Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

Patient-reported outcomes with direct-acting antiviral treatment for hepatitis C in West and Central Africa (TAC ANRS 12311 trial).

Background & Aims: Patient-reported outcomes (PROs) are poorly documented for patients with chronic hepatitis C on direct-acting antiviral (DAA) treatment in low-to-middle-income countries. We documented PROs during and after DAA treatment in participants of the TAC ANRS 12311 trial (West and Central Africa). Methods: Trial participants received a 12-week regimen containing either sofosbuvir plus ribavirin (HCV genotype 2, n = 40), or sofosbuvir plus ledipasvir (HCV genotypes 1 and 4, n = 80). Health-related quality of life (SF-12), fatigue (Piper Fatigue scale), and self-reported symptoms (35-symptom list) were assessed at enrolment (Week (W) 0), during treatment (W2, W4, W8 and W12) and after treatment (W24 and W36). These PROs were compared between W0 and W36 (Wilcoxon signed-rank or McNemar tests). Mixed-effects linear regression models helped identify correlates of physical and mental quality of life component summaries (PCS and MCS) in a longitudinal analysis. Results: Most PROs were significantly improved 24 weeks after treatment end (W36), without significant differences between treatment groups. For the post-treatment period, multivariable analysis showed significant increases in PCS for patients with cirrhosis and in MCS for patients in the sofosbuvir plus ribavirin group. A higher number of self-reported symptoms at W0 was associated with lower PCS and MCS, older age and cirrhosis with lower PCS, and male sex and HCV cure with higher PCS. Conclusions: Sofosbuvir-based DAA therapy was associated with a significant improvement in PROs 6 months after treatment end in patients with chronic HCV infection from Central and West Africa. These findings may guide HCV treatment providers in low-to-middle-income countries to deliver pre-treatment information concerning the benefits of DAAs beyond viral eradication. ClinicalTrialsgov Identifier: NCT02405013. Impact and implications: Perceptions and experiences (i.e. "patient-reported outcomes") of patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) are poorly documented in the African setting. This study shows significant improvements in health-related quality of life, fatigue, and self-reported symptoms 24 weeks after the end of a 12-week sofosbuvir-based DAA regimen in 120 patients from Central and West Africa. These findings substantially add to the body of knowledge about DAA therapy in the African setting. Treatment providers should be encouraged to inform patients of the benefits of DAAs beyond viral eradication, to increase treatment adherence and retention in care.

Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa.

BACKGROUND: Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d'Ivoire and Senegal. METHODS: Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country's predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo 'no DAA treatment' as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d'Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country's per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d'Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d'Ivoire and Senegal) and 0.2 (Cameroon) times the country's per-capita GDP. CONCLUSIONS: Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda.

Aspects socio-économiques de la prise en charge des hépatites virales chroniques en Côte-d'Ivoire / Socio-economic aspects of the management of chronic viral hepatitis in Côte-d'Ivoire

Contexte et objectifs. Les hépatites virales chroniques constituent un problème de santé publique en Côte-d'Ivoire. Très peu de malades accèdent au traitement en raison des coûts élevés du bilan et du traitement. L'objectif de la présente étude était d'évaluer les coûts du bilan et du traitement des hépatites virales chroniques. Méthodes. Il s'agissait d'une étude observationnelle transversale analytique réalisée, du 1er mars 2019 au 31 juillet 2019, en consultation d'hépato-gastroentérologie du CHU de Yopougon. Les variables étudiées étaient les paramètres sociodémographiques et économiques. Résultats. Au total, 136 patients (hommes 53, 6 %, âge moyen de 42 ans ± 12,2) ont été inclus. Plus de la moitié des patients (63,3 %) avaient un revenu mensuel n'excédant pas 490.39 USD. Le coût du bilan initial était de 223.13 USD et de 351.14 USD respectivement, pour l'hépatite virale B et C. Le ténofovir et l'interféron pégylé étaient gratuits. Le traitement par sofosbuvir + velpastavir coûtait 593.37 USD. Le bilan de suivi annuel était estimé à 237.02 USD pour l'hépatite virale B, 225.58 USD pour l'hépatite virale C. Conclusion. Le bilan et le traitement des hépatites virales chroniques ont un coût prohibitif pour les patients malgré la couverture maladie universelle.

Context and objectives. Chronic viral hepatitis is a public health problem in Côte-d'Ivoire. A significant number of patients have little access to treatment due to the high costs of assessment and treatment. The objective of our study was to evaluate the costs of assessments and treatment of chronic viral hepatitis. Methods. This was an analytical cross-sectional observational study from March 1, 2019 to July 31, 2019 in the HepatoGastroenterology Consultation Service at the Yopougon University Hospital. The variables studied were socio-demographic and economic parameters. Results. 136 patients (men 53.6 %, average age 42 ± 12.2 years) were included. More than half of the patients (63.3 %) had a monthly income not exceeding 490.39 USD. The cost of the initial assessment was 223.13 USD and 351.14 USD for viral hepatitis B and C, respectively. Tenofovir and pegylated interferon were free of charge. Treatment with sofosbuvir + velpastavir cost 593.37 USD. The annual follow-up assessment was estimated at 237.02 USD for viral hepatitis B and 225.58 USD for viral hepatitis C. Conclusion. The assessment and treatment of chronic viral hepatitis have a cost that remains high for patients despite the universal health coverage.

The Prognostic Values of Neutrophil-to-lymphocyte Ratio and Platelet-to-Lymphocyte Ratio at Baseline in Predicting the In-hospital Mortality in Black African Patients with Advanced Hepatocellular Carcinoma in Palliative Treatment: A Comparative Cohort Study.

BACKGROUND: The prognostic values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in predicting the in-hospital mortality of Black African patients with advanced hepatocellular carcinoma (HCC) in palliative treatment is unknown. AIM: To determine the prognostic value of NLR and PLR compared with that of Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD) scores and the Barcelona clinic liver cancer staging system (BCLC). METHODS: The cutoffs, accuracies and association with the mortality of these prognostic scores were determined using a time-dependent area under receiver operating characteristic curves (AUC), the log rank test and Cox proportional hazards ratio. RESULTS: A total of 104 patients with advanced HCC (median age=49.5 years, males=58.7%) were enrolled. All were hospitalized for an enlarged liver mass of at least 15.4 cm in size in the right thoracic quadrant. Overall, 46 (44.2%) patients died in hospital during follow-up. Patients with NLR >2.5 (log rank test=7.11, p=0.01) or PLR >92 (log rank test=5.63, p=0.02) had poor survival. Factors associated with the in-hospital mortality were the MELD score (p=0.01), NLR (p=0.03) and hemoglobin level (p=0.02). NLR exhibits better and stable accuracy in predicting the in hospital mortality at time points of 30 (AUC=0.618), 60 (AUC=0.680) and 90 (AUC=0.613) days of follow-up, compared with CTP, MELD scores, BCLC and PLR. However, PLR displayed an enhanced accuracy over 90 days of follow up (AUC=0.688). CONCLUSION: NLR is useful in predicting the in-hospital mortality in Black African patients with advanced stage HCC in clinical practice. NLR and PLR may be used concomitantly for long-term follow-up.

The Impact of Virologic Parameters and Liver Fibrosis on Health-Related Quality of Life in Black African Patients with Chronic Hepatitis B: Results from a High Endemic Area.

BACKGROUND: The effects of virologic parameters, liver fibrosis, and treatment on the HRQoL in black African patients with CHB are unknown. OBJECTIVE: To determine the magnitude and the effects of hepatitis B e antigen (HBeAg), hepatitis B surface antigenemia (HBs antigenemia), viral load, liver fibrosis and treatment on HRQoL impairment in black African patients with CHB using the SF36 (SF36) and chronic liver disease questionnaires (CLDQ). MATERIALS AND METHODS: HRQoL comparison was determined in a case-control study and enrolled 214 patients with CHB (mean age: 42 years, male: 65.9%) and 210 healthy controls subjects (mean age: 37.8 years; male: 63.8%). Control subjects were younger than those with CHB (p=0.01). Analysis of covariance, Welch test and linear regression were used to compare HRQoL between subgroups. RESULTS: Adjusted to age and gender, patients with CHB elicited low mean scores on the subscales of role-physical (66.9 vs 78, p=0.001), role-emotional (64 vs 77.5, p=0.01), bodily pain (70.8 vs 96.2, p=0.001), social functioning (74.6 vs 84.5, p=0.003) and general health (64.6 vs 74.4, p=0.03) in comparison with control subjects. Multivariate analysis showed that CHB impaired HRQoL on physical (ß= -16.7 (1.8), p<0.0001) and mental component summaries (ß= -5.1 (2.0), p=0.01) adjusted to others variables. Patients with HBeAg negative CHB elicited low scores on physical (p=0.004) and mental (p=0.05) component summaries and low CLDQ's average score (p=0.002) in comparison with those positive. Patients with low (≤1000 IU/mL) HBs antigenemia (p=0.03) or viral load (p=0.03) scored less on physical component summary and those with significant fibrosis or cirrhosis scored less (p=0.003) on mental component summary. CONCLUSION: Black African patients with CHB expressed poor HRQoL, particularly those with HBeAg negative CHB, low viral load, or HBs Antigenemia.

Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in Central and Western Africa.

BACKGROUND: Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. METHODS: Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. FINDINGS: In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8-25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. CONCLUSIONS: POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.

Long-term clinical benefits of Sofosbuvir-based direct antiviral regimens for patients with chronic hepatitis C in Central and West Africa.

BACKGROUND: In Sub-Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long-term clinical benefits of treating CHC with sofosbuvir-based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct-acting antiviral (DAAs) effectiveness in West and Central Africa. METHODS: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life-years saved (LYS); (b) life-years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty. RESULTS: Sofosbuvir-based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity. CONCLUSION: Sofosbuvir-based treatment could significantly reduce CHC-related mortality and help control CHC-related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures.

Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in people who use injecting drugs in Senegal.

BACKGROUND: Scaling-up the access to hepatitis C virus (HCV) diagnostics for people who use injecting drugs (PWID) is essential to reduce the HCV incidence in low and middle-income countries. METHODS: A decision tree model was developed to compare the cost-effectiveness of 12 strategies for diagnosing HCV in Senegal with a health sector perspective. Strategies included HCV-Ab screening and confirmation of viraemia (based on HCV-RNA or HCV core antigen detection) or only the latter step. Laboratory assays and decentralized tools (point-of-care (POC) tests and dried blood spot (DBS) samples) were included. The base-case assumed a 38.9% seroprevalence, as reported in the PWID population of Dakar. RESULTS: Compared to the cheapest strategy (POC HCV-Ab followed by POC HCV-RNA (S5)), one strategy remained un-dominated in the base-case: POC HCV-Ab followed by venepuncture-based laboratory HCV-RNA (S3). Above a lost to follow-up testing rate of 2.3%, combining POC HCV-Ab with HCV-RNA on DBS (S4) became more cost-effective than S3. Above this threshold, a single-step POC HCV-RNA (S12) was also found un-dominated (ICER to S5=€3,297.50). S5, S12 and S4 cost €14.21, €17.03 and €36.55/screened individual. Incremental cost-effectiveness ratios (€/additional true positive case) were 2,164.82 (S12 versus S5) and 3,297.50 (S4 versus S12). Whenever HCV seroprevalence reached 55.5%, S12 became more cost-effective than S5. Moreover, S4 required a budget 2 to 2.5 times higher than S5 or S12 for diagnosing 90% of HCV-infected PWID in Dakar. CONCLUSION: A two-step POC-based strategy (S5) would be the most cost-effective option among those proposed in this study for diagnosing HCV in PWID in Senegal. This study illustrates how the lack of secure financing and of data on PWID in LMICs, render difficult to identify the most sustainable strategy in those countries, as well as its implementation.

The burden of irritable bowel syndrome and chronic constipation on health-related quality of life in black Africans: a comparison with healthy control subjects in Côte d'Ivoire, West Africa.

Background: Although patients with irritable bowel syndrome (IBS) and chronic constipation (CC) have an impaired health-related quality of life (HRQoL), little is known in black African patients compared with control subjects. This study provided the magnitude and the influencing factors of HRQoL impairment in black African outpatients with IBS or CC compared with control subjects using the generic SF-36 questionnaire. Materials and methods: One hundred and four consecutive black African outpatients complaining with IBS (n=72, mean age=38.9 years, female=62.5%) and CC (n=32, mean age=37.4 years, female=75%) met Rome 3 criteria were compared with 210 control subjects (mean age=37.4 years, 63.8% male). The SF-36 scores in all domains of HRQoL with the corresponding physical (PCS) and mental (MCS) composite scores between groups were compared with post hoc analysis and multivariate linear regression analysis for the assessment of the influencing factors. Results: Overall, IBS and CC patients exhibited low SF-36 scores in the 8 domains of HRQoL in comparison with control subjects. IBS patients scored less in mental health (mean difference=-10.3, p=0.001), bodily pain (mean difference=-23.5, p≤0.0001), and social functioning domains (mean difference =-15.1, p=0.01) in comparison with CC patients. Post hoc analysis demonstrated a trend down of PCS (mean difference=-12.9, p<0.0001) and MCS (mean difference=-11.2, p=0.01) disfavoring IBS patients than those with CC in comparison with control subjects. In multivariate linear regression analysis, besides the negative impact of IBS and CC, factors influencing PCS were BMI (ß=0.4; p=0.01) and comorbidities (ß=-5.9; p=0.002). Those influencing MCS were the presence of remunerated activity (ß=2.7, p=0.02), and patient living alone (ß=9.4; p=0.04). Conclusion: IBS and CC impact negatively on the HRQoL in black African subjects and more importantly in those with IBS than CC.

Systemic inflammatory response syndrome and model for end-stage liver disease score accurately predict the in-hospital mortality of black African patients with decompensated cirrhosis at initial hospitalization: a retrospective cohort study.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and model for end-stage liver disease (MELD) predict short-term mortality in patients with cirrhosis. Prediction of mortality at initial hospitalization is unknown in black African patients with decompensated cirrhosis. AIM: This study aimed to look at the role of MELD score and SIRS as the predictors of morbidity and mortality at initial hospitalization. PATIENTS AND METHODS: In this retrospective cohort study, we enrolled 159 patients with cirrhosis (median age: 49 years, 70.4% males). The role of Child-Pugh-Turcotte (CPT) score, MELD score, and SIRS on mortality was determined by the Kaplan-Meier method, and the prognosis factors were assessed with Cox regression model. RESULTS: At initial hospitalization, 74.2%, 20.1%, and 37.7% of the patients with cirrhosis showed the presence of ascites, hepatorenal syndrome, and esophageal varices, respectively. During the in-hospital follow-up, 40 (25.2%) patients died. The overall incidence of mortality was found to be 3.1 [95% confidence interval (CI): 2.2-4.1] per 100 person-days. Survival probabilities were found to be high in case of patients who were SIRS negative (log-rank test= 4.51, p=0.03) and in case of patients with MELD score ≤16 (log-rank test=7.26, p=0.01) compared to the patients who were SIRS positive and those with MELD score >16. Only SIRS (hazard ratio (HR)=3.02, [95% CI: 1.4-7.4], p=0.01) and MELD score >16 (HR=2.2, [95% CI: 1.1-4.3], p=0.02) were independent predictors of mortality in multivariate analysis except CPT, which was not relevant in our study. Patients with MELD score >16 experienced hepatorenal syndrome (p=0.002) and encephalopathy (p=0.001) more frequently than that of patients with MELD score ≤16. SIRS was not useful in predicting complications. CONCLUSION: MELD score and SIRS can be used as tools for the prediction of mortality in black African patients with decompensated cirrhosis.

Twenty-Year Evolution of Hepatitis B Virus and Human Immunodeficiency Virus Prevalence and Incidence in Voluntary Blood Donors in Côte d'Ivoire.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common risk factors. The parallel description of their frequency over time may help capture their similarities and differences. METHODS: Using data from the National Transfusion Center of Abidjan, we estimated the following over a 20-year period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg) positivity at first contact; and (2) the incidence of HIV and HBsAg seroconversion in negative first-time blood donors. RESULTS: Between 1992 and 2012, 422319 donors (men [M] = 74%) provided 1063825 blood donations. For first-time donors, HIV prevalence decreased from 7.1% (M = 5.9%, women [W] =11.0%) in 1992-1994 to 1.1% (M = 0.8%, W = 2.0%) in 2010-2012. Prevalence of HBsAg positivity remained stable at 10.8% (M = 11.7%, W = 7.3%) in 1992-1994 to 11.1% (M = 12.5%, W = 7.1%) in 2010-2012. Among regular donors (N = 129256), the incidence of becoming HIV or HBsAg positive, respectively, decreased from 4.9 per 100 (M = 4.5, W = 8.6) and 7.3 per 100 person-years (M = 7.8, W = 2.3) in 1992-1994 to 0.07 (M = 0.06, W = 0.11) and 0.2 per 100 person-years (M = 0.2, W = 0.2) in 2010-2012. CONCLUSIONS: Human immunodeficiency virus prevalence and incidence decreased dramatically over time, whereas HBV prevalence remained stable. Incidence of HBsAg seroconversion, although decreasing, still reached unexpected levels, suggesting that the risk of HBV infection in adults may be higher than expected. Hepatitis B surface antigen-negative blood-donors should be offered HBV vaccination.

Evolution of hepatocellular carcinoma epidemiology in Côte d'Ivoire.

INTRODUCTION: Hepatocellular carcinoma is a major concern for Public health in West Africa. In Côte d'Ivoire, the bulk of our knowledge stems from studies conducted decades ago. Our aim was, thus, to assess whether the epidemiological features of this tumor changed recently. METHODS: Records from 863 patients diagnosed between 2007 and 2014 were analyzed. RESULTS: We observed major drifts concerning hepatocellular carcinoma with regards to the 1970-1980 period. Age at presentation is substantially delayed (49.4±14.1 years) whereas sex ratio decreased substantially (M:F=2.6). Patients seropositive for hepatitis B surface antigen and anti-hepatitis C virus represented 65% and 25% of cases whereas alcohol intake was reported in 36%. AFP level was above 400ng/mL in 36% of cases and tumors were already multinodular and/or metastatic at diagnosis in 77% and 26% of patients. Geographical and anthropological variations were observed with excesses of female cases affecting regions (Lagunes) or linguisitic groups (Kru). North-Mande speakers were more often identified as nonBnonC than others. DISCUSSION: Ivorian epidemiology of hepatocellular carcinoma was reshaped during the last decades. These changes, most likely due to the spread of hepatitis C virus, resulted in an older and feminized population of patients. We fear that the current and future prevalence of anti-HCV cases might thwart the expected benefits of anti-hepatitis B immunization. Appropriate measures should be taken to prevent further transmission of hepatitis C in the country.

Hepatitis B treatment eligibility in West Africa: Uncertainties and need for prospective cohort studies.

BACKGROUND & AIMS: While universal screening of hepatitis B virus (HBV) is recommended in high burden countries, little is known about the proportion of HBV-infected persons in need of antiviral therapy in these settings. METHODS: Prisoners in Senegal and Togo as well as female sex workers and men who have sex with men in Cote d'Ivoire were screened for HBV infection. All HBsAg-positive participants underwent transient elastography, alanine aminotransferase (ALT) and HBV viral load (VL) quantification. Individuals with cirrhosis or those aged >30 years with an HBV replication ≥20 000 IU/mL and elevated ALT were considered eligible for antiviral therapy. RESULTS: Of 1256 participants, 110 (8.8%) were HBsAg positive; their median age was 30 years [interquartile range: 25-33] and 96 (86.5%) were men. Three individuals (2.7%) had cirrhosis, while 28 (29.5%) of 94 participants with available measurements had an HBV VL ≥20 000 IU/mL. Overall, 11 (10.0%) subjects were considered eligible for immediate antiviral treatment (2.1% of participants in Dakar, 7.7% in Abidjan and 21.6% in Lome, P=.001) and 59 (53.4%) for close monitoring due to the presence of significant liver fibrosis, elevated ALT or significant HBV replication. CONCLUSIONS: Among vulnerable populations in West Africa, a minority of HBV-infected individuals were eligible for immediate antiviral therapy. Prospective cohort studies are necessary to evaluate anti-HBV treatment eligibility facing the significant proportion of individuals with active chronic HBV infection.

Alcohol use, viral hepatitis and liver fibrosis among HIV-positive persons in West Africa: a cross-sectional study.

INTRODUCTION: Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub-Saharan Africa. METHODS: The study was undertaken in three HIV referral clinics in Côte d'Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non-invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase-to-platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)-C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti-hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. RESULTS: A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36-50). Their median CD4 count was 393 cells/mm3 (IQR: 234-563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8-6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT-C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2-14.0), (Ref. AUDIT-C <4) and HBV infection (OR = 2.9, CI: 1.2-7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir-based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). CONCLUSION: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients.

[A plea for introduction of hepatitis B vaccination at birth in Côte d'Ivoire]. / Plaidoyer pour l?introduction du vaccin contre l?hépatite virale B à la naissance en Côte d?Ivoire.

The Côte d'Ivoire National Immunization Technical Advisory Group 2015 work plan included elaboration of an opinion on inclusion of hepatitis B vaccination at birth in the Expanded Program on Immunization (EPI) in Côte d'Ivoire. A task force was set up to conduct this assessment according to a systematized method. The task force analysed scientific articles on the burden of hepatitis B in Côte d'Ivoire, the burden of mother-child transmission, the impact of hepatitis B vaccination at birth in countries which have adopted this strategy, the efficacy and safety of hepatitis B vaccine in newborns, the cost-effectiveness of hepatitis B vaccination at birth, and the best strategy to introduce hepatitis B vaccination at birth in the EPI. The National Immunization Technical Advisory Group of Côte d'Ivoire finally recommended introduction of a dose of hepatitis B vaccine at birth in the context of the Expanded Program on Immunization with maintenance of three doses of pentavalent vaccine (DPT-HepB-Hib) at 6, 10, and 14 weeks of age.

HIV infection, viral hepatitis and liver fibrosis among prison inmates in West Africa.

BACKGROUND: Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS: Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.

How to optimize hepatitis C virus treatment impact on life years saved in resource-constrained countries.

UNLABELLED: In resource-constrained countries where the prevalence of hepatitis C virus (HCV) disease is usually high, it is important to know which population should be treated first in order to increase treatment effectiveness. The aim was to estimate the effectiveness of different HCV treatment eligibility scenarios in three different countries. Using a Markov model, we estimated the number of life-years saved (LYS) with different treatment eligibility scenarios according to fibrosis stage (F1-F4 or F3-4), compared to base case (F2-F4), at a constant treatment rate, of patients between 18 and 60 years of age, at stages F0/F1 to F4, without liver complications or coinfections, chronically infected by HCV, and treated with pegylated interferon (IFN)/ribavirin or more-efficacious therapies (i.e. IFN free). We conducted the analysis in Egypt (prevalence = 14.7%; 45,000 patients treated/year), Thailand (prevalence = 2.2%; 1,000 patients treated/year), and Côte d'Ivoire (prevalence = 3%; 150 patients treated/year). In Egypt, treating F1 patients in addition to ≥F2 patients (SE1 vs. SE0) decreased LYS by 3.9%. Focusing treatment only on F3-F4 patients increased LYS by 6.7% (SE2 vs. SE0). In Thailand and Côte d'Ivoire, focusing treatment only on F3-F4 patients increased LYS by 15.3% and 11.0%, respectively, compared to treating patients ≥F2 (ST0 and SC0, respectively). Treatment only for patients at stages F3-F4 with IFN-free therapies would increase LYS by 16.7% versus SE0 in Egypt, 22.0% versus ST0 in Thailand, and 13.1% versus SC0 in Côte d'Ivoire. In this study, we did not take into account the yearly new infections and the impact of treatment on HCV transmission. CONCLUSION: Our model-based analysis demonstrates that prioritizing treatment in F3-F4 patients in resource-constrained countries is the most effective scenario in terms of LYS, regardless of treatment considered.