Mutchnick M G, Lindsay K L, Schiff E R, Cummings G D, Appelman H D, Peleman R R, Silva M, Roach K C, Simmons F, Milstein S, Gordon S C, Ehrinpreis M N
Division of Gastroenterology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Viral Hepat. 1999 Sep;6(5):397-403. doi: 10.1046/j.1365-2893.1999.00181.x.
Previous clinical trials have suggested that thymosin alpha1 (Talpha1), an immunomodulatory peptide, may be effective in the treatment of chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of Talpha1 in a multicentre, placebo-controlled and double-blind study of 97 patients with serum hepatitis B virus (HBV) DNA- and hepatitis B e antigen (HBeAg)-positive CHB. Patients who had been hepatitis B surface antigen (HBsAg) positive for at least 12 months entered a 3-month screening period prior to randomization. Forty-nine patients received Talpha1 (1.6 mg) and 48 patients received placebo, twice weekly for 6 months, and were followed-up for an additional 6 months. At inclusion, both groups were comparable for age, gender, histological grading, and aminotransferase and HBV DNA levels. A complete response to treatment, defined as a sustained serum HBV DNA-negative status (two negative results at least 3 months apart) during the 12-month study, with negative HBV DNA and HBeAg values at month 12, was seen in seven (14%) patients given Talpha1 and in two (4%) patients treated with placebo (P = 0.084). Five (10%) patients given Talpha1 and four (8%) patients given placebo exhibited a delayed response (defined as sustained serum HBV DNA negativity achieved after the 12-month study period with negative HBV DNA and HBeAg values at the last assessment). A total of 12 (25%) patients given Talpha1 and six (13%) patients given placebo showed a sustained loss of HBV DNA with a negative HBeAg value during or following the 12-month study period (P < 0.11). These results do not confirm observations of treatment efficacy reported in other clinical studies.
既往临床试验提示，免疫调节肽胸腺肽α1（Tα1）可能对慢性乙型肝炎（CHB）治疗有效。本研究旨在通过一项多中心、安慰剂对照、双盲研究，确定Tα1对97例血清乙肝病毒（HBV）DNA及乙肝e抗原（HBeAg）阳性CHB患者的疗效。乙肝表面抗原（HBsAg）阳性至少12个月的患者在随机分组前进入为期3个月的筛查期。49例患者接受Tα1（1.6mg）治疗，48例患者接受安慰剂治疗，每周2次，共6个月，并额外随访6个月。纳入研究时，两组在年龄、性别、组织学分级、转氨酶及HBV DNA水平方面具有可比性。在为期12个月的研究中，定义为持续血清HBV DNA阴性状态（至少间隔3个月的两次阴性结果）且在第12个月时HBV DNA和HBeAg值为阴性的完全缓解，在接受Tα1治疗的7例（14%）患者及接受安慰剂治疗的2例（4%）患者中出现（P = 0.084）。接受Tα1治疗的5例（10%）患者及接受安慰剂治疗的4例（8%）患者出现延迟缓解（定义为在12个月研究期后实现持续血清HBV DNA阴性且在最后一次评估时HBV DNA和HBeAg值为阴性）。在12个月研究期间或之后，共有12例（25%）接受Tα1治疗的患者及6例（13%）接受安慰剂治疗的患者出现HBV DNA持续转阴且HBeAg值为阴性（P < 0.11）。这些结果未证实其他临床研究报道的治疗疗效观察结果。
