Interferon retreatment warning in HCV

Hepatitis C virus (HCV) patients who do not respond to interferon should not receive further treatment with the drug, say the authors of a new Cochrane review.

They found that patients with severe fibrosis who did not achieve a sustained viral response (SVR) with pegylated interferon and ribavirin had a high risk for mortality and adverse events when later given interferon monotherapy compared with patients who went without further treatment.

"Based on these results, interferon monotherapy cannot be recommended for chronic hepatitis C patients who have already failed one course of treatment and are being retreated," said author Ronald Koretz (Granada Hills, California, USA) in a press statement.

The authors reviewed data from seven trials including 1976 patients. In the complete data set, they found no association between repeated interferon treatment and overall mortality or hepatic mortality.

However, when they repeated their analyses using just two large trials with 1676 patients - "HALT-C" and "EPIC3" - that were considered to have a low risk of bias they found different results.

Patients who received low-dose pegylated interferon over 48 weeks had a 41% increased risk for death compared with patients who did not receive repeated treatment (9.4 vs 6.7%).

And, although patients who received further interferon were less likely to experience variceal bleeding than those who did not (0.5 vs 2.1%), there were no significant differences in rates of other end-stage liver disease manifestations such as encephalopathy, ascites, or hepatocellular carcinoma.

Furthermore, patients receiving the treatment experienced greater rates of adverse events like infections, flu-like symptoms, and rashes.

The authors note their review failed to find any evidence to support the use of SVR as a marker of treatment success. Patients receiving further treatment were 15 times more likely to achieve an SVR than untreated patients but there was no significant association between SVR and disease improvement or the risk for death.

"This tells us that as a treatment outcome it is not universally reliable and needs to be validated before it can be viewed as the goal of any therapy in other clinical scenarios," concludes Koretz.

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