- Category: HBV Treatment
- Published on Tuesday, 24 April 2012 00:00
- Written by Liz Highleyman
No patients treated with entecavir (Baraclude) after receiving liver transplants due to complications of chronic hepatitis B experienced virological recurrence, according to a study described at the 47th International Liver Congress (EASL 2012) last week in Barcelona.
Without preventive therapy, hepatitis B virus (HBV) recurrence after liver transplantation is common and can lead to graft failure and death. Traditionally, antiviral prophylaxis for transplant recipients has used hepatitis B immunoglobulin (HBIg), or injected antibodies.
Nucleoside/nucleotide analogs may be used in addition to or instead of HBIg, but older agents -- in particular lamivudine (3TC; Epivir) -- are limited by rapid emergence of drug resistance, and some have side effects. Entecavir is a newer nucleoside analog with a high barrier resistance, long-term efficacy, and a favorable safety profile.
Robert Perrillo from Baylor University Medical Center and colleagues designed a study to evaluate the safety and efficacy of entecavir, with or without HBIg, for preventing post-transplant HBV recurrence.
This open-label, single-arm Phase IIIb trial (Study ETV-109) included 65 participants undergoing orthotopic liver transplantation for chronic hepatitis B-related liver disease who had HBV DNA levels below 172 IU/mL, or about 1000 copies/mL, at the time of transplant.
Most patients (about 80%) were men, about 37% were Asian and 39% white, and the average age at the time of transplantation was 49 years. Most were hepatitis B "e" antigen (HBeAg) negative (89%) and hepatitis B surface antigen (HBsAg) positive (94%). The mean HBV DNA level was 0.9 log IU/mL.
A majority of participants were treatment-experienced, having previously used entecavir (40%), lamivudine (34%), or adefovir (Hepsera, 19%); only 1 had used tenofovir (Viread). Just over one-third were undergoing liver transplantation due to hepatocellular carcinoma (HCC). About 80% were cadaver donor transplants, the rest from living donors.
Participants received 1.0 mg once-daily entecavir for 72 weeks post-transplant. Almost all patients also received various regimens of HBIg in addition to entecavir, depending on the standard of care at their specific study site. The primary endpoint was the proportion of patients treated for at least 4 weeks who had undetectable serum HBV DNA (> 50 IU/mL) at week 72.
- 4 patients discontinued therapy before week 4, leaving 61 in the final analysis; within this group, 6 more stopped between weeks 4 and 72, leaving 55 who completed treatment.
- At week 72, none of the participants had experienced HBV recurrence (> 50 IU/mL).
- 2 people had HBsAg recurrence after becoming HBsAg negative.
- Almost all participants experienced some adverse events during the study -- with 55% having serious adverse events -- but no one discontinued for this reason.
- The most frequent serious adverse events were acute kidney failure (4 patients) and hepatic artery thrombosis (3 patients).
- 6 patients experienced alanine aminotransferase (ALT) flares, but none were associated with HBV DNA breakthrough or liver graft rejection.
- About 60% of patients experienced moderate and 30% experienced serious creatinine elevation (all of whom received calcineurin inhibitors for immunosuppression).
- There were 18 episodes (28%) of liver graft rejection.
- 1 participant experienced HCC recurrence.
- 4 patients (9%) died during the study period, with no deaths considered drug-related.
In this study of patients treated with entecavir +/- HBIg after chronic hepatitis B-related orthotopic liver transplantation, no patient experienced virological recurrence of HBV for up to 72 weeks after transplant," the investigators concluded. "The frequency and nature of observed adverse events were consistent with the expected safety events for this population of chronic hepatitis B patients, and were comparable to previous reports."
R Perrillo, M Buti Ferret, F Durand, et al. Safety and Efficacy of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Speaker. 47th Annual Meeting of the European Association for the Study of the Liver (EASL 2012). Barcelona, April 18-22, 2012. Abstract 535.