Interferon alpha-n1

Combination therapy between two immunomodulators used for treatment of chronic hepatitis B was explored based on reported therapeutic efficacy of interferon-α, and thymosin-α1 as monotherapeutic agents to determine if combination therapy was superior to interferon alone. This double-blinded, randomized, placebo-controlled trial compares the addition of thymosin-α1, 1.6 μg taken three times per week (combination therapy) or thymosin placebo (monotherapy) to lymphoblastoid interferon (Wellferon®), 5 million international units (MIU) taken three times per week, for 24 weeks. Entry criteria included positive hepatitis B e antigen (HBeAg); alanine aminotransferease (ALT) ≥1.5x upper normal limit, but ≤10xupper normal limit; positive HBV DNA; absence of cirrhosis; treatment naivety and no co-morbid factors. A total of 98 HBeAg-positive patients were recruited, of which 48 were randomized to combination therapy and 50 to monotherapy. The primary endpoint was the loss of HBeAg at 72 weeks. The secondary endpoints were HBeAg seroconversion, normalization of ALT, loss of HBV DNA and improvement in histology. The HBeAg loss was 45.8% and 28.0% for combination therapy and monotherapy, respectively (difference, 17.8%; 95% CI -1.2%-35.3%, P=0.067). There was a trend towards HBeAg loss when using combination therapy. There were also no statistically significant differences between the different therapies with respect to the secondary endpoints of HBeAg seroconversion, changes in histology, normalization of ALT or loss of HBV DNA. In conclusion, this trial showed a 17.8% improvement in HBeAg loss rates using combination therapy over interferon monotherapy. This could clinically indicate a potential important difference that would need confirmation in subsequent trials.

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. It is also a common long-term complication of chronic hepatitis B or C infections, with cirrhosis as a risk factor for premalignant development. Natural lymphoblastoid alpha-interferon (alpha N1-IFN) has been widely used in treating chronic HBV and HCV carriers. To investigate its long-term beneficial effect in reducing the development of HCC, 20 hepatitis B surface antigen (HBsAg) positive resected cirrhotic HCC patients who have undergone chemotherapy followed by long-term treatment of 3MU alpha N1-IFN daily for 10 days every 3 months were analyzed in a 14 year follow-up. Results indicated that these patients survived and remained free of HCC. In contrast, 10 other patients receiving chemotherapy alone after resection eventually had HCC recur. Similar recurrence of HCC was seen in patients who had either reduced dosage of alpha N1-IFN or stopped interferon therapy or received 30MU dose at 6-month intervals. Our findings indicate the therapeutic potential and long-term safety of alpha N1-IFN in suppressing the development of HCC in high-risk patients.