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Determining alanine aminotransferase (ALT) levels is the most common way to evaluate liver injury. However, several studies have clearly demonstrated that serum transaminase levels are not reliable predictors of liver fibrosis. A subset of patients coinfected with HIV and hepatitis C virus (HCV) have transaminase levels that are persistently in the normal range of the testing laboratory.
To evaluate the prevalence of this phenomenon and the degree of liver fibrosis in this subset of individuals, researchers studied patients at an HIV clinic in Spain who had chronic HCV coinfection. The presence of advanced hepatic fibrosis was assessed using a noninvasive technique called transient elastography (FibroScan; Echosens, Inc.), which involves transmission of a vibration that propagates through the liver and can be measured and correlated with liver stiffness.
Of 281 patients with HCV/HIV coinfection, 25 (8.9%) had persistently normal ALT levels (10–55 IU/L for at least 12 months). Those with genotypes 2 or 4 were more likely to demonstrate normal ALT levels than were those with genotypes 1 or 3. Overall, nearly 25% of patients with persistently normal ALT levels had advanced liver fibrosis (F3 or F4). Genotype was not significantly associated with fibrosis stage, nor was CD4-cell count, age, HIV RNA level, or sex. The authors suggest that these data support close monitoring of HCV/HIV-coinfected patients who have normal ALT levels.
Maida I et al. Liver fibrosis stage and HCV genotype distribution in HIV–HCV coinfected patients with persistently normal transaminases. AIDS Res Hum Retroviruses 2007 Jun; 23:801-4.
Comment
When assessing liver disease in HIV/HCV-coinfected patients, clinicians should not be lulled into complacency by normal serum ALT levels. The contribution of liver disease to overall morbidity and mortality is high in this population. Silent liver disease is common, and its recognition is critical to decisions regarding antiretroviral therapy and other management strategies.
Relying on ALT levels to determine the prevalence and severity of liver disease often results in underestimation. In a recent study of individuals with HCV monoinfection, investigators redefined the upper limit of normal ALT levels as 30 IU/L for men and 19 IU/L for women (Ann Intern Med 2002; 137:1). Given that the present study used higher ALT cutoff values than these, one could argue that the population identified as having persistently normal ALT levels with advanced disease might shrink if the newer standards were applied. Although transient elastography represents an exciting and promising new technology, this technique has not been well validated, and preliminary data presented at the 14th Retrovirus Conference (Abstract 910) and elsewhere suggest poor association with liver-biopsy findings in some series. The authors note that 12% of their original cohort could not be tested by this method because of obesity.