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Until recently, liver transplantation in patients with hepatitis B was associated with a high rate of graft loss and poor survival because of viral recurrence. 1-3 Favorable outcome following liver transplantation for hepatitis B virus (HBV)-related liver disease was made possible with long-term, high-dose, passive immunoprophylaxis using hepatitis B immune globulin (HBIG). 4,5 Hepatitis B still recurs, however, despite HBIG. Recurrence may be caused by saturation of the antibody binding capacity of HBIG by a high viral load, or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. 6,7 Overall recurrence rates with HBIG monotherapy vary from approximately 15% to 50%. 4,5,[8][9][10][11] Using a different dosing schedule, in early experience from our own institution HBV recurrence on HBIG was 44%. 12 The wide disparity in the data reflects differing patient populations, e.g., patients who are HBV-DNA-positive at the time of transplantation have higher rates of recurrence. Moreover, the different dosing regimens of HBIG are also likely to influence recurrence rates. 5,11,13 An alternative approach to preventing HBV recurrence became possible using the purine nucleoside analog reversetranscriptase inhibitor, lamivudine. Demonstration of its efficacy, in the nontransplantation setting, in suppressing HBV-DNA synthesis 14,15 led to studies using lamivudine following liver transplantation as prophylaxis against hepatitis B recurrence, 16,17 or as treatment of de novo or recurrent hepatitis B. 17,18 Although a DNA virus, HBV replicates via an RNA intermediate. As is seen in human immunodeficiency virus, 19 lamivudine escape mutations in the tyrosine, methionine, aspartate, aspartate (YMDD) locus of the HBV-DNA polymerase are increasingly being reported. [20][21][22][23] While prophylactic failures of HBIG have been treated successfully with lamivudine, there are no reports documenting successful treatment of patients with lamivudine-resistant HBV.Mechanistic evidence suggests that HBIG and lamivudine would be synergistic. By inhibiting viral replication with lamivudine, it would be less likely that the viral binding capacity of HBIG would be overwhelmed; furthermore, there would be little pressure to select for HBIG-resistant mutations in the HBsAg molecule. By providing humoral immunity, HBIG may limit viral spread, confining the virus to extraheAbbreviations: HBV, hepatitis B virus; HBIG, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen; anti-HBs, antibodies against hepatitis B surface antigen; PCR, polymerase chain reaction; HCC, hepatocellular carcinoma; HBeAg, hepatitis B envelope antigen.From

Recent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1beta appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Immediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7-10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.

Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

Liver transplantation provides excellent patient and graft survival rates for patients affected with PSC independent of pretransplant biliary tract surgery. Incidental cholangiocarcinoma does not affect patient survival significantly. However, known CCA or common duct frozen section biopsy specimen or both showing CCA are associated with poor recipient survival, and OLT should be proscribed in these cases. Recurrent PSC occurs in approximately 9% of cases but does not affect patient survival. Post-transplant colectomy does not affect patient survival adversely.