Use of TDF in Patients With Inactive Chronic Hepatitis B Infection

The Use of Tenofovir Disoproxil Fumarate (TDF) in the Management of Patients With Inactive Chronic Hepatitis B (CHB) Infection

Recent evidence suggests that patients with inactive chronic hepatitis B (CHB) may develop the same types of liver complications that patients in the active state of hepatitis B virus (HBV) infection experience. Treatment guidelines for patients in the active state of HBV infection indicate that HBsAg clearance is associated with definitive remission of the activity of chronic HBV & improved long-term outcome. Clinical data showed that HBsAg clearance is achievable, in a small population of patients on continuous treatment with potent oral antivirals (OAVs), such as tenofovir disoproxil fumarate (TDF). It is possible the same OAVs can have the same effect in patients with inactive CHB, but in a shorter treatment duration. The purpose of this study is to find out if TDF is effective in controlling HBV DNA & promoting seroconversion from HBsAg-positive to HBsAb-positive in patients with inactive CHB.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate

Detailed Description

Hepatitis B virus (HBV) infection is a major worldwide health problem. The course of the majority of patients with inactive chronic hepatitis B is usually benign; therefore, the current treatment guidelines recommend not treating these patients. However, recent evidence suggests that the prognosis of these inactive carrier is not exactly benign. For instance, patients may develop liver cancer despite their inactive carrier state. Also, approximately 20-30% of patients with inactive chronic hepatitis B may undergo spontaneous reactivation of hepatitis over time. Multiple episodes of reactivation or sustained reactivation can cause progressive liver damage and even liver decompensation. However, until there are data to support that treatment with oral antivirals can alter the outcome of these patients, they will remain untreated. Potent oral antivirals have been shown to suppress HBV DNA and normalize liver enzymes in patients with active chronic hepatitis B infection. With continued long-term treatment, some of these patients have gone on to clear hepatitis B surface antigen and develop hepatitis B surface antibody. Therefore, it is possible that the same oral antivirals can have the same effect in patients with inactive chronic hepatitis B, but in a shorter duration of treatment. This study will explore the possible use of tenofovir disoproxil fumarate in controlling HBV DNA and promoting hepatitis B surface antigen seroconversion in patients with inactive chronic hepatitis B.

After completion of all initial investigations, patients will be started on TDF 300mg daily. Patients will be reviewed at 6 monthly intervals as per standard of care. At each clinic visit, patients will have blood tests including complete blood count, renal function, electrolytes, liver enzyme and liver function tests, as well as HBV serology including quantitative HBsAg and HBV DNA. Patients will also receive an abdominal ultrasound, fibroscan and fibrotest on an annual basis. Treatment will be stopped when sAg+ve seroconverts to sAb+ve or at the end of 3 years whichever comes earlier.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network - Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients with inactive chronic hepatitis B, defined as someone who has HBV DNA ≤ log4, eAg-ve, eAb+, HBsAg+ve and normal ALT persistently for >6 months

Exclusion Criteria:

• Patients older than 75 years of age
• Presence of hepatoma at entry
• Presence of decompensated cirrhosis defined by a history of variceal bleed, ascites, or hepatic encephalopathy
• Presence of abnormal renal function defined as serum creatinine of>110µmol/L
• co-infection with HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tenofovir disoproxil fumarate; 300 mg, orally, once a day for 3 years or when sAg+ve seroconverts to sAb+ve whichever comes earlier	Drug: Tenofovir disoproxil fumarate; 300 mg, oral, once a day; Other Names: Viread

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion from hepatitis B surface antigen positive to hepatitis B surface antibody positive	Positive hepatitis B surface antibody result will indicate recovery from chronic hepatitis B virus infection.	Three years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Florence Wong, MD, University Health Network -Toronto General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: 15-8950; IN-CA-174-1708 (Other Identifier: Gilead Sciences, Inc.)