HAART May Reduce Liver Inflammation in HIV-HCV Coinfected Patients with High CD4 Cell Counts

By Liz Highleyman

Introduction

Considerable prior research has shown that HIV positive individuals with chronic hepatitis C virus (HCV) infection tend to experience more rapid liver disease progression than people with HCV monoinfection. But much of this research was done before the widespread adoption of effective early HAART, and some recent studies suggest that coinfected patients with well-preserved immune function may fare as well as those with HCV alone.

In a study published in the May 15, 2009 issue of AIDS, Jose Pascual-Pareja from La Paz Hospital in Madrid, Spain, and colleagues assessed the impact of HAART on liver damage in HIV-HCV coinfected patients with relatively well-preserved immune status, as indicated by a CD4 cell count of at least 350 cells/mm3 -- the threshold for initiating antiretroviral therapy according to current treatment guidelines.

This cross-sectional analysis looked at liver biopsy samples from 119 coinfected patients. All were negative for hepatitis B surface antigen and none had received prior hepatitis C treatment. At the time of biopsy, most participants (78%) were on HAART, 40% had undetectable HIV viral load, and the median CD4 cell count was 549 cells/mm3. The median ALT level was 87 IU/mL, half had high HCV viral load (> 800,000 copies/mL), and 74% had hard-to-treat HCV genotypes 1 or 4.

Necroinflammatory activity and degree of fibrosis were scored using the Scheuer staging system and steatosis (fat accumulation) was scored according to the percentage of affected hepatocytes. Necroinflammatory activity -- or liver inflammation and cell death -- is an indicator of active liver disease, but some people develop serious fibrosis despite persistently mild inflammation (indicated by low ALT and AST levels).

Results

Biopsies revealed that 23% of study participants had advanced fibrosis and 66% had significant steatosis.

In a univariate analysis, heavy alcohol use, elevated ALT, steatosis, and high fibrosis scores were significantly associated with higher necroinflammatory activity.

In a multivariate analysis controlling for confounding factors, a high ALT level, advanced fibrosis, and lack of HAART were associated with higher necroinflammatory activity.

Based on these findings, the researchers concluded, "Use of HAART was associated with lower levels of necroinflammatory activity."
"Necroinflammatory activity was strongly associated with higher fibrosis scores," they continued. "These results suggest that HAART might decrease hepatitis C activity in HIV-HCV coinfected patients with CD4 cell count of more than 350 cells/[mm3]."

Servicio de Medicina Interna, Hospital La Paz, Madrid, Spain.

6/19/09

Reference
JF Pascual-Pareja, A Caminoa, C Larrauri, and others. HAART is associated with lower hepatic necroinflammatory activity in HIV-hepatitis C virus-coinfected patients with CD4 cell count of more than 350 cells/microl at the time of liver biopsy. AIDS 23(8): 971-975. May 15, 2009.