Hepatitis B may increase all-cause mortality in HIV-positive people, according to meta-analysis

The first meta-analysis of all-cause mortality among people co-infected with hepatitis B and HIV has found this population to have a significantly higher rate of all-cause mortality than HIV-positive people without hepatitis B. The study is presented in the June 15^th edition of Clinical Infectious Diseases, along with an editorial commentary calling for greater efforts to prevent and treat hepatitis B in co-infected individuals.

The study authors began their inquiry with a retrospective analysis of the impact of hepatitis B in a cohort of 1729 Greek adults diagnosed with HIV between 1984 and 2003. About 6% of study participants tested positive for hepatitis B on two occasions at least six months apart, suggesting chronic infection. Hepatitis B/HIV co-infection was not found to be significantly associated with any of the three primary outcomes of interest: progression to AIDS, antiretroviral efficacy, and all-cause mortality.

The authors next conducted a meta-analysis by combining their data with data from all relevant published studies. When data from 12,382 people enrolled in 11 studies were pooled, hepatitis B/HIV co-infection was found to be significantly associated with all-cause mortality (pooled effect estimate, 1.36; 95% confidence interval [CI], 1.12–1.64).

Separate analyses for studies conducted before and after the advent of highly active antiretroviral therapy also yielded significant results. The pooled effect estimate for the earlier group of studies was 1.60 (95% CI, 1.07–2.39). The pooled effect estimate for the later group was 1.28 (95% CI, 1.03–1.60).

On the other hand, the pooled data provided no evidence of an association between hepatitis B/HIV co-infection and progression to AIDS.

Many of the studies in the meta-analysis took place in Western countries, and many enrolled men who have sex with men. The authors note that more research is needed among other populations before firmer conclusions can be drawn about the effect of hepatitis B/HIV co-infection on all-cause mortality.

One likely explanation for the higher rate of all-cause mortality in co-infected people is hepatitis B-related liver deterioration. Long-term hepatitis B infection can result in cirrhosis and liver cancer, both of which are potentially fatal.

However, the meta-analysis did not actually assess liver-related mortality, and it cannot be assumed that hepatitis B is the ultimate cause of the higher all-cause mortality rate. The editorial commentary accompanying the study observes that hepatitis B/HIV co-infection could be “a marker for other types of high-risk behavior that may place this population at an increased risk for death attributable to non-AIDS-related causes”.

In other words, the same behaviours that increase a person’s risk of acquiring hepatitis B, which is transmitted via bodily fluids, may also increase the person’s risk of developing other unrelated health problems that account for the higher all-cause mortality rate found in the meta-analysis.

Nonetheless, while the reasons for the higher mortality rate need to be further explored, what is already known about hepatitis B/HIV co-infection leads the author of the editorial review to make a series of recommendations. “Every HIV treatment provider must accurately diagnose hepatitis B infection, document the level of viremia prior to starting [antiretroviral therapy], and monitor hepatitis B … levels to ensure that suppression is achieved,” the article says. It also advises providers to tell hepatitis B/HIV co-infected patients about the effect of alcohol consumption on the liver, and to screen for liver cancer.

When hepatitis B infection occurs, the immune system often clears hepatitis B from the body on its own. However, for people who do not experience viral clearance, treatment may be advisable. Treatment is only successful in about one-third of cases.

Hepatitis B virus treatment options are limited, and some treatment regimens have major drawbacks. Some antiretroviral drugs also work against hepatitis B, although hepatitis B resistance is likely to occur in response to 3TC (lamivudine, Epivir). Two other antiretrovirals with anti-hepatitis B activity are tenofovir (Viread) and FTC (emtricitabine, Emtriva).

If a co-infected person’s health status warrants simultaneous treatment for HIV and hepatitis B, then an antiretroviral regimen that serves both purposes is recommended. However, when an HIV-positive person does not need antiretrovirals for management of HIV disease, using these drugs as hepatitis B treatment may be a questionable strategy given the risk of HIV resistance.

Because the risks and benefits of the various approaches to managing hepatitis B/HIV co-infection are not fully understood, more research is needed to inform treatment guidelines. The association between hepatitis B and all-cause mortality in the meta-analysis thus has important treatment implications. The accompanying editorial commentary states, “In light of the findings … aggressive treatment of hepatitis B is warranted, including treating hepatitis B with ART regardless of CD4 cell count. Additional studies are needed to examine whether this strategy will lead to the desirable outcome of a decrease in the rate of death.”