Treatment of Hepatitis B in Resource-limited Settings - a Pilot Program in East Africa

Viral hepatitis kills nearly one million people each year, even though effective treatment exists. The aim of this study is to establish a treatment protocol for hepatitis B, which is simple and cheap enough to be implemented in resource-limited settings.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Tenofovir disoproxil

Detailed Description

Chronic viral hepatitis is a major health problem globally. Each year nearly one million deaths are attributable to either hepatitis B or C. In Ethiopia 5-10% of the general population are infected with hepatitis B. Oral antiviral treatment of hepatitis B exists, but high costs and advanced laboratory requirements have been barriers to offer such treatment in resource-limited settings, resembling the situation in treatment of HIV/AIDS a decade ago.

The present study will investigate a simplified approach to hepatitis B treatment in resource-limited settings, inspired by the recent success of HIV treatment in such settings. The critical research question is how to identify patients with expected benefit of treatment in the absence of advanced laboratory support. A WHO expert panel recently suggested treatment criteria for use in settings without advanced laboratory facilities, but these criteria have not yet been tested out in real life. The present study will build on and develop the WHO approach to treatment of hepatitis B, aiming to develop a treatment protocol that can be feasible in other resource-limited countries. The potential public health benefit for poor people in low- and middle-income countries is substantial.

• Study Type: Observational
• Enrollment (Actual): 1350

Contacts and Locations

Study Locations

• Ethiopia
  • Addis Abeba, Ethiopia
    • St Paul Hospital Millennium Medical College

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All adults with a positive HBsAg rapid test are eligible for inclusion.

Description

Inclusion Criteria:

• Consenting adults (≥18 years) residing in Ethiopia who are HBsAg positive

Exclusion Criteria:

• Children <18 years, other terminal disease (cancer etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Urban; HBV patients in Addis Abeba. Eligible patients treated with tenofovir disoproxil fumarate 245 mg OD.	Drug: Tenofovir disoproxil
Rural; HBV patients in Harar. Eligible patients treated with tenofovir disoproxil fumarate 245 mg OD.	Drug: Tenofovir disoproxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death, HCC or decompensated cirrhosis	Patients will be reviewed every 3-6 months with liver function tests and/or ultrasound to detect the proportion of participants who develop liver decompensation or hepatocellular carcinoma.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral suppression and genotypic resistance	Proportion of patients with viral load suppression and absence of resistance after >1 year of antiviral treatment.	3 years
Regression of liver inflammation/fibrosis	Proportion of patients with normalization of ALT and improvement of liver stiffness (by transient elastography)	3 years
Adherence to therapy	Proportion of patients with >95% adherence measured by pill count and visual analogue scale	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of HBsAg rapid tests	Sensitivity and specificity of commonly used HBsAg rapid tests compared to a gold standard ELISA method	1 year

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: The Research Council of Norway; University of Agder; Addis Ababa University; St. Paul's Hospital Millennium Medical College, Ethiopia; South-Eastern Norway Regional Health Authority, Norway; Haramaya University,Ethiopia
• Investigators: Principal Investigator: Asgeir Johannessen, MD PhD, Oslo University Hospital; Principal Investigator: Nega Berhe, MD PhD, Addis Abeba University

Publications and helpful links

General Publications

• Desalegn H, Aberra H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Johannessen A. Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study. BMC Gastroenterol. 2019 May 15;19(1):74. doi: 10.1186/s12876-019-0993-1.
• Aberra H, Desalegn H, Berhe N, Mekasha B, Medhin G, Gundersen SG, Johannessen A. The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia. J Hepatol. 2019 Jun;70(6):1065-1071. doi: 10.1016/j.jhep.2019.01.037. Epub 2019 Mar 28.
• Desalegn H, Aberra H, Berhe N, Mekasha B, Stene-Johansen K, Krarup H, Pereira AP, Gundersen SG, Johannessen A. Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia. BMC Med. 2018 Dec 17;16(1):234. doi: 10.1186/s12916-018-1229-x.
• Aberra H, Gordien E, Desalegn H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Gerber A, Stene-Johansen K, Overbo J, Johannessen A. Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia. Liver Int. 2018 Jun;38(6):1000-1009. doi: 10.1111/liv.13607. Epub 2017 Oct 20.
• Aberra H, Desalegn H, Berhe N, Medhin G, Stene-Johansen K, Gundersen SG, Johannessen A. Early experiences from one of the first treatment programs for chronic hepatitis B in sub-Saharan Africa. BMC Infect Dis. 2017 Jun 19;17(1):438. doi: 10.1186/s12879-017-2549-8.
• Desalegn H, Aberra H, Berhe N, Gundersen SG, Johannessen A. Are non-invasive fibrosis markers for chronic hepatitis B reliable in sub-Saharan Africa? Liver Int. 2017 Oct;37(10):1461-1467. doi: 10.1111/liv.13393. Epub 2017 Mar 23.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimated): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Liver cirrhosis; Liver diseases; Antiviral agents
• 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 B; Hepatitis; Hepatitis A; 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: 2014/1146