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EASL 2013: HIV/HCV Coinfected Patients More Likely to Develop Cirrhosis, but Treatment Lowers Risk

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Sustained response to hepatitis C treatment leads to slow regression of liver fibrosis in people with HIV/HCV coinfection, but they remain at elevated risk for liver cirrhosis compared to those without HCV, researchers reported at the EASL International Liver Congress (EASL 2013) last month in Amsterdam.

HIV/HCV coinfected people experience more rapid liver progression, on average, than people with HCV alone. Over years or decades, chronic hepatitis C can lead to advanced liver disease including severe fibrosis, cirrhosis (scarring), and hepatocellular carcinoma (HCC, a type of primary liver cancer).

Effective treatment that permanently clears HCV -- known as sustained virological response (SVR), or a cure -- lowers the risk of disease progression for HCV monoinfected people. But even SVR does not eliminate the risk of liver complications among people with residual fibrosis. Long-term outcomes for HIV/HCV coinfected patients have not been as extensively studied.

Thierry Poynardand fellow investigators with the FibroFrance-GHPS Group compared outcomes among coinfected people who did and did not achieve SVR with interferon-based therapy. Using FibroTest -- a panel of demographic factors and blood biomarkers that predicts fibrosis progression, morbidity, and mortality -- they aimed to estimate the impact of SVR on 10-year survival rates and progression to cirrhosis.

The analysis included 933 chronic hepatitis C patients seen at Pitié Salpêtrière Hospital in Paris; 235 of them were HIV positive and 698 were HIV negative. Three-quarters of the coinfected participants and half of the HCV monoinfected patients were men, most were white, and mean ages were 44 and 51 years, respectively. About 60% had HCV genotype 1. About 60% of the coinfected group and 25% of the monoinfected group had the favorable IL2B CC gene pattern associated with good interferon response.

At baseline, 81% in the HIV positive group and 76% in the HIV negative group had fibrosis according to FibroTest (> 0.20). Transient elastometry (FibroScan) liver stiffness measurements were 10.8 and 8.8 kPa, respectively. Based on liver biopsies, about 55% in both groups had absent or minimal fibrosis (Metavir stage F0-F1), 38% had advanced fibrosis (stage F2 of higher), and 8% had cirrhosis (stage F4).

Approximately 20% of participants in both the HIV/HCV coinfected and HCV monoinfected group achieved SVR with interferon-based therapy, 35% and 49%, respectively, were non-responders, and the remainder were not treated for hepatitis C.

Results

  • Among participants with baseline fibrosis, 10-year survival, as estimated by FibroTest, was as follows:

o   Patients with SVR: HIV/HCV coinfected 66% vs HCV monoinfected 62% (p=0.04);

o   Non-responders: 82% vs 86%, respectively (p=0.13, non-significant);

o   Untreated: 7% vs 93%, respectively (p=0.009).

  • No significant differences were observed, however, based on FibroScan measurements.
  • Coinfected patients with SVR were 7 times more likely than HCV monoinfected sustained responders to transition to cirrhosis over 10 years (0.85 vs 0.12, respectively; p=0.003).
  • Among untreated participants, coinfected were 9 times more likely than HCV monoinfected to progress to cirrhosis over 10 years (1.41 vs 0.18, respectively; p < 0.001).
  • Rates of spontaneous transition to cirrhosis from birth to baseline were significantly higher for people with HIV, and were associated with nadir (lowest-ever) CD4 T-cell count:

o   Patients with SVR: HIV/HCV coinfected 0.65 vs HCV monoinfected 0.08 (p < 0.001);

o   Untreated: 0.41 vs 0.01, respectively (p < 0.001).

In HIV/HCV coinfected patients,repeated biomarker assessment permitted researchers "to quantify the impact of treatment on the very high spontaneous fibrosis progression rate."

"SVR was associated with a slow regression of fibrosis and a worrisome remaining risk of liver cancer," they concluded. Nadir CD4 count was independently associated with faster spontaneous progression to cirrhosis, "suggesting a role of HIV through immunosuppression."

5/30/13

Reference

T Poynard, MA Valantin, M Munteanu, et al (FibroFrance-GHPS Group). Long Term Survival of Liver Fibrosis after Virological Cure (SVR) in HIV-HCV Coinfected Patients: A Worrisome Latent Disease?
48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 487.