Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy.
OBJECTIVE
To compare the histological outcome of chronic hepatitis B (CHB) patients treated with entecavir (ETV) or lamivudine (LAM)-based therapy.


METHODS
We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis (baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baseline characteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ(2) test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.


RESULTS
Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74% (18/19) of the patients in the ETV arm and 95.65% (22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/mL. The majority of the patients (94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM (P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients (P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients (P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.


CONCLUSIONS
CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jia-Li
JL
Wang
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Xin-Fang
XF
Du
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Shao-Long
SL
Chen
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Yi-Qi
YQ
Yu
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jing
J
Wang
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Xi-Qi
XQ
Hu
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Ling-Yun
LY
Shao
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jia-Zhen
JZ
Chen
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Xin-Hua
XH
Weng
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Wen-Hong
WH
Zhang
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D016009:Chi-Square Distribution; D002681:China; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine
Advanced fibrosis; Chronic hepatitis B; Cirrhosis; Entecavir; Histological outcome; Lamivudine