AMSTERDAM, the Netherlands — Despite hepatitis B virus suppression provided by current drugs, many patients coinfected with hepatitis B and HIV have advanced liver fibrosis, according to new research.

"Of the patients we had liver biopsies on, 31 of 53 — more than half — had advanced fibrosis, bridging fibrosis, or cirrhosis. That was despite their hepatitis B being reasonably controlled," said Richard Sterling, MD, chief of hepatology at Virginia Commonwealth University in Richmond. "Liver enzymes were not that high, and most patients had low or undetectable hepatitis B DNA."

Dr. Sterling cited 2 possible reasons for this. "Many of these patients could have been on older antiretroviral therapy that included lamivudine, which we know is not a good long-term drug for hepatitis B. As a result, over time their liver disease progressed sort of under the radar of their HIV provider," he explained.

"We also know that hepatitis B liver disease is immune mediated," he added. "Perhaps immune reconstitution, when their HIV therapy was just starting, actually caused more liver disease, unbeknownst to the HIV provider."

Hepatitis B is prevalent in about 8% to 10% of patients infected with HIV and is controlled with some of the same drugs. However, few patients are biopsied, so little is known about liver disease in this population.

To learn more, Dr. Sterling and colleagues conducted a retrospective analysis of coinfected patients who had undergone liver biopsy. He presented the results here at the International Liver Congress 2013.

The researchers compared demographic and clinical characteristics of patients with and without advanced fibrosis. In 95% of patients, the level of HIV RNA was undetectable. In 30%, the level of hepatitis B DNA was undetectable; in 35%, it was below 1000 IU/mL. In 62%, the test for hepatitis B e antigen was positive.

 
I think the bottom line with hepatitis B is that it's forgotten but not gone.
 

Patients with advanced fibrosis had lower levels of hepatitis B DNA (= .03) than those without advanced fibrosis, and more were on antiretroviral therapy (P = .02). For those with advanced fibrosis, there was a trend toward higher levels of aspartate transaminase (P = .08) and lower CD4 counts (= .08).

There were no differences between patients with and without advanced fibrosis in terms of HIV RNA level, hepatitis B antigen status, the specific drugs used to treat hepatitis B, or the proportion with low or undetectable levels of hepatitis B DNA.

"The important thing is that the hepatitis B DNA was undetectable in the same proportion of patients who had mild disease and who had advanced disease," Dr. Sterling said. However, median levels were lower in the group with advanced fibrosis. "It's not clear whether they were lower because those patients were being treated and their hepatitis B was suppressed, or whether the virus count was lower because their disease was worse. We don't know which came first," he noted.

A high proportion of coinfected patients had advanced fibrosis despite hepatitis B suppression. Dr. Sterling explained that liver histology needs to be studied in a larger group of patients to define the spectrum of liver disease and to find biomarkers that predict advanced disease.

Limitations of this study were its retrospective nature and the selection bias of patients undergoing biopsy.

"I think the bottom line with hepatitis B is that it's forgotten but not gone," he said. Up to half of patients can have advanced fibrosis, despite having well-controlled HIV and, "on paper, not looking too bad as far as their hepatitis B, alanine transaminase, and DNA," he explained, "which certainly puts them at higher risk for developing hepatic decompensation and hepatocellular carcinoma."

Fabien Zoulim, MD, PhD, who was asked by Medscape Medical News to comment on the findings, said he agrees that coinfected patients can have advanced fibrosis even when hepatitis B has been suppressed. He is medical director of the Department of Hepatology at the Hospices Civils de Lyon, and scientific director of the Department of Immunology and Virology of an INSERM unit in Lyon, France, and was not involved with this study.

"The problem is that we don't know how long these patients have been treated, how many lines of antiviral therapy they've gone through. Have they failed an antihepatitis B regimen in the past?... I think it's difficult to make a good interpretation of their results" in light of these uncertainties, Dr. Zoulim explained.

Besides the question of whether hepatitis B was well controlled in the past, there is an issue of liver toxicity from previous antiretroviral treatments. "Some of these regimens in the past may have been toxic for the liver, and this may have induced liver fibrosis," Dr. Zoulim said. "This type of information is really important to know."

Dr. Zoulim advises that treating physicians get a very good assessment of the severity of liver disease in coinfected patients. That can involve noninvasive tests such as FibroScan or blood markers if the patients appear well. For abnormal liver function tests, he would do a biopsy because of the variety of conditions associated with older antiretroviral therapies and the hepatitis B itself, he explained.

With newer treatment regimens, the situation is "getting much better than it was 5 years ago," he said. For coinfected patients who start first-line treatment today, "I wouldn't predict major problems."

Dr. Sterling has disclosed no relevant financial relationships. Dr. Zoulim reports being is a consultant to Gilead, BMS, and Roche.

International Liver Congress 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL). Abstract 429. Presented April 25, 2013.

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