gastrointestinal tract to the liver, the hepatic portal vein accomplishes two tasks; namely, it
supplies the liver with metabolic substrates and it ensures that substances ingested are first
processed by the liver before reaching the systemic circulation. This accomplishes two things.
First, possible toxins that may be ingested can be detoxified by the hepatocytes before they are
released into the systemic circulation. Second, the liver is the first organ to absorb nutrients just
taken in by the intestines. After draining into the liver sinusoids, blood from the liver is drained
by the hepatic vein.
Common hepatic artery
The common hepatic artery (CHA) is a terminal branch of the coeliac artery.

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The CHA is a terminal branch of the coeliac artery, it passes to the right in the lesser sac, and
enters the lesser omentum to pass slightly upwards towards the porta hepatis. It gives off the
right gastric artery that runs along the lesser curvature of the stomach to anastomose with the
left gastric artery. The common hepatic artery then bifurcates into the gastroduodenal artery
and proper hepatic artery.
Branches
 right gastric artery
 proper hepatic artery
 gastroduodenal artery
Variation in hepatic arterial anatomy is seen in 40-45% of people. Classic branching of the
common hepatic artery from the coeliac artery, and the proper hepatic artery into right and left
hepatic arteries to supply the entire liver, is seen in only 55-60%.
Variation in hepatic arterial anatomy is seen in 40-45% of people. Classic branching of the
common hepatic artery from the coeliac artery, and the proper hepatic artery into right and left
hepatic arteries to supply the entire liver, is seen in 55-60% of the population.
In general, the common hepatic artery may arise from the abdominal aorta or superior mesenteric
artery (SMA) and all or part of the right and left hepatic arteries may arise from (be replaced to)
other vessels.
The two most common variants are:
 right hepatic artery replaced to the SMA
 left hepatic artery replaced to the left gastric artery
Another common finding, though not considered a variant by many authors, is trifurcation of the
common hepatic artery into right hepatic artery, left hepatic artery and gastroduodenal artery
(GDA). With this branching pattern there is no proper hepatic artery.

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Variant anatomy
Common hepatic artery
 from aorta: 2%
 from SMA: 2%
 trifurcation into RHA, LHA and GDA: ~6% (range 4-8%)
Right hepatic artery (RHA)
 from coeliac artery: ~2.5% (range 1-4%)
 from SMA: ~12.5% (range 9-15%)
 accessory RHA from SMA: ~4% (range 1-7%)
Left hepatic artery (LHA)
 from left gastric artery (LGA): ~7.5% (range 4-11%)
 accessory LHA from LGA: ~7.5% (range 4-11%)
Right and left hepatic arteries
 RHA from SMA and LHA from LGA: ~1% (range 0.5-2%)
 accessory RHA and LHA: 1%
Classification
Another classification method is the one described by Michel et al in 1955 6
 I: standard anatomy ~60% (range 55-61%)
 II: replaced LHA ~7.5% (range 3-10%)
 III: replaced RHA ~10% (range 8-11 %)
 IV: replaced RHA and LHA ~1%
 V: accessory LHA from LGA ~10% (range 8-11%)
 VI: accessory RHA from SMA ~5% (range 1.5-7%)
 VII: accessory RHA and LHA ~1%

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 VIII: accessory RHA and LHA and replaced LHA or RHA ~2.5%
 IX: CHA replaced to SMA ~3% (range 2-4.5%)
 X: CHA replaced to LGA ~0.5%
 unclassified:
o CHA separate origin from aorta ~2%
o double hepatic artery ~4%
o PHA replaced to SMA; GDA origin from aorta <0.5%
Internal Structure
The liver lobes are made up of microscopic units called lobules which are roughly hexagonal in
shape.
These lobules comprise of rows of liver cells (hepatocytes) which radiate out from a central
point. The hepatic cells are in close contact with blood-filled sinusoids and also lie adjacent to
canaliculi into which bile is secreted.
Situated around the perimeter of the lobule are branches of the hepatic artery, hepatic portal vein
and bile duct. These cluster together at the "corners" of the lobule forming what is called the
portal triad. At the mid-point of the lobule is the central vein. Blood flows out of the sinusoids
into the central vein and is transported out of the liver.
HEPATOCYTES

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Hepatocytes are the predominant cell type in the liver. An estimated 80% of the liver mass
is made of these cells. The hepatocytes are round in shape containing a nucleus and an
abundance of cellular organelles associated with metabolic and secretory functions.
Organelles include endoplasmic reticulum (smooth and rough) and Golgi apparatus for secretory
functions. Also there are high numbers of mitochondria to provide energy to support the many
metabolic functions on the liver.
Some of the hepatocytes lie adjacent to endothelial cells which form the walls of the sinusoids.
These two cell types are separated by small space called the space of Disse.
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 70-85%
of the liver's mass. These cells are involved in:
 Protein synthesis
 Protein storage
 Transformation of carbohydrates
 Synthesis of cholesterol, bile salts and phospholipids
 Detoxification, modification, and excretion of exogenous and endogenous substances
 Initiation of formation and secretion of bile
Structure
The typical hepatocyte is cubical with sides of 20-30 µm, (in comparison, a human hair has a
diameter of 17 to 180 µm).[1]The typical volume of a hepatocyte is 3.4 x 10−9 cm3.[2]
Smooth endoplasmic reticulum is abundant in hepatocytes, whereas most cells in the body have
only small amounts.[3]
Histology
Hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, and
basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes.
Brown lipofuscin granules are also observed (with increasing age) together with irregular

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unstained areas of cytoplasm; these correspond to cytoplasmic glycogen and lipid stores removed
during histological preparation. The average life span of the hepatocyte is 5 months; they are
able to regenerate.
Hepatocyte nuclei are round with dispersed chromatin and prominent nucleoli. Anisokaryosis (or
variation in the size of the nuclei) is common and often reflects tetraploidy and other degrees of
polyploidy, a normal feature of 30-40% of hepatocytes in the adult human liver.[4] Binucleate
cells are also common.
Hepatocytes are organised into plates separated by vascular channels (sinusoids), an arrangement
supported by a reticulin (collagen type III) network. The hepatocyte plates are one cell thick in
mammals and two cells thick in the chicken. Sinusoids display a discontinuous, fenestrated
endothelial cell lining. The endothelial cells have no basement membrane and are separated from
the hepatocytes by the space of Disse, which drains lymph into the portal tract lymphatics.
Kupffer cells are scattered between endothelial cells; they are part of the reticuloendothelial
system and phagocytose spent erythrocytes. Stellate (Ito) cells store vitamin A and produce
extracellular matrix and collagen; they are also distributed amongst endothelial cells but are
difficult to visualise by light microscopy.
Protein synthesis
The hepatocyte is a cell in the body that manufactures serum albumin, fibrinogen, and the
prothrombin group of clotting factors (except for Factors 3 and 4).
It is the main site for the synthesis of lipoproteins, ceruloplasmin, transferrin, complement, and
glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes.
Synthesis of proteins is by the rough endoplasmic reticulum (RER), and both the rough and
smooth endoplasmic reticulum (SER) are involved in secretion of the proteins formed.
The endoplasmic reticulum (ER) is involved in conjugation of proteins to lipid and carbohydrate
moieties synthesized by, or modified within, the hepatocytes.

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Carbohydrate metabolism
The liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and
glycerol. Hepatocytes also synthesize apoproteins with which they then assemble and export
lipoproteins (VLDL, HDL).
The liver is also the main site in the body for gluconeogenesis, the formation of carbohydrates
from precursors such as alanine, glycerol, and oxaloacetate.
Lipid metabolism
The liver receives many lipids from the systemic circulation and metabolizes chylomicron
remnants. It also synthesizes cholesterol from acetate and further synthesizes bile salts. The liver
is the sole site of bile salts formation.
Detoxification
Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such
as drugs, (drug metabolism), and insecticides, and endogenous compounds such as steroids.
The drainage of the intestinal venous blood into the liver requires efficient detoxification of
miscellaneous absorbed substances to maintain homeostasis and protect the body against
ingested toxins.
One of the detoxifying functions of hepatocytes is to modify ammonia into urea for excretion.
The most abundant organelle in liver cell is the smooth endoplasmic reticulum.
Hepatocyte isolation and culture
Primary hepatocytes are commonly used in cell biological and biopharmaceutical research. In
vitro model systems based on hepatocytes have been of great help to better understand the role of
hepatocytes in (patho)physiological processes of the liver. In addition, pharmaceutical industry
has heavily relied on the use of hepatocytes in suspension or culture to explore mechanisms of
drug metabolism and even predict in vivo drug metabolism. For these purposes, hepatocytes are

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usually isolated from animal or human whole liver or liver tissue by collagenase digestion, which
is a two-step process. In the first step, the liver is placed in an isotonic solution, in which calcium
is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a
solution containing collagenase is added to separate the hepatocytes from the liver stroma. This
process creates a suspension of hepatocytes, which can be seeded in multi-well plates and
cultured for many days or even weeks. For optimal results, culture plates should first be coated
with an extracellular matrix (e.g. collagen, Matrigel) to promote hepatocyte attachment (typically
within 1-3 hr after seeding) and maintenance of the hepatic phenotype. In addition, and overlay
with an additional layer of extracellular matrix is often performed to establish a sandwich culture
of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of
hepatocytes in culture. Freshly-isolated hepatocytes that are not used immediately can be
cryopreserved and stored They do not proliferate in culture. Hepatocytes are intensely sensitive
to damage during the cycles of cryopreservation including freezing and thawing. Even after the
addition of classical cryoprotectants there is still damage done while being cryopreserved.
Nevertheless, recent cryopreservation and resuscitation protocols support application of
cryopreserved hepatocytes for most biopharmaceutical application
Lobule Activity
The hepatic portal vein and hepatic artery deliver oxygen and nutrients into to the blood
sinusoids. This close relationship between the hepatocytes and surrounding blood enables many
metabolic processes to take place.
Blood flows out of the sinusoids into the central vein, removing detoxified substances and
metabolic end products. The central vein ultimately reunites with the hepatic vein transporting
these substances out of the liver.
Bile that is produced by the hepatocytes drains into tiny canals called bile canaliculi (singular
canaliculus). These drain into bile ducts located around the lobule perimeter.

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Understanding First Pass Metabolism
Drugs may be given in a number of ways. Oral administration is the most common and the
easiest way to give a drug. The amount of drug reaching the general circulation will depend on a
number of factors.
Drug Absorption
The drug is absorbed from the GI tract and passes via the portal vein into the liver where some
drugs are metabolised. Sometimes the result of first pass metabolism means that only a
proportion of the drug reaches the circulation.
First pass metabolism can occur in the gut and the liver. For example, first pass metabolism
occurs in the gut for benzylpenicillin and insulin and in the liver for propranolol, lignocane,
chloromethiasole and GTN.
Bypassing First Pass Metabolism
Two ways to bypass first pass metabolism involve giving the drug by sublingual and buccal
routes.
The drugs are absorbed by the oral mucosa in both methods. In sublingual administration the
drug is put under the tongue where it dissolves in salivary secretions. Nitroglycerine is
administered in this way.
In buccal administration the drug is placed between the teeth and the mucous membrane of the
cheek. Sublingual and buccal methods both avoid destruction by the GI fluids and first pass
effect of the liver
Activity
In this exercise you need to drag each drug name to the organ where it undergoes first pass
metabolism.

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Bile ducts
The liver, gallbladder and small intestine are connected by a series of thin tubes called ducts.
One function of the liver cells (hepatocytes) is to produce bile. Bile is a yellow-green fluid that
helps digest fat.
Bile travels through a series of ducts in the liver to the small intestine or to the gallbladder for
storage.
 Bile is collected from the liver in hepatic ducts.
 Two hepatic ducts leave the liver and join to form the common hepatic duct.
 The cystic bile duct leaves the gallbladder and joins the common hepatic duct to form the
common bile duct.
 The common bile duct empties bile into the duodenum (the first part of the small
intestine).
o If there is food in the small intestine, the bile will flow directly from the liver,
through the common hepatic duct and common bile duct into the duodenum to
help with digestion.
o If the small intestine is empty, the bile will collect in the common bile duct until it
backs up the cystic duct and into the gallbladder, where it is stored until it is
needed.

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FUNCTIONS OF LIVER
The liver performs many important functions in the body. The liver:
 produces bile
o Bile is made up of bile salts, cholesterol, bilirubin, electrolytes and water.
o Bile helps the small intestine digest fat and absorb fats, cholesterol and some
vitamins.
 absorbs and uses (metabolizes) bilirubin
o Bilirubin is a yellow-red substance formed from hemoglobin when red blood cells
(RBCs) break down. (Hemoglobin is a protein found in RBCs that carries oxygen
and gives blood its red colour.)
o The iron from the hemoglobin is stored in the liver or used by the bone marrow to
produce new RBCs.
 helps the body make blood-clotting (coagulation) factors
o The body needs bile, which is produced by the liver, to absorb vitamin K. The
body uses vitamin K to produce blood-clotting factors.
o If the liver does not produce enough bile, the body will absorb less vitamin K and
produce less blood-clotting factors.

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 helps the body metabolize fat
o Bile breaks down fat from food to make it easier to digest.
 metabolizes protein
o Liver enzymes break down proteins from food so they can be digested and used
by the body.
 metabolizes carbohydrates
o The body breaks down carbohydrates from food into glycogen, which is stored in
the liver. The liver breaks down glycogen into glucose and releases it into the
blood to maintain normal blood sugar levels.
 stores vitamins and minerals
o Vitamins A, D, E, K and B12 are stored in the liver.
o The liver stores iron in the form of ferritin, which it releases so the body can make
new RBCs.
o The liver stores and releases copper as needed.
 filters the blood
o The liver filters certain substances from the blood so that they don’t build up and
cause damage. These substances can come from within or outside the body.
 Substances that come from within the body include hormones, such as
estrogen, aldosterone and diuretic hormone.
 Substances that come from outside the body include alcohol and other
drugs, such as amphetamines, barbiturates and steroids.
Regeneration
The liver has the unique ability to regrow parts that have been removed so that it can continue to
function in the body.
 Up to 80% of liver function can be maintained even after a large part of the liver has been
removed.
 The regeneration process continues over several months until the missing liver tissue is
replaced.

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 The length of time for this process depends on the person’s age, nutrition, if there is any
liver damage and how much liver was removed.
Transplant surgeons, hepatologists and other researchers are developing liver cell-based
regenerative therapies for patients who'd otherwise need whole-liver transplants.
The liver has the greatest regenerative capacity of any organ in the body. Liver regeneration has
been recognized for many years, dating all the way back to Prometheus in ancient Greek
mythology.
When the liver is injured beyond its ability to regenerate itself, a liver transplant is the treatment
of choice. Transplants are used to treat a wide range of liver conditions, including liver cancer,
cirrhotic liver disease, acute liver failure and genetic liver disorders.
But as is true for most donor organs, livers are in short supply — the number of people awaiting
new livers far exceeds the number of donor livers available.
Focus areas
Mayo Clinic transplant surgeons, hepatologists and other researchers in the Center for
Regenerative Medicine are developing and refining a number of regenerative liver therapies for
patients who today must wait for whole-liver transplants.
 Living-donor transplants. Liver cancer and advanced cases of cirrhotic liver disease
may require liver transplants. Given the shortage of whole livers for transplant, Mayo
Clinic's campuses in Minnesota and Arizona have been performing living-donor liver
transplants for more than a decade — together, they represent one of the largest such
programs in the country.
In a living-donor transplant, a portion of a donor's liver is removed and used to replace a
patient's diseased liver. After surgery, the donor's liver regenerates back to full size, while
the patient's new liver also grows to a normal size.

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As the safety of living donors is paramount to the success of this program, Mayo Clinic
researchers have conducted a long-term assessment of donor outcomes, such as liver
regeneration and mental and physical well-being. The study's results were very
reassuring, as they showed that Mayo living liver donors do well after donation.
 Liver assist devices. Several types of bioartificial livers — devices that perform liver
functions for patients with liver failure — have been developed in recent years. These
devices support patients as their livers recover from disease or as they await liver
transplants.
Center for Regenerative Medicine researchers are refining their own version of a
bioartificial liver, known as the Spheroid Reservoir Bioartificial Liver. This device
contains pig liver cell (hepatocyte) spheroids, which replace a patient's liver function.
Research into using human hepatocytes in the device is underway.
Read more about Mayo Clinic's bioartificial liver in Discovery's Edge, Mayo's research
magazine.
 Patient-specific liver cell transplantation. Existing liver cell transplantation procedures
used to treat genetic liver diseases do not use patient-specific cells and require
immunosuppression. Center for Regenerative Medicine researchers are developing an
individualized approach to liver cell transplantation that uses the patient's own cells.
With this approach, cells from the patient would be collected, converted to induced
pluripotent stem cells in the laboratory and subsequently transformed into hepatocyte-like
cells. During this process, gene therapy would be used to correct the genetic defect
responsible for the patient's disease.
The hepatocyte-like cells would then be transplanted into the liver of a bioengineered pig,
where they'd grow into fully functioning, patient-specific human adult hepatocytes that
could be transplanted into the patient to regenerate the liver. As the new hepatocytes were
originally derived from the patient's own cells, no immunosuppressive drugs would be
needed.

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Processing nutrients absorbed from digestive tract The liver converts glucose into glycogen,
its storage form. This glycogen can then be transformed back into glucose if the body needs
energy. The fatty acids produced by the digestion of lipids are used to synthesize cholesterol and
other substances. The liver also has the ability to convert certain amino acids into others.
Despite the wide variety of functions performed by the liver, there is very little specialization
among hepatocytes (liver cells). Aside from the macrophages called Kupffer cells in the liver,
hepatocytes all seem to be able to perform the same wide variety of tasks.
One of the liver's most interesting abilities is self-repair and the regeneration of damaged tissues.
In clearing the body of toxins, the liver is damaged by exposure to harmful substances,
demonstrating why this capability is important. It also gives hope that if a failing liver can be
supported for a certain period of time, it might regenerate and allow the patient to survive and
regain a normal life.
Hemostasis Glucose
Proteins
fat and cholesterol
Hormones
vitamins, in particular fat-soluble ones (A, D, E, K)
Synthesis proteins including the clotting factors (~50g/day)
bile acids (important in fat digestion)
heparin (anti-coagulant)
somatomedins (homones that promote growth in bone, soft tissues)
Estrogen
angiotensinogen
Cholesterol
acute phase proteins
Storage vitamins
Glycogen
Cholesterol

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iron, copper
Fats
Excretion cholesterol, bile acids, phospholipids
Bilirubin
Drugs
poisons including heavy metals
Hormones
Filtering Poisons
nutrients including amino acids, sugars, and fats
bilirubin, bile acids
IgA
Drugs
dead or damaged cells in circulatory system
Immune excretes IgA into digestive tract
Kupffer cells (macrophages) filter out antigens

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HISTORY OF LIVER TRANSPLANTATION
The first human liver transplant was performed in 1963 by a surgical team led by Dr. Thomas
Starzl of Denver, Colorado, United States. Dr. Starzl performed several additional transplants
over the next few years before the first short-term success was achieved in 1967 with the first
one-year survival post transplantation. Despite the development of viable surgical techniques,
liver transplantation remained experimental through the 1970s, with one year patient survival in
the vicinity of 25%. The introduction of cyclosporin by Sir Roy Calne, Professor of Surgery
Cambridge, markedly improved patient outcomes, and the 1980s saw recognition of liver
transplantation as a standard clinical treatment for both adult and pediatric patients with
appropriate indications. Liver transplantation is now performed at over one hundred centers in
the US, as well as numerous centres in Europe and elsewhere. One-year patient survival is 80–
85%, and outcomes continue to improve, although liver transplantation remains a formidable
procedure with frequent complications. The supply of liver allografts from non-living donors is
far short of the number of potential recipients, a reality that has spurred the development of
living donor liver transplantation. The first altruistic living liver donation in Britain was
performed in December 2012 in St James University Hospital Leeds.
DEFINITION
A liver transplant is a surgical procedure to remove a diseased liver and replace it with a healthy
liver from a donor. Most liver transplant operations use livers from deceased donors, though a
liver may also come from a living donor.
PURPOSE
A liver transplant is needed when the liver's function is reduced to the point that the life of the
patient is threatened

26. 26
DEMOGRAPHICS
Compared to whites, those with African-American, Asian, Pacific Islander, or Hispanic descent
are three times more likely to suffer from end-stage renal disease (ESRD). Both children and
adults can suffer from liver failure and require a transplant.
Patients with advanced heart and lung disease, who are human immunodeficiency virus (HIV)
positive, and who abuse drugs and alcohol are poor candidates for liver transplantation. Their
ability to survive the surgery and the difficult recovery period, as well as their long-term
prognosis, is hindered by their conditions.
INDICATIONS
Liver transplantation is potentially applicable to any acute or chronic condition resulting in
irreversible liver dysfunction, provided that the recipient does not have other conditions that will
preclude a successful transplant. Uncontrolled metastatic cancer outside liver, active drug or
alcohol abuse and active septic infections are absolute contraindications. While infection with
HIV was once considered an absolute contraindication, this has been changing recently.
Advanced age and serious heart, pulmonary or other disease may also prevent transplantation
(relative contraindications). Most liver transplants are performed for chronic liver diseases that
lead to irreversible scarring of the liver, or cirrhosis of the liver. Some centers use the Milan
criteria to select patients with liver cancers for liver transplantation
Cholestatic Diseases: primary biliary cirrhosis, sclerosing cholangitis, secondary biliary
cirrhosis, biliary atresia, cystic fibrosis
Chronic Hepatitis: hepatitis B, hepatitis C, hepatitis D, autoimmune chronic active hepatitis,
cryptogenic cirrhosis, chronic drug toxicity or toxin exposure
Alcoholic Cirrhosis: Patients with alcoholic cirrhosis are considered for transplant if they meet
current criteria for abstinence and rehabilitation.
 Abstinence of alcohol for six months.
 Ongoing participation in formal alcohol treatment program.

27. 27
 Presence of adequate psychosocial supports as determined by social service and
psychiatry consultants.
Patients who do not meet the above criteria at the time of referral will be given the opportunity to
fulfill these criteria and undergo re-evaluation. Formal input from the psychiatry staff is required
to assess the risk of return to alcohol use following liver transplantation.
 Metabolic Diseases: hemochromatosis, Wilson's disease, Alpha-1-antitrypsin deficiency,
glycogen storage disease, tyrosinemia, familial amyloidotic polyneuropathy, other
metabolic disorders treatable by liver replacement.
 Fulminant Acute Hepatic Necrosis: viral hepatitis, drug toxicity, toxin, Wilson's
disease.
 Primary Hepatic Tumors: selected patients with hepatocellular carcinoma.
Milan criteria
In transplantation medicine, the Milan criteria are applied as a basis for selecting patients with
cirrhosis and hepatocellular carcinoma for liver transplantation.
The Milan criteria state that a patient is selected for transplantation when he or she has:
 one lesion smaller than 5 cm
 up to 3 lesions smaller than 3 cm
 no extrahepatic manifestations
 no vascular invasion
CONTRAINDICATIONS
While each patient is evaluated on an individual basis, the presence of one or more of the
following will frequently preclude acceptance as a candidate for liver transplantation:
 HIV infection
 Active alcohol or substance abuse
 Systemic infections

28. 28
 Life-limiting co-existing medical conditions: advanced heart, lung or neurologic
conditions.
 Uncontrolled psychiatric disorder
 Inability to comply with pre- and post-transplant regimens
TYPES OF LIVER TRANSPLANTATION METHODS
Liver transplant is performed in people who have severely damaged livers or have developed
liver failure. These people are usually put on waiting lists for the donor livers to be available for
transplant. As soon as a suitable liver is available the next person on the waiting list is contacted.
The new liver has to match the recipient’s blood group, tissue type and size. 1-6
From the time the transplant center contacts a potential recipient he or she is advised not to take
anything by mouth (not even water) so as to be ready for the operation as early as possible.
A liver transplant may be undertaken as soon as the general health check-up of the patient
including heart and lung functions are assessed. This surgery is a major one and requires general
anesthesia. For general anesthesia to be administered the person needs to remain on an empty
stomach and heart and lung functions need to be assessed.
TYPES OF LIVER TRANSPLANT
There are three different types of liver transplant that may be offered to a person:
 Orthotopic transplant or transplant of a liver from a recently deceased donor
 A living donor transplant
 A split type of liver transplant
Orthotopic transplant
An orthotopic transplant is the most common type of liver transplant. The whole liver is taken
from a recently deceased donor. This is usually from a donor who has pledged his or her organs

29. 29
for donation prior to death and has not transmissible illness or cancers that may be transmitted to
the recipient.
For the surgery the surgeon makes an incision over the abdomen and removes the diseased liver.
The donor liver will then be put in position and all the blood vessels and bile ducts would be
connected. The incision is then closed with dissolvable stitches or surgical staples.
Drainage tubes are attached to drain away extra fluids. These are left for several days after
surgery. Patient is then shifted to the intensive care unit for recovery.
Living donor transplant
Living donor transplant means the donor is a willing living person. The donor has the operation
first in which the surgeon removes either the left or right side (lobe) of their liver.
Right lobe transplants are usually recommended for adults while left lobes are used in children.
This is because the right lobe is bigger and better suited for adults, while the left lobe is smaller
and better suited for children.
The recipient is then opened up and the diseased liver is removed. Then the part of the liver
taken from the donor is replaced making the connections with blood vessels and bile ducts as in
an orthotopic transplant.
Following transplantation, the transplanted lobe will quickly regenerate itself. Even for the donor
the removed portion of the liver grows back. In the recipient the new lobe usually grows to 85%
of the original liver size within a week.
Split type of liver transplant
Split donation involves transplantation of a liver from a recently deceased individual to two
recipients. This is possible if the next suitable recipients are an adult and a child. The donated
liver will be split into the left and right lobes. The adult normally receives the larger right lobe
and the child will receive the smaller left lobe.

30. 30
As with living donor transplants, the transplanted portions of the liver grow back to the original
size by regeneration. This method benefits two persons at a time.
Auxiliary liver transplantation
Auxiliary liver transplantation is a variety of liver transplantation where the recipient’s own liver
is not completely removed. Its purpose is to retain the native liver in case of spontaneous
recovery or if there is a potential for future gene therapy in cases of hereditary or metabolic liver
diseases (except primary oxalosis, Wilson’s disease or tyrosinaemia in which there is a risk of
cancer in the residual liver).
Living donor liver transplantation (ldlt) has emerged in recent decades as a critical surgical
option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma
often attributable to one or more of the following: long-term alcohol abuse, long-term untreated
hepatitis c infection, long-term untreated hepatitis b infection. The concept of ldlt is based on (1)
the remarkable regenerative capacities of the human liver and (2) the widespread shortage of
cadaveric livers for patients awaiting transplant. In ldlt, a piece of healthy liver is surgically
removed from a living person and transplanted into a recipient, immediately after the recipient’s
diseased liver has been entirely removed.
Historically, ldlt began as a means for parents of children with severe liver disease to donate a
portion of their healthy liver to replace their child's entire damaged liver. The first report of
successful ldlt was by dr. Christoph broelsch at the university of chicago medical center in
november 1989, when two-year-old alyssa smith received a portion of her mother's liver.[5]
surgeons eventually realized that adult-to-adult ldlt was also possible, and now the practice is
common in a few reputable medical institutes. It is considered more technically demanding than
even standard, cadaveric donor liver transplantation, and also poses the ethical problems
underlying the indication of a major surgical operation (hemihepatectomy or related procedure)
on a healthy human being. In various case series, the risk of complications in the donor is around
10%, and very occasionally a second operation is needed. Common problems are biliary fistula,
gastric stasis and infections; they are more common after removal of the right lobe of the liver.
Death after ldlt has been reported at 0% (japan), 0.3% (usa) and <1% (europe), with risks likely

31. 31
to decrease further as surgeons gain more experience in this procedure.[6] since the law was
changed to permit altruistic non-directed living organ donations in the uk in 2006, the first
altruistic living liver donation took place in britain in december 2012.[7]
In a typical adult recipient ldlt, 55 to 70% of the liver (the right lobe) is removed from a healthy
living donor. The donor's liver will regenerate approaching 100% function within 4–6 weeks,
and will almost reach full volumetric size with recapitulation of the normal structure soon
thereafter. It may be possible to remove up to 70% of the liver from a healthy living donor
without harm in most cases. The transplanted portion will reach full function and the appropriate
size in the recipient as well, although it will take longer than for the donor.[8]
Living donors are faced with risks and/or complications after the surgery. Blood clots and biliary
problems have the possibility of arising in the donor post-op, but these issues are remedied fairly
easily. Although death is a risk that a living donor must be willing to accept prior to the surgery,
the mortality rate of living donors in the united states is low. The ldlt donor's immune system
does diminish as a result of the liver regenerating, so certain foods which would normally cause
an upset stomach could cause serious illness.
DIAGNOSIS/PREPARATION
The liver starts to fail only when more than half of it is damaged. Thus, once a person
demonstrates symptoms of liver failure, there is not much liver function left. Signs and
symptoms of liver failure include:
 jaundice
 muscle wasting (loss of muscle)
 forgetfulness, confusion, or coma
 fatigue
 itching
 poor blood clotting
 build-up of fluid in the stomach (ascites)
 infections
 bleeding in the stomach

32. 32
A doctor will diagnose liver disease; a liver specialist, a transplant surgeon, and other doctors
will have to be consulted, as well, before a patient can be considered for a liver transplant.
Before transplantation takes place, the patient is first determined to be a good candidate for
transplantation by going through a rigorous medical examination. Blood tests, consultations, and
x rays will be needed to determine if the patient is a good candidate. Other tests that may be
conducted are: computed tomography (CAT or CT) scan, magnetic resonance image (MRI),
ultrasound, routine chest x ray , endoscopy, sclerotherapy and rubber-band ligation, transjugular
intrahepatic portosystemic shunt (TIPS), creatinine clearance, cardiac testing (echocardiogram
[ECHO]) and/or electrocardiogram [EKG or ECG]), and pulmonary function test [PFTs]), liver
biopsy , and nutritional evaluation. A dietitian will evaluate the patient's nutritional needs and
design an eating plan. Since a patient's emotional state is as important as their physical state, a
psychosocial evaluation will be administered.
Once test results are reviewed and given to the liver transplant selection committee, the patient
will be assessed for whether he or she is an appropriate candidate. Some patients are deemed too
healthy for a transplant and will be followed and retested at a later date if their liver gets worse.
Other patients are determined to be too sick to survive a transplant. The committee will not
approve a transplant for these patients. Once a patient is approved, they will be placed on a
waiting list for a donor liver. When placed on the waiting list, a patient will be given a score
based on the results of the blood tests. The higher a patient's score, the sicker the patient is. This
results in the patient earning a higher place on the waiting list.
Suitable candidates boost their nutritional intakes to ensure that they are as healthy as possible
before surgery. Drugs are administered that will decrease organ rejection after surgery. The
medical committee consults with the patient and family, if available, to explain the surgery and
any potential complications. Many problems can arise during the waiting period. Medicines
should be changed as needed, and blood tests should be done to assure a patient is in the best
possible health for the transplant surgery. Psychological counseling during this period is
recommended, as well.
When a donor is found, it is important that the transplant team be able to contact the patient. The
patient awaiting the organ must not eat or drink anything from the moment the hospital calls. On

33. 33
the other hand, the liver may not be good enough for transplantation. Then, the operation will be
cancelled, although this does not happen often.
Liver donor requirements
CT scan performed for evaluation of a potential donor. The image shows an unusual variation of
hepatic artery. The left hepatic artery supplies not only left lobe but also segment 8. The anatomy
makes right lobe donation impossible. Even used as left lobe or lateral segment donation, it
would be very technically challenging in anastomosing the small arteries.
Any member of the family, parent, sibling, child, spouse or a volunteer can donate their liver.
The criteria for a liver donation include:
 Being in good health
 Having a blood type that matches or is compatible with the recipient's, although some
centres now perform blood group incompatible transplants with special immuno
suppression protocols
 Having a charitable desire of donation without financial motivation
 Being between 18 and 60 years old
 Being of similar or bigger size than the recipient
 Before one becomes a living donor, the donor must undergo testing to ensure that the
individual is physically fit. Sometimes ct scans or mris are done to image the liver. In
most cases, the work up is done in 2–3 weeks.
Benefits
There are several advantages of living liver donor transplantation over cadaveric donor
transplantation, including:
 Transplant can be done on an elective basis because the donor is readily available
 There are fewer possibilities for complications and death than there would be while
waiting for a cadaveric organ donor
 Because of donor shortages, UNOS has placed limits on cadaveric organ allocation to
foreigners who seek medical help in the USA. With the availability of living donor

34. 34
transplantation, this will now allow foreigners a new opportunity to seek medical care in
the USA.
Controversy over eligibility for alcoholics
The high incidence of liver transplants given to those with alcoholic cirrhosis has led to a
recurring controversy regarding the eligibility of such patients for liver transplant. The
controversy stems from the view of alcoholism as a self-inflicted disease and the perception that
those with alcohol-induced damage are depriving other patients who could be considered more
deserving.[14] It is an important part of the selection process to differentiate transplant candidates
who suffer from alcoholism as opposed to those who were susceptible to moderate non-
dependent alcohol use. The latter who retain control of alcohol use have a good prognosis
following transplantation. Once a diagnosis of alcoholism has been established, however, it is
necessary to assess the likelihood of future sobriety
Preservation of the liver before transplantation
The OrganOx Metra device is capable of maintaining the liver outside of the body for longer
periods than traditional preservation of the organ on ice (which usually can only be done for
about 12 hours- 20 at most- before it is damaged unfit for transplantation). The device, which
was invented and tested (in two liver transplantations at the hospital) by a team from Oxford
University and King's College Hospital, could be ready for use in 2014 after a pilot trial of 20
more transplantations. However this device has not shown that it is superior to cold static storage
or hypothermic machine perfusion that has been used successfully at Columbia University and
should be commercially available in 2015.
DONOR PREPARATION
Laboratory Studies
These are oriented toward determining the etiology of the disease, excluding HIV and other
infections that may compromise a successful LT, and screening for the presence of tumors. The
following laboratory tests are those most commonly ordered during a LT evaluation:

35. 35
 Liver function tests, total protein, albumin
 Hepatitis screen (A, B, C)
 Serologies - Cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus
(EBV), HIV
 Tumor markers
 Alpha-fetoprotein, cholinesterase
 Arterial blood gases
 Others (selective) - Carbohydrate antigen 19-9, cancer antigen 125
Evaluation and workup of prospective liver transplant recipients is as follows: The first step in
the process of evaluating a potential candidate for LT is to determine the severity of the liver
disease by clinical evaluation. In addition, an objective assessment, to include a comprehensive
laboratory and radiological evaluation, is undertaken. The goal of this evaluation is 3-fold. First,
it must establish a diagnosis of ESLD; second, it must exclude any absolute or relative
contraindication to the proposed procedure; finally, it must assess the suitability and degree of
illness of each patient to better allocate resources and optimize survival. The specific tests are
outlined below. Once the results are received, specific consultations are sought to clear the
patient for LT.
Mandatory consultations and clearances are as follows:
 Cardiopulmonary clearance
 Psychiatrist and social worker consultations
 Financial clearance
 Nephrologist, infectious diseases specialist, or dentist, as needed
One of the most important tools in this scheme is the Child-Turcotte-Pugh (CTP) scoring system,
which is the system most widely used to grade the severity of liver disease. A patient is
considered to be Child class A if he or she has fewer than 7 points, Child class B if he or she has
7-9 points, and Child class C if he or she has more than 10 points. For listing purposes, a patient
must have at least 7 points (ie, be at least a Child class B), according to the minimal listing
criteria consensus initially developed when the CTP score was the basis for organ allocation.

36. 36
Today, the CTP score is no longer the basis for organ allocation because this is now based on the
Model for End-Stage Liver Disease (MELD) scoring system (see below; also see the MELD
Score calculator).
Table. CTP Scoring System for Assessment of Severity of Disease (with respect to listing) (Open
Table in a new window)
Parameter 1 Point 2 Points 3 Points
Encephalopathy None Grade 1-2 Grade 3-4
Ascites None Medically controlled Uncontrolled
Albumin, g/dL >3.5 2.8-3.5 < 2.8
Bilirubin, mg/dL < 2 2-3 > 3
International normalized ratio < 1.7 1.7-2.3 >2.3
Although a good effort to grade severity of disease, this classification does not reflect the
severity of disease in persons with cholestatic diseases, such as primary biliary cirrhosis or
primary sclerosing cholangitis (PSC), because the bilirubin limits are significantly higher for
these conditions and the other manifestations are not present until very late in the disease. Thus,
recent developments in the allocation system are investigating the MELD scoring system as the
new basis for organ allocation.
Because of the many factors (ie, increasing number of deaths while on liver waiting list, inability
to accurately categorize liver patients according to severity of liver disease using the partially
subjective CTP classification, reports suggesting that waiting time correlates poorly with death
while on the waiting list), a consensus opinion emerged that a revised allocation scheme was
needed. The new liver allocation system implemented by the Organ Procurement Transplantation
Network in February 2002 is based primarily on the severity of liver disease as assessed by the
MELD and Pediatric End-Stage Liver Disease (PELD) survival models for all patients with
chronic liver disease.

37. 37
The MELD score is based on 3 biochemical variables, (1) serum bilirubin, (2) serum creatinine,
and (3) international normalized ratio, and has been shown in retrospective and prospective
studies to be highly predictive of 3-month mortality in patients with chronic liver disease.
Similarly, the PELD model for pediatric patients (see below; also see the PELD Score calculator)
was developed based on analyses of data from the Study of Pediatric Liver Transplantation
database and has been shown retrospectively to be predictive of waiting list mortality in pediatric
patients.
Model for End-Stage Liver Disease (MELD) scoring system:
 Serum creatinine (Log e value) 0.957
o The maximum serum creatinine considered within the MELD score equation is
4.0 mg/dL (ie, for candidates with a serum creatinine >4.0 mg/dL, the serum
creatinine level is set to 4.0 mg/dL).
o For candidates on dialysis, defined as having 2 or more dialysis treatments within
the prior week, or candidates who have received 24 hours of continuous
venovenous hemodialysis (CVVHD) within the prior week, the serum creatinine
level is automatically be set to 4.0 mg/dL.
 Serum bilirubin (Log e value) 0.378
 International normalized ratio (INR) (Log e value) 1.120
 Using these prognostic factors and regression coefficients, the UNetSM computerized
system assigns a MELD score for each candidate based on the following calculation:
MELD score = 0.957 x Log e (creatinine mg/dL) + 0. 378 x Log e (bilirubin mg/dL) +
1.120 x Log e (INR) + 0.643. Laboratory values < 1.0 are set to 1.0 for the purposes of
the MELD score calculation. [2]
 As an example, for a hypothetical candidate with cirrhosis caused by hepatitis C virus
who has a serum creatinine concentration of 1.9 mg/dL, a serum bilirubin concentration
of 4.2 mg/dL and an INR value of 1.2, the risk score would be calculated as follows:
MELD score = (0.957 x Log e 1.9) + (0.378 x Log e 4.2) + (1.120 x Log e 1.2) + 0.643 =
2.0039.
 The MELD score for each liver transplant candidate derived from this calculation is
rounded to the tenth decimal place and then multiplied by 10. The hypothetical candidate

38. 38
in the example described above, therefore, would be assigned a risk score of 20. The
MELD score is limited to a total of 40 points maximum.
 Pediatric End-Stage Liver Disease (PELD) scoring system:
o Albumin (Loge value) -0.687
o Total bilirubin (Loge value) 0.480
o INR (Loge value) 1.857
o Growth failure (<-2 standard deviations [SD]) 0.667
o Age (< 1 y) 0.436 (Scores for candidates listed for liver transplantation before the
candidate’s first birthday continue to include the value assigned for age (< 1 y)
until the candidate reaches 24 months of age.)
o UNetSM assigns a PELD score for each candidate based on the following
calculation: PELD score = 0.436 (age [< 1 y]) – 0.687 x Loge (albumin g/dL) +
0.480 x Loge (total bilirubin mg/dL) + 1.857 x Loge (INR) + 0.667 (growth failure
[<-2 SD present]). Laboratory values < 1.0 are set to 1.0 for the purposes of the
PELD score calculation.[2] Growth failure is calculated based on age and gender
using the current CDC growth chart.
o This is a much more precise method of ranking patients; therefore, patients most
in need will be given the highest priority for donated livers, rather than simply
allocating them to patients who have waited longer but who may be much more
stable. The MELD policy replaced status 2A, 2B, and 3 with a continuous scale in
February 2002 and is the current basis for liver allocation. Neither of these 2
scoring systems favors all patients, specifically patients with HCCs or exceptional
cases.
Listing of candidates
 Once the workup is complete, the patient and all workup results are presented to the
candidate selection committee for a decision about the suitability for transplantation. This
committee consists of transplantation surgeons, hepatologists, psychiatrists, social work
representatives, cardiologists, pulmonologists, anesthesiologists, and, occasionally, the
patient's primary care physician.

39. 39
 The following questions are posed to the committee before listing the patient for
transplantation:
o Does the patient need LT as therapy for his or her disease?
o Have the indications and contraindications been properly assessed?
o What is the surgical risk?
o Is the patient's medical condition such that he or she will be able to tolerate the
procedure and postoperative course?
o What are the chances of recurrent disease affecting graft and patient survival?
Volk et al found that the structure of committee meetings varies by center; however, the process
is uniform and primarily involves inductive reasoning to review suitability for transplantation. In
their observations, patients were excluded if they were too well, too sick, or too old or had
nonhepatic comorbid conditions, substance abuse problems, or other psychosocial barriers.
Imaging Studies
 Radiography (including chest radiography)
 Duplex ultrasonography
 Angiogram/magnetic resonance angiography (selective)
 Abdominal CT scanning
 Cardiopulmonary evaluation
 Stress thallium scanning, coronary angiography (as indicated)
 Echocardiography
In a study comparing the performance of imaging techniques for the detection of hepatocellular
carcinoma in pre-liver transplant patients with cirrhosis, contrast-enhanced T1-weighted imaging
(CE T1WI) outperformed diffusion-weighted MRI (DWI) with regard to per-patient sensitivity,
negative predictive value and per-lesion sensitivity. The latter difference, however, was
significant only for lesions between 1 and 2 cm, suggesting that DWI is a reasonable alternative
to CE T1WI for detection of hepatocellular lesions above 2 cm.

40. 40
Other Tests
 Electrocardiography
 Pulmonary function testing
Diagnostic Procedures
 During the workup of these patients, many tests may be ordered. Specific testing is
performed on a case-by-case basis.
 In the author's experience, most patients undergo both upper and lower GI endoscopies to
evaluate for the presence of esophageal or gastric varices or to exclude GI malignancy.
 Other common procedures may include paracentesis in patients with ascites, both for
diagnostic purposes (eg, to exclude SBP) and for therapeutic intent (eg, alleviation of
distention and hepatohydrothorax).
 Many patients undergo a TIPS procedure while awaiting LT because of complications
that warrant this approach. These conditions include esophageal or gastric variceal
bleeding, refractory ascites, and hepatorenal syndrome (HRS).
Histologic Findings
 Discussion of all the histopathological findings of the various diseases that lead to ESLD
is beyond the scope of this article. In general, they can be classified into 3 broad
categories: cirrhosis and fibroticlike states, acute hepatic necrosis, and malignancies.
How long is the wait?
 The length of time a person may wait for a liver transplant varies, depending on the
availability of a compatible donor. The time may be as short as several months to a year
or as long as four years. As of September 2003, there were 17,327 candidates on the
national waiting list, waiting for a liver transplant.

41. 41
LIVER TRANSPLANT PHYSICIANS AND TEAMS
The multidisciplinary liver transplant team at Penn Medicine is comprised of specialists who
manage patient care at every stage: from the evaluation visit through the transplant procedure
and postoperative care. The program's goal is to provide the best care and restore each patient to
a full and productive life.
While primarily committed to patient care, the liver transplant team is also actively engaged in
clinical and laboratory research designed to improve survival and quality of life for transplant
recipients.
The following members of the liver transplant team are involved in our patients' care throughout
the transplant process:
Liver Transplant Surgeons
Liver Transplant Hepatologists
Transplant Coordinators
Procurement Coordinators
Living Donor Team
Living Donor Advocate
Social Workers
Financial Coordinator
Transplant Nutritionist
Transplant Pharmacist
Transplant Psychiatrist
New Patient Referral Intake Coordinator
Transplant Outreach & Communication

42. 42
Clinical Director, Abdominal Organ Transplant.
TECHNIQUES OF LIVER TRANSPLANT SURGERY
The techniques involved in LDLT and DDLT are in principal the same. In an adult to adult
LDLT, a segment of liver equivalent to 60% of the total liver mass is removed from the donor. In
an adult to child LDLT, only 25% of the liver suffices. In DDLT, the entire liver is removed and
usually the whole organ is transplanted into the recipient. However, in certain ideal cases, the
deceased donor liver can be “split” and transplanted into two recipients (the smaller piece going
to a child and the larger piece going to another child or small adult).
During the LDLT donor “hepatectomy” (surgical removal of the liver), extreme care must be
taken to minimize blood loss or injury to critical structures such as bile ducts and blood vessels,
and the exact anatomy of these structures should be studied as best as possible prior to even
starting the operation.
A “total hepatectomy” is performed in the case of DDLT and care must be taken not to injure
any critical structures and to properly preserve the organ prior to transplant. The organ recovery
surgery (previously referred to as “harvesting” but this term has fallen out of favor: “organ
retrieval”, “organ recovery” or “organ procurement” are all acceptable alternatives) often
involves recovery of multiple organs including heart, lungs, liver, kidneys, pancreas and
intestines, depending on the availability of transplant center expertise, so many different surgical
recovery teams might be present. The deceased donor is declared brain dead (two independent

43. 43
clinical exams and confirmatory “apnea tests”) and consent from the family is obtained prior to
proceeding with multiorgan recovery.
The brain dead patient’s heart and lungs are maintained with mechanical and pharmacologic
assistance so even though the patient is legally and medically dead (brain death is irreversible
because there is no longer blood flow to the brain and all brain stem functioning has ceased), the
heart is still beating at the time of recovery surgery. All of the recovery teams start their organ
dissections simultaneously and when it is time to remove the organs from the body, the heart is
recovered first, then lungs, then liver, pancreas and kidneys. The heart and lungs can only be
outside of the body for 4-6 hours prior to transplant, whereas the liver should be transplanted
within 12 hours and the kidneys in less than 24 hours (less than 12 hours is ideal). Special organ
preservation solution is used to flush the organs so that they do not become too injured while on
ice without their blood supply.
The liver transplant procedure itself lasts anywhere between 4-10 hours and involves five major
steps.
The recipient’s diseased liver is first removed in its entirety. The recipient total hepatectomy, is
in fact, the most dangerous part of the surgery because the liver is not functioning properly so the
blood does not coagulate well and very large blood vessels such as the inferior vena cava and
portal vein must be carefully attended to in order to avoid excessive bleeding. “Hemostasis”, or
control of bleeding, is critical during the recipient hepatectomy and requires excellent surgical
technique and skilled anesthesia support to rapidly replace blood products (if needed) and
maintain “hemodynamic stability” (i.e., normal pulse and blood pressure).
Anhepatic Stage - The second phase, the “anhepatic” phase commences after the old liver is
removed and before the new liver is reconnected to its blood supply. Many metabolic and
bleeding issues need to be managed by the anesthesiologists at this point. The surgeon must
quickly connect the veins draining blood from the liver and reestablish portal vein flow into the
liver.

44. 44
Reperfusion Stage - The “reperfusion” phase occurs when portal blood inflow and hepatic
venous outflow is re-established. This third phase can be accompanied by hemodynamic
instability (low blood pressure), high potassium levels (leading to irritation of the heart) and
excessive bleeding (depending on the quality of surgical technique). Sometimes it can take
several minutes to hours for the new liver to begin functioning properly to synthesize blood
clotting factors and to clear acid out of the bloodstream.
Arterial Reperfusion Stage – The fourth phase, when the hepatic artery is “anastomosed”
(surgically connected) and opened up for more blood to flow into the liver.
Fifth phase - When the bile duct is anastomosed. The fourth and fifth phase are usually
relatively calm moments during the transplant, but care must be taken to perform these
connections properly to avoid complications such as hepatic artery thrombosis or biliary leak or
stricture.
As a result of improved surgical and anesthetic techniques, effective immunosuppression and
anti-infection medicines and practice of true multidisciplinary care, liver transplantation in well
selected recipients and donors is extremely successful in the modern transplant era. Both LDLT
and DDLT are accepted standards of care in the treatment of end stage liver disease.
Postoperative Care
First 24 to 48 hrs - Once the surgical operation is over the patient is usually kept in a special
intensive care unit where well trained specialist team of intensive care doctors and nurses takes
care of the patient to ensure that they are kept stable hemodynamically (blood pressure,
oxygenation, fluids and urine output are balanced and maintained. Function of the new liver is
monitored closely by blood tests and ultrasound examinations. The liver function tests should
demonstrate a trend towards normal during this time. On rare occasions (<2% of the time), the
new liver does not start working at all (“primary nonfiction”) or there might be a surgical
complication such as hepatic artery thrombosis that requires immediate retransplant.

45. 45
Normally for the first 24 to 48 hours the patient is kept on ventilator (a special machine that
keeps the lung expanded and the body well oxygenated) and the patients are kept deeply sedated
until it is time to remove the ventilator. Once the ventilator is removed, the patient is fully
conscious and can start eating and moving around slowly.
During this period a limited number of relatives maybe allowed to see the patient.
Postoperative Days (PODs) 3-10 days – Once the patient is extubated (ventilator removed) and
stable, he or she can be transferred out of the ICU to the regular liver transplant ward. Here,
nurses and doctors ensure adequate pain control and a normal recovery path, regularly
monitoring liver function tests and immunosuppression drug levels. The bladder catheter is
removed on Postoperative Day #3 and usually the surgical drains are all removed prior to
discharge home. The sutures closing the skin incision are not removed until 2-3 weeks after the
operation and this is done in the outpatient clinic.
When the patient’s liver function tests (and all other labs) normalized and they are ambulating
and tolerating a regular diet, the Transplant Pharmacist and/or Transplant Social Worker have
teaching sessions with the patient and family to ensure that everyone understands the many
different drugs that must be taken, their purpose, their doses and their potential side effects. Also,
general discharge advice about avoiding infection and when to return to the outpatient clinic are
imparted.

46. 46
POST OPERATIVE CARE
Following surgery, the patient will wake up in the surgical intensive care unit (SICU). During
this time, a tube will be inserted into the windpipe to facilitate breathing. It is removed when the
patient is fully awake and strong enough to breathe on his or her own. There may be other tubes
that are removed as the patient recovers. When safe to leave the SICU, the patient is moved to
the transplant floor. Walking and eating will become the primary focus. Physical therapy may be
started to help the patient become active, as it is an important part of recovery. When the patient
begins to feel hungry and the bowels are working, regular food that is low in salt will be given.
A patient should expect to spend about 10 to 14 days in the hospital, although some stays may be
shorter or longer. Before leaving the hospital, a patient will be advised of: signs of infection or
rejection, how to take medications and change dressings, and how to understand general health
problems. Infection can be a real danger, because the medications taken compromise the body's
defense systems. The doctors will conduct blood tests, ultrasounds, and x rays to ensure that the
patient is doing well.
The first three months after transplant are the most risky for getting such infections as the flu, so
patients should follow these precautions:
 Avoid people who are ill.
 Wash hands frequently.
 Tell the doctor if you are exposed to any disease.
 Tell the doctor if a cold sore, rash, or water blister appears on the body or spots appear in
the throat or on the tongue.
 Stay out of crowds and rooms with poor circulation.
 Do not swim in lakes or community pools during the three months following transplant.
 Eat meats that are well-cooked.
 Stay away from soil, including those in which house-plants are grown, and gardens,
during the three months following transplant.
 Take all medications as directed.
 Learn to report the early symptoms of infection.

47. 47
To ensure that the transplant is successful and that the patient has a long and healthy life, a
patient must get good medical care, prevent and treat complications, keep in touch with doctors
and nurses, and follow their advice. Nutrition plays a big part in the success of a liver transplant,
so what a patient eats after the transplant is very important.
MEDICATIONS NEEDED FOLLOWING LIVER TRANSPLANTATION
Immunosuppressant drugs
Successfully receiving a transplanted liver is only the beginning of a lifelong process. Patients
with transplanted livers have to stay on immunosuppressant drugs for the rest of their lives to
prevent organ rejection. Like most other allografts, a liver transplant will be rejected by the
recipient unless immunosuppressive drugs are used. The immunosuppressive regimens for all
solid organ transplants are fairly similar, and a variety of agents are now available .Although
many patients can reduce the dosage after the initial few months, virtually none can discontinue
drugs altogether. For adolescent transplant recipients, post transplantation is a particularly
difficult time, as they must learn to take responsibility for their own behavior and medication, as
well as balance their developing sexuality in a body that has been transformed by the adverse
effects of immuno-suppression. Long-term outcome and tailoring of immunosuppression is of
great importance.
Cyclosporine has long been the drug of experimentation in the immunosuppression regimen, and
has been well-tolerated and effective. Hypertension, nephrotoxicity, and posttransplant
lymphoproliferative disease (PTLD) are some of the long-term adverse effects. Tacrolimus has
been developed more recently, and has improved the cosmetic adverse effects of cyclosporine,
but has similar rates of hypertension and nephrotoxicity, and possibly a higher rate of PTLD.
Prednisone, azathioprine, and tacrolimus are often combined with cyclosporine for better results.
Newer immunosuppressive agents promise even better results.
There has been a recent, welcome development in renal sparing drugs, such as mycophenolate
mofetil, which has no cosmetic adverse effects, does not require drug level monitoring, and is
thus particularly attractive to teenagers. If started prior to irreversible renal dysfunction, recent
research demonstrates recovery of renal function with mycophenolate mofetil. There is little

48. 48
published data on the use of sirolimus (rapamycin) in the pediatric population, but preliminary
studies suggest that the future use of interleukin-2 receptor antibodies may be beneficial for
immediate post-transplant induction of immunosuppression. When planning immunosuppression
for adolescents, it is important to consider the effects of drug therapy on both males and females
in order to maintain fertility and to ensure safety in pregnancy. Adequate practical measures and
support should reduce noncompliance in this age group, and allow good, long-term function of
the transplanted liver,
. Most liver transplant recipients receive corticosteroids plus a calcineurin inhibitor such as
tacrolimus or cyclosporin plus a purine antagonist such as mycophenolate mofetil. Clinical
outcome is better with tacrolimus than with cyclosporin during the first year of liver
transplantation. If the patient has a co-morbidity such as active hepatitis B, high doses of
hepatitis B immunoglubins are administrated in liver transplant patients.
Liver transplantation is unique in that the risk of chronic rejection also decreases over time,
although the great majority of recipients need to take immunosuppressive medication for the rest
of their lives. It is possible to be slowly taken off anti rejection medication but only in certain
cases. It is theorized that the liver may play a yet-unknown role in the maturation of certain cells
pertaining to the immune system. There is at least one study by Thomas E. Starzl's team at the
University of Pittsburgh which consisted of bone marrow biopsies taken from such patients
which demonstrate genotypic chimerism in the bone marrow of liver transplant recipients.
Risks
Early failure of the transplant occurs in every one in four surgeries and has to be repeated. Some
transplants never work, some patients succumb to infection, and some suffer immune rejection.
Primary failure is apparent within one or two days. Rejection usually starts at the end of the first
week. There may be problems like bleeding of the bile duct after surgery, or blood vessels of the
liver may become too narrow. The surgery itself may need revision because of narrowing,
leaking, or blood clots at the connections. These issues may be solved with or without more
surgery depending on the severity.

49. 49
Infections are a constant risk while on immunosuppressive agents, because the immune system is
supposed to prevent them. A method has not yet been devised to control rejection without
hampering immune defenses against infections. Not only do ordinary infections pose a threat, but
because of the impaired immunity, transplant patients are susceptible to the same opportunistic
infections (OIs) that threaten acquired immune deficiency syndrome (AIDS) patients—
pneumocystis pneumonia, herpes and cytomegalovirus (CMV) infections, fungi, and a host of
bacteria.
Drug reactions are also a continuing threat. Every drug used to suppress the immune system has
potential problems. As previously stated, hypertension, nephrotoxicity, and PTLD are some of
the long-term adverse effects with immunosupressive drugs like cyclosporine.
Immunosuppressants also hinder the body's ability to resist cancer. All drugs used to prevent
rejection increase the risk of leukemias and lymphomas.
There is also a risk of the original disease returning. In the case of hepatitis C, reoccurrence is a
risk factor for orthotropic liver transplants. Newer antiviral drugs hold out promise for dealing
with hepatitis. In alcoholics, the urge to drink alcohol will still be a problem. Alcoholics
Anonymous (AA) is the most effective treatment known for alcoholism.
Transplant recipients can get high blood pressure, diabetes, high cholesterol, thinning of the
bones, and can become obese. Close medical care is needed to prevent these conditions.
COMPLICATIONS
Given the complexity of liver transplantation, it is surprising that complication rates are so low
and overall success is so high. The one year survival is 85-90% and at five years it is 70%. Death
during the procedure is a rare event, occurring less than 1% of the time.
Infections:
The most common cause of death after a liver transplant is infection, either a hospital acquired
sepsis or an opportunistic infection resulting from the necessity of immunosuppressive drug use.
Patients with liver failure tend to be naturally immunosuppressed, mostly as a result of
malnutrition, so it is important not to give anti-rejection medicines in too high doses. Simple

50. 50
urinary tract infections or pneumonias can rapidly transform into life threatening infections in the
liver transplant recipient.
Bleeding:
Bleeding is not uncommon in liver transplantation because the liver is a very vascular organ and
when the liver is not functioning properly, the blood becomes thin. Surgical bleeding is almost
always a controllable situation, even if it means returning the patient to the Operation Theater to
correct after the initial transplant. The newly transplanted liver usually starts synthesizing
appropriate amounts of coagulation factors within minutes to hours, so postoperative bleeding is
often surgical in nature.
Biliary leak or Strictures:
Biliary leak or strictures occur 30% of the time with Living Donor Liver Transplant (LDLT) and
15% of the time with Deceased Donor Transplant (DDLT). Often, biliary complications can be
managed non-surgically with the assistance of Hepatologists using endoscopy or Interventional
Radiologists using catheter based approaches. Chronic biliary strictures can cause significant
long term morbidity, including bile duct infections (cholangitis) and liver abscesses.
Primary Non Function of the Transplanted Liver:
Primary Non Function, when the newly transplanted liver does not work at all, is fortunately a
rare event (<1%) but requires immediate re-transplant to save the patient. Another complication
that may require immediate re-transplant is hepatic artery thrombosis (“HAT”).
Hepatic Artery Thrombosis (HAT):
occurs in 2-5% of cases and is more common when smaller vessels are being anastomosed (such
as with Living Donor Liver Transplant or in pediatric liver transplant). Even if re-transplant is
not required, there is significant morbidity associated with long term HAT, including repeated
infections of the bile ducts and liver.

51. 51
Venous Complications –
of liver transplant include portal vein thrombosis and hepatic venous outflow obstruction. If
portal vein thrombosis occurs early after transplant, it must be recognized and treated quickly,
usually surgically but sometimes with catheter infusion based treatments by the Interventional
Radiologists. Chronic portal vein thrombosis is usually well tolerated but can make re-transplant
(if ever required) difficult to impossible. Hepatic venous outflow obstruction occurs when the
veins draining blood from the liver into the inferior vena cava are too narrow (usually as a result
of surgery), leading to congestion of the liver. If severe and longstanding, this can lead to ascites
and renal failure.
Incisional Hernia:
is quite common after liver transplant because patients with chronic liver failure often have very
weak connective tissue as a result of malnutrition. The weak section of the abdomen leads to
protrusion of the abdominal contents in the hernia. Incisional hernia rarely causes life threatening
complications such as trapped (or “incarcerated”) bowel contents, but chronic discomfort can be
easily alleviated with a simple hernia repair surgery.
Medical Complications
Rejection –
After a liver transplantation, there are three types of graft rejection that may occur. They include
hyperacute rejection, acute rejection and chronic rejection. Hyperacute rejection is caused by
preformed anti-donor antibodies. It is characterized by the binding of these antibodies to antigens
on vascular endothelial cells. Complement activation is involved and the effect is usually
profound. Hyperacute rejection happens within minutes to hours after the transplant procedure.
Unlike hyperacute rejection, which is B cell mediated, acute rejection is mediated by T cells. It
involves direct cytotoxicity and cytokine mediated pathways. Acute rejection is the most
common and the primary target of immunosuppressive agents. Acute rejection is usually seen
within days or weeks of the transplant. Chronic rejection is the presence of any sign and
symptom of rejection after 1 year. The cause of chronic rejection is still unknown but an acute
rejection is a strong predictor of chronic rejections. Liver rejection may happen anytime after the

52. 52
transplant. Lab findings of a liver rejection include abnormal AST, ALT, GGT and liver function
values such as prothrombin time, ammonia level, bilirubin level, albumin concentration, and
blood glucose. Physical findings include encephalopathy, jaundice, bruising and bleeding
tendency. Other nonspecific presentation are malaise, anorexia, muscle ache, low fever, slight
increase in white blood count and graft-site tenderness,when the grafted liver gets rejected by the
body and this requires treatment. Usually it requires a biopsy to ascertain that there is rejection,
Opportunistic Infections –
an immunosuppressed patient is prone to infections and this can result in infections by bacteria
or viruses that normally cause no problems to a person.
Hospital acquired Vascular Complications:
Like Deep Venous Thrombosis or pulmonary embolism.
Cardiac complications – like myocardial infarction
Neurologic complications – like stroke or due to adverse drug reaction
A fine balance of immunosuppression must be maintained: too little and the liver will reject, too
much and the patient can easily suffer a life threatening infection.
Opportunistic infections are rarer in the current era of transplantation due to excellent
prophylaxis regimens, sensitive surveillance tests and effective treatments for diagnosed
infections. Other medical complications occur at similar rates as other major surgery patients, but
they are poorly tolerated. Attention to detail and vigilance are paramount in the postoperative
care of the liver transplant patient.
PROGNOSIS
Prognosis is quite good, but those with certain illnesses may differ.[3] There is no exact model to
predict survival rates; those with transplant have a 58% chance of surviving 15 years.[4] Failure
of the new liver occurs in 10% to 15% of all cases. These percentages are contributed to by many
complications. Early graft failure is probably due to preexisting disease of the donated organ.

53. 53
Others include technical flaws during surgery such as revascularization that may lead to a
nonfunctioning graft.
Twenty-five million or one in 10 Americans are or have been afflicted with liver or biliary
diseases. As of June 2003, there were 17,239 patients on the UNOS National Transplant Waiting
List who were waiting for a liver transplantation. For the previous year (July 1, 2001 to June 30,
2002), there were a total of 5,261 liver transplants performed. Of those, 4,785 were cadaver
donors (already deceased) and 476 living donors. For liver transplants performed from July 1,
1999 to June 30, 2001, the one-year survival rate was 86% for adults; 1,861 patients died while
on the UNOS waiting list for the year ending June 30, 2002. More than 80% of children survive
transplantation to adolescence and adulthood.
Since the introduction of cyclosporine and tacrolimus (drugs that suppress the immune response
and keep it from attacking and damaging the new liver), success rates for liver transplantation
have reached 80–90%.
Infections occur in about half of transplant patients and often appear during the first week.
Biliary complications are apparent in about 22% of recipient patients (and 6% of donors), and
vascular complications occur in 9.8% of recipient patients. Other complications in donors
include re-operation (4.5%) and death (0.2%).
There are potential social, economic, and psychological problems, and a vast array of possible
medical and surgical complications. Close medical surveillance must continue for the rest of the
patient's life.
PEDIATRIC TRANSPLANTATION
In children, living liver donor transplantations have become very accepted. The accessibility of
adult parents who want to donate a piece of the liver for their children/infants has reduced the
number of children who would have otherwise died waiting for a transplant. Having a parent as a
donor also has made it a lot easier for children - because both patients are in the same hospital
and can help boost each other's morale.

54. 54
ADVANTAGES OF LIVER TRANSPLANTATION
 Liver transplants provide patients a chance for a longer, more active life in the final
stages of liver disease or end-stage liver disease.
 There’s no question that transplant is a major operation. The recovery can sometimes be
the most taxing but anti-rejection medications are making the process easier.
 If the transplant is performed before the recipient's health deteriorates, he or she is better
able to tolerate the surgery and recovers more quickly.
 The donors and recipients recovered quickly, the donors were discharged in about a week
and the recipients in 2 to 3 weeks.
PATIENT EDUCATION AFTER LIVER TRANSPLANT
DIET AND NUTRITION
After your liver transplant, you may need to adjust your diet to keep your liver healthy and
functioning well and to prevent excessive weight gain. You should maintain a healthy weight,
which can help prevent infections, high blood pressure and other complications. Your nutrition
specialist (dietitian) and other members of your treatment team will work with you to create a
healthy-eating plan that meets your needs and complements your lifestyle.
Your dietitian will provide you with several healthy-food options and ideas to use in your eating
plan. Your dietitian's recommendations may include:
 Eating at least five servings of fruits and vegetables each day
 Eating lean meats, poultry and fish
 Eating whole-grain breads and cereals and other grains
 Having enough fiber in your daily diet
 Drinking low-fat milk or eating other low-fat dairy products, to help maintain enough
calcium
 Maintaining a low-salt and low-fat diet
 Following food safety guidelines

55. 55
 Avoiding alcohol
 Staying hydrated by drinking adequate water and other fluids each day
 Avoiding grapefruit and grapefruit juice due to its effect on a group of
immunosuppression medications (calcineurin inhibitors)
Follow-Up Care to be taken Post Liver Transplantation
 After liver transplantation, the patient must frequently visit the transplant surgeon, about
1-2 times a week over about 3 months.
 The transplant surgeon and hepatologist monitor the patient's progress through blood
tests. After a year of Liver transplantation, follow-up care becomes individualized.
 Post transplant, patient will be on several different medications especially
Immunosuppression medications which keep the body from fighting off the new organ.
You may be on other medications to control blood pressure, Insulin, antibiotics and
antivirals, diuretics, and vitamins.
 Typically, patients are seen every week for the first month post transplant, and then the
frequency is reduced over time.
 Additional testing to monitor your health and liver function may vary from patient to
patient. Tests may include abdominal scans, ultrasounds, and liver biopsies.
 There are few dietary restrictions. The patient is often advised to restrict salt (sodium)
intake. A well-balanced diet with adequate protein is necessary. For reasons that are not
clear, obesity frequently becomes a problem with liver transplant patients. To avoid this
problem, patients should take control of their calorie intake early on.

56. 56
WELCOME TO LIVER TRANSPLANT INDIA

57. 57
LIVER TRANSPLANTATION IN INDIA
Dr AS Soin is recognized the world over for pioneering and establishing liver transplantation in
India from 1998, when he did the country’s first successful transplant to now, when he leads the
country’s largest, and one of the world’s largest and most successful liver transplant programs at
Medanta.
With over 2500 liver transplants under his belt, he and his team have performed more than 2000
transplants in India. They currently perform 30 liver transplants a month with 95% success -
results which are at par with the world's best elsewhere. No wonder, he gets referrals from all
over South Asia, Middle East, Far East and Africa, and has transplanted nearly 500 patients from
these countries.
In addition, he has performed more than 12000 other complex liver, gall bladder and bile duct
surgeries in a career spanning 27 years.
List of ApprovedHospitals for Liver Transplantation as on 10.07.2015
S.No Name of the Hospital Registration Valid Upto
1
Director of Medical Services,
Apollo Hospitals Enterprises Ltd.,
No.21, Greams Lane, Off.Greams Road,
Chennai.
31/08/2016
2
Medical Superintendent,
Christian Medial College and Hospital,
Vellore 632 004
24.09.2019
3
Chief Operating Officer,
Global Hospitals,
Global Health City,
439 Cheran Nagar,
Perumbakkam,
Chennai 600 100
13.05.2019
4 The Dean,
Government Stanley Hospital,
27.01.2019

58. 58
Chennai 600 003
5
Medical Director,
Sri Ramachandra Medical College and Research
Institute,
Porur,
Chennai-116.
30.09.2014
6
The Chairman,
D.D. Hospital and D.D. Medical College,
No 66 DD Nagar,
Kunavalam Post,
Thiruvallur District
PIN 631 210
21.03.2015
7
The Madras Medical Mission,
4 A Dr. J. Jayalalitha Nagar,
Mogappair, Chennai 600 037
27.12.2015
8
Sri Ramakrishna Hospital
395 Sarojinin Naidu StÏ
Siddapudur, Coimbatore
18.05.2016
9
Cethar Hospitals
C-108, Fort Station Road, 5th Cross, Thillai Nagar,
Trichy 620 018
30.06.2018
10
Kovai Medical Centre and Hospital Ltd
Post Box No.3209, Avanashi Road
Coimbatore 641 014
16.09.2018
11
Kamakshi Memorial Hospital
No.1 Radial Road, Pallikarnai
Chennai 600 100
30.09.2018
12
Director of Medical Education and Medical
Superintendant, MIOT Hospitals, 4/112, Mount
Poonamallee, Manappakkam, Chennai 600 089
16.02.2017
13 Chettinad Hospital and Research Institute
IT Highway Kelambakkam
23.04.2018

59. 59
Kanchipuram District 603 103
14
PSG Hospitals
Avinashi Road
Peelamedu, Coimbatore 641004
01.06.2019
15
Apollo Speciality Hospitals
Lake View Road, K.K.Nagar
Madurai 625 020
16.12.2019
16
Gem Hospitals
45, Pankaja Mill Road
Ramanathapuram, Coimbatore 45
30.11.2019
17
SRM Institute for Medical sciences, No.1, Jawaharlal
Nehru Salai, 100 Feet road, Vadapalani, Chennai
600026
05.02.2020
18
SRM Medical College Hosp & Research Centre
SRM Nagar, Potheri, Kattankulathur 603203
12.02.2020
Why choose India for Liver Transplantation
Liver transplantation in India is performed through cutting- edge clinical solutions,
research, extraordinary patient care and infrastructure of world-class standards. This has
addressed concerns of many patients and has helped them get rid of complex and most end
stage liver diseases.Liver Transplant is a complex surgical exercise and need highly skilled
consultants, ingenious technical staff and advanced technology working with perfect
harmony, enormous dedication and team work. India offers a one stop solution for all those
seeking critical procedures such as Liver transplantation.
Cities in India that offers Liver Transplantation at some of the best multi specialty hospitals
are as follows;
Mumbai Hyderabad Kerala
Delhi Pune Goa

60. 60
Bangalore Nagpur Jaipur
Chennai Gurgaon Chandigarh
What is the Cost of Liver Transplantation in India?
Liver transplant cost in India allows people of every class and from every part of the world to
avail the best medical care suited to their pocket. Everything from finding a donor and
performing the surgery to the prolonged recovery period and lifelong medication, each factor
adds to the cost, making liver transplant difficult to afford for some people. Hospitals in India are
a perfect destination for medical tourism that combines health treatment with visits to some of
the most alluring and awe-inspiring places of the world at an attractively low cost.
Other costs associated with transplantation include:
 recovery and in-hospital stay
 extensive lab tests
 anesthesia
 fees for transplant surgeons and operating room personnel
 organ recovery
 transportation to hospital
 lodging, transportation and food for family members while the patient is hospitalized
 physical therapy and rehabilitation
 patient lodging following discharge
 anti-rejection drugs and other medications

61. 61
IN KERALA
List of Approved Hospitals for Liver Transplantationin Kerala
S.No Name of Hospital Address/Contact Details
License Valid
Until
1
Amrita Institute of Medical
Sciences and Research Centre
Amrita Lane AIMS Ponekkara Post,
Kochi 682 041
Phone: 0484 2801234, 2804321,
4001234
Email:
aimsinternational@aims.amrita.edu
Website: www.aimshospital.org
02/07/2015
2
Kerala Institute of Medical
Sciences
P.B.No.1, Anayara P.O,
Trivandrum 695 029
Phone: 0471 3041000, 2447575
Email: relations@kimskerala.com
Website: www.kimskerala.com
03/01/2018
3 Lakeshore Hospital
NH 47 Bypass, Maradu, Nettoor P.O,
Kochi 682 040
Phone: 0484-2701032/2701033
Email: info@lakeshorehospital.com
Website: www.lakeshorehospital.com
19/05/2015
4
Malabar Institute of Medical
Sciences Ltd.
Mini By-pass Road, Govindapuram
P.O,
Calicut 673 016
Phone: 0495 - 2744000
Email: mimsclt@mimsindia.com
Website: www.mimsindia.com
19/12/2017
5 Medical Trust Hospital
MG Road,
Kochi 682 016
Phone: 0484 2358001
09/05/2017

62. 62
S.No Name of Hospital Address/Contact Details
License Valid
Until
Email: medtrust@vsnl.com
Website:
www.medicaltrusthospital.com
COST OF A LIVER TRANSPLANTATION
As of 1997, the cost of a liver transplant in the United States was $314,500, including the
evaluation, procurement of the liver, hospitalization, physician fees and follow-up care and
medications for the first year. As of 2002, the cost of a liver transplant in the United States
averaged about $250,000 for immediate hospital and doctor expenses. Necessary pre- and post-
operative expenses brought the total to about $314,500.
In some cases Medicare provides coverage for liver transplants for some causes of liver failure.
Talk to your transplant center to see if they are Medicare approved and you meet the criteria for a
Medicare covered transplant. If you have private insurance, you should check with your
insurance representative about whether your policy covers liver transplants. This may help to pay
some of the costs.

63. 63
REVIEW OF LITERATURE

64. 64
REVIEW OF LITERATURE
Partial liver transplantation-living donor liver transplantation and split liver
transplantation
Sascha A. Müller ,Arianeb Mehrabi , Bruno M. Schmied
Abstract
In the last two decades, liver transplantation (LTx) has become the treatment of choice for
several liver diseases including hepatocellular carcinoma in selected cases. Improvements in
surgical and anesthesiological procedures have increased patient survival after LTx, resulting in
excellent 1-year survival rates. The rate-limiting factor to further increase the number of LTx is
the extreme shortage of suitable organs with the consequence that pediatric and adult patients are
dying on the waiting list. At present, mortality reported for pediatric and adult patients on the
waiting list is 10 to 20%. Living-donor liver transplantation and split liver transplantation are
measurements to reduce the severe lack of cadaveric grafts by expanding the donor pool. Major
centers around the world now routinely perform partial LTx in infants and adults with survival
success equivalent to that after full-size liver transplantation.
Frequency and Outcomes of Liver Transplantation for Nonalcoholic
Steatohepatitis in the United States
Michael R. Charlton,Justin M. Burns,Rachel A. Pedersen,Kymberly D. Watt,Julie K.
Heimbach,Ross A. Dierkhising
Background & Aims
The relative frequency of nonalcoholic steatohepatitis (NASH) as an indication for liver
transplantation and comparative outcomes following transplantation are poorly understood.

65. 65
Methods
We analyzed the Scientific Registry of Transplant Recipients for primary adult liver transplant
recipients from 2001 to 2009.
Results
From 2001 to 2009, 35,781 patients underwent a primary liver transplant, including 1959 for
who NASH was the primary or secondary indication. The percentage of patients undergoing a
liver transplant for NASH increased from 1.2% in 2001 to 9.7% in 2009. NASH is now the third
most common indication for liver transplantation in the United States. No other indication for
liver transplantation increased in frequency during the study period. Compared with other
indications for liver transplantation, recipients with NASH are older (58.5 ± 8.0 vs 53.0 ± 8.9
years; P < .001), have a larger body mass index (>30 kg/m2) (63% vs 32%; P < .001), are more
likely to be female (47% vs 29%; P < .001), and have a lower frequency of hepatocellular
carcinoma (12% vs 19%; P < .001). Survival at 1 and 3 years after liver transplantation for
NASH was 84% and 78%, respectively, compared with 87% and 78% for other indications (P =
.67). Patient and graft survival for liver recipients with NASH were similar to values for other
indications after adjusting for level of creatinine, sex, age, and body mass index.
Conclusions
NASH is the third most common indication for liver transplantation in the United States and is
on a trajectory to become the most common. Outcomes for patients undergoing a liver transplant
for NASH are similar to those for other indications.
Living Donor Liver Transplantation for High MELD Score Patients
H. Chou, C. Lee, R. Soong, T. Wu, T. Wu, K. Chan, W. Lee
Background: Liver transplantation is the only effective treatment for the very sick liver failure
patients. For the success of liver transplantation, it is better to have good donors for very sick
patients. However, liver donation is very short in Asian countries. Liver donor liver
transplantation is the only way to rescue the very sick patients. The aim of this study is to

66. 66
examine the results of living donor liver transplantation for the patients with high the model of
end-stage liver disease (MELD) scores.
Materials and methods: The living donor liver transplant recipients with MELD score more than
or equal to 25 were included in this study. The clinical profiles were recorded and survival rate
was calculated.
Results: From June 2004 to Oct. 2012, totally 61 patients receiving ABO-compatible living
donor liver transplantation were included in this study. The disease entities for transplantation
were 37 for hepatitis B-, 8 for hepatitis C-, 8 for alcoholic liver cirrhosis-, 4 for drug-induced and
4 for other disease-related liver failure. The mean MELD score was 31.4±5.9. Graft-recipient
weight ratio was 1.05±0.26%. Among these patients, 13 (21.3%) patients died within 3 months.
Ten of them died of infection and multiple organ failure, 2 patients died of acute humoral
rejection and one patient died of pulmonary embolism. The 3-month, 1-year and 3-year survival
rates were, 76.9%, 68.2% and 61.9%, respectively. MELD and GRWR could not predict
patients’ survival.Conclusion: Partial graft transplantation still can be used to rescue very sick
patients and achieve 68.2% of one-year survival in this study. Infection is the most etiology to
cause early patient death. Conclusively, living donor liver transplantation to rescue very sick
patients is feasible, however, infection control is essential.
Pediatric Liver Transplant Center Volume and the Likelihood of
Transplantation
Abbas Rana, MD,Zachary Pallister, MD, Karim Halazun, MD,
Abstract
BACKGROUND: Low case volume has been associated with poorer surgical outcomes in a
multitude of surgical procedures. We studied the association among low case volume, outcomes,
and the likelihood of pediatric liver transplantation.
METHODS: We studied a cohort of 6628 candidates listed in the Organ Procurement and
Transplantation Network for primary pediatric liver transplantation between 2002 and 2012;

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4532 of the candidates went on to transplantation. Candidates were divided into groups
according to the average volume of yearly transplants performed in the listing center over 10
years: >15, 10 to 15, 5 to 9, and <5. We used univariate and multivariate Cox regression analyses
with bootstrapping on transplant recipient data and identified independent recipient and donor
risk factors for wait-list and posttransplant mortality.
RESULTS: 38.5% of the candidates were listed in low-volume centers, those in which <5
transplants were performed annually. These candidates had severely reduced likelihood of
transplantation with only 41% receiving a transplant. For the remaining candidates, listed at
higher volume centers, the transplant rate was 85% (P < .001). Being listed at a low-volume
center was a significant risk factor in multivariate Cox regression analysis for both wait-list
mortality (hazard ratio, 3.27; confidence interval, 2.53–4.23) and posttransplant mortality
(hazard ratio, 2.21; confidence interval, 1.43–3.40).
CONCLUSIONS: 38.5% of pediatric transplant candidates are listed in low-volume transplant
centers and have lower likelihood of transplantation and poorer outcomes. If further studies
substantiated these findings, we would advocate consolidating pediatric liver transplantation in
higher volume centers.
Liver transplantation for porphyria: who, when, and how?
Seth AK1, Badminton MN, Mirza D, Russell S, Elias E.
Abstract
Porphyrias are a heterogenous group of diseases that may result in disabling or life threatening
neurovisceral symptoms and/or cutaneous photosensitivity. In acute intermittent porphyria, the
clinical features, particularly neurological symptoms, may be life-threatening and disabling.
Conventional treatment with human hemin, though effective in reducing symptoms, does not
reverse neuropathy when structural nerve damage has occurred and may cause intense phlebitis.
Liver transplantation (LT) may be considered as treatment for those with repeated life-
threatening acute attacks resulting in poor quality of life, requirement of ventilatory support, and
progressive loss of venous access due to hemin infusion. Patients with variegate porphyria (VP)

68. 68
present after puberty with neurovisceral symptoms and skin manifestations. LT resolved VP in
the 1 patient reported in the literature. Aminolaevulinic acid dehydratase deficient porphyria is a
rare autosomal recessive disorder and a child who presented with failure to thrive and required
transfusions and parenteral nutrition did not improve with LT. In erythropoietic protoporphyria
(EPP), there is excessive production of protoporphyrin in the bone marrow. Protoporphyrin is
hepatotoxic and pigment loading of hepatocytes and bile canalicular sludging may result in
progressive cholestasis and cirrhosis. LT is beneficial for such patients with end-stage liver
disease. Perioperative management includes use of filters on operative lights to prevent skin
burns and intestinal perforation. Other concerns include development of neuropathy, biliary
complications, and recurrent liver disease. This review addresses the rationale, patient selection,
evaluation, management issues, and technique of performing LT in various types of porphyria.
Liver transplantation for metabolic liver diseases in adults: indications and
outcome
Karl Heinz Weiss1, Daniel Gotthardt1, Jan Schmidt2,
Abstract
Orthotopic liver transplantation is the preferred treatment for many patients with complications
of end-stage liver disease. For metabolic liver diseases liver transplantation does not only replace
the diseased organ, but also can potentially correct the metabolic defect. Results of liver
transplantation for metabolic diseases have been encouraging. In Wilson's disease liver
transplantation is considered an effective treatment for the fulminant form and for end-stage liver
disease, associated with an excellent long-term outcome. However, it is still a matter of
controversy whether liver transplantation should be considered in Wilson's disease patients with
severe neurological impairment. Liver transplantation for hereditary haemochromatosis is
relatively uncommon and is associated with a decreased post-transplantation patient survival,
most likely due to infections and cardiac complications. Reduction of iron overload prior to liver
transplantation in patients with hereditary haemochromatosis might be associated with a better
outcome.

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Indications and Role of Liver Transplantation for Malignant Tumors
Rudolf Pichlmayr, Arved Weimann,
Abstract
Purpose. The indication for liver transplantation in malignant liver tumors has been controversial
due to disappointing results and shortage of donor organs. The authors evaluated the experience
and results of a single center in order to define present indications and selection criteria in
hepatobiliary malignancy.
Patients and Methods. Retrospective analysis of 212 patients who underwent liver transplantation
for malignant tumors between 1972 and 1995: Primary hepatobiliary tumors: hepatocellular
carcinoma, n = 124 (with underlying cirrhosis, n = 86; fibrolamellar subtype, n = 8); intrahepatic
bile duct (cholangiocellular) carcinoma, n = 24; proximal bile duct carcinoma, n = 29; other
uncommon entities (n = 15); secondary liver tumors: neuroendocrine, n = 11, and nonendocrine,
n = 9.
Results. Survival rates in primary liver cancer were correlated to International Union Against
Cancer (UICC) tumor stage. For hepatocellular and proximal bile duct carcinoma significantly
better outcome was found in UICC-tumor stage I and II versus III and IV. No long-term survival
was found after transplantation for intrahepatic bile duct carcinoma, hemangiosarcoma and
nonendocrine liver metastases. Comparison of transplant and resected patients with
hepatocellular carcinoma stage I and II with underlying cirrhosis showed better survival after
transplantation: 1-, 3-, 5-year survival rate of 83.3% versus 76.9%, 75.8% versus 44.0%, 60.6%
versus 44.0%, and median survival 96.5 versus 23.2 months. Although this difference was not
significant, no patient died from tumor recurrence in the transplant group versus three in the
resection group.
Discussion and Conclusions. Patients with malignant tumors can be selected for transplantation
with predictable likelihood for long-term survival. According to the present data, liver
transplantation can be considered in unresectable UICC-stage II hepatocellular and proximal bile
duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid

70. 70
hemangioendothelioma and hepatoblastoma as well as liver metastases from neuroendocrine
tumors. UICC-stage III and IV hepatocellular carcinoma as well as intrahepatic bile duct
carcinoma, hemangiosarcoma and metastases from nonendocrine tumors should be excluded
from transplantation alone. For hepatocellular carcinoma, multimodality treatment protocols
have had a proven impact on the prevention of early recurrence and prolongation of survival.
There is evidence that liver transplantation in still resectable hepatocellular carcinoma with
underlying cirrhosis might be more appropriate in order to cure the cancer-bearing disease.
Techniques of orthotopic liver transplantation
L Lladó and J Figueras
Abstract
Background
Throughout the history of liver transplantation many improvements have been made in the field
of surgical technique. It is beyond the scope of this paper to review all aspects of surgical
technique in liver transplantation; thus, in this review we focus on the description of our current
technique in most cases, which is orthotopic liver transplantation with preservation of the inferior
vena cava and temporary portocaval shunt. We advocate this technique because it has been
demonstrated that it achieves better haemodynamic stability during the anhepatic phase,
transfusion can be reduced and renal function is improved. The different options for vascular
anastomoses are described, particularly the options for arterial anastomoses in case of finding a
non-adequate recipient hepatic artery. Technical possibilities for patients with preoperative portal
vein thrombosis and the procedure in case of domino or sequential liver transplantation are
further explained

71. 71
Recent Advances in Liver Transplantation for the Practicing
Gastroenterologist
Ranjan Mascarenhas, MD and Ahmet Gurakar, MD
Abstract
Liver transplantation is the definitive therapy for end-stage liver disease of various etiologies as
well as acute liver failure and early-stage hepatocellular carcinoma. The Model for End-Stage
Liver Disease (MELD) score is essential for organ allocation in the United States. Addition of
the serum sodium level to the MELD score is a recent development that helps prognosticate
cirrhotic patients with hyponatremia, a commonly seen manifestation of end-stage liver disease.
The currently used Milan criteria for hepatocellular carcinoma have been expanded with some
success at certain transplant centers, and tumor downstaging prior to transplant is being used
more frequently. The tremendous shortage of donor organs continues to be the major limitation
of this life-saving therapy. This has led to the use of extended-criteria donors, donation after
cardiac death, split liver grafts, and live donor liver transplants. Renal dysfunction following
liver transplant requires close monitoring and dose adjustments of immunosuppressive
medications. Although most liver transplants in the United States are for chronic hepatitis C
infection and its sequelae, hepatitis C virus recurrence is a common problem that is challenging
to treat in the post-transplant population.
Major Challenges Limiting Liver Transplantation in the United States
J. A. Wertheim; H. Petrowsky; S. Saab; J. W. Kupiec-Weglinski; R. W. Busuttil
Abstract
Liver transplantation is the gold standard of care in patients with end-stage liver disease and
those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver
transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The

72. 72
expansion of liver transplantation is chiefly driven by scientific breakthroughs that have
extended patient and graft survival well beyond those expected 50 years ago. The success of liver
transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the
growing number of patients added to the national liver transplant waiting list. This review
focuses on three major challenges facing liver transplantation in the United States and discusses
new areas of investigation that address each issue: (1) the need for an expanded number of
useable donor organs, (2) the need for improved therapies to treat recurrent hepatitis C after
transplantation and (3) the need for improved detection, risk stratification based upon tumor
biology and molecular inhibitors to combat hepatocellular carcinoma
Liver transplantation for hepatocellular carcinoma beyond the Milan criteria
Abstract
Objective Liver transplantation is an optimal radical therapy for selected patients with
hepatocellular carcinoma. The stringent organ allocation system driven by the Milan criteria has
been challenged by alternative sets of expanded criteria. Careful analysis is needed to prove that
the Milan criteria can be expanded safely and effectively.
Design This study collectively reviewed 6012 patients of hepatocellular carcinoma from the
China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised
expansion with acceptable outcomes beyond the Milan criteria.
Results Compared with the Milan criteria, Valencia, University of California, San Francisco,
University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%,
19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded
criteria were comparable to that of the Milan criteria. The analysis of net reclassification
improvement and area under the receiver operating characteristic curves showed an excellent
efficiency in recurrence prediction for the expanded criteria compared with the Milan criteria. In
patients exceeding Milan but fulfilling the Hangzhou criteria (N=1352), α-fetoprotein (AFP)
>100 ng/mL and tumour burden>8 cm were the only two independent prognostic factors
(p<0.001). Accordingly, the Hangzhou criteria were stratified as type A (tumour burden ≤8 cm,

73. 73
or tumour burden >8 cm but AFP≤100 ng/mL) and type B (tumour burden >8 cm but AFP
between 100 and 400 ng/mL). Type A showed significantly higher 5-year tumour-free survival
rates compared with type B (p<0.001).
Conclusions The Milan criteria can be expanded safely and effectively. The prognostic
stratification system based on the Hangzhou criteria serves as a hierarchy of transplant
candidates for hepatocellular carcinoma.
Anesthesia for Liver Transplantation
Timothy H. Hall, BHB, MBChB, FANZCA,Achal Dhir, MBBS, MD, FRCA, FRCPC
Abstract
Orthotopic liver transplantation is the only definitive treatment for end-stage liver disease. More
than 6000 procedures are performed in the United States annually with excellent survival rates.
The shortage of donor organs leads to continued interest in techniques to enlarge the potential
donor pool. Patients presenting for liver transplant suffer from important cardiovascular,
respiratory, renal, neurological, and gastroenterological comorbidity. In the Western world, liver
failure is increasingly caused by steatohepatitis, and transplant candidates are thus becoming
older and more comorbid. The role of the transplant anesthesiologist is highly important in the
preoperative assessment, intraoperative management, and postoperative care of these complex
and sick patients. Appropriate investigation and management of comorbidities such as coronary
artery disease and portopulmonary hypertension is controversial and differs between programs.
The transplant procedure is a major surgery, and although massive transfusion is no longer
commonplace, there is potential for significant hemodynamic instability, coagulopathy, and
metabolic disturbance. Liver transplant surgery can be divided into the preanhepatic phase, the
anhepatic phase, and the reperfusion phase, with important anesthetic considerations at each
point. An understanding of the surgical techniques used for vascular exclusion of the liver and
the role of venovenous bypass is crucial for the anesthesiologist. Recent trends in perioperative
care include the use of antifibrinolytic drugs and point-of-care coagulation tests, intraoperative

74. 74
renal replacement therapy, and “fast-track” extubation and postoperative care. Care of patients
with fulminant hepatic failure or those receiving split-liver grafts requires special consideration.
Immunomodulating Options for Liver Transplant Patients
Ali Zarrinpar, MD, PhD; Ronald W. Busuttil, MD, PhD
Abstract
Much has changed since the early years of liver transplantation. Improvements in post-transplant
survival are largely due to more selective and less toxic immunosuppression regimens and
advances in operative and perioperative care. This has allowed liver transplantation to become an
extremely successful treatment option for patients with endstage liver disease. Beginning with
cyclosporine, a cyclic endecapeptide of fungal origin and the first of the calcineurin inhibitors to
find widespread use, immunosuppressive regimens have evolved to include additional
calcineurin inhibitors, steroids, mTOR inhibitors, antimetabolites and antibodies, mostly
targeting T-cell activation. This review will present currently available immunosuppressive
agents used in the perioperative period of liver transplantation, as well as maintenance
treatments, tailoring therapeutic strategies for specific populations, and advances in immune
monitoring and tolerance.

75. 75
CONCLUSION
The liver is the body's principle chemical factory. It receives all nutrients, drugs, and toxins,
which are absorbed from the intestines, and performs the final stages of digestion, converting
food into energy and replacement parts for the body. The liver also filters the blood of all waste
products, removes and detoxifies poisons, and excretes many of these into the bile. It further
processes other chemicals for excretion by the kidneys. The liver is also an energy storage organ,
converting food energy to a chemical called glycogen that can be rapidly converted to fuel.
When other medical treatment interferes with the functioning of a damaged liver, a transplant is
necessary. Since 1963, when the first human liver transplant was performed, thousands more
have been performed each year. Cirrhosis, a disease that kills healthy liver cells, replacing them
with scar tissue, is the most common reason for liver transplantation in adults. The most frequent
reason for transplantation in children is biliary atresia—a disease in which the ducts that carry
bile out of the liver, are missing or damaged. During a liver transplantation, the surgeon removes
the diseased liver and replaces it with a healthy one. Most transplant livers come from a donor
who has died. Sometimes there is a living donor. This is when a healthy person donates part of
his or her liver for a specific patient.The most common reason for a transplant in adults is
cirrhosis. This is scarring of the liver, caused by injury or long-term disease. The most common
reason in children is biliary atresia, a disease of the bile ducts.If you have a transplant, you must
take drugs the rest of your life to help keep your body from rejecting the new liver.

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