Severe Liver Disease Associated with Prolonged Antiretroviral Therapy

Liver disease is common among people with HIV, often due to coinfection with chronic hepatitis B or C, heavy alcohol use, or some other known cause. However, some cases of severe liver damage among this group do not have a readily apparent cause, and may be related to use of antiretroviral drugs.

A study in the June 2006 issue of the Journal of Acquired Immune Deficiency Syndromes attempted to shed light on the etiology of "cryptogenic liver disease," defined as persistently elevated aminotransferase (ALT and AST) levels in the absence of replicating hepatitis B or C virus or other common causes of liver disease such as use of alcohol or known hepatotoxic medications.

The authors retrospectively analyzed the medical records of all 3200 HIV-positive patients attending two large HIV/AIDS clinics in Spain during 2004; further assessment was conducted, if needed, to rule out less frequent causes of liver disease. Liver fibrosis stage was assessed by liver biopsy and/or elastography. HIV-positive patients without liver disease, matched for age, gender, and CD4 count, were selected as controls.

Results

Cryptogenic liver disease was diagnosed in 17 out of 3200 patients (0.5%). Among this subset of patients, 82% were men, the mean age was 43 years, 76% acquired HIV through homosexual relationships, and the mean time since HIV diagnosis was more than 15 years. All patients in this group had taken antiretroviral therapy. Use of nevirapine (Viramune), d4T (stavudine, Zerit), and ddI (didanosine, Videx) were more frequent among this subset compared to those without cryptogenic liver disease. None of these patients had liver function test abnormalities before initiating antiretroviral therapy. 10 patients (59%) developed advanced fibrosis or cirrhosis (METAVIR score F3-F4), and 9 patients (53%) developed symptomatic complications of liver disease including ascites (8), portal thrombosis (6), variceal bleeding (5), and/or encephalopathy (2). In a case-control comparison, prolonged use of ddI was the only independent predictor for developing cryptogenic liver disease in this population.

Conclusion

The authors concluded that cryptogenic liver disease is an uncommon condition in HIV-positive individuals and might be associated with prolonged exposure to ddI. They added that the condition may progress to severe liver disease with complications including variceal bleeding and portal thrombosis.

6/13/06

Reference
I Maida, M Nunez, MJ Rios, and others. Severe liver disease associated with prolonged exposure to antiretroviral drugs. Journal of Acquired Immune Deficiency Syndromes 42(2): 177-182. June 2006.