Liver transplantation can be successful in patients co-infected with HIV and hepatitis B

Christopher Gadd
Published: 04 May 2006

A small observational study has shown that liver transplantation can be successful in HIV-positive patients who have liver disease due to hepatitis B virus co-infection, even if they are resistant to 3TC (lamivudine, Epivir / Zeffix). The study’s findings were published in the May edition of Liver Transplantation.

The study also revealed that many doctors refer co-infected patients for liver transplants too late or when they are not suitable for transplantation, with some patients dying of liver-related causes before they can receive a transplant. This leads the investigators to call for doctors to be made aware of the best time to refer patients for transplantation.

Despite widespread vaccination in developed countries, the hepatitis B virus is relatively common. Some studies have found infection rates approaching 10% in people with HIV, notably in gay men and injecting drug users. Although up to 95% of adult patients clear hepatitis B after infection, long-term infection can lead to irreversible liver damage and eventually cancer, if it is not controlled effectively by antiviral drugs.

Liver transplantation is the best treatment for patients with hepatitis B who have end-stage liver disease. While outcomes of HIV-negative patients have improved over the past few years, there is less information on outcomes in patients co-infected with HIV. Accordingly, a group of doctors from the University of California at San Francisco assessed the outcome of 35 co-infected patients referred for liver transplantation at their hospital between July 2000 and September 2002.

The investigators were particularly interested in assessing the effect of 3TC resistance in these patients’ outcomes. Since 3TC is active against both viruses, long-term use of 3TC to treat HIV can lead to resistant hepatitis B virus emerging in co-infected patients. This may jeopardise the use of the drug to prevent hepatitis B infection from returning after transplantation

When they were referred, the patients had a median CD4 cell count of 273 cells/mm3. Two-thirds of the patients had levels of hepatitis B virus above 100,000 copies/ml after taking 3TC therapy for more than six months, regarded by the investigators as indicating 3TC resistance.

Nine (26%) of the patients were put on the waiting list for liver transplantation, with four receiving a transplant during the study period between three and 40 months after referral. All four patients were on antiretroviral and anti-hepatitis B therapy before transplantation, and they all survived with undetectable hepatitis B virus levels in the blood at the end of follow-up, between 18 to 48 months after transplantation. None of the patients rejected their new livers.

All four patients received prophylactic anti-hepatitis B treatment after the transplant. Three of these patients were resistant to 3TC, and received hepatitis B immunoglobulin (HBIG), 3TC and tenofovir (Viread) or adefovir (Hepsera). The fourth patient, who was susceptible to 3TC, received HBIG and 3TC for nine months, before adding tenofovir after hepatitis B virus DNA levels became detectable briefly.

“Patients with HIV-hepatitis B virus co-infection can successfully undergo liver transplantation without progression of viral disease, even in the setting of lamivudine resistance,” the investigators conclude.

One of the patients on the waiting list died 18 months after referral before receiving a new liver. In contrast, another patient was removed from the waiting list after an improvement in his condition. The remaining four patients were still awaiting a transplant at the end of the study.

Of the remaining patients in the study, three (9%) were too ill to receive a transplant and died of liver disease. A further four (11%) died, also of liver disease, during the evaluation period.

In addition, ten (28%) of the patients were found to be unsuitable for transplantation. Three of these were for HIV-related reasons including a history of Kaposi’s sarcoma or having a CD4 cell count below 100 cells/mm3. Two of these ten patients died after referral.

Finally, nine (26%) of the patients did not have liver damage that was advanced enough to warrant transplantation.

“Only 26% of referred patients are eligible candidates,” write the investigators. “This low rate of [eligibility] reflects, in part, a lack of knowledge on the part of referring physicians regarding the indications and appropriate timing for referral for liver transplantation.

“Since transplantation in HIV-infected individuals is relatively ‘new’ as a treatment option for end-stage liver disease, there is a need to educate referring gastroenterologists and infectious disease specialists regarding the indications and contraindications for transplantation in this population,” they add.

Reference

Terrault NA et al. Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation. Liver Transpl 12: 801-807, 2006.

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