Format

Send to

Choose Destination
Adv Ther. 2015 Aug;32(8):727-41. doi: 10.1007/s12325-015-0232-2. Epub 2015 Sep 2.

Long-Term Telbivudine Treatment Results in Resolution of Liver Inflammation and Fibrosis in Patients with Chronic Hepatitis B.

Author information

1
Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. jlhousmu@163.com.
2
Beijing Ditan Hospital, Beijing, China.
3
Department of Infectious Diseases, Huashan Hospital, Fu Dan University, Shanghai, China.
4
Shanghai Changhai Hospital, Shanghai, China.
5
Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.
6
Xiangya Hospital, Changsha, China.
7
School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
8
Shanghai Liver Disease Research Center of Nanjing Military Area, Shanghai, China.
9
Peking University People's Hospital, Beijing, China.
10
No. 1 Hospital, Changchun, China.
11
First Hospital of Peking, Beijing, China.
12
Chongqing Medical University 2nd Affiliated Hospital, Chongqing, China.
13
Xi Nan Hospital, Chongqing, China.
14
Beijing Friendship Hospital, Beijing, China.
15
Novartis Pharma Corporation, East Hanover, USA.
16
Novartis Pharma AG, Basel, Switzerland.

Abstract

INTRODUCTION:

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)).

CONCLUSION:

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.

FUNDING:

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

TRIAL REGISTRATION:

ClinicalTrials.gov # NCT00877149.

KEYWORDS:

Chronic hepatitis B; Ishak fibrosis score; Knodell necroinflammatory score; Liver biopsy; Telbivudine

PMID:
26329749
PMCID:
PMC4572721
DOI:
10.1007/s12325-015-0232-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center