HAART reduces liver damage in HIV / hepatitis C co-infected patients

This article is more than 19 years old. Click here for more recent articles on this topic

HIV-positive patients who are co-infected with the hepatitis C virus have similar rates of liver disease progression to patients with hepatitis C virus alone, if they are taking highly active antiretroviral therapy (HAART). These findings are published in the 15th January edition of Clinical Infectious Diseases.

The retrospective study found, however, that other types of anti-HIV therapy do not have the same effect as only being treated with HAART. These include nucleoside reverse transcriptase inhibitor (NRTI)-only therapy or HAART after a period of treatment with NRTIs alone. This leads the authors to suggest that early initiation of HAART could reduce the rate of liver damage in co-infected patients.

Around 30% of HIV-positive patients are co-infected with the hepatitis C virus. Patients with HIV experience more rapid progression of liver damage than those without HIV, due to the virus’s effects on the immune system. In addition, the extension of the lifespan of HIV-positive patients with effective antiretroviral therapy has led to liver disease emerging as a leading cause of illness and death in people with HIV.

Glossary

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

hepatic

To do with the liver.

Few studies have examined the effect of antiretroviral therapy on the development of liver damage by the hepatitis C virus. To understand the effect of HIV treatment on liver damage or ‘fibrosis’, investigators analysed the medical records of 381 patients with hepatitis C from Los Angeles County from between 1994 and 2004.

Eighty-five of the patients were co-infected with HIV. Of these, 22 patients were diagnosed HIV-positive after 1996 and had only received HAART as HIV treatment, with no prior antiretroviral therapy. HAART was defined as use of any two NRTIs with any protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI).

These patients had similar levels and rates of fibrosis to the 296 HIV-negative patients, based on the results of liver biopsies. Fibrosis was measured using the Ishak scale, from 0 to 6, while liver inflammation was measured on a scale of 0 to 18.

Stage of fibrosis was similar between the HAART and HIV-negative groups (mean 3.4 vs. 3.1), as were the rates of fibrosis progression (0.16 vs. 0.13 per year), liver inflammation (6.1 vs. 6.1) and cirrhosis (41 vs. 32%). Cirrhosis is irreversible scarring of the liver.

In contrast, the 25 patients who had received no HIV treatment or NRTIs alone had more advanced liver disease. This was reflected in fibrosis stage (mean 4.6; p

The remaining 38 patients had ‘sequential therapy’ for HIV. This included initial treatment with NRTIs, followed by a switch to HAART. Despite receiving HAART for longer than the HAART-only group (3.9 vs. 3.3 years), the sequential therapy group also had more advanced liver damage than the HIV-negative patients.

“This suggests that it is not just the presence or absence of HAART, but the promptness with which it is initiated after HIV diagnosis that favourably impacts hepatic fibrosis,” the researchers explain. “If HAART is initiated promptly after the diagnosis of HIV infection, there is a more pronounced decrease in necroinflammatory activity, which, in the medium to long term, translates into less severe hepatic fibrosis.”

Despite their findings, the researchers point out that treating hepatitis C virus infection may be a better solution for co-infected patients than relying on early initiation of HAART, to avoid the risks of HIV treatment itself causing liver problems. “In the presence of hepatitis C virus co-infection, it may be preferable to treat the hepatitis C virus infection first, before HAART initiation. This strategy reduces the risks of antiretroviral-induced adverse effects and may improve the degree of immune restoration once HAART is started,” they write.

In an accompanying editorial, however, Jade Ghosn remarks that, “patients who are not willing to receive pegylated interferon and ribavirin or who have contra-indications may benefit from early HAART.”

The investigators compared the liver damage in patients taking protease inhibitor- and NNRTI-based HAART, finding no significant differences between the groups. Patients taking the NNRTI nevirapine (Viramune), which can cause liver toxicity in some patients, also had similar levels of liver damage to patients not taking the drug.

They also saw no effects of hepatitis C virus genotype, hepatitis B virus co-infection or high-risk sexual behaviour on the degree of fibrosis.

“Overall, HAART recipients had less severe fibrosis than did those receiving no drugs, [other types of] antiretroviral therapy, or [other types of] antiretroviral therapy followed by HAART,” the investigators conclude. “It is not just the presence or duration of HAART, but the timing of its initiation that positively influences the course of liver fibrosis in HIV-hepatitis C virus-co-infected subjects.”

The investigators point out that their study is limited by being retrospective and insensitive to when HIV infection was acquired in relation to hepatitis C. “The sample size of the HIV-hepatitis C virus-co-infected subjects was small, and our results need to be validated by larger prospective studies,” they add.

References

Ghosn J. Liver fibrosis and antiretroviral therapy. Clin Infect Dis 42: XXX-XXX, 2006.

Verma S et al. Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients? Clin Infect Dis 42: XXX-XXX, 2006.