Clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia, west Africa: a prospective cohort study.

BACKGROUND: Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis. METHODS: In this prospective cohort study, we followed up adults who were consecutively diagnosed with cirrhosis or hepatocellular carcinoma between 2012 and 2015 in The Gambia, west Africa. Patients with chronic HBV infection and cirrhosis, without hepatocellular carcinoma, were offered TDF. Primary outcome was overall survival. To determine the effect of TDF on survival, we performed a Cox proportional hazard regression model with inverse probability of treatment weighting (IPTW) based on propensity score. FINDINGS: Of 529 patients enrolled in this study, 336 patients (252 with hepatocellular carcinoma and 84 with cirrhosis) were analysed. Patients were predominantly male (253 [75%] men and 83 [25%] women), with a median age of 42 years (IQR 33-55). 276 (84%) of 327 of patients with data were positive for HBV biomarkers, 31 (10%) of 311 were positive for hepatitis C virus antibodies, and 22 (10%) of 223 were positive for hepatitis D virus antibodies. 64% of patients with hepatocellular carcinoma had multifocal tumour, with a median size of 7·5 cm (IQR 5·4-10·8). 173 patients with hepatocellular carcinoma and 70 patients with cirrhosis were included in the survival analysis. Median survival was 1·5 months (95% CI 1·1-2·0) in patients with hepatocellular carcinoma and 17·1 months (11·2-24·0) in patients with cirrhosis (log-rank p<0·0001). In patients with hepatocellular carcinoma, ascites (hazard ratio [HR] 1·78, 95% CI 1·21-2·60), partial or complete portal thrombosis (HR 2·61, 1·58-4·30), and platelet count (HR 1·80, 1·19-2·70) were independent predictive factors of mortality at baseline. In HBV-infected patients with cirrhosis, median turnaround time between cirrhosis diagnosis and TDF initiation was 4·9 months (IQR 3·2-7·3). In IPTW analysis, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (adjusted HR 0·14, 0·06-0·34; p<0·0001). INTERPRETATION: These results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa. FUNDING: European Commission and Medical Research Council UK. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Mac-2 binding protein glycosylation isomer (M2BPGi) to evaluate liver fibrosis and cancer in HBV-infected patients in West Africa.

Background: To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In low-income countries, however, HBV-infected people have limited access to liver histopathology, a reference test. Recently, Asian studies have suggested the usefulness of an inexpensive serum biomarker called Mac-2 binding protein glycosylation isomer (M2BPGi) in staging liver fibrosis and predicting HCC in HBV-infected patients. Methods: We systematically searched PubMed for studies examining the performance of M2BPGi in staging liver fibrosis in HBV-infected people, published up to September 21, 2021, to elucidate the knowledge gap. We then conducted a cross-sectional study of 339 HBV-infected patients in The Gambia (cirrhosis = 65, HCC = 73, non-cirrhosis non-HCC = 201). We evaluated the association of M2BPGi with cirrhosis and HCC by computing odds ratios (ORs) derived from logistic regression. We also assessed the performance of M2BPGi to stage liver fibrosis in 49 patients who underwent liver biopsy (derivation set) and 217 patients with transient elastography (validation set). Using the derivation set we drew the receiver operating characteristics (ROC) curves to identify optimal M2BPGi thresholds to indicate significant fibrosis and cirrhosis using biopsy as a reference. We then applied these cut-offs to the validation set to obtain its sensitivity and specificity for indicating significant fibrosis and cirrhosis using transient elastography as a reference. Results: The systematic review identified 13 studies, all of which were conducted in East Asia and none in Africa. In The Gambia, positive M2BPGi was significantly associated with both cirrhosis (adjusted OR = 7.8, 95% CI = 3.1-19.7) and HCC (adjusted OR = 10.1, 2.6-40.2). The areas under the ROC curve (AUROC) in the derivation and validation set were 0.62 and 0.78, respectively, to diagnose significant fibrosis, and 0.80 and 0.89, respectively, to diagnose cirrhosis. By applying the optimal cut-offs, the sensitivity and specificity in the validation set were 61.5% and 93.4%, respectively, to diagnose significant fibrosis, and 72.5% and 92.2%, respectively, for cirrhosis. Conclusions: To the best of our knowledge, this is the first evaluation of M2BPGi in HBV-infected African population. The findings supported its accuracy in the diagnosis of cirrhosis in HBV-infected patients in West Africa.

Viral Diagnosis of Hepatitis B and Delta: What We Know and What Is Still Required? Specific Focus on Low- and Middle-Income Countries.

To achieve the World Health Organization's (WHO) goals of eradicating viral hepatitis globally by 2030, the regional prevalence and epidemiology of hepatitis B virus (HBV) and hepatitis delta virus (HDV) coinfection must be known in order to implement preventiveon and treatment strategies. HBV/HDV coinfection is considered the most severe form of vira l hepatitis due to it's rapid progression towards cirrhosis, hepatocellular carcinoma, and liver-related death. The role of simplified diagnosticsis tools for screening and monitoring HBV/HDV-coinfected patients is crucial. Many sophisticated tools for diagnoses have been developed for detection of HBV alone as well as HBV/HDV coinfection. However, these advanced techniques are not widely available in low-income countries and there is no standardization for HDV detection assays, which are used for monitoring the response to antiviral therapy. More accessible and affordable alternative methods, such as rapid diagnostic tests (RDTs), are being developed and validated for equipment-free and specific detection of HBV and HDV. This review will provide some insight into both existing and diagnosis tools under development, their applicability in developing countries and how they could increase screening, patient monitoring and treatment eligibility.

Clinical utility of the 'Determine HBsAg' Point-of-Care Test for Diagnosis of Hepatitis B Surface Antigen in Africa.

INTRODUCTION: Chronic infection with hepatitis B virus (HBV) is a leading cause of morbidity and death, especially in sub-Saharan Africa (SSA), where approximately 60 million adults are infected. More than 90% of these patients are unaware of their HBV status. AREAS COVERED: Scaling-up of HBV screening programs in SSA are essential to increase diagnosis, linkage to care, and access to treatment, and will ultimately reduce HBV disease burden to achieve WHO hepatitis elimination targets. Such scale up will rely on inexpensive rapid point-of-care (POC) tests, especially in remote areas where gold standard serological assays are not routinely available. This review discusses the diagnostic performance and clinical utility of the Determine™ (Abbott, USA) hepatitis B surface Antigen (HBsAg) POC test for improving HBV screening in SSA, in light with others available HBsAg rapid tests. EXPERT OPINION: The Determine™ HBsAg POC test has demonstrated relatively good diagnostic accuracy at the low cost, in the African field and laboratory and should be used for large scale mass screening of HBV infection in Africa.

Factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal.

BACKGROUND: Vaccination during pregnancy can protect pregnant women and their babies from infectious diseases. Tetanus vaccine, also known as tetanus toxoid, is the only vaccine given to pregnant women in The Gambia and Senegal, where it is given by antenatal care providers as part of the Expanded Programme on Immunization. A qualitative study was undertaken to explore factors influencing acceptance of vaccination during pregnancy in The Gambia and Senegal. METHODS: Focus group discussions and in-depth interviews were conducted across urban and rural settlements of The Gambia and Senegal. We explored the knowledge, attitudes, and perceptions of 152 women who were either pregnant or with an infant. NVivo 11 Qualitative Data Analysis Software was used for management and thematic analysis of the data. RESULTS: Women had sufficient knowledge of the need for tetanus vaccine from different information sources but insufficient knowledge of tetanus causes, signs and symptoms. Tetanus vaccine was perceived to be safe and side effects such as pain and swelling at site of injection did not deter uptake of future doses. Women overall had confidence in their sources of vaccine information and the health care workers who administered maternal vaccinations. Their willingness to accept vaccination during pregnancy was particularly influenced by their husbands and trusted healthcare workers. Women across all sites mentioned they would accept new maternal vaccines if they are sensitized beforehand about any potential risks and benefits to them and their babies. CONCLUSION: Vaccine acceptance can be influenced by several factors including contextual, individual or group influences and vaccine or vaccination-specific issues. Women across The Gambia and Senegal are generally vaccine acceptors with confidence in the health care workers who vaccinate them and few concerns about maternal vaccines. Women's acceptance of vaccination during pregnancy is based on previous vaccination experiences and individual weighing of risks and benefits.

The use of a speaking book® to enhance vaccine knowledge among caregivers in The Gambia: A study using qualitative and quantitative methods.

OBJECTIVES: To measure the usefulness of a Speaking Book (SB) as an educational tool for enhancing knowledge, understanding and recall of key vaccine-related information among caregivers in The Gambia, as well as its acceptability and relevance as a health promotion tool for caregivers and healthcare workers. DESIGN AND SETTING: We developed a multimedia educational tool, the vaccine Speaking Book, which contained prerecorded information about vaccines provided in The Gambia's Expanded Programme on Immunization. Using qualitative and quantitative methods, we then conducted a sequential study assessing the use of this tool among caregivers andhealthcare workers in The Gambia.Participants200 caregivers attending primary healthcare centres in The Gambia for routine immunisation services for their infants, and 15 healthcare workers employed to provide immunisation services at these clinics. OUTCOME MEASURES: We calculated the median knowledge scores on vaccine-related information obtained at baseline, 1-month and 3-month follow-up visits. Wilcoxon's matched-pairs signed-rank test was used to compare the difference in the median knowledge scores between baseline and 1-month, and between baseline and 3-month follow-up visits. RESULTS: Of the 113 caregivers who participated, 104 (92%) completed all three study visits, 108 (95.6%) completed the baseline and 1-month follow-up visits, and 107 (94.7%) completed the baseline and 3-month follow-up visits. The median knowledge score increased from 6.0 (IQR 5.0-7.0) at baseline to 11.0 (IQR 8.0-14.0) at 1-month visit (p<0.001), and 15.0 (IQR 10.0-20.0) at 3-month visit (p<0.001). Qualitative results showed high acceptability and enthusiasm for the Speaking Book among both caregivers and healthcare workers. The Speaking Book was widely shared in the community and this facilitated communication with healthcare workers at the primary healthcare centres. CONCLUSIONS: Context-specific and subject-specific Speaking Books are a useful communication and educational tool to increase caregiver vaccine knowledge in low/middle-income countries.

Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa.

BACKGROUND: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa. METHODS: Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan). RESULTS: A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82-.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88-.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88-.95]) with a sensitivity of 96.6% and specificity of 85.8%. CONCLUSIONS: HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.

Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up antiviral treatment through decentralized services. However, access to the conventional tools to assess treatment eligibility (liver biopsy/Fibroscan®/HBV DNA) is limited and not affordable in resource-limited countries. We developed and validated a simple score to easily identify patients in need of HBV treatment in Africa. METHODS: As a reference, we used treatment eligibility determined by the European Association for the Study of the Liver based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV DNA. We derived a score indicating treatment eligibility by a stepwise logistic regression using a cohort of chronic HBV infection in The Gambia (n = 804). We subsequently validated the score in an external cohort of HBV-infected Africans from Senegal, Burkina Faso, and Europe (n = 327). RESULTS: Out of several parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT level, constituting a simple score (treatment eligibility in Africa for the hepatitis B virus: TREAT-B). The score demonstrated a high area under the receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the validation set. The score of 2 and above (HBeAg-positive and ALT ≥20 U/L or HBeAg-negative and ALT ≥40 U/L) had a sensitivity and specificity for treatment eligibility of 85% and 77%, respectively. The sensitivity and specificity of the World Health Organization criteria based on the aspartate aminotransferase-to-platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS: A simple score based on HBeAg and ALT had a high diagnostic accuracy for the selection of patients for HBV treatment. This score could be useful in African settings. LAY SUMMARY: Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings.