A lot of people who have HIV are also dealing with Hepatitis C. Here is a report from the conference in San Francisco.

Coinfection with HIV and hepatitis C virus (HCV) is frequent, particularly in areas where injecting drug use is the primary route of HIV transmission. The course of chronic hepatitis C seems to be accelerated by HIV coinfection.

However, this more rapid progression of chronic hepatitis C was overshadowed by the high rate of mortality caused by HIV-related opportunistic diseases before the introduction of protease inhibitors (PI) in clinical practice. HAART effectively prevents AIDS. Because of this, liver failure is now a leading cause of morbidity and mortality among HIV/HCV-coinfected patients.

HAART regimens do not suppress HCV replication. Instead, they are associated with transient flares of HCV replication. The latter may increase the liver damage in chronic hepatitis C. Moreover, many antiretroviral drugs commonly used in HAART combinations are hepatotoxic.

For these reasons, HAART could be associated with more severe liver damage and, as a consequence, with progression of liver fibrosis. On the other hand, HAART-related immune restoration could contribute to lessen the liver damage associated with HCV infection.

The data on the effect of protease inhibitors (PI) on liver fibrosis are scant and contradictory. No information is available on the relationship between non-nucleoside analogue therapy (NNRTI) and liver fibrosis in co-infected patients.

The purpose of the present cross-sectional study was to investigate the associations between the use of different antiretroviral drugs and the liver fibrosis in patients with HIV and HCV infections.

All HIV/HCV co-infected patients with an available liver biopsy and known or estimated duration of HCV infection seen at an Infectious Diseases Unit were included in the study. The fibrosis stage and the fibrosis progression rate were evaluated.

Results

The inclusion criteria were fulfilled by 152 patients. Age at HCV infection < 20 years and nevirapine-based HAART were associated with fibrosis stage F3. The variables associated with fibrosis progression rate > 0.2 units/year were age at HCV infection < 20 years, CD4 cell counts ¡Ü 250 ¡Á 106/l at liver biopsy, PI-based HAART and nevirapine-based HAART.

The authors conclude, ¡°HAART regimens including nevirapine are associated with faster liver fibrosis progression in HIV-infected patients with chronic hepatitis C. In contrast, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.¡±

Discussion
In this study, the researchers found that the use of HAART regimens including nevirapine is associated with an increased degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. On the contrary, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.

The investigators did not find a significant association between sex, alcohol intake and estimated duration of HCV infection and liver fibrosis. They report, for the first time, more advanced stage of liver fibrosis and faster liver fibrosis progression among coinfected patients exposed to nevirapine. A previous report on this issue included too few patients on NNRTI to draw any conclusion. Nevirapine is a well-characterized hepatotoxic agent. Nevirapine-associated severe hepatotoxicity is more common in patients with hepatitis C infection.

The study results showed that PI-based antiretroviral regimens were associated with non-advanced liver fibrosis. The results also showed a lower rate of fibrosis progression among patients exposed to PI, in agreement with a previous report.

The authors conclude, ¡°The results of this study suggest that HAART including PI could be more advantageous in terms liver fibrosis progression than nevirapine-based regimens in this setting. Whether the associations found in this study have a clinical impact need to be confirmed by randomized prospective studies with hard clinical end-points, such as development of decompensated cirrhosis or death attributable to liver failure.¡±

03/22/04

Reference
J Mac¨ªas and others. Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine. AIDS 18(5): 767-774. March 26, 2004.