You have reached the HIVandHepatitis.com legacy site. Please visit our new site at hivandhepatitis.com
and Hepatitis.com Coverage of the
XVIII International AIDS Conference (AIDS 2010) July 18 - 23, 2010, Vienna, Austria
People with HIV Have Higher Rate of Severe Liver Disease, Antiretroviral Therapy Cuts Risk
Numerous studies have found that liver problems are common among people with HIV, and that liver-related death is one of the major causes of mortality in the combination antiretroviral therapy (ART) era. Liver damage in this population may be due to chronic hepatitis B or C coinfection, drug-related toxicity, heavy alcohol use, persistent systemic inflammation, or other factors.
William Towner and colleagues performed an observational cohort study comparing rates and risk factors for liver failure among 20,277 HIV positive adult Kaiser Permanente health plan members in Northern and Southern California over the period 1996-2007, comparing them with 202,313 HIV negative members matched according to sex, age, year, and medical center.
Most study participants (90%) were men and the average age was 40 years. Within the HIV positive group, 51% were white, 20% were Hispanic, 17% were black, 4% were Asian, and 9% were of unknown race/ethnicity; among the control subjects, the corresponding percentages were 27%, 15%, 7%, 8%, and 44%.
As is true overall in California, a majority of HIV positive Kaiser members are gay or bisexual men. The mean baseline CD4 count in this group was 389 cells/mm3 and the average HIV viral load was approximately 50,000 copies/mL. HIV positive people were more than twice as likely to have a history of alcohol or drug abuse (19% vs 8%) and were much more likely to have hepatitis B or C (4% for B and 8% for C, compared with 1% each in the HIV negative group).
Liver problems in people with HIV are often identified based on alanine and aspartate aminotransferase levels (ALT and AST), biomarkers of liver inflammation that may not accurately predict subsequent liver failure, the investigators noted as background. Fulminant or acute liver failure has been less well studied than progressive liver fibrosis in HIV positive people.
analysis, fatal hepatic failure was defined as having a primary or secondary
liver-related cause of death, or death preceded by a recent diagnosis
of liver failure. The researchers identified cases of non-fatal liver
failure by searching for mentions of hepatic failure, hepatic encephalopathy,
or bleeding esophageal varices in hospital discharge databases, as well
as laboratory tests showing elevated levels of ammonia (>
upper limit of normal [ULN]), INR (> 1.2), or AST/ALT (>
5 x ULN).
risk for both hepatic failure and death increased in HIV positive vs.
HIV negative persons," the Kaiser investigators concluded. "Risk
[was] lower in the more recent ART era."
ART did not increase the likelihood of hepatic failure or liver-related death, indicating that drug-related liver toxicity is unlikely to be a major concern in the modern ART era.
Reducing T-cell decline may mitigate some of the detrimental effects of viral hepatitis coinfection, Towner suggested. While the link between ART and reduced liver failure risk did not reach statistical significance, he nevertheless said these findings support early use of ART as a primary intervention to reduce hepatic failure and liver-related death.
Kaiser Permanente, Infectious Diseases, Los Angeles, CA; Kaiser Permanente, Research and Evaluation, Pasadena, CA; Kaiser Permanente, Division of Research, Oakland, CA; Kaiser Permanente, Infectious Diseases, Hayward, CA.