Weekly peginterferon alfa-2a therapy, with or without daily adefovir, cleared hepatitis D virus (HDV) RNA in about one quarter of patients who participated in the Hep-Net-International Delta Hepatitis Intervention Trial.
“Treatment with peginterferon alfa-2a for 48 weeks resulted in sustained HDV RNA clearance in more than 25% of patients and a sustained biochemical response in 40%,” Heiner Wedemeyer, MD, of Hannover Medical School in Hannover Germany, and colleagues wrote in New England Journal of Medicine.
Currently, there is no cure for the patients with the virus, which can progress to fulminant acute hepatitis, severe chronic hepatitis, cirrhosis or hepatocellular carcinoma in long-term carriers of the disease that are co- or super-infected with hepatitis B virus (HBV).
The researchers randomly assigned patients with HDV infection to receive one of three treatment regimens for 48 weeks: 180 µg peginterferon alfa-2a weekly plus 10 mg adefovir daily (n=31); 180 µg peginterferon alfa-2a weekly plus placebo (n=29); or 10 mg adefovir weekly (n=30).
Only two patients in each of the peginterferon group achieved the primary end point of normalized alanine aminotransferase levels and HDV RNA clearance at week eight, and none in the adefovir treatment group.
However, the researchers found that 28% of patients both of the peginterferon alfa-2a groups had negative results on HDV-RNA tests after 24 weeks of follow-up.
Ten patients in the combination therapy group, two in the peginterferon plus placebo group and no patients in the adefovir group experienced declines in hepatitis B surface antigen levels (HBsAg) of more than 1 log10 IU per mL from baseline to week 38.
“Further studies are needed to determine whether patients with a slow response to treatment who have clinically significant declines in HDV RNA levels during treatment without becoming HDV RNA-negative would benefit from a longer period of treatment,” the researchers wrote.
They added that study results do not support the use of nucleoside or nucleotide monotherapy for HDV infection among patients with suppressed or very low HBV replication.
A total of 318 adverse events were reported in 66 patients, 17 of which were serious. Because one patient in the peginterferon alfa-2a group who had baseline platelet counts of 74,000 per cubic millimeter experienced hepatic decompensation during treatment, the researchers caution against using the drug in patients with platelet counts below 90,000 per cubic millimeter.
Hep-Net — the German Network of Excellence on Viral Hepatitis — F. Hoffmann-La Roche and Gilead Sciences provided funding for the trial.