Reuters Health Information (2011-03-29): HCV-related liver fibrosis progresses with antiretroviral therapy interruption
HCV-related liver fibrosis progresses with antiretroviral therapy interruption
Last Updated: 2011-03-29 17:59:31 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Liver fibrosis progression follows interruption of antiretroviral therapy (ART) in patients co-infected with HIV and hepatitis C virus (HCV), researchers from Canada report in the February 16th online issue of AIDS.
"HIV treatment interruptions may be particularly harmful for patients co-infected with HIV and hepatitis C," Dr. Marina B. Klein from McGill University in Montreal told Reuters Health in an email. "Efforts are needed to engage patients in care and support their long-term adherence to therapy so as to reduce the burden of liver disease among co-infected persons."
Dr. Klein and colleagues in the Canadian Co-infection Cohort Study (CTN222) used the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), a validated surrogate marker for liver fibrosis, to assess the impact of ART interruption on fibrosis progression in 541 HIV/HCV-co-infected patients followed for a median of 1.02 years.
"We had hypothesized that treatment interruptions might be related to liver fibrosis progression, particularly because the results of treatment interruption trials such as the SMART study suggested that hepatitis co-infected persons are at particular risk for adverse events, probably because of enhanced inflammation when HIV rebounds after stopping treatment. The liver could also be susceptible to such inflammation and thus be further damaged in the setting of a treatment interruption," Dr. Klein explained.
There were 55 treatment interruptions of at least 14 days in 53 patients. Among the 21 patients with complete data, the median change in platelet count after the treatment interruption was -2 billion/L and the median change in AST after the treatment interruption was 21 U/L.
After adjustment for other factors, treatment interruption was significantly associated with progression of liver fibrosis. Baseline APRI score of at least 0.5 also predicted fibrosis progression, whereas CD4+ T cell count, HIV viral load, age, and gender were not significant predictors.
Treatment interruption was associated with a significant increase in APRI score to at least 1.5 (predictive of significant fibrosis) after adjustment for time-varying confounders (hazard ratio 2.52). The association with an increase in APRI score to at least 2.0 (predictive of cirrhosis) failed to reach statistical significance in the multivariate model.
"A possible explanation for the association of interruption with developing liver fibrosis even after accounting for changes in CD4+ T cell counts and HIV RNA may be that interruption increases inflammatory processes," the researchers say.
"Our findings underscore the need to find better strategies to improve continuous ART exposure among co-infected persons," the authors conclude.
"We are currently planning to investigate how inflammation may contribute to liver disease over time and to assess how HIV and HCV treatments may affect the inflammatory response," Dr. Klein concluded.