Efficacy of thymosin alpha1 in patients with chronic hepatitis B - a randomized, controlled trial

Randomized trial conducted by the Yun-Fan Liaw group in Taiwan — one of the most productive centers worldwide in viral hepatology — comparing thymosin alpha-1 (Tα1, Zadaxin) as monotherapy versus untreated control in chronic hepatitis B patients. The study was part of the evidence base that led to Zadaxin approval in several Asian countries for hepatitis B indication.

Ninety-eight patients with HBeAg-positive chronic hepatitis B were enrolled, randomized into three groups: group A (26 weeks of Tα1), group B (52 weeks of Tα1) and group C (untreated control). The dose was 1.6 mg subcutaneous twice weekly, the standard subsequently adopted by most Zadaxin protocols. The primary outcome was complete virological response, defined as clearance of serum HBV DNA and loss of HBeAg.

At 18 months follow-up, the complete virological response rate was 40.6% in group A, 26.5% in group B and only 9.4% in group C (p<0.05). Interestingly, the shorter treatment (26 weeks) was more effective than the long one (52 weeks) — possibly due to a more intense "reactive immunomodulation" effect in short courses, without desensitization. There was significant hepatic histological improvement in treated groups, without relevant adverse effects attributable to Tα1.

This was one of the first robust RCTs to establish that thymosin alpha-1 alone (without interferon) can produce sustained virological response in chronic hepatitis B. The current therapeutic paradigm has changed — with nucleos(t)ide analogs (tenofovir, entecavir) and HCV direct-acting antivirals, Tα1 has lost its central place in viral hepatitis treatment. But the study remains a historical reference and mechanistic foundation for the immunomodulatory use of Tα1, now redirected to sepsis, oncology and other indications.