Immunoprophylaxis against and prevention of recurrent viral hepatitis after liver transplantation

Abstract

The reinfection of the hepatic allograft with hepatitis B virus and hepatitis C virus can have important sequelae that result in poor long-term patient and graft survival. Although a response to treatment with antiviral medications can improve these outcomes, not all patients tolerate these medications or experience viral eradication. Avoiding reinfection of the graft is the most effective means of improving the long-term outcomes for these patient populations. This review is focused on the prevention of viral hepatitis reinfection after liver transplantation. Liver Transpl 18:514-523, 2012. V C 2012 AASLD.Received July 2, 2011; accepted February 2, 2012.Although recurrent disease after liver transplantation (LT) can occur with most indications for LT, it is a particular issue with viral hepatitis. The dampening of immune mechanisms by immunosuppression can lead to the recurrence of chronic viral hepatitis from hepatitis B virus (HBV) or hepatitis C virus (HCV) in the graft and can alter its natural history significantly. In fact, an untreated graft reinfection can lead to the rapid progression of fibrosis and early graft loss. The timing and natural history of recurrent viral hepatitis after transplantation can vary according to number of factors, including surgical factors and donor or recipient factors. The treatment of recurrent disease can be more problematic (more so with HCV) in transplant patients versus nontransplant patients because of decreased efficacy and potentially increased side effects. The impact of recurrent disease on overall patient and graft survival can be reduced by the understanding and prevention of recurrent viral hepatitis. This review outlines the progress in prophylaxis focused on reducing the recurrence of HBV and HCV after LT, and it underscores the areas in need of further investigation so that the effects of recurrent disease on posttransplant outcomes can be reduced. HBVThe first experiences with LT for HBV-related disease were marred by high rates of graft failure and patient mortality due to aggressive recurrent disease. These poor outcomes compelled some centers to declare a moratorium on LT for HBV-related disease. Advances in the prevention and treatment of recurrent disease after LT have resulted in overall survival rates now as high as 90% at 5 years, 1 and they have made HBV-related liver disease an acceptable indication for LT worldwide. With appropriate prophylaxis and proper patient adherence, recurrence rates are now consistently less than 10%. Recurrent HBV after transplantation is due to a failure Abbreviations: ADV, adefovir dipivoxil; anti-HBc, antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface

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“…12 However, major disadvantages of highdose IV HBIg for prevention of posttransplant HBV reinfection include its high cost, decreased efficacy in patients who are HBVDNA/HBeAg positive at time of transplant, and development of resistance due to genetic HBV mutants. [12][13][14] To reduce the amount of HBIg needed, individualized doses of HBIg are based on anti-HB titers; many transplant centers adjust the dose of HBIg accordingly, to maintain the anti-HB titer at a protective level. 15 Additionally, intramuscular administration of HBIg reduces the amount of HBIg needed.…”

Hepatitis B Immunoglobulin Prophylaxis after Liver Transplantation: Experience in a Tertiary Transplant Centre

“…19 Several attempts 9,10,12,13 have been made in the past to reduce the cost of post LT maintenance prophylaxis against HBV recurrence. These include switching over from intravenous to intramuscular administration of HBIG, prolonging the interval between HBIG dose and finally tailoring the dose without following a fixed time schedule, 15,20 HIP has been used in some centers 16,20,21 as a cheap and effective alternative to commercial HBIG. The target with any form of treatment has been to attain a safe anti HBs titer (from 300 to 500 IU/L to 100 IU/L).…”

Management of Chronic Hepatitis in Special Hosts and Special Situations: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

“…Dekompanse sirozu olan KHB hastalarında ölümlerin çoğunun tedavinin ilk 6 ayında meydana geldiği ve tedavi öncesindeki bilirübin, kreatinin ve HBV DNA düzeylerinin artmış olmasının yüksek risk faktörleri olduğu saptanmış-tır. HBV replikasyonunun erken baskılanmasıyla olumlu sonuçlar alınması mümkündür (5 aşamada uygulanır: [1] Karaciğer nakli süresince, anhepatik fazda, intravenöz (İV) olarak 4000-10000 İÜ; [2] nakil sonrası 3-7 gün süresince, intramüsküler (İM) veya İV 2000-10000 İÜ/gün; [3] nakli izleyerek anti-HBs düzeyi 100 İÜ/lt üzerinde tutulacak şekilde yüksek doz (10000 İÜ/ay) ya da düşük doz (400-2000 İÜ/14 gün veya 3000-6000 İÜ/ay veya 10000 İÜ/2-3 ay) verilir (6,8). İdame dozu ya seçilen sabit bir miktarda uygulanır ya da çoğu merkezde yeğlendiği gibi alıcının anti-HBs düzeyi izlenerek belirlenir.…”

“…Ancak optimal anti-HBs düzeyi hakkında bir görüş birliği yoktur. Bazen anti-HBs düzeyi >100 İÜ/lt olarak tutulmaya çalışılırken; bazen de ilk 14 gün >500 İÜ/lt, sonra >100-200 İÜ/lt, 6. aydan sonra ise >100 İÜ/lt olarak tutulması hedeflenmektedir (8,13). Avustralya ve Yeni Zelanda'da İM HBIG, LAM ile kombine olarak kullanılmaktadır.…”

“…Avustralya ve Yeni Zelanda'da İM HBIG, LAM ile kombine olarak kullanılmaktadır. Anti-HBs düzeyi, nakil sırasında 800 İÜ, sonra 1 hafta 800 İÜ/gün ve daha sonra 800 İÜ/ay olanlarda 5 yılda yaklaşık %4 nüks bildirilmiştir (8,12). Ancak bu çalışmalar bire bir veya randomize kontrollü çalışmalar değildir.…”