Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B.
One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) resulted in significantly improved liver histology and virological and biochemical endpoints in comparison with lamivudine. Patients who received at least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term rollover study and underwent long-term liver biopsy were evaluated for improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological improvement was analyzed for 57 patients who had adequate baseline biopsy samples, baseline Knodell necroinflammatory scores > or =2, and adequate long-term biopsy samples. At the time of long-term biopsy, all patients in the cohort had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized alanine aminotransferase level. Histological improvement (> or =2-point decrease in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis score) was observed in 96% of patients, and a > or =1-point improvement in the Ishak fibrosis score was found in 88% of patients, including all 10 patients with advanced fibrosis or cirrhosis at the phase 3 baseline.


CONCLUSIONS
The majority of nucleoside-naive patients with CHB who were treated with entecavir in this long-term cohort achieved substantial histological improvement and regression of fibrosis or cirrhosis.
Chang
Ting-Tsung
TT
Department of Internal Medicine, National Cheng Kung University Medical College, Tainan, Taiwan. ttchang@mail.ncku.edu.tw
Liaw
Yun-Fan
YF
Wu
Shun-Sheng
SS
Schiff
Eugene
E
Han
Kwang-Hyub
KH
Lai
Ching-Lung
CL
Safadi
Rifaat
R
Lee
Samuel S
SS
Halota
Waldemar
W
Goodman
Zachary
Z
Chi
Yun-Chan
YC
Zhang
Hui
H
Hindes
Robert
R
Iloeje
Uchenna
U
Beebe
Suzanne
S
Kreter
Bruce
B
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001706:Biopsy; D015331:Cohort Studies; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; C413685:entecavir; D006147:Guanine