Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers

BACKGROUND: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. METHODS: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. RESULTS: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. CONCLUSIONS: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs

Cost-effectiveness of adding a birth dose of hepatitis B vaccine in the Dafra district of the Hauts-Bassins Region in Burkina Faso (NéoVac Study)

International audienceBackground: The World Health Organization (WHO) recommends a first hepatitis B vaccine dose within 24 h of birth (HepB-BD) to prevent mother-to-child transmission. Evidence for this strategy's economic value in Africa is limited. We assessed the costs and cost-effectiveness of adding HepB-BD to the current three-dose pentavalent schedule (HepB3) in the Dafra district of the Hauts-Bassins Region in Burkina Faso.Methods: Using a decision tree combined with a Markov model, we estimated the expected number of life-years (LY) and disability-adjusted life-years (DALYs) saved, incremental costs, and incremental cost-effectiveness ratios (ICER) of HepB-BD + HepB3 versus HepB3 alone in Dafra's 2017 birth cohort (n = 11,462). Institutional delivery rates, vaccine coverage, and vaccination costs from a health system perspective were estimated from field-collected data. We estimated the effectiveness of HepB-BD, age-specific transition probabilities, and horizontal transmission risks using data from previous African studies. Costs and health outcomes were discounted at an annual rate of 3%. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty.Results: In the base-case analysis without discounting, HepB-BD + HepB3 yielded a net cost saving of US$18,979 and saved 163 DALYs compared with HepB3 alone. With discounting, HepB-BD + HepB3 compared with HepB3 resulted in an incremental cost of US$554 and 31 DALYs averted, translating into an ICER of US$18/DALY averted. In one-way sensitivity analyses, HepB-BD + HepB3 remained cost-effective (at the cost-effectiveness threshold of US$671 i.e. the Burkina Faso per-capita gross domestic product) for all parameter changes. However, results were very sensitive to variations in HepB-BD unit cost per vaccinated neonate and perinatal transmission risk in mothers carrying the hepatitis B e antigen. The probabilities of HepB-BD + HepB3 being cost-effective were 71.7% and 86.7%, at the cost-effectiveness thresholds of US$335 and US$671, respectively.Conclusion: Introducing HepB-BD in Burkina Faso is likely to be cost-effective

Le cancer primitif du foie à Ouagadougou, Burkina Faso: le virus de l’hépatite B est-il toujours le joueur principal ?

Le carcinome hépatocellulaire est la tumeur primitive du foie la plus fréquente dans le monde. Cette étude visait à déterminer la proportion des cancers primitifs du foie associée à une infection par le virus de l’hépatite B à Ouagadougou. C’était une étude descriptive avec collecte retrospective de données dans le contexte d’une étude cas/témoins, du 1er Janvier 2012 au 31 Décembre 2015 dans le service de gastro-entérologie de l’hôpital Yalgado Ouédraogo pour les cas et à la banque de sang du centre regional de transfusion sanguine de Ouagadougou pour les témoins. Les témoins ont été appariés aux cas selon l’âge et le sexe. L’âge moyen des malades était de 43,9 (deviation standard ± 11,8 ans contre 41,9 (± 9,2) ans chez les témoins. Le sex ratio (homme/femme) était de 3 contre 2,5 respectivement chez les cas et les témoins. L’antigène HBs était positif chez 70/92 (76,1%) malades et 9,8 % de nos témoins. L’anti-corps anti HBc était positif chez 59/66 (89,4 %) malades. L’étiologie des cancers primitifs du foie au Burkina Faso reste dominée par l’infection par le virus de l’hépatite B. Les politiques de prevention doivent continuer à mettre l’accent sur la vaccination et la sensiblisation pour des comportements sexuels sains.Mots-clés: Carcinome hépato-cellulaire. Virus de l’hépatite B. Burkina Faso. Afrique sub-saharienneEnglish Title: The hepato-cellular carcinoma in Ouagadougou, Burkina Faso : is the hepatitis B virus still the major playor?English AbstractThe hepatocellular carcinoma is the most frequent liver cancer in the world. This study aimed to determine the magnitude of liver cancers related to infections by the hepatitis B virus. It was a descriptive analysis, with retrospective data collection from 1st January 2012 to 31st December 2015 in the context of a case/control study. We matched the controls to the cases, considering their age and sex. The patients’ mean age was 43.9 (standard deviation ± 11.8) years Vs 41.9 (± 9.2) years for the controls. The male/female sex ratio was 3 Vs 2.5 for the cases and controls respectively. The HBs antigen was found in 70/92 (76.1%) of the cases and 9.8 % of the controls. The antibody anti HBc was positive in 59/66 (89.4 %) of the cases The etiologies of liver cancers in Burkina Faso remained overwhelmingly dominated by the hepatitis B virus infections. The prevention strategies should go on emphasizing on the prevention of the infections by the hepatitis B virus through expanding immunization programs, safe sexual behaviors and blood transfusion practices.Keywords: Hepato-cellular carcinoma, hepatitis B virus, Burkina Faso, Sub-Saharan Afric

Effect of the COVID-19 pandemic on viral hepatitis services in sub-Saharan Africa

International audienc

Hepatitis B in Africa collaborative Network (HEPSANET): Cohort profile and analysis of baseline data.

Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterized, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, singlecentre cohorts, with limited follow-up time. The Hepatitis B in Africa collaborative network (HEPSANET) was established in 2022 to harmonize the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next five years were agreed through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and median age was 34 years (interquartile range 28-42). 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region

Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B

International audienceThe clinical utility of quantifying hepatitis B surface antigen (qHBsAg) levels in African subjects with chronic hepatitis B virus (HBV) infection has been poorly documented. From a multicentre cohort of 944 HBV-infected African patients, we aimed to assess whether qHBsAg alone can accurately identify i) those in a HBeAg-negative chronic HBV infection phase at low risk of liver disease progression and ii) those in need of antiviral therapy according to the 2017 EASL guidelines. We analysed 770 HBV mono-infected treatment-naïve patients, mainly males (61%) from West Africa (92%), median age 35 years (IQR: 30-44), median HBV DNA: 95.6 IU/ml (10.0-1,300.0), median qHBsAg 5,498 IU/ml (1,171-13,000) and HBeAg-pos 38 (5%). A total of 464/770 (60.2%) patients were classified as HBeAg-negative chronic infection (median age 36 years (31-46), median ALT 23 IU/l (18-28), median HBV-DNA 33.5 IU/ml (3.8-154.1), median LSM 4.8 kPa (4.1-5.8)) and qHBsAg levels had poor accuracy to identify these subjects with an AUROC at 0.58 (95%CI: 0.54-0.62), sensitivity 55.0% and specificity 55.6%; 118/770 (15.3%) patients were eligible for treatment according to the 2017 EASL criteria. qHBsAg correlated poorly with HBV DNA and had poor accuracy to select patients for antiviral therapy with an AUROC at 0.54 (0.49-0.60), sensitivity 46.6% and specificity 46.9%. In African treatment-naïve HBV-infected subjects, the clinical utility of qHBsAg to identify subjects in HBeAg-negative infection phase or subjects eligible for antiviral therapy seems futile. Whether qHBsAg levels can be used as a predictor of long-term liver complications in Africa needs to be further investigated

Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa.

In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5-20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting

Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B

International audienceThe clinical utility of quantifying hepatitis B surface antigen (qHBsAg) levels in African subjects with chronic hepatitis B virus (HBV) infection has been poorly documented. From a multicentre cohort of 944 HBV-infected African patients, we aimed to assess whether qHBsAg alone can accurately identify i) those in a HBeAg-negative chronic HBV infection phase at low risk of liver disease progression and ii) those in need of antiviral therapy according to the 2017 EASL guidelines. We analysed 770 HBV mono-infected treatment-naïve patients, mainly males (61%) from West Africa (92%), median age 35 years (IQR: 30-44), median HBV DNA: 95.6 IU/ml (10.0-1,300.0), median qHBsAg 5,498 IU/ml (1,171-13,000) and HBeAg-pos 38 (5%). A total of 464/770 (60.2%) patients were classified as HBeAg-negative chronic infection (median age 36 years (31-46), median ALT 23 IU/l (18-28), median HBV-DNA 33.5 IU/ml (3.8-154.1), median LSM 4.8 kPa (4.1-5.8)) and qHBsAg levels had poor accuracy to identify these subjects with an AUROC at 0.58 (95%CI: 0.54-0.62), sensitivity 55.0% and specificity 55.6%; 118/770 (15.3%) patients were eligible for treatment according to the 2017 EASL criteria. qHBsAg correlated poorly with HBV DNA and had poor accuracy to select patients for antiviral therapy with an AUROC at 0.54 (0.49-0.60), sensitivity 46.6% and specificity 46.9%. In African treatment-naïve HBV-infected subjects, the clinical utility of qHBsAg to identify subjects in HBeAg-negative infection phase or subjects eligible for antiviral therapy seems futile. Whether qHBsAg levels can be used as a predictor of long-term liver complications in Africa needs to be further investigated

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations

Abstract Background The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. Methods Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. Results Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). Conclusions The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted