Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis
Hong-Lian Gui 1 , Chang-Qing Zhao 2 , Yan Wang 3 , Hong-Tu Gu 2 , Wei-Jing Wang 1 4 , Wei Cai 1 , Qing Guo 1 , Shi-San Bao 5 , Lie-Ming Xu 2 , Qing Xie 1
Affiliations
Affiliations
1
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Department of Liver Cirrhosis, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
3
Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
4
Department of Infectious Diseases, Ruijin North Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5
Discipline of Pathology, School of Medicine Sciences and Bosch Institute, Charles Perkin Centre, University of Sydney, New South Wales, Australia.
Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.