Chronic hepatitis B: Prevent, diagnose, and treat before the point of no return.

Hepatitis B remains a significant global health challenge, contributing to substantial morbidity and mortality. Approximately 254 million people worldwide live with Chronic hepatitis B (CHB), with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions. Alarmingly, only about 13.4% of the individuals infected with this disease have been diagnosed, and awareness of hepatitis B virus (HBV) infection status is as low as 1% in sub-Saharan Africa. In 2022, CHB led to 1.1 million deaths globally. The World Health Organization (WHO) has set a target of eliminating hepatitis B as a public health concern by 2030; however, this goal appears increasingly unattainable due to multiple challenges. These challenges include low vaccination coverage; a large number of undiagnosed cases; a low proportion of patients eligible for treatment under current guidelines; limited access to healthcare; and the costs associated with lifelong treatment. Treatment of HBV can yield significant clinical benefits within a long window of opportunity. However, the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage. This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.

An appraisal of the WHO hepatitis B treatment guidelines applicability to Africans

Navigating the Maze of Hepatitis B Treatments

Antisense oligonucleotides (ASOs) in chronic hepatitis B infection: Opportunities and challenging the orthodoxy.

Hepatitis B—More Treatments, More Testing, Not Enough Data

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

Natural history of chronic hepatitis B in Euro-Mediterranean and African Countries

The molecular basis of the failed immune response in chronic HBV: Therapeutic implications

Chronic Hepatitis B: A Critical Appraisal of Current Approaches to Therapy

In sub-Saharan Africa, hepatitis B virus (HBV) infection is the principal cause of liver cirrhosis and hepatocellular carcinoma (HCC). Mortality from cirrhosis and HCC is projected to rise beyond 2030 unless adult HBV treatment programmes are implemented. Infant HBV vaccination was introduced across sub-Saharan Africa between 1994-2014, and in Malawi in 2002 where it is given at 6, 10 and 14 weeks of life. Hepatitis C virus (HCV) is an important contributor to liver disease globally, with an estimated population prevalence of 1% in sub-Saharan Africa. In Southern Africa there is a paucity of HCV prevalence data, with no previous random probability-sampling community studies. A hospital-based study of cirrhosis and HCC in a tertiary hospital, and seroprevalence studies in an urban township, were conducted in Blantyre, Malawi, to determine HBV and HCV prevalence and HBV vaccine impact. Of 97,386 censused individuals, single stage non-replacement age-stratified probability sampling was used to select 6,073 individuals who were tested for hepatitis B surface antigen (HBsAg) in a community serosurvey. HBsAg-positive individuals aged ≥16 were recruited to assess treatment eligibility. Among individuals aged ≥16 in the serosurvey, 1661 (51%) were randomly selected for HCV antigen/antibody (Ag/Ab) testing with confirmatory HCV RNA PCR. Prevalence estimates were standardised to census age and sex distribution using post-stratification proportional fitting. In the hospital study, the population attributable fraction (PAF) of HBV to cirrhosis and HCC was 23.1% (95% CI 15.7- 29.8) and 71.5% (59.3- 80.1) respectively among 250 consecutively recruited patients. For HCV the PAF was 1.6% (95% CI -0.4 – 3.6) for cirrhosis and 4.8% (-0.1, 9.5) for HCC. Patients with HCC were diagnosed at an advanced stage with a median tumour size of 12.6cm and a median survival of 1.3 months. Six-month survival was 67% (59.0- 73.8) among patients with cirrhosis. Standardised HBsAg prevalence in serosurvey participants born prior to, and after HBV vaccine introduction, was 5.1% (95% CI 4.3- 6.1) and 0.3% (95% CI 0.1- 0.6) respectively. Three-dose vaccination coverage was 97.4% (1141/1171) among 1171/2085 children aged ≤10 years with known vaccine status. By comparison of participants born 5 years before and after vaccine introduction, vaccine impact was 95.9% (95% CI 70.6- 99.4). Treatment eligibility was assessed in 94/150 HBsAg positive people aged ≥16 years from the serosurvey, of whom 24/93 (26%) were HIV positive, and 16/24 (67%) were receiving antiretroviral therapy containing tenofovir, with HBV DNA suppression. Among 69 HIV-negative HBsAg positive individuals, 3,6 and 9% were eligible for HBV treatment by WHO, EASL and AASLD criteria respectively. Standardised HCV Ag/Ab prevalence was 0.78% (95% CI 0.46- 1.33) and HCV RNA prevalence was 0.18% (95% CI 0.06- 0.53). HCV Ag/Ab positive individuals were older than the general population but no differences in sex, educational, employment or marital status were observed. In an urban township in Malawi, HBV prevalence was intermediate at 5.1% among unvaccinated adults. Infant HBV vaccination was associated with a vaccine impact of 96%. Among HBsAg-positive adults, one quarter were HIV-positive and 3-9% of HIV-negative adults were eligible for antiviral therapy. Estimated population HCV RNA prevalence was 0.2%. Future prevalence studies should sample rural communities and specific risk groups. HCC is diagnosed at an advanced stage with a poor prognosis in Malawi, and HBV is an important cause. The burden of HBV and HCV associated liver disease represents both a challenge, and an opportunity to implement public health treatment programmes to reverse rising liver-related mortality in Southern Africa.

A new role for an old marker, HBsAg

RNA interference-mediated control of hepatitis B virus and emergence of resistant mutant

Rescue therapy for drug resistant hepatitis B: Another argument for combination chemotherapy?

Treatment options for chronic hepatitis B not responding to interferon

Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease in HBeAg-Negative Patients