SUMMARY: HIV positive people coinfected with hepatitis C virus (HCV) had an elevated mortality rate compared with the general population in Spain, but this was not the case for individuals with HIV alone, according to a study presented at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna.

Since the advent of effective combination antiretroviral therapy (ART) in the late 1990s, liver disease has become a growing cause of illness and death among people with HIV. As the proportion of deaths due to AIDS-related opportunistic infections has fallen, the proportion due to liver disease and other non-AIDS conditions has grown. Several studies have found liver disease to be a leading cause of death for HIV positive people in the ART era, though some suggest rates have gone down in recent years.

In part this is because people with HIV are surviving long enough for chronic liver damage -- for example related to viral hepatitis or heavy alcohol use -- to progress to an advanced stage. An estimate one-third of HIV positive people are coinfected with hepatitis B or C. HIV infection itself and antiretroviral drug toxicity may also play a role in liver problems.

In the study presented at AIDS 2010, Santiago Perez-Cachafeiro and colleagues compared liver-related mortality rates in the general population against those of HIV positive patients in 2 Spanish multicenter cohorts, CoRIS-MD (1997-2003) and CoRIS (2004-2008, though follow-up in this analysis extended only through 2006).

The study included 4634 participants, contributing a total of 13,701 person-years of follow-up data. Eligible individuals were HIV positive, ART-naive at study entry, had available HCV test results, and were followed for at least 6 months. Most (about 75%) were men and the median age was 35 years. Nearly 40% had a history of injection drug use and about one-quarter were men who have sex with men; 43% were HIV/HCV coinfected. The median CD4 cell cohort when joining the study was about 270 cells/mm3.

Standardized mortality ratios (SMRs) were estimated by comparing sex- and age- speci?c liver-related mortality rates between the CoRIS cohorts and the Spanish general population as obtained from the National Institute of Statistics from 1997 through 2006.

Results

	18 liver-related deaths were reported during the study period.
	16 of these deaths were of HIV/HCV coinfected patients, while 2 were HCV negative.
	No liver-related deaths occurred between 2004 and the end of data collection in 2006.
	The resulting liver-related mortality rate was 0.13 per 100 person-years.
	Liver-related SMRs between the cohort participants and general population varied according to patient characteristics.
	The liver-related SMR for the overall HIV positive population was 10.0, or 10 times greater risk of death.
	HIV positive women had a higher risk of liver-related death than men:
	Men with HIV: SMR 7.9; Women with HIV: SMR 35.4.
	Injection drug users had the highest risk among HIV risk categories:
	People presumed infected via heterosexual transmission: SMR 9.4; Men who have sex with men: SMR 4.7; Injection drug users: SMR 15.0.
	After age 30, younger individuals had a greater relative increase in risk:
	Participants under age 30: no liver-related deaths; Participants age 30-34 years: SMR 30.0; Participants age 35-39 years: SMR 10.9; Participants age 40 or older: SMR 8.4.
	People with an AIDS diagnosis had an SMR of 11.2 compared with 9.7 for those who had not progressed to AIDS.
	A large difference in increased risk was observed according to hepatitis C status:
	HCV uninfected: SMR 2.0; HIV/HCV coinfected: SMR 20.5, or more than 20 times the risk of liver-related death.

"HIV infected subjects died from liver-related causes 10 times more than the general population but this risk was very different according to HCV co," the investigators concluded. "While HIV monoinfected subjects do not present significant differences compared to the general population, co-infected subjects died 20 times more."

Investigator affiliations: Instituto de Salud Carlos III, Centro Nacional de Epidemiología, Madrid, Spain; Universite de Bordeaux, Bordeaux, France; Hospital Donostia, San Sebastian, Spain; Hospital La Fe, Valencia, Spain; Hospital de Elche, Elche, Spain; Hospital Universitario de Canarias, Tenerife, Spain; Hosptial San Cecilio, Granada, Spain; Hospital San Pedro, Logrono, Spain; Hospital Joan XXIII, Tarragona, Spain; Hospital Ramón y Cajal, Madrid, Spain.

8/3/10

Reference
S Perez-Cachafeiro, C Lewden, V Hernando, and others. Liver-related mortality in HIV-infected patients compared to liver-related mortality in the general population: data from the Spanish cohorts CoRIS and CoRIS-MD. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract TUPE0220.