Sustained response to interferon improves fibrosis in HIV/HCV co-infected patients

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HIV-positive people who achieve a sustained virological response (SVR) to hepatitis C treatment using pegylated interferon plus ribavirin may experience regression of fibrosis and even cirrhosis, according to study findings presented on Wednesday at the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Cape Town, South Africa.

Considerable research has shown that liver fibrosis (build-up of scar tissue) tends to develop more rapidly in HIV-positive people co-infected with hepatitis C virus (HCV) than in those with hepatitis C alone. Over time, fibrosis can lead to cirrhosis, liver cancer, and end-stage liver failure.

Spanish researchers conducted a study with a dual aim: to assess fibrosis progression in patients who underwent combination hepatitis C treatment and to evaluate the accuracy of transient elastometry (FibroScan) for staging liver disease in a HIV/HCV co-infected cohort.

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.

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

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. 

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

biopsy

A procedure to remove a small sample of tissue so that it can be examined for signs of disease.

Liver biopsy is considered the "gold standard" for assessing liver damage, but it is uncomfortable, expensive and carries a small risk of complications. Researchers have therefore explored a variety of non-invasive methods including blood biomarkers and imaging. FibroScan uses sound waves to measures liver "stiffness."

This prospective cohort study included 294 HCV/HIV co-infected patients treated for hepatitis C between 2000 and 2008. A subset of 171 participants underwent a liver biopsy before treatment and 157 also were tested using FibroScan during follow-up. Liver fibrosis was staged on a scale ranging from 1 (absent or mild fibrosis) to 4 (cirrhosis). Fibrosis regression was defined as a decrease of at least 1 point.

Most participants (80%) were men and the mean age was 41 years. They had been infected with HCV for about 18 years on average. Half had hard-to-treat HCV genotype 1 and just over one-third had genotype 3. At baseline, about half had mild or moderate fibrosis, but 23% had evidence of cirrhosis.

The group had well-controlled HIV disease. They were receiving antiretroviral therapy if indicated and 78% had HIV viral load below 50 copies/ml. At study entry, the average CD4 cell count was about 500 cells/mm3, but the lowest-ever count was 172 cells/mm3 and about one-quarter had received an AIDS diagnosis.

Participants were treated with pegylated interferon plus weight-adjusted ribavirin. Treatment was planned for 48 weeks, and about half completed the full year. Overall, 43% achieved SVR, or continued undetectable HCV viral load six months after finishing treatment.

FibroScan testing was done a median of 44 months after treatment (with a range from one to 88 months). Outcomes were fairly evenly distributed, with 28% experiencing fibrosis regression or improvement, 35% having no change, and 37% experiencing progression or worsening.

Patients who achieved SVR were significantly more likely than non-responders to experience fibrosis regression: 38% of sustained responders had at least a one-point drop reduction in fibrosis score and 24% had at least a two-point drop.

Even some patients with cirrhosis experienced improvement, characterized as "cirrhosis reversal." Again, this was more likely amongst patients who achieved SVR.

A subset of 96 patients received a second FibroScan test a median of 52 months after treatment (or about eight months after the first one). Results were similar or better, indicating continued improvement over time.

After adjusting for other factors, SVR was the only factor significantly associated with fibrosis regression. In contrast with past studies, HCV genotype, baseline HCV viral load, CD4 cell count, type of hepatitis C treatment, and antiretroviral therapy did not predict treatment outcomes.

The researchers concluded that fibrosis improvement occurs in a substantial proportion of sustained responders to interferon-based treatment. Though less common, some non-responders also experienced fibrosis regression.

These findings, they said, support wider use of hepatitis C treatment in HIV/HCV co-infected patients. The goals of future therapies, they added, should be fibrosis regression as well as viral eradication.

Further information

A powerpoint presentation by Jose Luis Casado and a webcast of the conference session in which it was presented are available on the IAS 2009 website.