Frequency, Severity and Impact of Pegylated Interferon Alpha–Associated Flares in Hepatitis D Infection

We analysed the frequency, severity and impact of hepatitis flares in a large Phase 2 study investigating pegylated interferon-alfa-2a (PEG-IFNa) for the treatment of hepatitis D. In the HIDIT-II study, 120 patients were treated for 96 weeks with PEG-IFNa (180 μg weekly) in combination with tenofovir disoproxil fumarate (TDF, 300 mg once daily) or placebo. Hepatitis flares were defined as ALT increases above 10 times the upper limit of normal or increases of more than 2.5-fold above baseline or nadir values. ALT flares occurred in 28 patients (23%) during treatment (< 96) and in 14 patients post-treatment until follow-up Week 24. There were no differences in the flare frequency between the two treatment arms (12 PEG-IFNa + placebo vs. 16 PEG-IFNa + TDF). The frequency of ALT increases did not differ between cirrhotic and noncirrhotic patients. None of the patients with cirrhosis experienced liver decompensation during or after a flare. Fifty-four per cent of the patients with ALT flare experienced a decrease in HDV RNA (> 1 log10 cop/ml) during subsequent study visits. Mean ALT levels early during treatment were higher in patients with HBsAg loss at follow-up Week 24. More than a third of hepatitis D patients undergoing PEG-IFNa therapy may experience ALT flares during or after treatment. ALT flares in this study posed no obvious safety risk to patients and should not lead to premature withdrawal from treatment. If ALT flares may be beneficial in single patients requires further investigation. Clinical Trial Registration: NCT00932971, EudraCT 2008-005560-13.