SUMMARY: HIV positive gay and bisexual men in the log-running Multicenter AIDS Cohort Study (MACS) were significantly more likely to die of liver-related causes than HIV negative participants, and those coinfected with hepatitis B virus (HBV) had about double the risk of death than those with hepatitis C virus (HCV) coinfection, according to a poster presented at the 18th Conference on Retroviruses and Opportunistic Infection (CROI 2011) last week in Boston.

By Liz Highleyman

Since the advent of effective antiretroviral therapy (ART), liver disease has become a leading cause of death among people with HIV. Over years or decades, chronic HBV and HCV infection can progress to severe liver disease including cirrhosis, liver cancer, and ultimately end-stage liver failure; evidence indicates that this process may happen faster in HIV positive people.

Oluwaseun Falade-Nwulia from Johns Hopkins University and colleagues compared rates of liver-related mortality between participants in the MACS cohort who were infected with HBV or HCV.

MACS is an ongoing prospective study of the natural history and HIV treatment outcomes of men who have sex with men (MSM) in Baltimore, Chicago, Pittsburgh and Los Angeles. The study has enrolled approximately 7000 men, both HIV positive participants and HIV negative control subjects.

Men in the present analysis had either chronic hepatitis B (HBsAg positive) or chronic hepatitis C (HCV antibody and HCV RNA positive) at study entry; men with both viruses were excluded.

A total of 680 men were included in the analysis. About 75% were white and the median age was 35 years. Of these, 472 men (69%) were HIV positive, 337 had chronic hepatitis B, and 343 had chronic hepatitis C; thus, 229 were HIV/HBV coinfected and 243 were HIV/HCV coinfected.

Participants were followed for a median of 7 years (ranging from just 5 months to 25 years). The researchers obtained causes of death from death certificates, and compared rates of liver-related mortality and all-cause mortality in HBV-infected and HCV-infected men, adjusting for potential confounding factors.

Results

	There were a total of 51 liver-related deaths during 6249 person-years of follow-up:
	36 among people with HBV (10.3 deaths per 1000 person-years); 15 among people with HCV (5.5 deaths per 1000 person-years).
	Liver-related mortality was about twice as high for the chronic hepatitis B group than the chronic hepatitis C group, after adjusting for race/ethnicity, age, HIV status, CD4 cell count, and alcohol use.
	A majority of participants (46) who died from liver-related causes were HIV positive.
	The liver-related death rate was 14.5 per 1000 person-years in the HIV/HBV coinfected group, compared with 8.0 per 1000 person-years in the HIV/HCV coinfected group.
	Among people with HIV, liver-related death remained about twice as high among HIV/HBV compared with HIV/HCV coinfected men after adjusting for race/ethnicity, age, CD4 count, alcohol use, and use of antiretroviral drugs active against HBV (IRR 2.16).
	A similar model, however, did not show any difference in all-cause mortality between HIV/HBV and HIV/HCV coinfected participants (RR 1.06).
	Among people with hepatitis B or HIV/HBV coinfection, liver-related mortality rose between 1984-1996 and 1997-2002, but then fell during 2003-2010.
	All-cause mortality decreased from the first to the second period, and fell further from the second to third.
	Use of antiretrovirals active against HBV as well as HIV did not independently predict less liver-related death, though mortality did start to decline in 2003 when tenofovir (Viread) became widely available.
	Lower CD4 cell count was associated with a significantly greater risk of liver-related death.

"In this cohort of MSM, the majority of liver-related deaths were in HIV-infected individuals," the MACS investigators concluded. "Chronic HBV infection was associated with a higher risk of liver-related death than was chronic HCV infection in all subjects and in the HIV-infected subgroup."

These results, they added, underscore the need for expansion of HBV screening, vaccination to protect against HBV infection, and treatment of HIV/HBV coinfected individuals with dually active drugs."

Investigator affiliation: Johns Hopkins Univ School of Medicine, Baltimore, MD.

3/11/11

Reference
O Falade-Nwulia, E Seaberg, C Rinaldo, and others. Liver-related Mortality Risk Is Greater from Chronic HBV than from Chronic HCV: MACS, 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 968.