Hepatitis: Patterson SJ

Patterson SJ, Angus PW. · Victorian Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. · Curr Opin Organ Transplant. · Pubmed #19373086 No free full text.

Abstract: PURPOSE OF REVIEW: The established gold standard for prophylaxis against hepatitis B virus (HBV) recurrence post-liver transplant is combination hepatitis B immune globulin (HBIG) and lamivudine. This therapy reduces the risk of recurrence to less than 5% at 5 years; however, the cost of HBIG has led to the investigation of alternatives. This paper reviews the HBIG-sparing alternatives achieved with lamivudine and the prospects for the newer anti-HBV agents in post-liver transplant prophylaxis. RECENT FINDINGS: When used with lamivudine as part of combination prophylaxis, low-dose intramuscular HBIG is equivalent to high-dose intravenous HBIG. There is recent evidence that in patients receiving HBIG/lamivudine, HBIG can be replaced with adefovir dipivoxil at 6-12 months post-liver transplant without precipitating recurrence. Furthermore, a recent study showed that primary prophylaxis with combination adefovir/lamivudine therapy without the use of long-term HBIG was effective and well tolerated as primary prophylaxis. SUMMARY: Although there are few studies of potent newer anti-HBV agents such as entecavir or tenofovir being used as HBV prophylaxis, the properties of these drugs suggest that they should replace lamivudine within HBV prophylaxis regimes.

Angus PW, Patterson SJ. · Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia. · Liver Transpl. · Pubmed #18825721 No free full text.

Abstract: 1. Prophylaxis using the combination of lamivudine and high-dose intravenous hepatitis B immunoglobulin (approximately 10,000 IU monthly) reduces the long-term risk of recurrence of hepatitis B in hepatitis B surface antigen-positive transplant recipients to 5% to 10%. However, this therapy is expensive and inconvenient for patients. 2. Recent studies have shown that similar results can be obtained, at far less cost, with much lower doses of intramuscular hepatitis B immune globulin (400-800 IU monthly) in combination with pretransplant and posttransplant lamivudine therapy. 3. The development of lamivudine resistance pre-transplant can lead to hepatic decompensation and increases the risk of posttransplant recurrence in patients receiving hepatitis B immune globulin/lamivudine prophylaxis. Newer nucleos(t)ide analogues with lower resistance rates such as entecavir, adefovir, and tenofovir should therefore replace lamivudine in hepatitis B prophylaxis. 4. Combination therapy with these newer agents and low-dose intramuscular hepatitis B immune globulin is likely to be the most cost effective hepatitis B immune globulin-containing regimen for the prevention of hepatitis B recurrence post-transplant. 5. Some form of hepatitis B virus prophylaxis needs be continued indefinitely post-transplant. However, the use of antivirals with very low rates of drug resistance will make it possible to stop hepatitis B immune globulin therapy in many patients currently receiving hepatitis B immune globulin/nucleos(t)ide combination therapy.

Angus PW, Patterson SJ, Strasser SI, McCaughan GW, Gane E. · Victorian Liver Transplant Unit, Austin Health, Victoria, Australia. · Hepatology. · Pubmed #18925641 No free full text.

Abstract: Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen-positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 micromol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine. CONCLUSION: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost.