By Liz Highleyman

Numerous studies indicate that liver fibrosis tends to progress more rapidly in HIV-HCV coinfected people than in those with hepatitis C virus (HCV) infection alone. Some research in HIV negative patients has demonstrated that interferon-based therapy may stabilize or even reverse fibrosis, but this has not been extensively studied in coinfected patients.

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

Spanish researchers assessed fibrosis outcomes among HIV-HCV coinfected patients who underwent hepatitis C treatment between 2000 and 2008. They also evaluate the accuracy of FibroScan for estimating liver damage in this population.

Most participants (80%) were men, with a mean age of 41 years. Half had hard-to-treat HCV genotype 1 and about one-third had genotype 3. At baseline, about half had mild or moderate fibrosis and 23% had evidence of cirrhosis. Overall, the patients had well-controlled HIV disease; 78% had HIV RNA < 50 copies/mL and the average CD4 cell count was about 500 cells/mm3, though the lowest-ever count was 172 cells/mm3 and about one-quarter had received an AIDS diagnosis.

Patients were treated with pegylated interferon alfa (either Pegasys or PegIntron) plus 800-1200 mg/day weight-adjusted ribavirin. Treatment was planned for 48 weeks, and about half completed the full course.

Out of 294 participants in the treatment study, a subset of 171 underwent a liver biopsy before treatment,157 also were tested using FibroScan during follow-up (median 44 months after treatment), and 96 received a second FibroScan (a median 52 months after treatment, or about 8 months after the first test). Fibrosis scores ranged from 1 (absent or mild fibrosis) to 4 (cirrhosis). Fibrosis regression was defined as a decrease of at least 1 point.

Results

	Overall, 43% of the patients achieved sustained virological response (SVR), or continued undetectable HCV viral load 6 months after the end of treatment.
	Fibrosis outcomes were fairly evenly distributed: 28% experienced regression; 35% had no change; 37% experienced progression.
	People who achieved SVR were significantly more likely than non-responders to experience fibrosis regression: At least a 1 point decrease: 38% of sustained responders vs 22% of non-responders; At least a 2 point decrease: 24% of sustained responders vs 6% of non-responders.
	Some participants with more advanced liver disease experienced cirrhosis reversal. At least a 1 point decrease: 44% of sustained responders vs 23% of non-responders; At least a 2 point decrease: 33% of sustained responders vs 18% of non-responders.
	Among patients who received a second FibroScan test, results were similar or better, indicating continued improvement over time.
	The mean decrease in fibrosis score was -0.36 according to the first FibroScan, with an additional decline of -0.21 according to the second test.
	After adjusting for potential confounding variables, SVR was the only factor significantly associated with fibrosis regression (relative risk 0.76).
	In contrast with prior studies, HCV genotype, baseline HCV viral load, CD4 cell count, and type of hepatitis C treatment, and use of antiretroviral therapy were not significant predictors of response.

"Our study demonstrates fibrosis improvement after HCV therapy in an important proportion of HCV-HIV [coinfected] patients," especially those who achieve sustained virological response, the investigators concluded.

Though less common, fibrosis regression and a lower fibrosis progression rate were also observed in some virological non-responders, which the researchers attributed to the anti-fibrogenic and pro-fibrolytic properties of the treatment.

These findings support wider use of hepatitis C treatment in HIV-HCV coinfected patients, they suggested, stating that the "goals of future therapies for viral hepatitis should be aimed towards fibrosis regression as well as viral eradication."

7/24/09

Reference
P Marti-Belda, C Quereda, JL Casado, and others. Fibrosis regression in HIV/HCV coinfected patients with sustained virological response to pegylated interferon plus ribavirin. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract TuAb201.

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