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Desalegn H, Rossvoll L, Hunduma F, Berhe N, Johannessen A. Hepatitis B treatment in Africa: learning points from a scale-up programme in Ethiopia. Lancet Gastroenterol Hepatol 2025; 10:190-192. [PMID: 39954687 DOI: 10.1016/s2468-1253(24)00396-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 11/24/2024] [Indexed: 02/17/2025]
Affiliation(s)
- Hailemichael Desalegn
- Medical Department, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia; Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Lasse Rossvoll
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg 3103, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Fufa Hunduma
- Medical Department, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Nega Berhe
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg 3103, Norway; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg 3103, Norway; Sustainable Health Unit (SUSTAINIT), University of Oslo, Oslo, Norway.
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Weldemariam AG, Lin SI, Li WY, Wolday D, Yang MH, Alemu YA, Sarusi D, Maayan S, Chen YMA, Chuang KP, Tyan YC, Dai CY. Molecular epidemiology of hepatitis B, hepatitis C, and HIV-1 co-infections in Ethiopia: Implications for disease burden and intervention strategies. Acta Trop 2024; 257:107318. [PMID: 39002738 DOI: 10.1016/j.actatropica.2024.107318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/15/2024]
Abstract
BACKGROUND Hepatitis B virus (HBV) exhibits high prevalence rates within Ethiopia. The genetic diversity of HBV, marked by mixed genotype infections, may hold significant implications for the trajectory of disease and responses to treatment. Ethiopia grapples with a substantial public health challenge posed by co-infections involving HBV, hepatitis C virus (HCV), and human immunodeficiency virus 1 (HIV-1), particularly among vulnerable populations. METHODS A comprehensive investigation into HBV, HCV, and HIV-1 co-infection was conducted. A total of 7,789 blood samples were meticulously analyzed, among which 815 exhibited HBV positivity. Among the HBV-positive samples, 630 were subjected to genotyping procedures, resulting in the identification of a prevalent trend of mixed infections characterized by HBV genotypes A/E/F (67.30%). Serological assessments were performed on 492 specimens to ascertain the presence of HCV and HIV-1 co-infections, revealing respective co-infection rates of 13.02% for HBV/HIV, 3.31% for HBV/HCV, and 2.07% for triple infection. RESULTS The investigation revealed the intricate prevalence of co-infections in Ethiopia, notably underlining the continued transmission of viruses. The prominent occurrence of mixed HBV genotypes A/E/F suggests dynamic viral interactions and ongoing transmission pathways. These findings accentuate the necessity for targeted interventions and enhanced patient care, as co-infections carry significant clinical complexities. CONCLUSIONS This study furnishes crucial insights into the molecular epidemiology of HBV, HCV, and HIV-1 co-infections in Ethiopia. The acquired knowledge can contribute to the advancement of strategies for clinical management and the formulation of public health interventions aimed at ameliorating the burden of viral infections within the nation.
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Affiliation(s)
| | - Su-I Lin
- LumiSTAR Biotechnology, Inc, Taipei, Taiwan
| | - Wei-You Li
- Graduate Institute of Biomedical and Pharmacological Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Dawit Wolday
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia; Department of Biochemistry and Biomedical Sciences, Health Sciences, McMaster University, Hamilton, Canada
| | - Ming-Hui Yang
- Division of General & Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Deborah Sarusi
- Division of Infectious Diseases, Barzilai Medical Center, Ashkelon, Israel
| | - Shlomo Maayan
- Division of Infectious Diseases, Barzilai Medical Center, Ashkelon, Israel
| | - Yi-Ming Arthur Chen
- Graduate Institute of Biomedical and Pharmacological Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Laboratory of Important Infectious Diseases and Cancer, Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan
| | - Kuo-Pin Chuang
- Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan
| | - Yu-Chang Tyan
- Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan; Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Chia-Yen Dai
- School of Medicine & Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Ismael NY, Usmael SA, Belay NB, Mekonen HD, Johannessen A, Orlien SM. Chronic hepatitis B virus infection in Eastern Ethiopia: Clinical characteristics and determinants of cirrhosis. World J Hepatol 2024; 16:995-1008. [PMID: 39086536 PMCID: PMC11287608 DOI: 10.4254/wjh.v16.i7.995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/14/2024] [Accepted: 07/05/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia. AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment. METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program. RESULTS A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis. CONCLUSION This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.
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Affiliation(s)
- Nejib Y Ismael
- Department of Internal Medicine, Haramaya University, College of Health and Medical Sciences, Harar 252, Ethiopia
| | - Semir A Usmael
- Department of Internal Medicine, Haramaya University, College of Health and Medical Sciences, Harar 252, Ethiopia.
| | - Nega B Belay
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa 1000, Ethiopia
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
| | - Hailemichael Desalegn Mekonen
- Internal Medicine, Gastroenterology and Hepatology Unit, Saint Paul's Hospital Millennium Medical College, Addis Ababa 1000, Ethiopia
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
| | - Asgeir Johannessen
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
- Institute of Clinical Medicine, Oslo University, Oslo 0318, Norway
| | - Stian Ms Orlien
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
- Department of Pediatrics, Oslo University, Oslo 0450, Ullevål, Norway
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Lebbie W, Allan-Blitz LT, Nyama ET, Swaray M, Lavalie D, Mhango M, Patiño Rodriguez M, Gupta N, Bitwayiki R. Barriers to longitudinal follow-up for hepatitis B treatment in rural Sierra Leone: A mixed methods study of retention in care. Clin Liver Dis (Hoboken) 2024; 23:e0225. [PMID: 38831767 PMCID: PMC11146505 DOI: 10.1097/cld.0000000000000225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 04/03/2024] [Indexed: 06/05/2024] Open
Abstract
HBV disproportionately affects resource-limited settings, and retaining patients in longitudinal care remains challenging. We conducted a mixed methods investigation to understand the causes of losses to follow-up within an HBV clinic in rural Sierra Leone. We developed a multivariable logistic regression model of baseline clinical and sociodemographic factors predicting losses to follow-up, defined as failing to present for a follow-up visit within 14 months of enrollment. We included patients enrolled between April 30, 2019 and March 1, 2020, permitting 14 months of follow-up by April 30, 2021. We then developed a survey to solicit patient perspectives on the challenges surrounding retention. We interviewed randomly selected patients absent from HBV care for at least 6 months. Among 271 patients enrolled in the Kono HBV clinic, 176 (64.9%) did not have a follow-up visit within 14 months of the study end point. Incomplete baseline workup (aOR 2.9; 95% CI: 1.6-4.8), lack of treatment at baseline (aOR 5.0; 95% CI: 1.7-14.4), and having cirrhosis at baseline (aOR 3.3; 95% CI: 0.99-10.8) were independently associated with being lost to follow-up. For the patient survey, 21 patients completed the interview (median age 34 years [IQR: 25-38]). Travel-related factors were the most frequently reported barrier to retention (57%). Almost 30% suggested improved customer care might support retention in care; 24% requested to be given medication. In our setting, factors that might reduce losses to follow-up included expanded criteria for treatment initiation, overcoming transportation barriers, reducing wait times, ensuring against stockouts, and scaling up point-of-care testing services.
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Affiliation(s)
| | - Lao-Tzu Allan-Blitz
- Division of Global Health Equity, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | | | - Mohamed Swaray
- Partners In Health, Freetown, Sierra Leone, Britannica, WA
| | - Daniel Lavalie
- Ministry of Health and Sanitation, Freetown, Sierra Leone, Britannica, WA
| | - Michael Mhango
- Partners In Health, Freetown, Sierra Leone, Britannica, WA
| | | | - Neil Gupta
- Division of Global Health Equity, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | - Remy Bitwayiki
- Partners In Health, Freetown, Sierra Leone, Britannica, WA
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Tappata M, Farah M, Anugwom C, Bisrat E, Seid AS, Debes JD. Clinical, Gender, Socioeconomic Characteristics and Outcomes of Individuals Receiving Hepatitis B Treatment in Ethiopia: 18-Month Follow-Up. Am J Trop Med Hyg 2023; 109:1161-1165. [PMID: 37696510 PMCID: PMC10622489 DOI: 10.4269/ajtmh.23-0236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/16/2023] [Indexed: 09/13/2023] Open
Abstract
There is a lack of real-world data on hepatitis B (HBV) treatment in Africa. We conducted a single-center 18-month prospective cohort study in Ethiopia to understand clinical, laboratory, and demographic variables associated with HBV treatment. One hundred fifty HBV-positive patients were included: 51 on treatment, 99 with no treatment. Median age was similar between groups. Those on treatment were more likely to be male (86%), report higher coffee intake (90% versus 70%, P < 0.05), lower khat intake (0% versus 9%, P = 0.08), lower alcohol consumption (0% versus 5%, P = 0.1), and had attained higher levels of education (56% versus 42%, P = 0.19). Individuals on treatment had higher median aspartate aminotransferase (AST), alanine aminotransferase (ALT), HBV DNA, and median Aminotransferase-to-Platelet Ratio Index and Fibrosis-4 scores. At 6 and 12 months, those on treatment showed a decrease in median AST, ALT, and fibrosis scores and had less hepatocellular carcinoma development at 6 months (2% versus 4%). Our study highlights potential demographic disparities in HBV treatment as well as benefits in a real-life setting in Africa.
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Affiliation(s)
- Manaswita Tappata
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Marina Farah
- Department of Medical Education, University of Balamand, Beirut, Lebanon
| | - Chimaobi Anugwom
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- HealthPartners Digestive Care, St. Paul, Minnesota
| | - Eden Bisrat
- Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Amir S. Seid
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Jose D. Debes
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota
- Department of Gastroenterology, Erasmus MC, Rotterdam, The Netherlands
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Woldemedihn GM, Aberra H, Desalegn H, Berhe N, Belay DB, Rueegg CS, Johannessen A. Renal Safety of Long-term Tenofovir Disoproxil Fumarate Treatment in Patients With Chronic Hepatitis B. Open Forum Infect Dis 2023; 10:ofad404. [PMID: 37614515 PMCID: PMC10443609 DOI: 10.1093/ofid/ofad404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 07/26/2023] [Indexed: 08/25/2023] Open
Abstract
Background Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individuals with chronic hepatitis B (CHB) are inconsistent. The current study aimed to assess the effect of long-term TDF treatment on renal outcomes in adult patients with CHB. Methods From a CHB cohort in Ethiopia, we included 233 patients treated with TDF and 126 untreated controls. Levels of creatinine and creatinine clearance over time were described in patients with and without TDF treatment. Linear mixed effects models with a treatment × time interaction were used to investigate the effect of TDF on creatinine and creatinine clearance. In treated patients only, change in creatinine and creatinine clearance was estimated separately in the first year as compared with subsequent years via linear mixed effects models. Results Median follow-up in the treated group was 51 months (IQR, 27-72), and 75% of patients were male (median age, 33 years; IQR, 26-40). Median follow-up in the untreated group was 69 months (IQR, 66-72), and 48% of participants were male (median age, 33 years; IQR, 27-41). We found no change in creatinine over time in TDF-treated patients as compared with a slight increase in untreated patients (P interaction = .003). There was a decrease in creatinine clearance over time in both groups, which was stronger in patients without TDF treatment (P interaction = .007). In TDF-treated patients, changes in creatinine and creatinine clearance occurred mainly within the first 12 months after treatment initiation. Conclusions This study showed no evidence of long-term renal toxicity of TDF treatment in patients with CHB.
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Affiliation(s)
- Gezahegn M Woldemedihn
- Department of Statistics, Hawassa University, Hawassa, Ethiopia
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Hanna Aberra
- Medical Department, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Hailemichael Desalegn
- Medical Department, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
| | - Nega Berhe
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital–Ullevål, Oslo, Norway
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Corina S Rueegg
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital–Ullevål, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Schmit N, Nayagam S, Lemoine M, Ndow G, Shimakawa Y, Thursz MR, Hallett TB. Cost-effectiveness of different monitoring strategies in a screening and treatment programme for hepatitis B in The Gambia. J Glob Health 2023; 13:04004. [PMID: 36655869 PMCID: PMC9853089 DOI: 10.7189/jogh.13.04004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Background Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring. Methods We used a mathematical model of HBV transmission and natural history, calibrated to all available West African data, to project the population-level health impact, costs and cost-effectiveness of different monitoring strategies for HBV-infected individuals not initially eligible for antiviral treatment. We assumed that these patients were found in the year 2020 in a hypothetical community-based screening programme in The Gambia. Monitoring frequencies were varied between every 5 and every 1 year and targeted different age groups. Results The currently recommended annual monitoring frequency was likely to be not cost-effective in comparison with other strategies in this setting. 5-yearly monitoring in 15-45-year olds, at US$338 per disability-adjusted life year averted, had the highest probability of being the most effective cost-effective monitoring strategy. Conclusions Monitoring less frequently than once a year is a cost-effective strategy in a community-based HBV screening and treatment programme in The Gambia, with the optimal strategy depending on the cost-effectiveness threshold. Efficiencies may be gained by prioritising the 15-45-year age group for more intensive monitoring.
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Affiliation(s)
- Nora Schmit
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK
| | - Shevanthi Nayagam
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Maud Lemoine
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Gibril Ndow
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
- Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Yusuke Shimakawa
- Unité d’Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - Mark R Thursz
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Timothy B Hallett
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK
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Johannessen A, Stockdale AJ, Henrion MYR, Okeke E, Seydi M, Wandeler G, Sonderup M, Spearman CW, Vinikoor M, Sinkala E, Desalegn H, Fall F, Riches N, Davwar P, Duguru M, Maponga T, Taljaard J, Matthews PC, Andersson M, Mboup S, Sombie R, Shimakawa Y, Lemoine M. Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa. Nat Commun 2023; 14:45. [PMID: 36596805 PMCID: PMC9810658 DOI: 10.1038/s41467-022-35729-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 12/20/2022] [Indexed: 01/05/2023] Open
Abstract
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.
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Affiliation(s)
- Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital, Tønsberg, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Alexander J Stockdale
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Marc Y R Henrion
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Edith Okeke
- Faculty of Medical Sciences, University of Jos, Jos, Nigeria
| | - Moussa Seydi
- Service de Maladies Infectieuses et Tropicales, Centre Regional de Recherche et de Formation, Centre Hospitalier National Universitaire de Fann, Dakar, Senegal
| | - Gilles Wandeler
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Michael Vinikoor
- Department of Internal Medicine, University of Zambia, Lusaka, Zambia
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Edford Sinkala
- Department of Internal Medicine, University of Zambia, Lusaka, Zambia
| | - Hailemichael Desalegn
- Department of Infectious Diseases, Vestfold Hospital, Tønsberg, Norway
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Fatou Fall
- Department of Hepatology and Gastroenterology, Hopital Principal de Dakar, Dakar, Senegal
| | - Nicholas Riches
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Pantong Davwar
- Faculty of Medical Sciences, University of Jos, Jos, Nigeria
| | - Mary Duguru
- Faculty of Medical Sciences, University of Jos, Jos, Nigeria
| | - Tongai Maponga
- Division of Medical Virology, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Jantjie Taljaard
- Division of Infectious Diseases, Department of Medicine, Tygerberg Hospital and Stellenbosch University, Cape Town, South Africa
| | - Philippa C Matthews
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
- The Francis Crick Institute, London, UK
- University College London, London, UK
| | - Monique Andersson
- Division of Medical Virology, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Souleyman Mboup
- L'Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formations (IRESSEF), Dakar, Senegal
| | - Roger Sombie
- Yalgado Ouédraogo University Hospital Center, Ouagadougou, Burkina Faso
| | - Yusuke Shimakawa
- Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
| | - Maud Lemoine
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Hepatology section, Imperial College London, London, UK
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Sow A, Lemoine M, Toure PS, Diop M, Lo G, De Veiga J, Pape OT, Seck K, Ndow G, Bojang L, Kane A, Oudiane M, Howell J, Nayagam S, Moutchia J, Chemin I, Mendy M, Toure-Kane C, Thursz M, Ka M, Shimakawa Y, Mboup S. HBV continuum of care using community- and hospital-based screening interventions in Senegal: Results from the PROLIFICA programme. JHEP Rep 2022; 4:100533. [PMID: 36052221 PMCID: PMC9424572 DOI: 10.1016/j.jhepr.2022.100533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND & AIMS Strategies to implement HBV screening and treatment are critical to achieve HBV elimination but have been inadequately evaluated in sub-Saharan Africa (sSA). METHODS We assessed the feasibility of screen-and-treat interventions in 3 real-world settings (community, workplace, and hospital) in Senegal. Adult participants were screened using a rapid HBsAg point-of-care test. The proportion linked to care, the proportion who had complete clinical staging (alanine transaminase [ALT], viral load, and FibroScan®), and the proportion eligible for treatment were compared among the 3 intervention groups. RESULTS In 2013-2016, a total of 3,665 individuals were screened for HBsAg in the community (n = 2,153) and in workplaces (n = 1,512); 199/2,153 (9.2%) and 167/1,512 (11%) were HBsAg-positive in the community and workplaces, respectively. In the hospital setting (outpatient clinics), 638 HBsAg-positive participants were enrolled in the study. All infected participants were treatment naïve. Linkage to care was similar among community-based (69.9%), workplace-based (69.5%), and hospital-based interventions (72.6%, p = 0.617). Of HBV-infected participants successfully linked to care, full clinical staging was obtained in 47.5% (66/139), 59.5% (69/116), and 71.1% (329/463) from the community, workplaces, and hospitals, respectively (p <0.001). The proportion eligible for treatment (EASL criteria) differed among community- (9.1%), workplace- (30.4%), and hospital-based settings (17.6%, p = 0.007). Acceptability of antiviral therapy, adherence, and safety at 1 year were very good. CONCLUSIONS HBV screen-and-treat interventions are feasible in non-hospital and hospital settings in Senegal. However, the continuum of care is suboptimal owing to limited access to full clinical staging. Improvement in access to diagnostic services is urgently needed in sSA. LAY SUMMARY Hepatitis B infection is highly endemic in Senegal. Screening for infection can be done outside hospitals, in communities or workplaces. However, the hepatitis B continuum of care is suboptimal in Senegal and needs to be simplified to scale-up diagnosis and treatment coverage.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine transaminase
- APRI, AST-to-platelet ratio index
- AST, aspartate aminotransferase
- Africa
- Diagnosis
- GGT, gamma-glutamyl transferase
- HBsAg, hepatitis B surface antigen
- HCC, hepatocellular carcinoma
- Hepatitis B
- LSM, liver stiffness measurement
- POC, point of care
- PROLIFICA, Prevention of Liver Fibrosis and Cancer in Africa
- Screening
- TDF, tenofovir disoproxil fumarate
- Treatment
- WHO, World Health Organization
- aOR, adjusted odds ratio
- cOR, crude odds ratio
- eGFR, estimated glomerular filtration rate
- qPCR, quantitative polymerase chain reaction
- sSA, sub-Saharan Africa
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Affiliation(s)
- Amina Sow
- Institut de Recherche en Santé de Surveillance Epidemiologique et de Formation (IRESSEF) Laboratoire CHNU Dalal Jamm Guediawaye, IRESSEF Diamnoadio Dakar, Senegal
- Laboratoire de Virology, Hopital Le Dantec, Dakar, Senegal
| | - Maud Lemoine
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Section of Hepatology, St Mary’s Hospital, Imperial College London, London, UK
- Medical Research Council the Gambia Unit at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Papa Souleymane Toure
- UFR des Sciences de la Sante, Thies, Senegal
- Centre hospitalier de Tivaoaune, Service de Medecine interne, Thies, Senegal
| | - Madoky Diop
- UFR des Sciences de la Sante, Thies, Senegal
| | - Gora Lo
- Institut de Recherche en Santé de Surveillance Epidemiologique et de Formation (IRESSEF) Laboratoire CHNU Dalal Jamm Guediawaye, IRESSEF Diamnoadio Dakar, Senegal
- Laboratoire de Virology, Hopital Le Dantec, Dakar, Senegal
| | - Jean De Veiga
- Hopital Saint Jean de Dieu, Service d’Hepatologie et Gastroenterologie, Thies, Senegal
| | - Omar Thiaw Pape
- Hopital Saint Jean de Dieu, Laboratoire d’analyse biochimique et hématologique, Thies, Senegal
| | - Khady Seck
- Centre hospitalier régional de Thies, Service de Medecine interne, Thies, Senegal
| | - Gibril Ndow
- Medical Research Council the Gambia Unit at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Lamin Bojang
- Medical Research Council the Gambia Unit at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Arame Kane
- UFR des Sciences de la Sante, Thies, Senegal
- Centre hospitalier de Tivaoaune, Service de Medecine interne, Thies, Senegal
| | - Marina Oudiane
- UFR des Sciences de la Sante, Thies, Senegal
- Centre hospitalier de Tivaoaune, Service de Medecine interne, Thies, Senegal
| | - Jess Howell
- Disease Elimination, Burnet Institute, Department of Gastroenterology, St. Vincent's Hospital Department of Epidemiology and Preventive Medicine, Monash University Melbourne, Melbourne, Victoria, Australia
| | - Shevanthi Nayagam
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Section of Hepatology, St Mary’s Hospital, Imperial College London, London, UK
- MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Jude Moutchia
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur Paris, France
| | - Isabelle Chemin
- INSERM U1052, CNRS 5286, Université Lyon, Université Claude Bernard Lyon 1, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, F-69000, Lyon, France
| | - Maimuna Mendy
- International Agency for Research on Cancer (IARC), Lyon, France
| | - Coumba Toure-Kane
- Institut de Recherche en Santé de Surveillance Epidemiologique et de Formation (IRESSEF) Laboratoire CHNU Dalal Jamm Guediawaye, IRESSEF Diamnoadio Dakar, Senegal
- Laboratoire de Virology, Hopital Le Dantec, Dakar, Senegal
| | - Mark Thursz
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Diseases, Section of Hepatology, St Mary’s Hospital, Imperial College London, London, UK
| | - Mourtalla Ka
- UFR des Sciences de la Sante, Thies, Senegal
- Centre hospitalier de Tivaoaune, Service de Medecine interne, Thies, Senegal
| | - Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur Paris, France
| | - Souleymane Mboup
- Institut de Recherche en Santé de Surveillance Epidemiologique et de Formation (IRESSEF) Laboratoire CHNU Dalal Jamm Guediawaye, IRESSEF Diamnoadio Dakar, Senegal
- Laboratoire de Virology, Hopital Le Dantec, Dakar, Senegal
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10
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Shear Wave and Strain Elastography in Crohn's Disease-A Systematic Review. Diagnostics (Basel) 2021; 11:diagnostics11091609. [PMID: 34573952 PMCID: PMC8468946 DOI: 10.3390/diagnostics11091609] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/30/2021] [Accepted: 09/01/2021] [Indexed: 12/31/2022] Open
Abstract
One modern imaging technique used in the diagnosis of Crohn’s disease (CD) is sonoelastrography of the intestine. Guidelines regarding the use of bowel sonoelastography in CD have still not been specified. The aim of our research was to conduct a systematic review of the use of sonoelastography in the diagnosis, assessment, and monitoring of strictures in the course of CD. A systematic review was conducted according to the PRISMA guidelines statement. The following databases were searched in January 2021: MEDINE via PubMed, Embase and Scopus. The search utilised the following MeSH tags: ‘Ultrasound Shear Wave’, ‘Elastography’, ‘elastogram’, ‘elastographies’ AND ‘Crohn disease’. The inclusion criteria were as follows: from 2010 or later, articles with abstracts, articles in English, human-based studies and original articles. Articles were assessed independently by two reviewers. Out of 181 articles, only 15 met the criteria and were included in the review. Due to a small number of studies and significant methodological differences, the feasibility of using sonoelastography for Crohn’s disease must be proven through further research and analysis. In the future, standardised assessment criteria and cut-off points should be established for both strain elastography (SE) and shear wave elastography (SWE).
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11
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Johannessen A, Mekasha B, Desalegn H, Aberra H, Stene-Johansen K, Berhe N. Mother-to-Child Transmission of Hepatitis B Virus in Ethiopia. Vaccines (Basel) 2021; 9:vaccines9050430. [PMID: 33925930 PMCID: PMC8145487 DOI: 10.3390/vaccines9050430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 11/16/2022] Open
Abstract
High viral load and positive hepatitis B e-antigen (HBeAg) results are risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV). In sub-Saharan Africa, little is known about the distribution of these risk factors, as well as early childhood HBV transmission. In this study, Ethiopian women aged 18–45 years with chronic hepatitis B were assessed for the presence of HBeAg and high viral load. Their children below 4 years of age were invited for assessment of viral markers, defining active HBV infection as a positive hepatitis B s-antigen (HBsAg) and/or detectable HBV DNA. In total, 61 of 428 HBV-infected women (14.3%) had a positive HBeAg result and/or a high viral load. Of note, 26 of 49 women (53.1%) with viral load above 200,000 IU/mL were HBeAg negative. Among 89 children born of HBV-infected mothers (median age 20 months), 9 (10.1%) had evidence of active HBV infection. In conclusion, one in seven women with chronic hepatitis B had risk factors for MTCT, and HBeAg was a poor predictor of high viral load. One in ten children born of HBV-infected women acquired HBV-infection despite completing their scheduled HBV vaccination at 6, 10 and 14 weeks of age.
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Affiliation(s)
- Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital Trust, 3103 Tønsberg, Norway
- Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, 0315 Oslo, Norway
- Regional Centre for Imported and Tropical Diseases, Ullevål, Oslo University Hospital, 0424 Oslo, Norway;
- Correspondence: ; Tel.: +47-97983264
| | - Bitsatab Mekasha
- Medical Department, St. Paul’s Hospital Millennium Medical College, 1230 Addis Ababa, Ethiopia; (B.M.); (H.D.); (H.A.)
| | - Hailemichael Desalegn
- Medical Department, St. Paul’s Hospital Millennium Medical College, 1230 Addis Ababa, Ethiopia; (B.M.); (H.D.); (H.A.)
| | - Hanna Aberra
- Medical Department, St. Paul’s Hospital Millennium Medical College, 1230 Addis Ababa, Ethiopia; (B.M.); (H.D.); (H.A.)
| | | | - Nega Berhe
- Regional Centre for Imported and Tropical Diseases, Ullevål, Oslo University Hospital, 0424 Oslo, Norway;
- Aklilu Lemma Institute of Pathobiology, University of Addis Ababa, 1230 Addis Ababa, Ethiopia
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12
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Woldemedihn GM, Rueegg CS, Desalegn H, Aberra H, Berhe N, Johannessen A. Validity of a point-of-care viral load test for hepatitis B in a low-income setting. J Virol Methods 2020; 289:114057. [PMID: 33359613 DOI: 10.1016/j.jviromet.2020.114057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/11/2020] [Accepted: 12/20/2020] [Indexed: 12/20/2022]
Abstract
The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log10 to>7 log10 IU/mL were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log10 IU/mL higher viral load result of the Xpert kit; 4 samples differed by>1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94 %, specificity of 71 %, positive predictive value of 70 %, and negative predictive value of 95 %. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.
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Affiliation(s)
| | - Corina Silvia Rueegg
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, PO Box 4950, Nydalen, 0424, Oslo, Norway.
| | - Hailemichael Desalegn
- Medical Department, St. Paul's Hospital Millennium Medical College, PO Box 1271, Addis Ababa, Ethiopia.
| | - Hanna Aberra
- Medical Department, St. Paul's Hospital Millennium Medical College, PO Box 1271, Addis Ababa, Ethiopia.
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; Regional Centre for Imported and Tropical Diseases, Oslo University Hospital Ullevål, PO Box 4956, Nydalen, 0424, Oslo, Norway.
| | - Asgeir Johannessen
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital Ullevål, PO Box 4956, Nydalen, 0424, Oslo, Norway; Department of Infectious Diseases, Vestfold Hospital Trust, PO Box 2168, 3103, Tønsberg, Norway.
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Tan M, Bhadoria AS, Cui F, Tan A, Van Holten J, Easterbrook P, Ford N, Han Q, Lu Y, Bulterys M, Hutin Y. Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020; 6:106-119. [PMID: 33197397 PMCID: PMC7801814 DOI: 10.1016/s2468-1253(20)30307-1] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 09/08/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND In 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines. METHODS In this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345. FINDINGS Of the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8-10), ranging from 6% (4-8) in community settings to 10% (9-11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18-20), ranging from 12% (6-18) for studies in community settings to 25% (19-30) in clinic settings. INTERPRETATION Many studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12-25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions. FUNDING WHO and US Centers for Disease Control and Prevention.
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Affiliation(s)
- Mingjuan Tan
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland; Department of Medicine, National University Health System, Singapore
| | - Ajeet S Bhadoria
- All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Fuqiang Cui
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | | | - Judith Van Holten
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | | | - Nathan Ford
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Qin Han
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Ying Lu
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Marc Bulterys
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland
| | - Yvan Hutin
- Department of HIV/AIDS and Global Hepatitis Programme, WHO, Geneva, Switzerland.
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14
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Sonderup MW, Dusheiko G, Desalegn H, Lemoine M, Tzeuton C, Taylor-Robinson SD, Spearman CW. Hepatitis B in sub-Saharan Africa-How many patients need therapy? J Viral Hepat 2020; 27:560-567. [PMID: 31800145 DOI: 10.1111/jvh.13247] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 11/07/2019] [Indexed: 12/13/2022]
Abstract
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.
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Affiliation(s)
- Mark W Sonderup
- Division of Hepatology, Department of Medicine, Faculty of health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
| | - Geoffrey Dusheiko
- Liver Unit, Kings College Hospital, London, UK
- Division of Medicine, University College London Medical School, London, UK
| | - Hailemichael Desalegn
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Maud Lemoine
- Department of Surgery and Cancer, Liver Unit, St Mary's Hospital NHS, Imperial College London, London, UK
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, Liver Unit, St Mary's Hospital NHS, Imperial College London, London, UK
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, Faculty of health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
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Vinikoor MJ, Sinkala E, Kanunga A, Muchimba M, Zanolini A, Saag M, Pry J, Nsokolo B, Chisenga T, Kelly P. Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia. PLoS One 2020; 15:e0227041. [PMID: 31929556 PMCID: PMC6957183 DOI: 10.1371/journal.pone.0227041] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/10/2019] [Indexed: 01/26/2023] Open
Abstract
INTRODUCTION We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. MATERIALS AND METHODS Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. RESULTS Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). CONCLUSION Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.
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Affiliation(s)
- Michael J. Vinikoor
- Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | - Edford Sinkala
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
- Department of Medicine, University Teaching Hospital, Lusaka, Zambia
| | - Annie Kanunga
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Mutinta Muchimba
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Arianna Zanolini
- Department for International Development, Dar Es Salaam, Tanzania
| | - Michael Saag
- Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Jake Pry
- Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
- University of California at Davis, Davis, California, United States of America
| | - Bright Nsokolo
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | | | - Paul Kelly
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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16
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Desalegn H, Aberra H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Johannessen A. Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study. BMC Gastroenterol 2019; 19:74. [PMID: 31092203 PMCID: PMC6521482 DOI: 10.1186/s12876-019-0993-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 05/09/2019] [Indexed: 12/22/2022] Open
Abstract
Background Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. Methods Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. Results Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26–276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23–173.48; p = 0.002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73–7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02–1.10; p = 0.007). Conclusions Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients. Trial registration NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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Affiliation(s)
- Hailemichael Desalegn
- Medical Department, St. Paul's Hospital Millennium Medical College, Po. Box 1271, Addis Ababa, Ethiopia.
| | - Hanna Aberra
- Medical Department, St. Paul's Hospital Millennium Medical College, Po. Box 1271, Addis Ababa, Ethiopia
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.,Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Girmay Medhin
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Bitsatab Mekasha
- Medical Department, St. Paul's Hospital Millennium Medical College, Po. Box 1271, Addis Ababa, Ethiopia
| | - Svein Gunnar Gundersen
- Research Unit, Sørlandet Hospital HF, Kristiansand, Norway.,Department of Global Development and Planning, University of Agder, Kristiansand, Norway
| | - Asgeir Johannessen
- Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.,Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
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Shimakawa Y, Njie R, Ndow G, Vray M, Mbaye PS, Bonnard P, Sombié R, Nana J, Leroy V, Bottero J, Ingiliz P, Post G, Sanneh B, Baldeh I, Suso P, Ceesay A, Jeng A, Njai HF, Nayagam S, D'Alessandro U, Chemin I, Mendy M, Thursz M, Lemoine M. Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa. J Hepatol 2018; 69:776-784. [PMID: 30104154 DOI: 10.1016/j.jhep.2018.05.024] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 03/02/2018] [Accepted: 05/02/2018] [Indexed: 12/15/2022]
Abstract
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.
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Affiliation(s)
- Yusuke Shimakawa
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France.
| | - Ramou Njie
- The Gambia Hepatitis Intervention Study, IARC, c/o MRC Unit, Fajara, The Gambia
| | - Gibril Ndow
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia; Department of Surgery and Cancer, Liver Unit, Imperial College London, UK
| | - Muriel Vray
- Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France; Unité d'Épidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Dakar, Senegal
| | - Papa Saliou Mbaye
- Département d'Hépato-gastroentérologie, Hôpital Principal, Dakar, Senegal
| | | | - Roger Sombié
- Département d'Hépato-gastroentérologie, Centre Hospitalier Universitaire Yalgado Ouédraogo, Ouagadougou, Burkina Faso
| | - Jean Nana
- Université Grenoble Alpes, Grenoble, France
| | | | - Julie Bottero
- Infectious Disease Department, St Antoine Hospital, AP-HP, Paris, France
| | | | - Gerrit Post
- Center for Infectiology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Bakary Sanneh
- National Public Health Laboratory, Banjul, The Gambia
| | | | - Penda Suso
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia
| | - Amie Ceesay
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia
| | - Adam Jeng
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia
| | - Harr Freeya Njai
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia
| | - Shevanthi Nayagam
- Department of Surgery and Cancer, Liver Unit, Imperial College London, UK
| | - Umberto D'Alessandro
- Medical Research Council (MRC) Unit, The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia
| | - Isabelle Chemin
- INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie, Université Claude Bernard, Lyon, France
| | - Maimuna Mendy
- International Agency for Research on Cancer (IARC), Lyon, France
| | - Mark Thursz
- Department of Surgery and Cancer, Liver Unit, Imperial College London, UK
| | - Maud Lemoine
- Department of Surgery and Cancer, Liver Unit, Imperial College London, UK.
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Vinikoor MJ, Sinkala E, Kanunga A, Muchimba M, Nsokolo B, Chilengi R, Wandeler G, Mulenga J, Chisenga T, Bhattacharya D, Saag MS, Foster G, Fried MW, Kelly P. Chronic hepatitis B virus monoinfection at a university hospital in Zambia. World J Hepatol 2018; 10:622-628. [PMID: 30310540 PMCID: PMC6177566 DOI: 10.4254/wjh.v10.i9.622] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 05/23/2018] [Accepted: 07/10/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia.
METHODS Hepatitis B surface antigen-positive adults (n = 160) who were HIV-negative and referred to the hospital after a routine or clinically-driven HBV test were enrolled. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), platelet count, hepatitis B e-antigen, and HBV DNA were measured. Liver fibrosis/cirrhosis was assessed by physical examination, AST-to-platelet ratio index, and transient elastography. In antiviral therapy-naïve individuals, we described HBV stages and antiviral therapy eligibility per World Health Organization (WHO) and by HBV test (routine vs clinical). Elevated ALT was > 19 in women and > 30 U/L in men. Among treatment-experienced individuals, we described medication side effects, adherence, and viral suppression.
RESULTS The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified via routine testing (at the blood bank, community events, etc.). Among 120 treatment-naïve individuals, 2.5% were categorized as immune tolerant, 11.7% were immune active, 35.6% were inactive carriers, and 46.7% had an indeterminate phenotype. Per WHO guidelines, 13 (10.8%) were eligible for immediate antiviral therapy. The odds of eligibility were eight times higher for those diagnosed at clinical vs routine settings (adjusted odds ratio, 8.33; 95%CI: 2.26-29.41). Among 40 treatment-experienced HBV patients, virtually all took tenofovir, and a history of mild side effects was reported in 20%. Though reported adherence was good, 12 of 29 (41.4%) had HBV DNA > 20 IU/mL.
CONCLUSION Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.
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Affiliation(s)
- Michael J Vinikoor
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
- Centre for Infectious Disease Research in Zambia, Lusaka 34681, Zambia
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States
| | - Edford Sinkala
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
| | - Annie Kanunga
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
| | - Mutinta Muchimba
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
| | - Bright Nsokolo
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
| | - Roma Chilengi
- Centre for Infectious Disease Research in Zambia, Lusaka 34681, Zambia
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern 3012, Switzerland
- Institute of Social and Preventive Medicine, University of Bern, Bern 3012, Switzerland
| | - Joseph Mulenga
- Zambia National Blood Transfusion Service, Private Bag RW1X Ridgeway, Lusaka 50110, Zambia
| | - Tina Chisenga
- Zambian Ministry of Health, Ndeke House, Lusaka 30205, Zambia
| | - Debika Bhattacharya
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90035, United States
| | - Michael S Saag
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States
| | - Graham Foster
- Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Michael W Fried
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States
| | - Paul Kelly
- Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia
- Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom
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19
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Transmission of Hepatitis B and D Viruses in an African Rural Community. mSystems 2018; 3:mSystems00120-18. [PMID: 30246145 PMCID: PMC6143728 DOI: 10.1128/msystems.00120-18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 08/21/2018] [Indexed: 12/12/2022] Open
Abstract
According to the World Health Organization (WHO), an estimated 257 million people worldwide are chronically infected with hepatitis B virus (HBV), with approximately 15 million of them being coinfected with hepatitis D virus (HDV). To investigate the prevalence and transmission of HBV and HDV within the general population of a rural village in Cameroon, we analyzed serum samples from most (401/448) of the villagers. HBV surface antigen (HBsAg) was detected in 54 (13.5%) of the 401 samples, with 15% of them also containing anti-HDV antibodies. Although Cameroon has integrated HBV vaccination into their Expanded Program on Immunization for newborns in 2005, an HBsAg carriage rate of 5% was found in children below the age of 5 years. Of the 54 HBsAg-positive samples, 49 HBV pre-S/S sequences (7 genotype A and 42 genotype E sequences) could be amplified by PCR. In spite of the extreme geographical restriction in the recruitment of study participants, a remarkable genetic diversity within HBV genotypes was observed. Phylogenetic analysis of the sequences obtained from PCR products combined with demographic information revealed that the presence of some genetic variants was restricted to members of one household, indicative of intrafamilial transmission, which appears to take place at least in part perinatally from mother to child. Other genetic variants were more widely distributed, reflecting horizontal interhousehold transmission. Data for two households with more than one HBV-HDV-coinfected individual indicate that the two viruses are not necessarily transmitted together, as family members with identical HBV sequences had different HDV statuses. IMPORTANCE This study revealed that the prevalence of HBV and HDV in a rural area of Cameroon is extremely high, underlining the pressing need for the improvement of control strategies. Systematic serological and phylogenetic analyses of HBV sequences turned out to be useful tools to identify networks of virus transmission within and between households. The high HBsAg carriage rate found among children demonstrates that implementation of the HBV birth dose vaccine and improvement of vaccine coverage will be key elements in preventing both HBV and HDV infections. In addition, the high HBsAg carriage rate in adolescents and adults emphasizes the need for identification of chronically infected individuals and linkage to WHO-recommended treatment to prevent progression to liver cirrhosis and hepatocellular carcinoma.
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20
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Massaquoi TA, Burke RM, Yang G, Lakoh S, Sevalie S, Li B, Jia H, Huang L, Deen GF, Beynon F, Sahr F. Cross sectional study of chronic hepatitis B prevalence among healthcare workers in an urban setting, Sierra Leone. PLoS One 2018; 13:e0201820. [PMID: 30096162 PMCID: PMC6086405 DOI: 10.1371/journal.pone.0201820] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 07/23/2018] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Hepatitis B is a serious public health problem across sub-Saharan Africa. Sierra Leone has no national hepatitis B strategy plan or high quality estimates of prevalence. Healthcare workers are perceived as an at-risk group for hepatitis B. We assessed the prevalence of hepatitis B among healthcare workers at two hospital sites in Freetown, Sierra Leone. METHODS In October 2017, healthcare workers were offered voluntary testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) using rapid lateral flow assay for all samples, followed by Enzyme Immunosorbent Assay to confirm positive results. Participants completed a questionnaire about knowledge, attitudes and practices concerning hepatitis B. HBsAg positive participants were invited to a clinic for further assessment. RESULTS Overall, 447 participants were tested for hepatitis B. Most (90.6%, 405/447) participants were nurses, 72.3% (323/447) were female and 71.6% (320/447) were 30 years or older. The prevalence of chronic hepatitis B (HBsAg positivity) was 8.7% (39 / 447, 95% CI 6.3-11.7%). There was no significant difference in prevalence by sex, age group, site of work or type of job. None of the 66.7% (26 / 39) of participants with chronic hepatitis B who attended the clinic met the 2015 WHO criteria to start treatment for hepatitis B on the basis of cirrhosis. Most participants (96.9% 432 / 446) stated that they were worried about their risk of hepatitis B at work. CONCLUSIONS Hepatitis B is highly prevalent among healthcare workers in Sierra Leone. It is unclear whether this reflects high community prevalence or is due to occupational risk. No participants with chronic hepatitis B needed to start treatment. In order to achieve the WHO target of elimination of viral hepatitis by 2030, introduction of birth dose vaccine for infants and catch-up vaccines for healthcare workers and healthcare students, together with a national hepatitis B screen and treat programme is advisable for Sierra Leone.
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Affiliation(s)
- Thomas A. Massaquoi
- 34 Military Hospital, Wilberforce Barracks, Freetown, Sierra Leone
- * E-mail: (TAM); (LH)
| | - Rachael M. Burke
- Centre for Global Health and Health Partnerships, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom
- Kings Sierra Leone Partnership, Connaught Hospital, Freetown, Sierra Leone
| | - Guang Yang
- Chinese Military Medical Expert Group in Sierra Leone, 302 Military Hospital, Beijing, China
| | - Suliaman Lakoh
- University Sierra Leone Teaching Hospital Complex, Connaught Hospital, Freetown, Sierra Leone
| | - Stephen Sevalie
- 34 Military Hospital, Wilberforce Barracks, Freetown, Sierra Leone
| | - Bo Li
- Chinese Military Medical Expert Group in Sierra Leone, 302 Military Hospital, Beijing, China
| | - Hongjun Jia
- Chinese Military Medical Expert Group in Sierra Leone, 302 Military Hospital, Beijing, China
| | - Lei Huang
- Chinese Military Medical Expert Group in Sierra Leone, 302 Military Hospital, Beijing, China
- * E-mail: (TAM); (LH)
| | - Gibrilla F. Deen
- University Sierra Leone Teaching Hospital Complex, Connaught Hospital, Freetown, Sierra Leone
| | - Fenella Beynon
- Centre for Global Health and Health Partnerships, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom
- Kings Sierra Leone Partnership, Connaught Hospital, Freetown, Sierra Leone
| | - Foday Sahr
- 34 Military Hospital, Wilberforce Barracks, Freetown, Sierra Leone
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21
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Dionne-Odom J, Njei B, Tita ATN. Elimination of Vertical Transmission of Hepatitis B in Africa: A Review of Available Tools and New Opportunities. Clin Ther 2018; 40:1255-1267. [PMID: 29983265 PMCID: PMC6123260 DOI: 10.1016/j.clinthera.2018.05.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 05/21/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE This review article focuses on preventing vertical transmission of hepatitis B virus (HBV) among pregnant women living in sub-Saharan Africa (SSA), where disease is endemic and the estimated maternal HBV seroprevalence is >8%. Available interventions that have been studied in low- and middle-income countries are compared in terms of efficacy and effectiveness in clinical practice. Global disease-elimination targets, barriers to HBV-prevention efforts, and critical research gaps are discussed. METHODS A PubMed literature search in February 2018 identified relevant studies of interventions to reduce or prevent the transmission of HBV during pregnancy or in the peripartum period. Studies that focused on interventions that are currently available or could be made available in SSA were included. Trials conducted in SSA and other low-income countries were prioritized, although studies of interventions in middle- and high-income countries were included. FINDINGS Among 127 studies and reports included in the review, 60 included data from SSA. The most cost-effective intervention to reduce HBV infection rates in SSA is timely birth-dose vaccination followed by completion of the 3-dose infant-vaccination series. The identification and treatment of pregnant women with elevated HBV viral load to further reduce the risk for vertical transmission in SSA show promise, but efficacy and tolerability trials in Africa are lacking. IMPLICATIONS Scale-up of currently available tools is required to reach HBV disease-elimination goals in SSA. Many countries in SSA are in the process of rolling out national birth-dose vaccination campaigns; this roll out provides an opportunity to evaluate and improve processes in order to expand coverage. Early antenatal care, promotion of facility deliveries, and increased awareness of HBV prevention are also key components of prevention success. Future studies in SSA should identity an HBV-prevention package that is effective, well tolerated, and feasible and can be administered in the antenatal clinic and tailored to vertical-transmission risk.
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Affiliation(s)
- Jodie Dionne-Odom
- Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham, Alabama.
| | - Basile Njei
- Department of Medicine, Section of Digestive Disease, Yale University, New Haven, Connecticut
| | - Alan T N Tita
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Center for Women's Reproductive Health, University of Alabama, Birmingham, Alabama
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22
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Béguelin C, Fall F, Seydi M, Wandeler G. The current situation and challenges of screening for and treating hepatitis B in sub-Saharan Africa. Expert Rev Gastroenterol Hepatol 2018; 12:537-546. [PMID: 29737218 DOI: 10.1080/17474124.2018.1474097] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis B virus (HBV) infection is the most important cause of hepatocellular carcinoma in sub-Saharan Africa (SSA). Although the tools to curb the epidemic are known, only a minority of HBV-infected persons are currently diagnosed and treated. Areas covered: We discuss HBV epidemiological trends in SSA, describe important determinants of its natural history, and summarize current knowledge on the continuum of HBV care. Using the results of a systematic review of the literature, we describe the proportion of patients with liver fibrosis at presentation for care. Throughout the manuscript, we highlight major research gaps and explore potential ways to improve uptake of HBV testing, evaluation of liver disease, access to antiviral therapy and monitoring of complications. Expert commentary: Less than 1% of HBV-infected individuals are diagnosed in SSA, despite the availability of rapid tests with good diagnostic accuracy. Up to 15% of individuals enter care with liver cirrhosis, a clear indication for antiviral therapy. Although the proportion of patients eligible for immediate antiviral treatment is generally below 20%, there are few published data from prospective cohort studies. The incidence of hepatocellular carcinoma could be reduced with improved access to antiviral therapy.
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Affiliation(s)
- Charles Béguelin
- a Department of Infectious Diseases , Bern University Hospital, University of Bern , Bern , Switzerland
| | - Fatou Fall
- b Division of Gastroenterology and Hepatology , Hôpital Principal , Dakar , Senegal
| | - Moussa Seydi
- c Department of Infectious Diseases , Hôpital Fann , Dakar , Senegal
| | - Gilles Wandeler
- a Department of Infectious Diseases , Bern University Hospital, University of Bern , Bern , Switzerland.,c Department of Infectious Diseases , Hôpital Fann , Dakar , Senegal.,d Institute of Social and Preventive Medicine, University of Bern , Bern , Switzerland
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23
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Aberra H, Gordien E, Desalegn H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Gerber A, Stene-Johansen K, Øverbø J, Johannessen A. Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia. Liver Int 2018; 38:1000-1009. [PMID: 28980394 DOI: 10.1111/liv.13607] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 09/25/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. METHODS In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. RESULTS Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). CONCLUSIONS HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis.
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Affiliation(s)
- Hanna Aberra
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Emmanuel Gordien
- Centre National de Référence des Hépatites B, C et Delta, Hôpitaux Universitaires Paris- Seine-Saint-Denis, Paris, Bobigny, France
| | - Hailemichael Desalegn
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Nega Berhe
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.,Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Girmay Medhin
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Bitsatab Mekasha
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Svein G Gundersen
- Research Unit, Sørlandet Hospital HF, Kristiansand, Norway.,Department of Global Development and Planning, University of Agder, Kristiansand, Norway
| | - Athenaïs Gerber
- Centre National de Référence des Hépatites B, C et Delta, Hôpitaux Universitaires Paris- Seine-Saint-Denis, Paris, Bobigny, France
| | | | - Joakim Øverbø
- Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health, Oslo, Norway
| | - Asgeir Johannessen
- Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway
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24
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Ambachew H, Zheng M, Pappoe F, Shen J, Xu Y. Genotyping and sero-virological characterization of hepatitis B virus (HBV) in blood donors, Southern Ethiopia. PLoS One 2018; 13:e0193177. [PMID: 29462187 PMCID: PMC5819820 DOI: 10.1371/journal.pone.0193177] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 02/06/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatitis B virus (HBV) prevalence is highest in Sub-Saharan Africa including Ethiopia. HBV genotypes have distinct geographic distributions and play a role in course of infection and treatment management. However, in Ethiopia there is paucity of information about distribution of HBV genotypes. This study was done to determine genotype, mutation and sero-virological profiles of HBV isolates in Southern Ethiopia. Cross-sectional, laboratory based study was conducted on 103HBsAg sero-positive samples from a total of 2,237 screened blood donors. HBV serological markers and biochemical assays were done. Serum viral load was measured using quantitative real-time PCR. Partial HBV S-gene was amplified with nested PCR and sequenced. Bioinformatics tools were utilized to determine genotypes, serotypes and mutations. Of 103 HBsAg reactive serum samples, 14.6% and 70.9% were sero-positive for HBeAg and HBeAb, respectively. Ninety-eight samples gave detectable viral load with a median of 3.46(2.62-4.82) log IU/ml. HBeAg sero-positive donors carried elevated levels of viral load. Eighty five isolates were successfully amplified, sequenced and genotyped into 58 (68.2%) genotype A (HBV/A) and 27 (31.8%) genotype D (HBV/D). HBV serotypes found were adw2 (74.1%), ayw2 (24.7%), and ayw3 (1.2%). In twenty-four (28.2%) samples mutations in the major hydrophilic region (MHR) were observed. Donors infected with HBV/A had higher viral load and more frequent MHR mutation than HBV/D infected donors. This study illustrated distribution of HBV genotype A and D among blood donors in southern Ethiopia. It also demonstrated occurrence HBV variants that may influence clinical aspects of HBV infection. The study contributes in narrowing the existing gap of HBV molecular study in Ethiopia.
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Affiliation(s)
- Henock Ambachew
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia
| | - Meijuan Zheng
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
| | - Faustina Pappoe
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
- Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Jilong Shen
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
| | - Yuanhong Xu
- Department of Clinical Laboratory, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Clinical Laboratory Diagnostics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
- Department of Immunology and Parasitology, Provincial Laboratory of Microbiology and Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, Anhui, China
- * E-mail:
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