HIV treatment does not cause cryptogenic liver disease. Nor is there an association between any individual anti-HIV drug and the development of the disease, UK investigators report in the April edition of the Journal of Acquired Immune Deficiency Syndromes. Their findings contradict the results of earlier research that suggested an association between ddI (didadosine, Videx) treatment and the development of cryptogenic liver disease.
Liver disease is now a major cause of illness and death amongst people with HIV. Causes include co-infection with hepatitis B, hepatitis C (or both), excess alcohol consumption and drug-related toxicities.
Some HIV-positive individuals develop elevations in their liver enzymes that can lead to serious liver damage for no apparent reason. This is often called 'cryptogenic' liver disease.
Earlier research had suggested that long-term treatment with ddI was a cause of cryptogenic liver disease. Investigators from the Chelsea and Westminster Hospital in London undertook further research to determine if long-term treatment with antiretroviral drugs generally or any specific drug were a cause of this condition.
Cryptogenic liver disease was defined as persistently elevated liver enzymes (ALT and AST) in the absence of hepatitis co-infection or any other obvious cause.
Out of the 4500 HIV-positive patients attending the Chelsea and Westminster Hospital, a total of 90 met this criteria and had liver biopsies between early 2004 and July 2007.
The medical records of these individuals were reviewed for history of antiretroviral treatment and the presence of other conditions or infections that could lead to the development of cryptogenic liver disease.
A total of 13 patients met the diagnostic criteria for cryptogenic liver disease. They were matched with a control patient of similar age, sex, race, duration of HIV infection and CD4 cell count.
The patients all had experience of treatment with the three main classes of antiretroviral drugs. Mean age was 45 years and most (ten, 77%) were men. The median CD4 cell count at the time of liver biopsy was 187 cells/mm3. All but one of the patients had an undetectable viral load. Results of the liver biopsies showed that liver damage was widespread with 69% having portal fibrosis.
Three patients developed a blood clot in their portal vein, four developed decompensated liver disease with bleeding into the stomach, and two developed portal vein hypertension. One patient subsequently died as a result of cryptogenic liver disease.
Case-controlled analysis revealed no association between antiretroviral therapy and the development of cryptogenic liver disease. Although ddI was the most frequently used drug (ten patients) and for the longest duration (median 45 months), the case-controlled analysis failed to show an association between treatment with the drug and the development of cryptogenic liver disease (p = 0.096).
Mitochondrial damage due to ddI treatment had been suggested as a cause of cryptogenic liver disease. The investigators discount this theory, pointing out that no association has been found between other drugs associated with mitochondrial toxicity and the development of this condition.
Nor do they think that HIV itself is the cause as all but one patient had an undetectable viral load, and the remaining patient had a viral load below 400 copies/ml.
The investigators conclude, “our study does not confirm an association between the development of cryptogenic liver disease and the prolonged use of antiretroviral drugs”.
Stebbing J et al. The relationship between prolonged antiretroviral therapy and cryptogenic liver disease. J Acquir Immune Defic Syndr 50: 554-55, 2009.