HBV elimination in Africa-Current status and challenges.

1_n81kbjgsKaltura.

Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa.

Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as ß blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.

A simplified point-of-service model for hepatitis C in people who inject drugs in South Africa.

BACKGROUND: Globally, 9% of people who inject drugs (PWID), a key hepatitis C-infected population, reside in sub-Saharan Africa. In South Africa, hepatitis C seroprevalence in PWID is high. It is almost 84% in Pretoria and hepatitis C genotypes 1 and 3 predominate. Access to hepatitis C care for PWID is inadequate given low referral rates, socio-structural barriers, homelessness and limited access to harm reduction. Traditional care models do not address the needs of this population. We piloted a simplified complete point-of-service care model, a first of its kind in the country and sub-continental region. METHODS: Community-based recruitment from Pretoria's PWID population occurred over 11 months. Participants were screened with point-of-care rapid diagnostic tests for HBsAg (Alere Determine™), hepatitis C and HIV antibodies (OraQuick®). Qualitative HCV viremia was confirmed on site with Genedrive® (Sysmex), similarly at week 4, end of treatment and to confirm sustained virological response. Viremic hepatitis C participants were initiated on 12 weeks of daily sofosbuvir and daclatasvir. Harm reduction and adherence support, through directly observed therapy, peer support, a stipend and transport, was provided. RESULTS: A total of 163 participants were screened for hepatitis C antibody, and 66% were positive with 80 (87%) viremic. An additional 36 confirmed hepatitis C viremic participants were referred. Of those eligible to initiate treatment, 87 (93%) were commenced on sofosbuvir and daclatasvir, with 98% (n = 85) male, 35% (n = 30) HIV co-infected, 1% (n = 1) HBV co-infected and 5% (n = 4) HIV/HBV/HCV triple infected. Some 67% (n = 58) accessed harm reduction packs, 57% (n = 50) opioid substitution therapy and 18% (n = 16) stopped injecting. A per protocol sustained virological response of 90% (n = 51) was achieved with 14% (n = 7) confirmed reinfections following a sustained virological response. HCV RNA qualitative testing performance was acceptable with all sustained virological responses validated against a laboratory assay. Mild adverse effects were reported in 6% (n = 5). Thirty-eight percent (n = 33) of participants were lost to follow-up. CONCLUSION: In our setting, a simplified point-of-service hepatitis C care model for PWID yielded an acceptable sustained virological response rate. Retention in care and follow-up remains both challenging and central to success. We have demonstrated the utility of a model of care for our country and region to utilize this more community acceptable and simplified practice.

Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa.

Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.

Global Disparities in Hepatitis B Elimination-A Focus on Africa.

In 2016, WHO member states at the World Health Assembly adopted a Global Health Sector Strategy that included a policy of eliminating viral hepatitis. Clear targets were established to assist in achieving this by 2030. The strategy, while achievable, has exposed existing global disparities in healthcare systems and their ability to implement such policies. Compounding this, the regions with most disparity are also those where the hepatitis B prevalence and disease burden are the greatest. Foundational to hepatitis B elimination is the identification of both those with chronic infection and crucially pregnant women, and primary prevention through vaccination. Vaccination, including the birth dose and full three-dose coverage, is key, but complete mother-to-child transmission prevention includes reducing the maternal hepatitis B viral load in the third trimester where appropriate. Innovations and simplified tools exist in order to achieve elimination, but what is desperately required is the will to implement these strategies through the support of appropriate investment and funding. Without this, disparities will continue.

Health-care provision and policy for non-alcoholic fatty liver disease in sub-Saharan Africa.

Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and diabetes, enhance the risk of non-alcoholic fatty liver disease (NAFLD), yet this remains an unrecognised complication of metabolic syndrome. There are no guidance documents on NAFLD from sub-Saharan Africa, and non-communicable disease (NCD) guidance documents do not include the associated burden of fatty liver disease. Combating the health and socioeconomic burden of NAFLD requires an integrated liver health approach, with task-shifting to primary health care. Using clear guidance documents to link education and management of HIV, viral hepatitis, NAFLD, and associated NCDs is also crucial to an integrated approach to infectious diseases and NCDs, which requires targeted funding from both governments and international development agencies.

Epidemiology, risk factors, social determinants of health, and current management for non-alcoholic fatty liver disease in sub-Saharan Africa.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.

COVID-19 and the liver: A 2021 update.

In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China and has since resulted in a global pandemic in excess of 165 million reported infections and 3.4 million attributable deaths. COVID-19 is primarily a respiratory illness, which may be complicated by pneumonia and acute respiratory distress syndrome. SARS-CoV-2 is also responsible for numerous extrapulmonary manifestations involving the haematologic, cardiovascular, renal, gastrointestinal and hepatobiliary, endocrinologic, neurologic, ophthalmologic and dermatologic systems. This review will discuss the pathophysiology of COVID-19; focusing on the mechanisms and outcomes of liver injury associated with COVID-19; its impact on chronic liver disease (CLD); management of CLD during the COVID-19 pandemic and the long-term impact of COVID-19 on CLD.

Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017).

BACKGROUND: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. METHODS: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. RESULTS: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). CONCLUSIONS: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.

Hepatitis B in sub-Saharan Africa-How many patients need therapy?

Hepatitis B is endemic in sub-Saharan Africa with ~60 million people chronically infected. While prevention, through vaccination, is central to elimination strategies, only 11 countries have birth dose vaccination and full vaccine coverage remains at suboptimal levels. Furthermore, to fully realize elimination, those chronically infected need to be identified, assessed for therapy and then linked to care. Given current treatment criteria, the precise quantum of people warranting therapy, according to criteria, is essentially unknown. The issue is further complicated by data to suggest differences in the numbers of people requiring treatment when applying WHO as compared to European Association for the Study of the Liver, EASL, criteria. Optimal determination of treatment eligibility is further hindered by the lack of available tools to adequately assess individual patients. It is conceivable that accurately determining the number of those requiring treatment, given the heterogeneity of hepatitis B in Africa, is difficult. Better studies and data are required. More signifcantly, improved access and availability to the diagnostic tools needed to assess patients in additon to access to drugs are as, if not more important, to achieve elimination.

Understanding hepatitis B, hepatitis C and HIV among people who inject drugs in South Africa: findings from a three-city cross-sectional survey.

BACKGROUND: People who inject drugs (PWID) are at high risk for hepatitis C (HCV), hepatitis B (HBV) and HIV without accessible harm reduction programmes. Coverage of needle and syringe and opioid substitution therapy (OST) services in South Africa is below global recommendations and no hepatitis services exist for PWID. We assessed HCV, HBV and HIV prevalence and risk factors among PWID accessing harm reduction services in Cape Town, Durban and Pretoria to inform policy and programming. METHODS: We conducted a cross-sectional survey among PWID in these cities between August 2016 and October 2017. Participants were opportunistically sampled while accessing services. Study team members administered a questionnaire that assessed sociodemographic characteristics, drug use and sexual risk practices. We tested for HCV (antibody, viral load and genotype), HBV surface antigen (HBsAg) and HIV. Bivariate and multivariate analyses assessed associations with HCV serostatus. RESULTS: Nine hundred and forty-three PWID were included in the per protocol analysis. The majority (87%, 819/943) were male, the overall median age was 29 and most lived on the street (66%, 626/943). At last injection, 77% (722/943) reported using a new needle and syringe and 17% (163/943) shared equipment. HIV prevalence was 21% (196/926), HBsAg positivity 5% (47/936), HCV seroprevalence 55% (513/937), HCV viraemic prevalence (proportion tested with detectable HCV) 43% (404/937) and HCV viraemic rate (proportion HCV antibody positive with detectable HCV) 79% (404/513). HCV genotype 1a (73%, 270/368) was the most prevalent. In multivariate analysis, HCV infection was positively associated with residing in Pretoria (adjusted odds ratio (aOR) 1.27, 95% CI 1.21-1.34), living on the street (aOR 1.90, 95% CI 1.38-2.60), frequent injecting (aOR 1.58, 95% CI 1.15-2.16) and HIV infection (aOR 1.69, 95% CI 1.15-2.47), and negatively associated with black race (aOR 0.52, 95% CI 0.36-0.74) and sexual activity in the previous month (aOR 0.61, 95% CI 0.42-0.88). CONCLUSIONS: HCV and HIV are major health threats affecting PWID in these cities. Access to OST and needle and syringe services needs to be increased and integrated with HCV services. Social and structural factors affecting PWID who live on the street need to be addressed.

Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission.

Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.

The investment case for hepatitis B and C in South Africa: adaptation and innovation in policy analysis for disease program scale-up.

Even though WHO has approved global goals for hepatitis elimination, most countries have yet to establish programs for hepatitis B and C, which account for 320 million infections and over a million deaths annually. One reason for this slow response is the paucity of robust, compelling analyses showing that national HBV/HCV programs could have a significant impact on these epidemics and save lives in a cost-effective, affordable manner. In this context, our team used an investment case approach to develop a national hepatitis action plan for South Africa, grounded in a process of intensive engagement of local stakeholders. Costs were estimated for each activity using an ingredients-based, bottom-up costing tool designed by the authors. The health impact and cost-effectiveness of the Action Plan were assessed by simulating its four priority interventions (HBV birth dose vaccination, PMTCT, HBV treatment and HCV treatment) using previously developed models calibrated to South Africa's demographic and epidemic profile. The Action Plan is estimated to require ZAR3.8 billion (US$294 million) over 2017-2021, about 0.5% of projected government health spending. Treatment scale-up over the initial 5-year period would avert 13 000 HBV-related and 7000 HCV-related deaths. If scale up continues beyond 2021 in line with WHO goals, more than 670 000 new infections, 200 000 HBV-related deaths, and 30 000 HCV-related deaths could be averted. The incremental cost-effectiveness of the Action Plan is estimated at $3310 per DALY averted, less than the benchmark of half of per capita GDP. Our analysis suggests that the proposed scale-up can be accommodated within South Africa's fiscal space and represents good use of scarce resources. Discussions are ongoing in South Africa on the allocation of budget to hepatitis. Our work illustrates the value and feasibility of using an investment case approach to assess the costs and relative priority of scaling up HBV/HCV services.

Aiming at the Global Elimination of Viral Hepatitis: Challenges Along the Care Continuum.

A recent international workshop, organized by the authors, analyzed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include providing hepatitis B birth-dose vaccination to all infants within 24 hours of birth, preventing the transmission of blood-borne viruses through the expansion of national hemovigilance schemes, implementing the lessons learned from the HIV epidemic regarding safe medical practices to eliminate iatrogenic infection, adopting point-of-care testing to improve coverage of diagnosis, and providing free or affordable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country offers valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programs.

Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030.

In 2016, WHO adopted a strategy for the elimination of viral hepatitis by 2030. Africa, and more specifically, sub-Saharan Africa, carries a substantial portion of the global burden of viral hepatitis, especially chronic hepatitis B and hepatitis C virus infections. The task that lies ahead for sub-Saharan Africa to achieve elimination is substantial, but not insurmountable. Major developments in the management of hepatitis C have put elimination within reach, but several difficulties will need to be navigated on the path to elimination. Many of the challenges faced are unique to sub-Saharan Africa and the development of strategies is complicated by a scarcity of good data from countries and regions within sub-Saharan Africa. However, this hindrance should not act as a barrier to delay interventions in screening, detection, and linkage to care. Moreover, by sharing experiences from across sub-Saharan Africa, countries can create supranational synergies to develop their programmes and work together in a more cohesive manner to tackle the burden of hepatitis C in sub-Saharan Africa. In this Series paper, several issues related to hepatitis C in sub-Saharan Africa are addressed, including prevalence, risk factors, and fibrosis assessment, and recommendations are given by experts from across the region. Simplified diagnostic algorithms and treatment regimens for both HIV co-infected and hepatitis C mono-infected patients are suggested. The recommendations are consensus based and provided to guide the development of programmes in sub-Saharan Africa. Political will and appropriate funding will be required to provide impetus to implement these recommendations.

Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets.

The WHO global health sector strategy on viral hepatitis, created in May, 2016, aims to achieve a 90% reduction in new cases of chronic hepatitis B and C and a 65% reduction in mortality due to hepatitis B and C by 2030. Hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and despite the introduction of universal hepatitis B vaccination and effective antiviral therapy, the estimated overall seroprevalence of hepatitis B surface antigen remains high at 6·1% (95% uncertainty interval 4·6-8·5). In this Series paper, we have reviewed the literature to examine the epidemiology, burden of liver disease, and elimination strategies of hepatitis B in sub-Saharan Africa. This paper reflects a supranational perspective of sub-Saharan Africa, and recommends several priority elimination strategies that address the need both to prevent new infections and to diagnose and treat chronic infections. The key to achieving these elimination goals in sub-Saharan Africa is the effective prevention of new infections via universal implementation of the HBV birth-dose vaccine, full vaccine coverage, access to affordable diagnostics to identify HBV-infected individuals, and to enable linkage to care and antiviral therapy.