Liver transplantation; extensive notes of DM/DNB/Specialists. This was my notes for my exam compiled from several sources, credit goes to original authors. This is just for quick revision

1. LIVER TRANSPLANTATION
Pratap Sagar Tiwari
Total slides 115

2. Note:
• This is a compilation slides and is for academic purposes only. All
credit goes to the authors of the Books/ journals (references given).
2

3. Content
• Introduction
• Timing of Referral for Evaluation
• Indications for Liver Transplantation
• Exceptional Priority for LT
• Contraindications to LT
3

4. Introduction: Liver transplantation (LT)
• Since the first successful human liver transplant performed in 1967 by Thomas Starzl
[1] (March 11, 1926 – March 4, 2017) at the University of Colorado, advances in surgical
technique, immunosuppression, and pt selection have made the procedure a standard
lifesaving RX for pts with decompensated acute and chronic liver diseases.
4
Photo by Bill Cramer/Wonderful Machine
1. Starzl TE, Marchioro TL, Porter KA, Brettschneider L. Homotransplantation of the liver. Transplantation. 1967;5:790–803.
LT has revolutionized the prognosis of acute liver failure, causing
survival to increase from 10–20% (all causes combined) to 75–80%
at 1 year and 70% at 5 years. [EASL2015]
Thomas Starzl

5. Liver transplants in the USA by diagnosis
5
Proportion of liver transplants performed for specific
indications, 1992 to 2007.
Ref: O’Leary JG, Lepe R, Davis GL. Indications for liver transplantation. Gastroenterology 2008; 134:1764-76)

6. Liver Disease of Pediatric Transplant Recipients
in the United States, 1987-2013
6

7. Patient Survival for Deceased-Donor LT in the US
7

8. Timing of Referral for Evaluation
• Pts with decompensated liver disease, regardless of the cause, should be considered as
potential candidates for LT.
8
Urgency of a referral should be assessed.
Several clinical tools exist to assist in assessment of the degree of liver disease, both acute
and chronic.
Next slide: Schemes for Predicting Mortality and Need for LT in Acute Liver Failure

9. Schemes for Predicting Mortality and Need for
LT in Acute Liver Failure
• Although the King’s College criteria provide a high accuracy in predicting death without LT (PPV of 80-100%),
they are less effective in predicting who will recover spontaneously (NPV of 23-70%).
• Therefore, although a pt with ALF meeting the KCC will likely require LT, a pt not meeting these criteria does
not accurately predict a lack of a need for LT.
9

10. Other scoring models used in Acute Liver Failure
10

11. Prognostic Scoring Systems in Chronic Liver Failure
11

12. 3-Month Mortality Based on MELD Scores
12
United Network for Organ Sharing Liver Disease Severity Score Committee (2003). "Model for end-stage liver disease (MELD) and allocation of donor livers". Gastroenterology. 124 (1): 91–6.

13. Etc.: Prognostic Scoring Systems in CLD stages
13
1. D’Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. Journal of Hepatology, 44(1), 217–
231. doi:10.1016/j.jhep.2005.10.013
Clinical stages of Cirrhosis and 1 year outcome probabilities.

14. What does AASLD says ?
• Guidelines from the AASLD recommend pts with LC be referred for LT evaluation when
the MELD score reaches 15, or when the pt develops the first major complication
(ascites, VH, HE, HRS).
14
• The pediatric end-stage liver disease (PELD) score includes five factors (total bilirubin, albumin, INR, age
<1 year, and growth failure) and, like the MELD score, has been shown to accurately predict short-term
waiting list mortality in pediatric pts with CLD.
• Children with CLD are recommended to have a transplant evaluation when they show evidence of poor
weight gain or growth failure, or evidence of portal hypertensive complications.

15. Exploring Alternatives to Liver Transplantation
• Despite the success of LT as a RX for acute and CLD, transplant surgery and post-LT
immunosuppression are a/with significant morbidity and mortality; therefore feasible
alternatives to LT should be duly considered.
15
• The challenge of assessing the risk-benefit ratio of LT is most evident in ALF, where the most gravely ill
pt can, on occasion, have a dramatic and complete recovery without LT and avoid lifelong
immunosuppression and the associated morbidity.
• Pts with some CLD, such as AIH, WD, and HBV or HCV cirrhosis, may avoid the need for LT with timely
and appropriate intervention.
• However, concurrent pursuit of transplantation for critically ill pts with decompensated liver disease
where the response to therapeutics is uncertain is reasonable.

16. • Options exist to reduce risks for pts with CLD and delay transplantation.
• Among them are means of reducing portal pressure, and the most commonly used is
TIPS, which is frequently used to address portal hypertensive bleeding and ascites.
• Pts with difficult-to-control HE, elevated right-sided heart pressures, PVT, and elevated
MELD scores are often not candidates for TIPS; however, the ideal pt is one with a
MELD score too low for LT but with significant risks from variceal hemorrhage or
refractory ascites.
16

17. Indications for Liver Transplantation
17
All states of CLD are not indicated straight-
forward, certain exceptions,
contraindications etc. ..overall benefit-risk
should be well evaluated.
note

18. Comprehensive LT evaluation algorithm
18

19. Recognized Diagnosis and Criteria for Standardized
Exceptional Priority for LT in the United States
19

20. Recognized Diagnosis and Criteria for Standardized
Exceptional Priority for LT in the United States
20

21. Evaluation
21

22. Comprehensive LT evaluation algorithm 22

23. Contraindications to LT
• The goal of LT is to improve a pt’s survival and quality of
life.
• Assessing whether LT can achieve these goals is
fundamental to the pretransplant evaluation and is
individualized within a transplant center.
• Medical, psychosocial, and technical issues, individually or
in summation, may establish that LT is contraindicated.
• No consensus exists on an absolute minimum threshold for
graft survival after LT; however, general guidelines include
avoidance of listing for LT with a 5-year graft survival
below 50% and consideration of delisting when the
expected 1-year graft survival falls below 50%.
23

24. Contraindications to LT
• The goal of LT is to improve a pt’s survival and quality of
life.
• Assessing whether LT can achieve these goals is
fundamental to the pretransplant evaluation and is
individualized within a transplant center.
• Medical, psychosocial, and technical issues, individually or
in summation, may establish that LT is contraindicated.
• No consensus exists on an absolute minimum threshold for
graft survival after LT; however, general guidelines include
avoidance of listing for LT with a 5-year graft survival
below 50% and consideration of delisting when the
expected 1-year graft survival falls below 50%.
24

25. Medical Issues
• Pts who are not expected to survive LT
surgery or have a meaningful neurologic
or functional recovery should not undergo
the procedure.
25
This assessment can be complicated and typically
requires a multidisciplinary approach.

26. Cardiovascular Disease
• Despite cirrhotic physiology limiting HTN and reduced hepatic lipid production,
coronary artery disease (CAD) is prevalent among potential LT candidates, and even
after exclusion of pts with a history of MI, angina, or bypass, moderate to severe CAD is
present in an estimated 13.3% of LT candidates older than 50 years.124
• Cardiac CI to LT include symptomatic IHD, advanced cardiomyopathy, severe
ventricular dysfunction, severe pulmonary HTN, and severe VHD.
• Cardiovascular complications are one of the leading causes of non–graft-related death
after LT.125-27
26

27. Know the risk factors
• LT candidates are increasingly older, more obese, and enriched in atherosclerotic
disease owing to the rising proportion of NASH-induced cirrhosis.128-129
• There are several risk factors–based approaches for triaging pts, including noninvasive
testing, or (invasive) direct cardiac catheterization, although there is likely variability
between individual centers.
27
Risk factors :
DM, NASH,
Previous CAD
Peripheral vascular disease
Age >50
HTN
Dyslipidemia,
Cigarette smoking
obesity
• Analysis of these risks drives decisions for noninvasive
functional testing to identify those who may benefit from
invasive angiography and revascularization.

28. Initial noninvasive testing is usually achieved with
a. Direct inotropic stimulation with dobutamine stress echo or
b. Nuclear imaging techniques.
28
• Exercise stress testing is usually not attempted secondary to reduced exercised tolerance in cirrhotic pts.
• In predicting significant intraoperative cardiac events, dobutamine stress echo has NPV and PPV of 78% and 30%
respectively yet is indeterminate in 37% of LT candidates.

29. Dobutamine stress echo
• Dobutamine echo with <82% of maximal HR or peak rate-pressure <16, especially in those with a MELD
>24, may identify pts at higher risk of perioperative cardiac events.
29
Should undergo coronary angiography.
• Considered for other noninvasive testing, such as myocardial perfusion imaging or cardiac CT with calcium scoring.
Pts with nondiagnostic dobutamine stress test results
Those with positive noninvasive testing
• For candidates at intermediate or high risk of coronary events on the basis of their RF assessment, their
proceeding directly to coronary angiogram may be preferable.

30. Coronary revascularization
Percutaneous coronary revascularization can be attempted before LT.
• The degree of coagulopathy, the risk of GIB, and especially the anticipated time to LT
influence the choice of balloon angioplasty, bare metal stent, or drug-eluding stent.
Surgical revascularization before LT may be CI by perioperative risks posed by the pt’s
cirrhosis.
• Bypass grafting simultaneous with or shortly after LT has been reported.
Note: Increasingly, nonischemic cardiac disease has been implicated in cardiovascular complications following LT,
including myocarditis with fibrosis due to hepatitis C or hemochromatosis, cirrhotic cardiomyopathy, and cardiac
chronotropic incompetence.
30

31. Pulmonary Disease
• Pulmonary CIs to LT include advanced pulmonary fibrosis, severe COPD, and severe
Pulmonary HTN.
Pts with CLD are at risk of two distinct pulmonary vascular disorders:
1. Portopulmonary syndrome
2. Hepatopulmonary syndrome
Portopulmonary syndrome occurs in approx 6% of transplant candidates. It is characterized by elevated mean PAP (>25
mg Hg), ↑ed pulmonary vascular resistance (>240 dyn/cm5), and either a low pulmonary artery occlusion pressure
(<15 mm Hg) or an elevated transpulmonary gradient (>12 mm Hg) in the setting of PHTN.
31

32. Hepatopulmonary syndrome
• HPS occurs in 5-32% of pts with LC, and is characterized by IPVD with right to left
extracardiac shunting and arterial hypoxemia (A-a gradient <15mm Hg) in the setting of
PHTN. The degree of hypoxemia correlates with the degree of PHTN and the risk of
death without LT.
• PaO2 of ≤ 50 mm Hg alone or in combination with an MAA shunt fraction of ≤20% is
correlated with ↑ed mortality after LT.
• Pts with HPS are eligible for increased priority for LT if they have clinical evidence of
PHTN, evidence of intrapulmonary shunt, PaO2 <60 mm Hg when breathing room air,
and no significant clinical evidence of underlying primary pulmonary disease.
32

33. • Confirmation of the absence of other causes of pulmonary HTN is important, most
notably left-sided heart failure.
• Echocardiogram can estimate right ventricular systolic pressure as the initial screening
test, but confirmation with direct right-sided heart catheterization and pressure
measurement is required.
• Posttransplant mortality from severe uncontrolled pulmonary HTN (>50 mm Hg)
approaches 100% and remains prohibitively high at moderate levels exceeding 35 mm
Hg.
33

34. Renal Failure
• Pretransplant renal dysfunction is also a/with ↑ed post-LT morbidity and mortality but
is not a CI.
• Common creatinine-based measures (MDRD, Cockcroft-Gault) of the GFR overestimate
renal function in cirrhotic pts because of muscle wasting.
• Renal insufficiency in the setting of liver disease can be related to the liver disease
(HRS, hepatitis C MPGN, hepatitis B MN), to intrinsic renal disease (diabetic or
nondiabetic glomerulosclerosis, ischemic nephropathy), or to a mixture of both.
• Complete renal recovery from HRS after LT is common yet the time to recovery is
dependent on its duration and severity before LT and the presence of other
concomitant renal diseases.
34

35. SLKT
Beyond these two conditions, in a candidate with high priority for LT due to a high MELD score, the option of
SLK may be considered in the presence of RFs for underlying undiagnosed CKD (DM, HTN, abnormal renal
imaging and proteinuria >2 g/day)
SLK is also indicated in pts with cirrhosis and sustained AKI irrespective of its type, including HRS-AKI when
refractory to drug therapy, in the following conditions:
a) AKI on RRT for ≥4 weeks or
b) estimated GFR ≤ 35 ml/min or measured GFR ≤25 ml/min ≥4 weeks.
SLK can be indicated in pts with cirrhosis and CKD in the following conditions:
a) estimated GFR (using MDRD6 equation) ≤40 ml/min or measured GFR using iothalamate clearance ≤30
ml/min,
b) proteinuria ≥2 g a day,
c) kidney biopsy showing >30% global glomerulosclerosis or >30% interstitial fibrosis, or
d) inherited metabolic disease.
35

36. Infection
• Pts with ESLD are immunocompromised and prone to infection.
• Uncontrolled sepsis is an absolute CI to LT.
• Other infections should be treated aggressively before the procedure.
• Pts with evidence of latent TB should undergo RX before LT when possible, yet caution
is advised given the potential toxicity of ATT. (refer to my slide of ATT in CLD)
• If RX before LT is not possible, starting RX in the near posttransplant period is
advisable.
36

37. Infection
• HIV infection is no longer an absolute CI to LT.
• The causes of liver disease in HIV-infected people include coinfection (with HCV or
HBV), hepatotoxicity (highly active antiretroviral therapy, alcohol), HCC related to HBV
or HCV infection, NASH, and immune reconstitution inflammatory syndrome.
• Proper candidate selection and care by an experienced multidisciplinary team are
paramount to the success of LT in the HIV-infected pt, including psychosocial
considerations.
• Available data suggest that compared with non–HIV-infected liver transplant recipients,
recipients with HIV and HBV infection or HIV infection alone have similar survival.
37
Suggested selection criteria for HIV-infected pts include CD4>100 cells per microliter, HIV RNA that is suppressible by
ART, and no history of untreatable AIDS–defining events (progressive multifocal leukoencephalopathy, chronic
cryptosporidiosis, multidrug-resistant systemic fungal infection, and HIV-associated lymphoma).

38. Extrahepatic Malignancy
• Active extrahepatic malignancy, with rare exception, is a CI to LT.
• Exceptions include nonmelanoma skin cancer, neuroendocrine tumors (carcinoid
gastrinoma, insulinoma, somatostatinoma), and hemangioendothelioma.
• Prior nonhepatic malignancy is not an absolute CI, although these pts are likely at
higher risk of recurrence because of posttransplant immunosuppression.
low-risk (<10%) prior malignancies intermediate-risk (11- 25%) prior
malignancies
high risk (>25%) prior malignancies.
Incidental renal tumors,
lymphomas, thyroid cancer, and
carcinoma of the testis, uterus, and
cervix
uterine body carcinoma, Wilms tumor,
and carcinoma of the prostate and breast
bladder carcinoma, sarcoma,
malignant melanoma, symptomatic
renal carcinoma, and nonmelanoma
skin cancer and myeloma
There is no consensus on the optimal tumor-free duration. An observation period of at least 2 years following
curative cancer treatment is generally recommended, with longer periods of up to 5 years for malignant melanomas
and breast and colon carcinomas.
38

39. Advanced Age
• Advanced age by itself is not a contraindication to LT.
• Five-year posttransplant outcomes in pts >70 years may be similar to those in younger
pts; however, older age is a/with worse postLT survival 10 years after LT.
• A thorough evaluation for comorbid conditions should be performed during the
transplant evaluation, with consideration for a synergistic negative effect of advanced
age.
39

40. Obesity
• On the basis of WHO, there are 400 million obese (BMI >30 kg/m2) adults worldwide
and the proportion of obese patients undergoing LT increased from 15% in the 1990s to
more than 25% by 2003.
• The obese, particular those with fatty liver, are at ↑ed risk of CVD and DM.
• Perioperative outcomes such as length of stay and wound infection appear to be worse
in morbidly obese pts. After LT, the rate of obesity ↑ from 24% soon after LT to 41% at 3
years, along with ↑ in the incidence of metabolic syndrome and CVD.
• Recently, the combination of an intensive pretransplant weight loss program and
sleeve gastrectomy at the time of transplantation appeared effective and safe
compared with the weight loss program and transplantation without gastrectomy.
40

41. Cachexia, Sarcopenia, and Frailty
• The functional status of the transplant candidate impacts both pre and posttransplant
outcomes, and efforts to identify and validate objective measures are underway.
• Skeletal muscle loss, or sarcopenia, most commonly measured as the thickness of the
psoas muscle on CSI, is a/with both pretransplant and posttransplant death, as well as
other perioperative outcomes.
• Other potential anthropomorphic and functional measures of deconditioning include
the 6-minute walk test, BMI, and routine cardiopulmonary testing.
• Cachexia, sarcopenia, and frailty are potentially modifiable with interventions such as
physical therapy and supplemental nutrition.
41

42. Psychosocial Issues
• Significant psychiatric comorbitidies or social difficulties, including transportation,
support, and financial limitations, can impair a pt’s ability to adopt a healthy lifestyle,
form a productive relationship with the medical team, and adhere to complex
medication regimens.
42

43. Active Alcohol or Substance Abuse
• LT is CI in the setting of active alcohol or substance abuse yet may proceed once sincere
recovery has been established. Addiction is frequent in pts with ESLD, and recidivism is
common in addiction.
• Formal evaluation and MX by an addiction specialist can aid in risk stratification and
mitigation. Common substances of abuse include alcohol, tobacco, prescription
medications such as narcotics and benzodiazepines, and recreational and illicit drugs.
• Documentation of ongoing participation in a formal recovery plan is generally
mandated by transplant centers and third-party payers and often includes random drug
screening.
• Tobacco product use cessation should be mandated as it can improve operative
outcomes.
43

44. Technical Issues
• Advances in surgical technique and preoperative imaging have reduced the list of
technical CIs to liver transplant.
• Portal vein thrombosis is not an absolute CI yet does pose greater technical challenges
particularly if the entirety of the portal venous system is occluded or atrophied.
• However, more extensive thrombosis occluding the entire portomesenteric system can
be prohibitive of LT alone and require consideration of combined liver and intestine
transplantation.
44

45. Monitoring and Management
45

46. Monitoring and Management
• Once the pt has been selected as a candidate and registered on the waiting list, ongoing
and well-coordinated monitoring and MX is critical.
• Timely and clear communication among the transplant center, the primary care
provider, and the pt and the patient’s home support team improves delivery of the
often complicated care plans.
46

47. • Pts with ESLD require complex medical care and are at ↑ risk of the development of
complications.
• Regular updating of MELD results is required by the UNOS to evaluate the progression
of liver disease and update the pt’s priority status on the waiting list.
• The frequency of this requirement increases as priority increases: MELD<10, yearly;
MELD 11-18, every 90 days; MELD 19-24, every 30 days; and MELD ≥25, every 7 days.
• Routine health maintenance includes age-specific cancer screening and vaccinations.
47

48. • Identification of HCC with regular surveillance imaging, depending on the stage, may
give the pt an opportunity for additional transplant priority. This is also true for HPS and
controlled portopulmonary syndrome.
• Generally, cirrhotic pts should not restrict protein intake given the significant risks of
cachexia.
• Sodium restriction (<2 g/day) is difficult for many pts but important for volume
optimization when portal hypertensive fluid retention is present.
• Regular exercise, as tolerated, should be encouraged to minimize debilitation, frailty,
and sarcopenia.
48

49. Allocation and Distribution Systems
• Prioritization for LT is most commonly done with an urgency based system where
candidates with the highest likelihood of dying LT receive the greatest priority.
• In the United States and several countries worldwide, the MELD and PELD scores are
used to assess the risk of death and hence priority for transplantation.
• The MELD score has been shown to have several advantages as an allocation tool,
including improved accuracy and reproducibility because of the avoidance of subjective
predictors such as ascites and HE.
49

50. Allocation and Distribution Systems
• Distribution of available donor organs to a waiting list is regulated according to local
norms, in some countries it is defined by a transplant center’s assigned donor area.
• In pt based distribution, as in the US, donor organ offers generally go first to the
highest-priority pt in the local area, known as a designated service area, then to a larger
regional area, then nationally.
• An initial exception to this schema was made for pts with an estimated survival of <7
days without LT and listed as “status 1.” Status 1 candidates are eligible for regional
organs before local pts who are not listed as status 1.
50

51. Live-donor LT
• Adult-to-child and adult-to-adult live-donor
liver donation using either the left or the right
liver lobe as a liver graft is used in many
centers to increase access to LT for pts whose
MELD/PELD scores are not competitive for
Deceased donation liver grafts.
• At experienced centers, pt and graft survival
after LDLT are similar to those DDLT yet the
rates of biliary complications and
hospitalizations are higher.
• Ethical considerations become more
complicated with living donation because the
donor would not otherwise require a surgical
procedure nor assume the associated risks.
Right lobes (segments 5 to 8), extended right grafts
(segments 4 to 8), or left hepatic grafts (segments 2 to 4)
have been used successfully in adult-to-adult LDLT. 51

52. Live donor issues
• The estimated mortality for live liver donors is different during the early postdonation
period and long-term follow-up.
• For example, the risk of death for live liver donors within the first 90 days after donation
has been estimated to be 1.7 per 1000, which is higher than the risk of death for healthy
age-matched persons but not significantly different from the risk of death in live kidney
donors.
• Cumulative long-term mortality estimates, however, are not different between live
liver donors, live renal donors and healthy matched persons up to 11 years after
donation.
• Up to 38% of donors experience complications related to hepatic donation during the
first 2 years that follow, including biliary leaks, bacterial infections, surgical site
infections, intraabdominal abscesses, incisional hernias, pleural effusions, and
neurapraxia.
52

53. Donor factors
• In contrast to other types of organ transplants, including kidney and hematopoietic cell,
absence of HLA compatibility does not appear to affect liver graft survival.
• Donor-recipient matching is based primarily on ABO blood compatibility and recipient
weight.
• In critically ill recipients, an ABO-incompatible organ may be implanted, with the
recognition that graft survival may be diminished.
53

54. Donor factors
• The typical deceased donor has had a catastrophic head injury or an intracerebral bleed,
with brain death but without multisystem organ failure.
• Electrolyte imbalance and hepatic steatosis in the donor are predictors of graft
nonfunction.
• A “donor risk index” has been derived to assess the likelihood of good graft function.
Key adverse factors include older donor age (> 60 yrs), use of a split/partial graft, and a
non–heart-beating donor, from which the organs are harvested after the donor’s cardiac
output ceases, in contrast to the more typical deceased donation in which the organs
are harvested prior to CV collapse.
• Use of non–heart-beating donors is a/with ↓ rates of long-term graft survival and an ↑
risk of biliary complications and correlates with the duration of “warm ischemia” after
CV collapse and before retrieval of the organ.
• With the critical shortage of deceased organ donors, expansion of the donor pool has
included acceptance of donors 70 years of age and older. 54

55. Split liver grafts
• Good-quality deceased-donor livers can be
split to provide grafts for two recipients,
generally one pediatric pt and one adult pt.
• When split liver grafts are from younger
donors (<30 years old) and lack other poor
prognostic factors, outcomes can be
comparable to those for whole liver grafts.
Donor warm ischemia time (DWIT) is defined as the interval from withdrawal of life support to initiation of cold organ
preservation.
Graft warm ischemia time (WIT) is defined as the interval from removal from cold storage to establishment of
reperfusion of the liver graft.
Graft cold ischemia time (CIT) is defined as the interval from initiation of donor in vivo cold organ preservation to
removal of the graft from 4°C cold storage.
55

56. Auxiliary liver transplantation
• Auxiliary partial orthotopic liver transplantation (APOLT) is a technique where a partial
liver graft is implanted in an orthotopic position after leaving behind a part of the native
liver. This technique is used mainly in cases of ALF, especially in children and young adults,
and in cases of metabolic defects, where there is a chance the pt’s own liver will
regenerate, allowing for the possibility of immunosuppression withdrawal.
• Complications, particularly PVT and primary graft non‐function, are increased.
• In time the auxiliary graft is likely to atrophy.
• Long‐term follow‐ up of 20 children with ALF who underwent APOLT at King’s College
Hospital demonstrated a 10‐year pt survival of 85% with 65% immunosuppression‐free
survival 23 months after LT.
• In small adults and children, the recipient undergoes an extended left hepatectomy and a left lateral segment or left
lobe graft is used.
• In adults, a right hepatectomy is performed and right lobe graft is used.
56

57. Domino liver transplantation
• Structurally normal livers are removed to control a metabolic defect such as familial
amyloid polyneuropathy.
• Such a liver may be offered for transplant to an older recipient who has given full consent.
• The consequences of the metabolic defect will be delayed for between 10 and 20 years
although there are reports of this occurring within an earlier timeframe in the transplant
recipient. Transplanted liver grafts have been successfully reused.
57

58. Hepatocyte transplantation
• Transplantation of human hepatocytes is being developed to treat metabolic liver disease
where a supply of normally functioning liver cells can correct a genetic deficiency.
• However, the recipient will require long-term immunosuppression.
• Transplanted hepatocytes may be used to replace a missing or inactive enzyme, as in the
Crigler–Najjar syndrome, glycogen storage disease type 1a, and urea cycle disorders, or
to inactivate a disease‐inducing gene or over‐express a normal gene. However,
hepatocyte transplantation still has many challenges.
58

59. Xenotransplantation
• Several non‐human livers including pig, baboon, and chimpanzee livers have been
transplanted into humans.
• Starzl carried out the first chimpanzee to human liver transplantation in 1966 and in 1992,
his patient survived for 70 days following a baboon liver transplant.
• The main limitation is immunological, including hyperacute and delayed xenograft
rejection and T‐celldependent xenograft rejection.
• Various control strategies are under investigation but the problems will be difficult to
overcome.
• Zoonotic infections, particularly viruses (especially porcine endogenous retroviruses) may
be introduced with the xenotransplant. There are ethical difficulties in accepting
xenotransplantation.
59

60. The harvesting team
• The harvesting team makes a visual and, if necessary, histologic assessment of the
donor organ.
• Particular attention is paid to anatomic variants in the hepatic artery that may
complicate the graft arterial anastomosis in the recipient.
• Once donor circulation is interrupted, the organ is rapidly infused with cold
preservation solution.
• Donor iliac arteries and veins are also retrieved in case vascular grafting is required.
60

61. Native Hepatectomy
• Removal of the native liver is the most technically
challenging part.
• Previous abdominal surgery, especially a portosystemic
shunt, and severe PHTN add to the complexity of
hepatectomy, which is technically easier after placement
of a TIPS compared with a surgical portosystemic shunt.
• Hilar dissection is performed to access the major hepatic
vessels and devascularize the liver.
Stages of Surgery
Liver transplantation is divided into 3 intraoperative stages:
• The dissection phase: where the surgeon makes the incision, drains ascites and prepares to remove the
dysfunctional liver.
• The anhepatic phase: after the vessels to the liver are clamped and liver is explanted.
• The reperfusion stage: with the completion of PV anastomosis and the perfusion of the transplanted liver.
61

62. • Clamping of the PV during hepatectomy and liver implantation
results in increased bleeding during dissection, mesenteric
congestion, and production of lactate, whereas clamping of the
IVC aggravates venous stasis and causes renal hypertension,
with diminished venous return to the heart.
• To circumvent these problems, venovenous bypass is achieved
by cannulation of the PV and IVC via the femoral vein and return
of blood via the axillary vein to the right side of the heart.
• This technique is commonly performed in adults and older
pediatric recipients.
62

63. Piggyback (PB) technique
In 1989, Tzakis et al. popularized the so-called PB technique to help preserve blood
flow to the heart during the anhepatic phase. In PB technique, the recipient IVC
is not removed. Instead, the retrohepatic and caudate venous branches are ligated,
preserving the entire IVC. Once the HVs are clamped and the diseased liver removed,
the donor IVC (just above the hepatic vein orifice) is sewn onto the recipient cava
opening. In this manner, the recipient IVC is not completely cross-clamped and
venovenous bypass obviated. There are some other proposed advantages to this PB
technique as compared to IVC replacement:
• Volume management—Using PB techniques negates the need to infuse large
amounts of fluid and the complications that may ensue from volume overload.
• ICU length of stay—Some reviews have reported ↓length of stay for this technique.
• Technical ease—minimizes retroperitoneal dissection and needs only one
anastomosis compared to two anastomoses for the bicaval technique. Retransplant
is often easier if needed following a PB transplant.
• Potentially better preservation of renal function by maintaining flow to kidneys.
63

64. IMMUNOSUPPRESSION
• Immunosuppression is divided into induction (initial) and maintenance (long-term)
phases.
• The goals of immunosuppressive therapy in LT recipients are:
1. prevention of allograft rejection
2. optimization of graft function
3. minimization of side effects of the immunosuppressive regimen
• Episodes of acute cellular and chronic ductopenic rejection require additional
immunosuppression.
64

65. Immunosuppressive Agents Used in LT
65

66. 66

67. 67

68. Approach to the Care of the LT Recipient
The First 90 Days
• Typically, an uncomplicated LT recipient spends up to 3 days in the ICU, and 7 to14 days
in the hospital following the operation.
• Following discharge from the hospital, blood tests are performed once or twice weekly
initially, with the interval between blood tests extending as the pt recovers.
• The cause of liver dysfunction following LT is broad. However, the cause
of graft dysfunction also changes as the time from LT increases.
• Rejection of the allograft remains one of the MC causes of this
dysfunction across all time spans after LT.
• Although the immunogenicity of the liver allograft decreases with time,
it is greatest during the first 90 days: approx 60% of episodes of acute
cellular rejection (ACR) occur in this period.
68

69. • All liver allografts are subjected to a period of inadequate vascular perfusion during
preservation, followed by reperfusion, which results in an ischemic-reperfusion injury.
• This is manifested by AT often as high as 1000 U/L in the first postop week.
• Typically, the AT start to recover in 1 to 2 days, along with stabilization of the INR and
gradual improvement in serum bilirubin level.
69

70. • Primary nonfunction (PNF) of the allograft is an umbrella term describing the failure of
the allograft to establish normal function immediately after the LT.
• PNF is due to the combined effects of ischemia-repulsion and donor factors, especially
macrovesicular steatosis.
• For this reason it is common practice to decline donor organs with >25% macrovesicular
fat content on pretransplant assessment.
• Occlusion or stenosis of the HA or PV may also present as PNF.
• Biliary strictures may also present in the early period with liver enzyme level
abnormalities, typically in a cholestatic pattern.
70

71. • As the first 90 days after LT is when the highest doses of immunosuppressive
medications are used, it is also the time of greatest risk of infection.
• One must be vigilant for the onset of UTI, wound infections, pneumonias, infected
intravenous cannulae, and septicemia.
71

72. Technical complications
• Subcapsular hepatic necrosis: This is related to disproportionate size between donor and
recipient. It can be visualized by CT scanning and usually resolves spontaneously.
• Bleeding: Bleeding in the immediate posttransplant setting is more likely if the removal
of a diseased liver has left a raw area on the diaphragm, or if there have been adhesions
from previous surgery or infection, or with split liver lobes. Treatment is by transfusion
and reoperation if necessary.
72

73. Beyond the First 90 Days
• Most LT pts are healthy, albeit at risk of the AE of immunosuppression and the
recurrence of the underlying disorders that lead to their LT.
73

74. Rejection
• Immunologically, the liver is a privileged organ with regard to transplantation, having a
higher resistance to immunological attack than other organs. The liver cell probably
carries fewer surface antigens. Nevertheless, episodes of rejection, of varying severity,
are not uncommon.
• Cellular rejection is initiated through the presentation of donor HLA antigens by
antigen‐presenting cells to host helper T cells in the graft.
• These helper T cells secrete IL2 which activates other T cells.
• The accumulation of activated T cells in the graft leads to T‐cell mediated cytotoxicity
and a generalized inflammatory response.
74

75. Acute Allograft Rejection
• Acute cellular rejection (ACR) is a misnomer as ACR may occur even years after
transplantation. The word acute in acute cellular rejection (ACR) actually alludes to a
process that has not yet caused chronic damage to the graft, and the ductular
structure, though inflamed, is still viable.
• ACR is most common in the first 90 days after LT, after which the immunogenicity of the
LT allograft gradually declines.
75

76. Acute Allograft Rejection: DX
• ACR has no characteristic biochemical presentation, and may present with any of the
common patterns of liver injury.
• Liver biopsy remains the gold standard for DX with Banff criteria.
76

77. Acute Allograft Rejection:
• The decision to perform a biopsy is based on clinical
judgment and on such factors as prior experience of
rejection, adherence by the pt to the
immunosuppressive regimen, the severity of
biochemical disturbance, and the pt’s overall well-
being.
• ACR arising later in the clinical course suggests
either overly rapid reduction or lack of adherence
to the immunosuppressive regimen.
77

78. Acute Allograft Rejection: RX
• Initial treatment of ACR consists of high-dose intravenous or oral
corticosteroids, which may be started before the final biopsy results are
available.
• There is no widely agreed dosing regimen for corticosteroids to be used in ACR
episodes.
• Maintenance immunosuppressive therapy may be maintained at prior doses or
increased while pulse corticosteroids are administered.
• ACR that fails to respond to high-dose corticosteroids is called corticosteroid-
resistant rejection.
• T cell–depleting agents are used to treat episodes of corticosteroid-resistant
rejection.
78

79. Grading of acute allograft rejection
79

80. Chronic Ductopenic Rejection (CDR)
• CDR denotes damage and eventual loss of bile ducts in portal tracts.
• Although called chronic, it can occur in the first few months after LT.
• CDR occurs as a consequence of corticosteroid-resistant rejection or de novo.
• Multiple RFs for the development of CDR have been identified in various studies:
Ductopenic rejection is a challenging complication to treat; it
may respond to increased doses of tacrolimus,
plasmapheresis, and intravenous immune globulin. When all
other treatment fails, CDR requires retransplantation.
80

81. Antibody-Mediated Rejection
• The CM of AMR are protean, ranging from typical lymphocyte predominant rejection
that is poorly responsive to standard therapy to ductopenia, fibrosis, plasma cell–rich
hepatitis, and biliary strictures.
• The condition of AMR is recognized by measurement of circulating Donor specific
antibodies (DSAs) in a/with the identification on liver biopsy of diffuse C4d
deposition( classical pathway complement degradation product) in the portal tracts
(DSA positive /diffuse C4d positive).
• The use of cyclosporine (as opposed to tacrolimus) are a/with ↑ed risk of de novo DSA
formation, whereas a calculated MELD> 15 at LT and recipient age >60 years are a/with
lower risk.
81

82. Antibody-Mediated Rejection: RX
• The best methods to prevent the onset of AMR or to treat AMR have not been defined.
• Antihumoral agents and techniques used in kidney transplant recipients, such as
plasmapheresis, intravenous immune globulin, rituximab, bortezomib, and
eculizumab, are most commonly used as multimodality regimens but the relative
contribution of the component therapies in managing AMR is difficult to ascertain.
82

83. Complications Occurring After Liver Transplantation
• Persistent Portal Hypertension After Liver Transplant
• Biliary Complications
• Vascular Complications: Arterial, Venous
• Metabolic Complications
83

84. Persistent Portal Hypertension After LT
• Most clinical manifestations of PHTN resolve quickly after LT.
• Although vestigial EV/GOV may remain, VH is very rare, unless it is in the presence of a
new source of PHTN such as PVT.
• Persistent ascites after LT is uncommon. An extended cold ischemia time and recurrent
hepatitis C virus infection are RFs for post-LT ascites.
• Post-LT ascites is initially managed by a low-salt diet and diuretics.
• Many transplant recipients have splenomegaly for years after LT, and it may contribute
to persistent thrombocytopenia.
• The presence of HE after LT in the absence of cirrhosis of the allograft should prompt a
search for a portosystemic shunt.
84

85. Biliary Complications
• The bile ducts in the allograft are very sensitive to ischemia. Ischemic insults,
particularly at the time of cold ischemia, can result in biliary leaks, biliary tract
strictures, and bile duct stones.
• Consequently, biliary complications are more common in pts who receive an allograft
from a cardiac death donor.
• The risk of biliary complications is also higher in pts who undergo live donor LT.
• The choledochocholedochal anastomosis is the MC site of stricture formation.
• Bile duct damage, strictures, and stones may result from hepatic artery stenosis or
HAT.
• Ischemic strictures are often intrahepatic, and may progress to formation of
intrahepatic and extrahepatic biliary casts (the so-called biliary cast syndrome) .
85

86. • Doppler USG is a useful initial test to determine HA patency in pts with biliary strictures
after LT.
• Most strictures of the bile duct can be managed successfully with ERCP.
86

87. Biliary cast syndrome
• Biliary cast syndrome presents as elevated cholestatic liver enzyme levels (alk phos and
GGT), elevated levels of ATs, and eventually elevated levels of serum bilirubin.
• Itching is often a prominent symptom.
• Pts may also demonstrate features of ascending cholangitis: abdominal pain, jaundice,
and fever.
• MX is challenging, and is best achieved with a multidisciplinary approach involving the
transplant team and interventional radiology.
• When accompanied by allograft failure, biliary cast syndrome may require
retransplantation.
87

88. Bile leaks
• Bile leaks tend to be early (first 30 days) related to the bile duct anastomosis.
• Abdominal pain and peritoneal signs may be masked by immunosuppression.
• Early leaks are diagnosed by ERCP or percutaneous cholangiography.
• HIDA scanning may be useful.
• They are usually treated by the endoscopic insertion of a stent.
88

89. Extrahepatic anastomotic strictures
• Extrahepatic anastomotic strictures present after about 5 months as intermittent fever
and fluctuating serum biochemical abnormalities.
• They are DX by MRI cholangiography, ERCP, or percutaneous cholangiopancreatography
and treated by balloon dilation and/or insertion of plastic stents.
• Hepatic arterial patency must be confirmed.
• They are more common with split grafts whether from deceased or live donors.
89

90. Non‐anastomotic or ‘ischaemic‐type’ biliary strictures
• Develop in 2–19% after several months. They develop in the donor common hepatic
duct, with variable extension into the main intrahepatic ducts.
• On cholangiography, the wall of the duct may appear irregular and hazy, presumably
reflecting areas of necrosis and oedema.
• Attempts are made to treat them by balloon dilation and stenting.
• Hepaticojejunostomy is sometimes possible.
• Re‐transplant may be necessary.
They are associated with multifactorial damage to the hepatic arterial plexus around bile ducts.
Factors include prolonged cold ischaemia time, HAT, ABO blood group incompatibility, rejection, foam cell arteriopathy.
They are more common with donation after cardiac death donors.
90

91. Biliary stones, sludge, and casts
• Biliary stones, sludge, and casts can develop any time following transplant.
• Obstruction, particularly biliary stricture, may be important.
• Foreign bodies such as Ttubes and stents may serve as a nidus for stone formation.
• Ciclosporin is lithogenic.
• Treatment is by endoscopic sphincterotomy and stone extraction.
91

92. Pulmonary complications
• In infants, and rarely in adults, death during LT may be related to platelet aggregates in
small lung vessels. Intravascular catheters, platelet infusions, and cell debris from the
liver may contribute.
• In the ICU, pulmonary infiltrates are most frequently due to pulmonary oedema and
pneumonia. Other causes are atelectasis and respiratory distress syndrome.
• In the first 30 days, pneumonia is usually due to methicillin‐resistant Staphylococcus
aureus, Pseudomonas, and less frequently Aspergillosis. After 4 weeks, pneumonia due
to CMV and Pneumocystis is seen.
92

93. Non‐specific cholestasis
• This is frequently seen in the first few days, with the serum bilirubin peaking at 14–21
days.
• Liver biopsy suggests extrahepatic biliary obstruction but cholangiography is normal.
• Factors involved include mild preservation injury, sepsis, haemorrhage, and renal
failure.
• If infection is controlled, liver and kidney function usually recover but a prolonged stay
in the ICU is usually necessary.
93

94. Vascular Complications
Arterial
• HAT, and its variant hepatic artery stenosis, may cause graft dysfunction at any point
from the perioperative period to years after the LT.
• In a systematic review the incidence of early HAT was 4.4% (8.3% in children and 2.9% in
adults).
• HAT immediately after LT often presents as PNF. Later it may cause abnormal liver
enzyme levels, bile duct injury (strictures, biliary cast syndrome), or sterile bile
collections, often called bilomas. When the latter become infected, they form hepatic
abscesses.
• Doppler sonography is an excellent tool to identify HAT, with SN approaching 100%.
• Early HAT requires urgent intervention because of high mortality rates without
revascularization or retransplantation.
94

95. • Fever and abdominal pain are the most common presenting symptoms associated with
infected bilomas, but one third of pts present asymptomatically.
• Whereas infected bilomas in the absence of HAT may resolve with percutaneous
drainage and use of intravenous antibiotics, in the presence of HAT medical MX leads to
resolution of only a minority of infected bilomas.
• In these circumstances the patients need repeated transplantation.
95

96. Venous
• Thromboses of the hepatic or portal veins are uncommon after LT, and present with
complications of portal hypertension.
• Thrombosis of the hepatic or portal veins is managed medically with anticoagulation,
although subsequent endoscopic, radiologic, or surgical interventions may be required.
96

97. Metabolic Complications
• Hypertension
• Diabetes Mellitus
• Dyslipidemia
• Obesity
• Cardiovascular Disease
• Renal Disease
• Metabolic Bone Disease
97

98. Hypertension
• HTN, whether essential or de novo after LT, is common in the LT population and is
exacerbated by immunosuppressive RX as corticosteroids and CNI.
• Lifestyle modifications are fundamental to MX and include a low sodium, high
potassium diet, smoking cessation, weight loss, and exercise.
• Calcium channel blockers (nifedipine) and beta blockers (carvedilol) are the preferred
pharmacologic agents as these improve calcineurin inhibitor–induced vasoconstriction.
• Unlike the nontransplant pt, ACE inhibitors likely have a lesser role to play in the
posttransplant pt at least in the first year owing to low circulating levels of renin.
• There are data that suggest that ACE inhibitors and angiotensin II receptor blockers
(ARBs) prevent and/or reduce calcineurin inhibitor–induced kidney injury.
98

99. Diabetes Mellitus
• In addition to the usual risk factors for DM, in the post-LT pt there are additional RFs of
diabetogenic medications (corticosteroids, tacrolimus), viruses (hepatitis C virus), and
obesity.
• Diabetes can be transient (typically related to corticosteroid use in the early
posttransplant period) or persistent.
• MX of DMis similar to that in the general population. However, caution should be used
in the setting of unstable graft function because many oral diabetic drugs are
metabolized by the liver.
• Insulin is deemed the safest medication under these circumstances.
99

100. Dyslipidemia
• Although genetics and environmental factors play a role, immunosuppressive agents are
the most important contributors to posttransplant hyperlipidemia.
• Corticosteroids and calcineurin inhibitors are the usual culprits.
• The mTOR inhibitors are the most potent cause of hyperlipidemia among the
immunosuppressants.
• Statins are first-line therapy.
100

101. Obesity
• Weight gain is very common after LT because of restored wellbeing and the appetite-
stimulating effects of corticosteroids.
• The management of obesity and metabolic syndrome in LT recipients mirrors that in the
general population.
• In circumstances where the patient is unable to lose weight, bariatric surgery may be
considered, although experience is limited.
101

102. Cardiovascular Disease
• The RFs for CVD after LT include HTN, DM, obesity, hyperlipidemia, and tobacco use.
• Cardiovascular events account for 21% of deaths among LT recipients who survive for
more than 3 years after LT.
• To reduce the cardiovascular risk profile, each of the individual RFs must be addressed,
such as cessation of tobacco use, control of hypertension, and euglycemia, and the
immunosuppressive regimen must be carefully tailored.
102

103. Renal failure
• Renal injury, both acute and chronic, is common following LT.
• The causes include pre‐existing kidney disease, intraoperative or postoperative
hypotension and shock, sepsis, suboptimal donor quality, primary nonfunction, acute
HAT, nephrotoxic antibiotics, and ciclosporin or tacrolimus.
• The cumulative incidence of stage ≥4 CKD at 5 years following LT is 18%.
• During the first 10-years after LT, kidney failure needing maintenance dialysis arises in
up to 8% of recipients. Furthermore, kidney failure arising in LT recipients accounts for
1.0% of all kidney transplants in the US.
• The estimated GFR at the time of LT has been shown to be the only independent
predictor of post LT CKD. For every 10 mL decrease in estimated GFR, the risk of post LT
CKD ↑ by 33%.
103

104. Renal Disease
• The injurious effects of calcineurin inhibitors can be reduced, often with replacement by
mycophenolate or an mTOR inhibitor.
• Such reductions run the risk of precipitating ACR, which affected 13% of pts in one
study.
• Use of mTOR inhibitors is contraindicated in the presence of proteinuria.
104

105. Metabolic Bone Disease
• LT recipients are at ↑ed risk of bone mineral loss, occurring in two overlapping phases.
• In the first 4 months after LT, almost all recipients experience bone loss. This is
attributed to postoperative exposure to corticosteroids, although CNI may exacerbate
bone loss.
• After 4 months, in LT recipients with normal allograft function, bone mineral density
starts to increase and the frequency of fractures declines. In this phase, BMD is the
most important factor determining fracture risk, and the incidence is highest in pts who
have undergone LT for chronic cholestatic disease.
105

106. Metabolic Bone Disease
• One single-center series suggested that during a mean radiologic follow-up of just over
5 years, 25% of pts who underwent LT for chronic cholestatic liver disease developed de
novo fractures.
• The AASLD guidelines recommend that along with vitamin D and calcium
supplementation, BMD should be measured annually in osteopenic pts and every 2 to 3
years in patients with normal BMD in the early years.
• Frank osteoporosis should be treated with bisphosphonates.
106

107. Posttransplant Malignancies
• The incidence of malignancy is much higher in posttransplant pts compared with the
general population.
• Several factors contribute, including loss of immunologic surveillance of oncogenic
clones, effects of cancer-promoting viruses, and direct carcinogenic effects of
immunosuppressive medications.
• Among the immunosuppressive medications, the mTOR inhibitors have antiproliferative
and therefore antioncogenic effects and may be beneficial choices in LT pts.
• Studies establishing a benefit are lacking, but many programs have adopted mTOR
inhibitors for pts who have received an LT for HCC once the initial recovery interval has
passed.
107

108. Skin Cancers
• Melanoma and nonmelanoma skin cancers together account for approximately half of
the malignancies seen in the post-LT population.
• It is thus advised that, starting at 5 years after LT, all posttransplant pts should undergo
dedicated skin checks annually.
• For patients with a history of skin cancer before LT, close follow-up should begin at 1
year after LT.
• In addition, LT recipients, particularly fair-skinned pts, should avoid sun damage by
wearing sunblock, long sleeves, and a hat when in the sun.
108

109. Posttransplant Lymphoproliferative Disorder
• PTLD is a B-cell lymphoma arising in immunosuppressed pts.
• In many cases, PTLD is a/with EBV infection of B lymphocytes, either due to primary
infection or reactivation. However, negative EBV PCR does not preclude the DX of PTLD.
• RFs include Epstein-Barr virus seronegativity status of the recipient, young age, and
intensity of immunosuppression.
• More than half the cases of PTLD occur within the first year.
• PTLD presents with nonspecific constitutional symptoms such as fatigue, anemia, weight
loss, or fever. PTLD may arise in the allograft and may be discovered during the work-up
of elevated liver enzyme levels.
• The DX is made by histopathologic evidence of lymphoproliferation and confirmation is
by flow cytometry.
109

110. • The WHO classification system describes four major histopathologic subtypes, which
likely represent the spectrum of PTLD:
1. early hyperplastic lesions
2. polymorphic lesions
3. monomorphic lesions
4. classic Hodgkin-type lymphomas
• Current treatment strategies for PTLD all begin with reduction of immunosuppression.
• Additional therapy is on a case-by-case basis and includes some combination of anti–B-
cell monoclonal antibodies and/or cytotoxic chemotherapy to destroy lymphoma cells,
antiviral therapy to eliminate EBV, and surgical excision for localized disease.
110

111. Solid Organ Malignancy
• Because solid organ cancers account for approx 1/3RD of postLT de novo malignancies,
screening for cancer is an integral component of regular posttransplant health
maintenance.
• Cigarette smokers, often pts who have undergone LT for ALD, are at ↑ed risk of cancers
of the aerodigestive tract.
• Pts who receive an LT for PSC are at risk of colorectal cancer if they have concomitant
UC.
• Female LT recipients must be carefully monitored for human papillomavirus–associated
cervical cancer.
111

112. Solid Organ Malignancy
• Pts who have had an HCC in their explanted liver are at risk of recurrence.
• In one single-center series of 268 pts with HCC who received an LT, 51 (19%)
experienced recurrence, 6% in the first year, and 13.5% within the first 3 years.
• Thus patients who have undergone LT for HCC need serial surveillance for recurrence for
the first 5 years.
112

113. Infectious Disease Complications
• Posttransplant pts are at increased risk of both common and opportunistic infections.
• RFs that have been identified include high-dose immunosuppression, marked debility,
poor baseline nutritional status, and the catabolic effect of a major operative
procedure.
• Like many hospital in-pts, LT recipients are at increased risk of nosocomial infections,
specifically catheter-associated UTI, central line–associated bloodstream infection,
ventilator-associated pneumonia, SSIs, and Clostridium difficile enterocolitis.
CMV is the most significant pathogen on this list. CMV-seronegative recipients of CMV-seropositive donor organs are at
the highest risk of infection, and should receive prophylaxis with ganciclovir or valganciclovir for a minimum of 3
months after LT.
Patients who have progressive disease despite high-dose ganciclovir therapy may have resistant virus. The next step is
genotypic analysis and consideration of foscarnet.
113

114. Prophylactic Strategies for Common Organisms That
Affect Liver Transplant Recipients
114

115. Preferred Antifungal Agents for Use in Liver
Transplant Recipients
115

116. Reproductive Health
• After a successful LT, menstruation and ovulation return in 90% of physiologically
capable women often within 1 or 2 months.
• Pregnancy in an LT recipient carries increased risks for both the mother and the baby.
• Maternal risks include hypertension and preeclampsia.
• Fortunately, maternal death is rare and not more frequent than in the general
population.
• Pregnancies that survive the first trimester may proceed to a live birth, albeit with a
greater incidence of prematurity and/or low birth weight.
• According to National Transplant Registry guidelines, women who have undergone LT
should postpone pregnancy until at least 1 year after LT, and once the allograft
function has stabilized with immunosuppression at a low maintenance level.
116

117. • Stable medication regimens should be continued during pregnancy with as little
alteration as possible, and close maternal and fetal surveillance are required.
• There is no single best immunosuppressive protocol for LT recipients who are pregnant.
• Pts taking mTOR inhibitors and mycophenolic acid or mycophenolate mofetil are
advised to avoid pregnancy on account of their teratogenic potential.
• The aim is to maintain stable allograft function on minimum immunosuppression, while
liver enzyme levels are monitored frequently.
• With LT there is no specific contraindication for vaginal delivery.
117

118. Recurrence of primary disease
• Certain diseases, such as α-1-antitrypsin deficiency, WD, and polycystic liver disease,
are cured by LT and will not affect the allograft.
• Most other diseases, such as AIH, PBC, PSC, fatty liver disease, and viral hepatitis, can
recur in the posttransplant setting and represent an ongoing MX challenge for the
transplant community.
• In many cases, these diseases can be aggressive and ultimately cause graft failure,
need for retransplant, or death.
• The autoimmune diseases AIH, PBC, and PSC all recur at a rate of approx 20%.
118

119. Repeated LT: Recurrent Disease and Graft Failure
• Repeated LT is a relatively uncommon procedure yet accounted for 9.7% of all LT
procedures annually in the US during the years 1988 to 2013 and 357 (5.3 %) of the
6729 LT in 2014.
• The vast majority of repeated LT are performed early in the posttransplant period (<90
days) for primary graft nonfunction, hepatic artery thrombosis, or technical reasons
related to the first procedure.
• Repeated LT performed later are generally for ischemic-type biliary lesions, chronic
rejection, or recurrent disease.
• Allograft rejection is a comparatively rare cause of allograft loss leading to repeated
transplantation.
• Nearly all diseases that prompted the first LT can reoccur in the liver graft.
119

120. • Survival rate after repeated LT is approx 15% to 20% lower than that for first transplant
recipients at most time points but can be much worse, particularly in those with early
aggressive recurrent hepatitis C.
• Several models exist to assist with candidate selection by predicting survival. In most
models, increasing recipient age, bilirubin, creatinine, and time to repeated LT were
a/with worse outcome.
• In comparison with first LT, where the threshold for survival benefit is a MELD >15, the
threshold for survival benefit from repeated LT is a MELD >21 because of the lower graft
survival in the repeated LT recipients.
120

121. End of slides
121