By Liz Highleyman

Several past studies have shown that HIV positive people with chronic hepatitis C virus (HCV) coinfection tend to experience more rapid and perhaps more severe liver disease progression, leading some experts to suggest that such patients should perhaps start interferon-based therapy sooner.

Data are not entirely consistent, however, with some recent studies indicating that coinfected patients on effective antiretroviral therapy who maintain a high CD4 cell count may fare nearly as well as HIV negative individuals with chronic hepatitis C.

As reported at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) last week in Washington, DC, Spanish investigators evaluate factors, including HAART use, associated with liver damage in HIV-HCV coinfected patients with a CD4 count > 350 cells/mm3 -- the threshold for starting anti-HIV therapy in the current U.S. and European treatment guidelines.

The analysis included 119 coinfected patients who had > 350 cells/mm3 at the time of liver biopsy. Patients previously treated for hepatitis C, those with hepatitis B virus (HBV) triple infection, and those with poor adherence to HAART were excluded.

Most participants (78%) were men, all were Caucasian, the average age was about 38 years, about 70% had HCV genotypes 1 or 4, and the median duration of HCV infection was 20 years. The median CD4 count was about 550 cells/mm3, although the median nadir (lowest-ever) level was 210 cells/mm3. About 80% were on HAART and 60% had baseline HCV RNA < 400 copies/mL.

All liver biopsies were evaluated by a single pathologist. Necroinflammatory activity (NA) and fibrosis were scored according to the Scheuer System. Steatosis (fat accumulation in the liver) was scored according to the percentage of hepatocytes affected.

Since this was a cross-sectional study, the researchers explained that they selected necroinflammatory activity as the main variable because they believe using or not using HAART probably has a less time-dependent impact on necroinflammation than on fibrosis progression.

Results

• One-quarter of study participants had a necroinflammatory activity score > 3, while 75% had lower scores.

• About one-fifth (19%) had stage F3 fibrosis, while 3% had cirrhosis (stage F4).

• Patients with NA > 3 were significantly more likely than those with lower NA scores to also have a fibrosis score > 3 (77% vs 4%; OR 131.9; P < 0.001).

• Conversely, 85% of patients with F3-F4 fibrosis had NA > 3.

• Patients with NA ? 3 were more likely to be heavy alcohol users than those with NA < 3 (40% vs 19%), but the difference did not reach statistical significance.

• Steatosis was more common in people with NA ? 3 (83% vs 58%), but again the difference did not reach significance.

• The following factors did not differ significantly between patients with high and low NA scores:

• Duration of time on HAART;
• C urrent CD4 cell count;
• Nadir (lowest-ever) CD4 count;
• HIV RNA < 400 copies/mL;
• HCV RNA > 800,000 copies/mL;
• HCV genotype 1 or 4.

• Individuals with a NA score > 3 were less significantly likely to be receiving HAART at the time of biopsy compared to those with lower scores (67% vs 82%; odds ratio [OR] 0.16; P = 0.024).

Based on these findings, the investigators concluded that, "Use of HAART at the time of liver biopsy was associated with lower levels of necroiflammatory activity."

"NA 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 > 350 CD4."

The mechanisms underlying accelerated of liver disease progression in HIV-HCV coinfected people remain to be fully elucidated, but the role of necroinflammation is interesting in light of the growing evidence that immune activation and inflammation due to ongoing HIV replication in the absence of suppressive antiretroviral therapy may contribute to conditions such as heart and liver disease that have not traditionally been defined as HIV-related.

Hosp. La Paz, Madrid, Spain.

11/04/08

Reference
J Pascual Pareja, A Caminoa, J Larrauri, and others. HAART is Associated with a Lower Level of Hepatic Necroinflamatory Activity in HIV-HCV Coinfected Patients with CD4 > 350 at the Time of Liver Biopsy. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-2319.