ALT levels may not give true picture of liver disease in HIV/HCV coinfected, suggests study

The majority of HIV-positive individuals coinfected with hepatitis C virus who, according to a key blood test, have normal liver function are, in fact, suffering from mild to severe liver damage, according to an Italian study published in the January 1^st edition of the Journal of Acquired Immune Deficiency Syndromes.

Using liver biopsies the researchers established that 25% of patients with normal alanine aminotransferase (ALT) levels - a key marker of liver function – have such severe liver damage that they require anti-hepatitis C treatment, with 13% having cirrhosis, permanent scarring of the liver.

Doctors in Milan conducted a retrospective study, involving 326 HIV/hepatitis C coinfected patients who had a liver biopsy between 1997 and 2003. None of the patients had taken anti-hepatitis C treatment. The patients were divided into groups according to whether they had persistently normal or elevated ALT levels in the twelve months before their liver biopsy. The stage of liver disease was then compared between the two groups and the investigators conducted statistical analysis to see if there were any factors that predicted which patients with normal ALT levels were more likely to have liver damage.

In total 15 individuals (24%) had persistently normal ALT levels. There were no significant differences between these patients and those with elevated ALT levels with respect to age, gender, HIV risk group, CD4 cell count, or the use of HIV therapy. Individuals with normal ALT scores, however, were statistically more likely to have an undetectable HIV viral load (63% vs 35%, p = 0.014).

Unsurprisingly, liver biopsies showed that patients with normal ALT levels were much more likely to have no, or very mild fibrosis (75% vs. 31%, p = 0.0001).

However, the investigators noted that 25% of individuals whose ALT blood tests suggested that they had normal liver function in fact had a degree of liver fibrosis (score 2 – 6) severe enough to require anti-hepatitis C treatment. In addition, two further patients (8%) with normal ALT levels had cirrhosis (level 7 fibrosis or above).

The investigators then looked at the characteristics of the patients with normal ALT scores whose liver biopsies had mild to severe fibrosis. They found that these individuals were older (p = 0.01) and had a lower CD4 cell count (below 500 cells/mm³, p = 0.03).

Finally, investigators conducted long-term follow-up of patients with persistently normal ALT levels. The median duration was five years, and 91% of patients did not show any progression of their HIV disease, with 33% remaining HIV treatment-naïve. However, 42% of patients had experienced hepatitis C disease progression including six patients who required anti-hepatitis C therapy, one patient who died of liver disease and one individual who developed decompensated cirrhosis.

“These findings highlights the threat hidden by persistently normal ALT levels, which are too often considered a sign of well-balanced liver status in HIV-positive subjects with chronic hepatitis C virus infection”, conclude the investigators.