Outcome of patients with hepatitis B and HIV infections referred for liver transplantation

A new study on HIV patients who also had Hepatitis B virus (HBV) found that better outcomes are possible if they are referred early for transplant and treated with a combination of drugs for HBV. It is essential to monitor the HBV status of these patients, however, in order to control the emergence of drug-resistant HBV infection.

The results of this study appear in the May 2006 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience.

In the past, HIV patients were largely excluded from consideration for liver transplants due to high death rates from HIV-related complications. However, in recent years HIV-related deaths have declined due to the development of highly active antiretroviral therapy (HAART). At the same time, a greater number of deaths are due to liver complications (such as those caused by HBV) have been seen in HIV-infected persons. Simultaneously, there have been advances in immunosuppression and the treatment of post-transplant complications, leading to an increasing number of transplant centers performing liver transplants on HIV-infected patients. Outcomes for HBV patients undergoing liver transplants have improved, overall, in recent years, but until now it was not known how HIV patients with HBV fared when undergoing liver transplantation.

In the first study to assess the outcomes of HBV-HIV liver transplant candidates, researchers led by Norah A. Terrault of the University of California in San Francisco, followed 35 HBV-HIV patients referred to UCSF for liver transplantation between July 2000 and September 2002. Of these, nine (26 percent) were wait-listed, 10 (28 percent) were not eligible for transplant for various reasons, 9 (26 percent) were too early in the course of their liver disease for a transplant, 3 (9 percent) were too sick for a transplant and four (11 percent) died during the evaluation process. The prolonged use of the drug lamivudine, which is used to treat both HIV and HBV, has led to lamivudine resistance in recent years and 67 percent of the referred patients had lamivudine-resistant HBV. Almost half of these patients were taking additional anti-HBV medications (tenofovir and/or adefovir) that are effective against lamivudine-resistant HBV. After the initial referral, 10 patients died of liver-related complications (the median follow-up was 7.5 months), the majority within three months of referral. A total of four patients ultimately underwent liver transplants and all of them survived and are without evidence of HBV recurrence.

"Our limited experience indicates patients with HIV-HBV coinfection can successfully undergo liver transplantation without progression of viral (HBV) disease, even in the setting of lamivudine resistance," the authors state. They suggest that the low rate of eligible candidates may be partially due to a lack of knowledge on the part of referring physicians about the indications and timing for liver transplants for HBV-HIV-infected patients. Patients taking tenofovir and/or adefovir were more likely to survive with or without a transplant, indicating that controlling HBV is an important factor in HIV-infected patients with liver disease. The authors conclude: "Ongoing close monitoring of HBV replication status in HBV-HIV coinfected patients will be essential in identifying the emergence of drug-resistant HBV and in making therapeutic decisions to minimize the risk of liver-related complications."

In an accompanying editorial in the same issue, Didier Samuel and Jean-Charles Duclos-Vallee of the Centre Hipatobillaire in Villejuif, France note that since liver transplants in HIV patients are relatively new, questions about several issues have been raised, such as the ideal timing in HIV-HBV or HIV-HCV (Hepatitis C) patients, the risk of HIV progression after transplant, and the risk of liver toxicity with HAART. They note that although the current study is small, its message is important, particularly with regard to the fact that many potential candidates die either while on the waiting list or while being evaluated for transplant. "A particular effort should be made to inform physicians caring for HIV patients of the possibility of liver transplantation in this patient population and the importance of a prompt referral to liver transplantation centers," the authors state. They also suggest that studies need to be conducted to determine factors that might indicate a poor prognosis in these patients. "In conclusion, liver transplantation for HIV patients is an emerging field with good preliminary results in HIV-HBV infected patients and pending results in evaluation of HIV-HCV patients," the authors state. They add that discussions among hepatologists, transplant physicians and HIV specialists need to take place regarding the best timing for liver transplantation and the choice of HAART in order to avoid the emergence of drug-resistant HBV.

http://www.interscience.wiley.com/journal/livertransplantation