Long-Term Telbivudine Treatment Results in Resolution of Liver Inflammation and Fibrosis in Patients with Chronic Hepatitis B.
BACKGROUND
The long-term goal of chronic hepatitis B (CHB) treatment is improvement of liver disease and prevention of cirrhosis. The aim of this study was to assess whether prolonged telbivudine treatment improves liver inflammation and fibrosis. The primary objective was to evaluate the proportion of patients with absence/minimal inflammation (Knodell necroinflammatory score ≤3) on liver biopsy at Year 5.


METHODS
Fifty-seven patients aged 16-70 years with a clinical history of CHB and active viral replication (38 hepatitis B e antigen [HBeAg] positive and 19 HBeAg negative) were followed for 6 years: 33 received telbivudine 600 mg/day continuously for 5 years; 24 received lamivudine 100 mg/day for 2 years and then telbivudine for 3 years. Liver biopsies were taken pre-treatment and after 5 years of treatment.


RESULTS
At baseline, mean (standard deviation) serum hepatitis B virus (HBV) DNA load was 8.5 (1.7) log10 copies/mL, Knodell necroinflammatory score was 7.6 (2.9), and Ishak fibrosis score was 2.2 (1.1). After antiviral treatment (median duration: 261 weeks), liver histology improved with increased proportions of patients with absence/minimal liver inflammation (Knodell necroinflammatory score ≤3), from 16% (9/57) at baseline to 98% (56/57), and absence/minimal fibrosis (Ishak score ≤1), from 25% (14/57) at baseline to 84% (48/57). At Year 5, HBV DNA load was <300 copies/mL for all patients; cumulative HBeAg loss and seroconversion rates were 88% and 77%, respectively. At Year 6, 95% of patients with abnormal baseline glomerular filtration rate (60-90 mL/min/1.73 m(2)) improved to normal GFR (>90 mL/min/1.73 m(2)).


CONCLUSIONS
Long-term telbivudine treatment with profound and durable viral suppression significantly improved liver histology, thus achieving the long-term goals of CHB treatment. FibroScan(®) results after 5 and 6 years of treatment (in almost 20% of patients) were consistent with this information.


BACKGROUND
Novartis and National Science and Technology Major Project (2012ZX10002003).


BACKGROUND
ClinicalTrials.gov # NCT00877149.
Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. jlhousmu@163.com.
Jin-Lin
JL
Hou
Beijing Ditan Hospital, Beijing, China.
Daozheng
D
Xu
Department of Infectious Diseases, Huashan Hospital, Fu Dan University, Shanghai, China.
Guangfeng
G
Shi
Shanghai Changhai Hospital, Shanghai, China.
Mobin
M
Wan
Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.
Zachary
Z
Goodman
Xiangya Hospital, Changsha, China.
Deming
D
Tan
School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
Qing
Q
Xie
Shanghai Liver Disease Research Center of Nanjing Military Area, Shanghai, China.
Chengwei
C
Chen
Peking University People's Hospital, Beijing, China.
Lai
L
Wei
No. 1 Hospital, Changchun, China.
Junqi
J
Niu
First Hospital of Peking, Beijing, China.
Qinhuan
Q
Wang
Chongqing Medical University 2nd Affiliated Hospital, Chongqing, China.
Hong
H
Ren
Xi Nan Hospital, Chongqing, China.
Yuming
Y
Wang
Beijing Friendship Hospital, Beijing, China.
Jidong
J
Jia
Novartis Pharma Corporation, East Hanover, USA.
Weibin
W
Bao
Novartis Pharma AG, Basel, Switzerland.
Yuhong
Y
Dong
Novartis Pharma AG, Basel, Switzerland.
Aldo
A
Trylesinski
Novartis Pharma AG, Basel, Switzerland.
Nikolai V
NV
Naoumov
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D000077712:Telbivudine; D013936:Thymidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013995:Time; D016896:Treatment Outcome
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077712:Telbivudine; D013936:Thymidine
Chronic hepatitis B; Ishak fibrosis score; Knodell necroinflammatory score; Liver biopsy; Telbivudine