Preoperative Evaluation For Living Donor Liver Transplantation
Preoperative Evaluation For Living
Donor Liver Transplantation
Ahmed Adel Abdelhakeem
Assistant Lecturer ,
Internal Medicine Dept , GI & Hepatology Unit
Asyut University Hospital
- Thomas Earl Starzl
-The father of modern
- Performed the first human
liver transplant in 1963 , and
The first successful human liver
transplant in 1967 , both at the
university of Colorado health
- Sir Roy Yorke Calne
- Performed the first liver
transplantation operation in
Europe in 1968
- Professor of Surgery at
Cambridge between 1965 and
- First who introduced
cyclosporine as an
What is liver 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
What is liver transplantation ?
- One-year patient survival is
- Outcomes continue to
- The supply of liver allograft
from non-living donors is far
short of the number of
potential recipients, a reality
that has spurred the
development of living donor
Living Donor Liver Transplantation
- 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
-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
Living Donor Liver Transplantation
-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.
- Surgeons eventually realized that
adult-to-adult LDLT was also
possible, and now the practice is
- It is considered more technically
demanding than even standard,
cadaveric donor liver transplantation
Status of liver transplantation in Arab
Area and Egypt
The first DDLT in the Arab World was performed in 1990 at Riyadh
Military Hospital in Saudi Arabia.
The first LDLT was performed in 1991 at the National Liver Institute in
We have 27 liver transplant centers from 11 countries ( now 28 ).
80 % of cases are LDLT
The largest percentage of liver transplantation has been performed by
13 transplant centers in Egypt (56%), moreover 70% of LDLT in Egypt,
while 90% of DDLT in KSA
Since 1991 , only 5 reported cases of donor death out of 3052 cases ( less
than 0,2 % ).
- Patient selection ( indications & contraindications ).
- Timing of the operation.
- Is every patient with chronic liver disease a
candidate for liver transplantation NOW?
- Patient preparation.
-Patients on waiting list.
Liver transplantation :
1 – Assessment
2 – Waiting
3 – The operation
4 – Immediate postoperative
5 – Long term management
Indications of LTX ( WHO )
1 – ESLD ( LCF and other complications )
2 – Hepatocellular Carcinoma :
3 – Other less frequent indications :
- Autoimmune hepatitis
- Fulminant hepatic failure ( King’s college criteria )
- Primary sclerosing cholangitis
- Metabolic liver diseases
- Budd-Chiari syndrome
End Stage Liver Disease
Patients with child score above 9 ( Child C ) and MELD score above 15
are accepted candidates for liver transplantation. Numbers below this
may be listed.
Exceptions of MELD are those with refractory ascitis , uncontrollable
recurrent GI bleeding , repeated encephalopathy , port pulmonary
hypertension , HPS , HCC and metabolic liver diseases.
Patients with MELD score less than 15 and Child B are listed and
followed up until they become child C or develop HCC or any condition
as a MELD exception.
Patients with high MELD ( above 30 ) score are risky with more
postoperative morbidity and mortality , so , every case should be
Patients with HCC are exceptions of the MELD score , and they receive a MELD of 20
once it is diagnosed even if the patient is child A.
The Milan criteria are currently the benchmark for the selection of HCC
patients for liver transplantation , and the basis for comparison with other suggested
Milan Criteria : Single HCC less than 5 cm , or , 3 HCC the maximum size of each is/or
less than 3 cm.
Barcelona Expanded criteria : Single HCC ≤7cm
Multinodular HCC: 3 nodules ≤5cm, 5 nodules ≤3cm
San Francisco criteria ( UCSF ) : one tumour ≤ 6·5 cm , three nodules at most with the
largest ≤ 4·5 cm , and total tumour diameter ≤ 8 cm.
No malignant vascular invasion , no distant metastasis.
AFP is a valuable marker to predict tumour load and microvascular metastases (
omit if more than 400 ) but should be combined with imaging modalities.
Milan criteria and its modifications are not applicable to patients with
HCC developing in a non-cirrhotic liver.
Such patients with non - resectable HCC and absence of macrovascular
invasion and extra hepatic spread may be considered as appropriate
candidates for liver transplantation.
patients with HCC in a non-cirrhotic liver, who were treated by
resection and have intrahepatic recurrence of HCC and no evidence of
macrovascular invasion or extrahepatic spread, may be considered for
1- Advanced age ( > 70 yrs , biological age is important ).
2 – Uncontrolled active sepsis.
3 – Advanced cardiopulmonary disease.
4 – HIV infection.
5 – Hepatocellular carcinoma beyond acceptable criteria.
6 – Extensive occlusion of splanchnic venous flow ( non-malignant , non-extensive
PV thrombosis is not a contraindication ).
7 – BMI > 30
8 – Previous upper abdominal surgery.
9 –Active ongoing Alcoholism.
10 – Extrahepatic malignancy
LT should be considered in any patient with liver disease in whom the
procedure would extend life expectancy beyond what the natural
history of under-lying liver disease would predict or in whom LT is likely
to improve quality of life.
Patients should be selected if expected survival in the absence of
transplantation is 1 year or less, or if the patient has an unacceptable
quality of life because of liver disease.
Physicians have to determine which patients have liver disease that will
endanger their lives before life-threatening systemic complications
occur. This consideration is balanced by the risk of surgery and
immunosuppressive treatment of LT if it is performed too early.
MELD score is an algorithm based on objective measures comprising
creatinine , bilirubin and INR. The MELD was developed initially to
determine the short-term prognosis for patients undergoing TIPS. It was
considered to be highly accurate for predicting liver-related death.
patients with MELD scores ≤ 14 , the mortality rate with transplantation
was found to be higher than that of patients with the same MELD score
who had not undergone transplantation. Consequently, a MELD score
higher than 15 is now considered a valid indication of LT in patients with
Exceptions of MELD score ( mentioned previously )
Management of patient s on waiting list
1 – Management of complications while patient with ESLD is on transplant
waiting list :
- Acute upper GI bleeding
- Hepatic encephalopathy
- Hepatorenal syndrome
- Refractory ascitis
2 – Down staging for patients with HCC ( TACE – RFA )
3 – Frequency of outpatient visits / update of MELD
Upper GI bleeding
Primary prophylaxis : beta blockers with target 25% reduction in HR not -
less than 55 b/m , not so valuable in patients with child C.
Endoscopic therapy : band ligation as a primary prophylaxis if risky on
TIPS : risk of complications and malfunction.
Secondary prophylaxis :
Beta blockers with endoscopic therapy.
TIPS if failed combined medical and endoscopic therapy.
Acute bleeding : usual management of acute variceal bleeding.
- Most common complication of portal hypertension.
- Patient is managed as usual : salt restriction and diuretics with the
- Sodium restriction is mandatory in ensuring response.
-The most reliable method for assessing response is : urinary sodium
excretion ( normally in afebrile cirrhotics is < 10 mmol / day ) , the goal is
to achieve urinary sodium level of > 78 mmol/day.
- Hyponatremia in advanced cirrhosis is common and chronic and rarely
problematic , take care not to correct it rapidly. Patients with serum Na <
120 are temporarily excluded until improvement (usually by fluid
- Nocturnal muscle cramps are a frequent complication and usually
resolves with magnesium administration.
Ascitis not responsive to sodium restricted diet and full dose of diuretics
in the absence of prostaglandin inhibitors.
Serial large volume paracentesis ( 5 liters at least ) with albumin
replacement ( 5 – 8 g/L of fluid ) every 2 weeks ( or according ) is the
therapy of choice in such cases.
Avoid frequent unnecessary tapping.
TIPS may be effective and superior to medical therapy in these patients
but carries high risk of developing encephalopathy with higher mortality.
- Diagnosed by clinical and laboratory methods.
- Clinical : a patient with ascitis who develops diffuse abdominal pain ,
tenderness , fever and vomiting is highly suggestive to have SBP.
- Laboratory : leucocytosis + mild rise of renal chemistry + diagnostic
paracentesis ( more than 250 PMNL and/or positive culture ).
- Sometimes the diagnosis is made by suspicion and diagnostic tapping
as the full picture may be absent.
- Once diagnosis is suspected , a 3rd generation cephalosporin or a
quinolones should be started ….. If no response tazobactam / piperacillin
OR imipenem / levofloxacin combination is a good offer , but it is better
to wait for culture results.
Patients who Should receive short term oral quinilone prophylaxis :
Low ascitic protein ( < 1 g/dl )
Survived attack of SBP
Patients with previous attack of SBP should receive long term
Admit and manage according to guidelines.
Such patients should be an exception of MELD score.
If no improvement :
Revise diagnosis ( alternative etiology )
Ensure sufficient therapy
Treat precipitating factors.
The hallmark of HRS is : reversible renal vasoconstriction + mild systemic
hypotension + normal structure of the kidney in a patient with advanced
cirrhosis and absent other etiology for renal dysfunction.
It is crucial to diagnose the exact etiology of renal impairement : Acute
prerenal failure , contrast nephropathy , intrinsic renal failure , drug
toxicity or HRS.
Baseline renal function should be determined at first evaluation of the
recipient by : complete urine analysis , urea , creatinine , uric acid , 24 hr
urine for proteins and clearance and renal ultrasound.
The best management of HRS is liver transplantation , but still these
patients have higher mortality and morbidity than others.
Renal sparing regimen should be put in consideration during the
operation and postoperative (postpone CNIs , give basiliximab D0,4)
Admit and treat with conventional therapy : terlipressin , albumin and
- Any transplant recipient who is hypoxic should be screened for HPS.
- Clinically : chronic liver disease complicated by PHT that develops
cyanosis , clubbing , platypnea , orthodeoxea that is relieved by
- Investigations : ABG , Pulse oximetry while sitting if positive ( hypoxia )
then do contrast echo or MAA Scan to confirm diagnosis.
- Usually HPS is a condition that improves with transplantation.
- High Preoperative risk for increased postoperative morbidity and
mortality are : PaO2 < 50 mmHg + MAA scan > 20 %.
- Routine Echo is done for every recipient.
- One of the main parameters to be looked at is the pulmonary pressure
- If RVSP is :
< 45 : OK
45 – 55 : RISKY patient , careful decision should be made with therapy
with sildenafil citrate.
> 55 : excluded from the list.
Portal Vein Thrombosis
- Malignant PV thrombosis is a contraindication to surgery.
- Non malignant , non extensive PV thrombus is permissible for
Grades of PV thrombus :
G1 : partially thrombosed main PV < 50% of lumen.
G2 : > 50% occlusion of main PV + or – minimal extension to SMV.
G3 : complete PV thrombosis + - proximal SMV extension.
G4 : complete PV thrombosis + proximal _ distal SMV extension.
Chronic HBV Patients
- Preoperative therapy until HBV PCR negative ( Enticavir 0.5 – 1 mg/day )
- HBVIG is given as following :
4000 IU bolus dose intraoperative ,
2000 IU daily for 7 days
2000 IU every week for 1 month
2000 IU monthly for 1 year
- Serum HBsAb level should exceed 300
- Postoperative antiviral therapy for life.
- All recipients and donors should be vaccinated against HBV.
HCC Patients On Waiting List
- Patients with HCC should be listed according to Milan criteria.
- HCC patients are exceptions of MELD score.
- Dropout of HCC patients on the waiting list is common because of
- Follow up is done for every patient every 3 months ( or one month after
any bridge therapy to assess response ).
- Follow up is done by Triphasic MSCT abdomen and AFP.
HCC Patients On Waiting List
BRIDGE THERAPY :
- using loco regional therapy ( alcohol injection , radiofrequency ablation
(RFA) , transarterial chemoembolisation (TACE) , transarterial
radioembolisation (TARE), or liver resection ).
(1) - to decrease the tumour size and number in patients initially
presenting with tumours that do not meet locally acceptable criteria for
(2) -To keep the patient within Milan criteria if transplantation is
expected to be delayed more than 6 months.
HCC Patients On Waiting List
BRIDGE THERAPY :
- α-fetoprotein concentrations before and after downstaging may add
- Based on existing evidence, no recommendation can be made for
preferring a specific locoregional therapy for downstaging over others.
- No recommendation can be made on bridging therapy in patients
With lesions ≤2 cm.
- Patients with progressive disease in whom locoregional intervention is
not considered appropriate, or is ineffective, should be removed from
the waiting list
Criteria of suitable donor
1 – Age should be less than 45 yrs
2 – No chronic systemic medical diseases and good general condition ( mild
controlled HTN is permitted ).
3 –Compatible blood group
4 – BMI less than 28
5 – No previous upper abdominal surgery (cholecystectomy is an exception)
6 – Relative ( recommended )
7 – Serologically negative
8 – Psychologically stable
9 – No drug abuse
10 – No pregnancy or hormonal therapy for 1 year postoperative.
Good News :
PHASE (1) EVALUATION :
Full history and examination
Basic lab. Investigations ( Liver , kidney , bleeding , lipid , electrolytes ).
Virology ( HAV , HBV , HCV , HIV )
Basic imaging : U/S , CXR , duplex abdomen , mammography