1. Adult Liver Transplantation
Michael J. Moritz, M.D.
Drexel University College of Medicine

2. Case Presentation: 16yo HF transferred to HUH
History
2 wks of lethargy, anorexia, nausea
? days of dark urine, light stools
2 days of jaundice

3. ER Encephalopathy Dense icterus, mild ascites, splenomegaly, edema
Elevated LFT’s, total bilirubin 30mg/dL
Anemia, thrombocytopenia, coagulopathy
Oliguria and elevated creatinine

4. Diagnostic Testing 1) Ultrasound 2) Blood tests 3) Specialty exam
Cirrhosis, patent portal vein with hepatopetal flow, edematous gall bladder
2) Blood tests
Ceruloplasmin, serum copper
3) Specialty exam
Slit lamp with Kayser-Fleischer rings
4) Bx
Copper content per gram of liver tissue
5) Specific confirmatory testing
Urinary copper excretion, gene analysis

5. Wilson’s Disease Copper overload
Defective ATP7B copper transmembrane transporter in the Golgi apparatus
Copper not appropriately transferred out of hepatocytes to ceruloplasmin and bile
Accumulates in liver, CNS, red cells, bone
Fulminant (hepatic) vs. chronic (neuropsychiatric) presentation
Gene frequency 1:90 Homozygosity 1:30,000

6. Wilson’s Disease Medical Treatment
Copper chelation: trientene, D-penicillamine, tetrathiomolybdate
Zinc supplementation
Low copper diet (avoid organ meats, shellfish, dried beans, peas, whole wheat, chocolate,…)

7. Wilson’s Disease Transplantation
Corrects the genetically defective liver
Life long immunosuppression
Indications: FHF or Chronic Liver Dz

8. Explant—FHF Wilson’s Disease

9. Liver Transplantation
Liver transplantation is the OPTIMAL treatment for end stage liver disease (ESLD)
ESLD has 2 forms: Acute and Chronic
Acute=Fulminant Hepatic Failure
Chronic=Cirrhosis

10. Common Diagnoses in Liver Tplt. Pts. Last 118 Pts. 1°Dx 2°Dx
Hepatitis C %
Alcoholism % 12%
Cryptogenic %
FHF, Autoimmune 7%
PBC %
Hepatitis B % %
PSC %
HCC %

11. Less Common Diagnoses in Adults for Liver Transplantation
Wilson’s Dz—acute and chronic
Hemachromatosis
Budd-Chiari Syndrome
Congenital Hepatic Fibrosis
Polycystic Disease
Inborn errors of metabolism
Familial Amyloidotic Polyneuropathy

12. Fulminant Hepatic Failure (FHF)
Synonymous with Acute Liver Failure
Definition: Development of encephalopathy within ~8 weeks of the onset of symptoms or within ~2 weeks of the onset of jaundice
Pathology: Panlobular or Submassive necrosis

13. Causes of FHF Idiopathic Acetaminophen toxicity
Hepatitis B, A, E, other viruses
Drug reactions (INH, halothane, others)
Wilson’s Disease
Mushroom poisoning

14. FHF-Clinical Manifestations
Encephalopathy
Coagulopathy
Hypoglycemia
Cerebral edema
Sepsis—Multiorgan Failure

15. FHF-Prognosis
A race between progressive liver failure and its complications vs. liver regeneration
Age
Etiology
Rapidity of onset

16. FHF-Treatment Supportive ICU care Support of renal fxn, plasmaphoresis
ICP monitoring
Transplantation

17. Chronic Liver Disease—Indications for Transplantation
Ultimately, the decision to transplant is based upon the patient’s likelihood of survival
Survival with transplantation:
One-year ~85-90%
Two-year ~80-88%
Five-year ~65-75%

18. Patient Survival After Primary Liver Transplantation

19. Chronic Liver Disease—Indications for Transplantation
Ascites
Encephalopathy
Portal Hypertensive Bleeding
Hepatocellular Carcinoma in the setting of Cirrhosis

20. Chronic Liver Disease—Indications for Transplantation
Ascites
Ascites has a two-year mortality of 50%
SBP has a two-year mortality of 80%
Usual treatment-diuretics; when severe-Large Volume Paracentesis with Albumin Replacement
At its end stage, ascites and resultant ARF is called HepatoRenal Syndrome

21. Requirements for Transplantation
End stage liver disease
Physiologic ability to tolerate surgery
Cardiac, pulmonary, renal, cerebral function
Portal inflow
Social support
No extrahepatic infection or malignancy
Alcohol abstinence for 6 months

22. Contraindications Age>70? Cardiac-pulmonary-renal-cerebral function
Inability to safely be immunosuppressed
Substance problems
EtOH, tobacco, opiate analgesics, illicit drugs
Social problems

23. Hepatitis C-Natural History
Approx. 3 million infected in the US
Only 25% of infected individuals develop cirrhosis
Median--innoculation to cirrhosis=20years
Median—innoculation to HCC=30 years, prevalence of HCC unknown

24. Hepatitis C and Liver Transplantation
Near universal recurrence of viremia at high levels, 40% with hepatitis at one-year (bx)
40% with or mild hepatitis-negligible risk
40% with moderate hepatitis-not in <5years
20% with severe hepatitis and cirrhosis within 5 years of transplantation

25. Hepatitis C and Liver Transplantation-New News
The newest interferons (Pegylated interferon and consensus interferon) plus ribavirin have a 15-20% Sustained Viral Response in post-transplant patients!

26. Alcoholic Cirrhosis
Alcoholics have a post-tplt prognosis no different from patients with other diagnoses
Risk of Recidivist Drinking
10% pathologic drinking within one year
Predictors of Increased Risk Recidivism
Abstinence<6 months
Psychiatric dx, character disorder
Polysubstance abuse

27. Liver Transplant--Numbers
UNOS Waiting List 17,231 (2/8/05)
5,657 Cadaver donor liver transplants in from 6,549 cadaver donors (2004)
298 Living donor liver transplants (2004)
Waiting list mortality~15%
Cirrhotic complications
Progression HCC
Substance and social issues

28. Donor Liver

29. Donor Liver

30. Diagram of Piggyback Orthotopic Liver Transplant

31. Schematic of Venovenous Bypass

32. Liver Transplantation: Outcomes
Patient Survival at 1, 3, and 5 years 86% 78% 72%
Graft Survival 81% 71% 64%
Immunosuppression/Tolerance
Recurrent Dz
Immunosuppressive risks

33. Review—Liver Transplantation
Diagnoses—acute, chronic
Indications and contraindications
Hepatitis C, Alcohol
Insufficient numbers of cadaver donors to meet demand

36. Conclusions
With appropriately selected patients, Liver Transplantation offers an excellent chance for long-term, good quality of life survival for patients facing death from ESLD
Post-transplant Recurrent Hepatitis C is the largest clinical problem at present
Donors are in short supply

37. Organ Allocation for Adults
Status 1
FHF, Acute Wilson’s Disease
Early Post-transplant Complications: PNF, HAT <7 Days
Allocated by Waiting Time, Blood Group
Status 2
All Others
Allocated by MELD Score
Waiting Time at that score as tie breaker

38. MELD Score R=9.57ln(creat)+3.78ln(bili)+11.2ln(INR) +6.43
Scale from 6-40
Validation, c=0.82 for 90-day mortality for cirrhotics, almost the same as Child-Turcotte-Pugh score (c=0.84)

39. MELD Special Cases Hepatocellular Carcinoma Hepatopulmonary Syndrome
Familial Amyloidosis
OTC Deficiency, Crigler-Najjar Syn., etc.
Currently Special Cases constitute:
0 of 19 Status %
52 of 138 with MELD >30 38%
214 of 807 with MELD %
7 OF 6844 with MELD %
0 of 6228 with MELD < %

40. MELD UNOS: Transplanted 3/02-7/02 1786+570 HCC 428
Hepatopulmonary Syndrome
Portopulmonary Hypertension
Familial Amyloidotic Polyneuropathy
Oxalosis
Hepatoblastoma
Other Special Cases
Total

41. MELD & HCC
Evaluation of # and size of tumors (US, CT or MR of abdomen and chest, bone scan) and
Enhancing tumor >1cm, or
AFP >200, or
+ arteriogram, or
+ biopsy, or
Have had treatment with PEI, RITA, cryo, or TACE, and
Not be a candidate for resection

42. Conclusions
Liver transplantation is the optimal treatment for many end stage liver diseases
Allocation of deceased donor organs is driven by acuity (MELD) and exceptions
Survival outcomes are steadily improving, hampered by
Donor limitations
Recurrent disease