Thymosin ␣ 1 (T␣) is an immune modifier that has been shown in a pilot study to be effective for chronic hepatitis B; this requires confirmation. Ninety-eight patients with clinicopathologically proven chronic hepatitis B were randomly allocated to 3 groups: 1) group A received a 26-week course of T␣ with a 1.6-mg subcutaneous injection two times a week (T 6 group); 2) group B received the same regimen as group A, but T␣ therapy extended for 52 weeks (T 12 group); and 3) group C served as a control group and was followed up for 18 months without specific treatment (T 0 group). The three groups were comparable in clinicohistological features at entry. The complete virological response rate (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%) (group A vs. group C: P ؍ .004; group B vs. group C: P ؍ .068) when assessed 18 months after entry, although complete response rates among these three groups were similar when first assessed at the end of therapy. There was a trend for complete virological response to increase or accumulate gradually after the end of T␣ therapy. None of the responders lost hepatitis B surface antigen. Blinded histological assessment showed a significant improvement in treated patients, particularly in lobular necroinflammation and scores excluding fibrosis. No significant side effects were observed. These results suggest that a 26-week course of T␣ therapy is effective and safe in patients with chronic hepatitis B. (HEPATOLOGY 1998;27:1383-1387.)
Chronic hepatitis B virus (HBV) infection is a serious problem because of its worldwide distribution and possible adverse sequalae, such as cirrhosis and hepatocellular carcinoma. The ultimate goals of therapy for chronic hepatitis B are to prevent progression to cirrhosis and to prevent development of hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. 6,7 Among them, interferon alfa (IFN-␣) has been shown to be effective, because 30% to 40% of adult white patients with elevated alanine transaminase (ALT) levels lost hepatitis B e antigen (HBeAg) and HBV DNA when treated with IFN-␣ at a dose of 5 MU daily or 10 MU three times a week for 16 weeks. However, the response rate is far from satisfactory, particularly in Asian patients, although corticosteroid priming may enhance the efficacy of interferon therapy. Thymosin ␣ 1 (T␣) is an immune modifier that has been shown to trigger maturational events in lymphocytes, to augment T-cell function, and to promote reconstitution of immune defects. A small pilot study conducted by Mutchnick et al. showed an 80% complete response associated with clinical, immunological, and histological improvement in patients with chronic hepatitis B. However, a multicenter American study involving 97 patients only showed a marginally significant benefit. Thus, the efficacy of T␣ still requires confirmation. We therefore conducted a randomized, controlled trial of T␣ in patients with chronic hepatitis B.