Antiviral Therapy in Hepatitis B Virus (HBV)-Related Advanced Liver Disease Patients

Yonsei University

Status and phase

Unknown

Phase 4

Conditions

Hepatitis B, Chronic

Treatments

Drug: Lamivudine

Drug: Entecavir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00823550

4-2008-0296

Details and patient eligibility

About

This is a randomized, open label, phase IV, multicenter study for efficacy and safety of lamivudine versus entecarvir therapy in HBV-related advanced liver disease patients with high viral load and normal or slightly elevated transaminase.

Full description

Currently, treatment guidelines for the management of chronic hepatitis B (CHB) recommend that patients with serum HBV DNA > 105 copies/ml and elevated ALT levels greater than two times the upper limit of normal (ULN) are obvious candidates for antiviral therapy. Guidelines also suggest that antiviral therapy be considered in CHB patients with high viral load, if a biopsy shows significant liver disease despite ALT ≤ 2× ULN. Data from recent trials in hepatitis B patients who present with normal to minimally elevated ALT (≤ 2× ULN) indicate that significant hepatic pathology could still be found. Serum ALT level may not accurately predict activity of liver damage. ALT is a poor predictor of outcome and therefore is not a suitable criterion for antiviral therapy in chronic hepatitis B infection. Also, a recent large randomized controlled clinical trial comparing lamivudine maintenance and placebo in advanced fibrosis (Ishak fibrosis score ≥ 4) suggests that sustained viral suppression with antiviral therapy is linked to reduced risk for disease progression. (Liaw YF et al. NEJM 2004;351:1521-1531)

Enrollment

462 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

Male and female, 18 years of age or older
HBsAg positive for more than 6 months
Serum HBV DNA > 2,000 IU/ml
Serum ALT < 2 X ULN on two consecutive occasions at least 3 months apart
Naïve to nucleoside or nucleotide therapy
On liver biopsy, fibrosis score ≥ 3 according to METAVIR scoring system (within 2 years of Day 0)
If liver biopsy is not available, subjects must have two of the following items
- Overt findings of cirrhosis by radiologic evidence (MRI, CT, US)
- Gastrointestinal varices
- Platelet count < 100,000,Splenomegaly (Spleen size - 12cm)
The patient who is willing and able to provide written informed consent to participate in this study

Exclusion criteria

A history of SBP, variceal bleeding, HEP, HCC
Decompensated liver disease (Child-Pugh score > 10)
Co-infected with HCV or HIV
History of any other forms of liver disease.
Patient who is pregnant or breastfeeding
Treatment with immunosuppressive, immunomodulatory agents or antiviral agents within 6 months prior to study entry
A history of liver transplantation or planned for liver transplantation
A history of any other medical disease or condition that would make the patients unsuitable for the study.
Patient is currently abusing alcohol or illicit drugs or has a history of alcohol abuse or illicit substance abuse within the preceding 2 years.
Patient is enrolled or plans to enroll in another clinical trial of an investigational agent while participating in this study.