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ICAAC 2011: Interferon May Reduce Liver Disease Progression in HIV/HCV Coinfected Relapsers

Unsuccessful interferon-based therapy for chronic hepatitis C virus (HCV) infection appeared to improve or slow liver fibrosis progression in HIV/HCV coinfected people, but this was usually temporary, according to 2 studies presented the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) last month in Chicago.

HIV positive people coinfected with HCV tend to experience more rapid liver disease progression compared to those with hepatitis C alone; unfortunately, they also do not respond as well on average to treatment with interferon.

In the first study, José Antonio Carton from Oviedo University Medical School in Spain and colleagues used transient elastometry (FibroScan) and various non-invasive biomarkers to compare outcomes among coinfected patients according to their responses to hepatitis C therapy.

This analysis including 210 HIV/HCV coinfected participants who completed at least 12 weeks of standard therapy using pegyalted interferon alfa plus ribavirin. Another 118 coinfected people who decided against HCV therapy made up the control group. Overall, people in the control group had less advanced liver disease, as such patients do not require treatment so urgently.

Participants were evaluated at baseline, at the end of HCV treatment, and 38-42 months thereafter using FibroScan to measure liver stiffness and the APRI, Forns, and FIB-4 biomarker indices. They underwent liver biopsy at baseline, but this was not repeated. Most studies find that non-invasive methods do a good job of distinguishing absent or minimal fibrosis versus severe fibrosis or cirrhosis, but do not do as well determining intermediate stages.

Results

• 80 patients achieved sustained virological response (SVR).
• 130 were non-responders, meaning they still, or again, had detectable HCV RNA 24 weeks after completing treatment.
• There were significant differences between the 2 groups in baseline characteristics including duration of HCV infection, HCV RNA, and HCV genotype.
• All treated groups experienced significant decreases in liver stiffness during therapy, but this was maintained after treatment only in patients with SVR.
• Among sustained responders, the proportion having severe (stage F3) fibrosis fell, while the proportion with moderate (stage 2) fibrosis rose.
• Non-responders' fibrosis levels remained stable.
• Untreated control patients experienced significant worsening, with severe fibrosis rising and moderate fibrosis falling.

"SVR was usually followed [by] regression of non-invasive fibrosis markers; on the contrary [non-responders] and HCV non-treated patients followed a poorer outcome," the researchers concluded.

In the second analysis, the same research team looked at the 130 coinfected patients who failed to clear HCV with treatment. Here, they were divided into 81 non-responders who still had detectable HCV RNA at the end of treatment, and 49 responder-relapsers who had undetectable HCV upon completion of therapy but experienced viral rebound during post-treatment follow-up. The 118 untreated patients again served as the control group.

Results

• During HCV treatment, liver stiffness and biomarker indices improved significantly compared with baseline values.
• However, these changes were only sustained for responder-relapsers.
• No significant long-term changes in fibrosis progression or regression were seen in either group.

"Whatever the virological response, treatment for HCV infection was associated with an improvement of non-invasive liver fibrosis values, compared to control non-treated patients," the researchers concluded.

The researchers suggested that anti-inflammatory changes during treatment might be responsible for transient improvements in liver stiffness, more than producing a true reversal of liver fibrosis.

Investigator affiliations (abstracts H3-812 and H3-813): Hosp. Univ. Central de Asturias, Oviedo Univ Med School, Oviedo, Spain; Hosp. Cabueñes, Gijon, Spain; Hosp. Galdacano, Galdacano, Vizcaya, Spain.

10/11/11

References

JA Carton, B De La Fuente, J Collazos, and V Asensi. Longitudinal Assessment of Liver Fibrosis (LF) by Non-Invasive Methods in HIV-HCV Coinfected Patients After HCV Chemotherapy. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H3-812.

JA Carton, B De La Fuente, J Collazos, and V Asensi. Responder-Relapser (RR) Patients Might Obtain Benefit in Liver Fibrosis, after HCV Chemotherapy, in Comparison to Non-Responders (NR) or Non-Treated (control) HIV-HCV Coinfected Patients. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H3-813.