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1. The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease

Author: Zobair M. Younossi, Saleh A. AlQahtani, Jesús Funuyet-Salas, Manuel Romero-Gómez, Yusuf Yilmaz, Caglayan Keklikkiran, Khalid Alswat, Ming-Lung Yu, Chun-Jen Liu, Jian-Gao Fan, Ming-Hua Zheng, Patrizia Burra, Sven M. Francque, Laurent Castera, Jörn M. Schattenberg, Philip N. Newsome, Alina M. Allen, Mohamed El-Kassas, Sombat Treeprasertsuk, Saeed Hameed, Vincent Wai-Sun Wong, Shira Zelber-Sagi, Hirokazu Takahashi, Takumi Kawaguchi, Marlen I. Castellanos Fernández, Ajay Duseja, Marco Arrese, Mary Rinella, Ashwani K. Singal, Stuart C. Gordon, Michael Fuchs, Wayne Eskridge, Naim Alkhouri, Kenneth Cusi, Rohit Loomba, Jane Ranagan, Achim Kautz, Janus P. Ong, Marcelo Kugelmas, Yuichiro Eguchi, Moises Diago, Lynn Gerber, Brian Lam, Lisa Fornaresio, Fatema Nader, C. Wendy Spearman, Stuart K. Roberts, Wah-Kheong Chan, Marcelo Silva, Andrei Racila, Pegah Golabi, Prooksa Ananchuensook, Linda Henry, Maria Stepanova, Patrizia Carrieri, and Jeffrey V. Lazarus
Subjects: patient-reported outcomes, metabolic liver disease, NASH, MASLD, MASH, SLD, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p
Published: 2024
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2. Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers

Author: Yasir Shitu Isa, Jonathan Sicsic, Henry Njuguna, John Ward, Mohamed Chakroun, Mohamed El-Kassas, Rado Ramanampamonjy, Salim Chalal, Jeanne Perpétue Vincent, Monique Andersson, Hailemichael Desalegn, Fatou Fall, Asgeir Johannessen, Philippa C. Matthews, Gibril Ndow, Edith Okeke, Nicholas Riches, Moussa Seydi, Edford Sinkala, C. Wendy Spearman, Alexander Stockdale, Michael J. Vinikoor, Gilles Wandeler, Roger Sombié, Maud Lemoine, Judith E. Mueller, and Yusuke Shimakawa
Subjects: Hepatitis B, Mother-to-child transmission, Elimination, Rapid diagnostic test, Preferences, Discrete choice experiment, Medicine
Abstract: Abstract Background Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. Methods Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. Results A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. Conclusions African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.
Published: 2023
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3. A multisociety Delphi consensus statement on new fatty liver disease nomenclature

Author: Mary E. Rinella, Jeffrey V. Lazarus, Vlad Ratziu, Sven M. Francque, Arun J. Sanyal, Fasiha Kanwal, Diana Romero, Manal F. Abdelmalek, Quentin M. Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D. Byrne, Graciela E. Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R. Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D. Guy, Stephen A. Harrison, Seung Up Kim, Bart G. Koot, Marko Korenjak, Kris V. Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R. Morgan, Elisabeth E. Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C. Sookoian, C. Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B. Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, and Philip N. Newsome
Subjects: Specialties of internal medicine, RC581-951
Abstract: The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Published: 2024
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4. Systematic review and individual-patient-data meta-analysis of non-invasive fibrosis markers for chronic hepatitis B in Africa

Author: Asgeir Johannessen, Alexander J. Stockdale, Marc Y. R. Henrion, Edith Okeke, Moussa Seydi, Gilles Wandeler, Mark Sonderup, C. Wendy Spearman, Michael Vinikoor, Edford Sinkala, Hailemichael Desalegn, Fatou Fall, Nicholas Riches, Pantong Davwar, Mary Duguru, Tongai Maponga, Jantjie Taljaard, Philippa C. Matthews, Monique Andersson, Souleyman Mboup, Roger Sombie, Yusuke Shimakawa, and Maud Lemoine
Subjects: Science
Abstract: Authors carry out a systematic review and meta-analysis to evaluate the performance of fibrosis biomarkers for the diagnosis of fibrosis and cirrhosis in patients with chronic hepatitis B virus infection living in sub-Saharan Africa.
Published: 2023
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5. Reply to: 'Does currently recommended maternal antiviral prophylaxis against mother-to-child transmission of hepatitis B virus require enhancement?'

Author: Philippa C. Matthews, Ponsiano Ocama, Su Wang, Manal El-Sayed, Anna Turkova, Deborah Ford, Judith Torimiro, Ana Cristina Garcia Ferreira, Angélica Espinosa Miranda, Fernando Pio De La Hoz Restrepo, Emmanuel Seremba, Robinson Mbu, Calvin Q. Pan, Homie Razavi, Geoffrey Dusheiko, C. Wendy Spearman, and Saeed Hamid
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Published: 2023
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6. Africa Guidelines for Hepatocellular Carcinoma Buildup Process

Author: Ghassan K. Abou-Alfa, Mary Afihene, Marinela Capanu, Yuelin Li, Joanne F. Chou, Akwi Asombang, Olusegun Isaac Alatise, Adda Bounedjar, Lina Cunha, Hailemichael Desalegn Mekonnen, Papa Saloum Diop, Reda Elwakil, Mahamat Moussa Ali, Ntokozo Ndlovu, Jerry Ndumbalo, Precious Takondwa Makondi, Christian Tzeuton, Tiago Biachi de Castria, Adwoa Afrakoma Agyei-Nkansah, Fiyinfolu Balogun, Alain Bougouma, Blaise Irénée Atipo Ibara, Eduard Jonas, Stephen Kimani, Peter Kingham, Reshad Kurrimbukus, Nazik Hammad, Mona Fouad, Noha El Baghdady, Eloumou Bagnaka Servais Albert Fiacre, Vikash Sewram, C. Wendy Spearman, Ju Dong Yang, Lewis R. Roberts, and Ashraf O. Abdelaziz
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: PURPOSEHepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors.METHODSAn open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world.RESULTSOf 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided.CONCLUSIONSimilarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.
Published: 2023
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7. Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: implications for oral pre-exposure prophylaxis roll out

Author: Dvora Joseph Davey, Nei-yuan Hsiao, C. Wendy Spearman, Mark Sonderup, Nai-Chung Hu, Nyiko Mashele, Rufaro Mvududu, and Landon Myer
Subjects: Pre-exposure prophylaxis, Pregnant, Hepatitis B, HIV, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use. Methods We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV. Results We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%). Conclusion The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.
Published: 2022
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8. Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virusKey points

Author: Philippa C. Matthews, Ponsiano Ocama, Su Wang, Manal El-Sayed, Anna Turkova, Deborah Ford, Judith Torimiro, Ana Cristina Garcia Ferreira, Angélica Espinosa Miranda, Fernando Pio De La Hoz Restrepo, Emmanuel Seremba, Robinson Mbu, Calvin Q. Pan, Homie Razavi, Geoffrey Dusheiko, C. Wendy Spearman, and Saeed Hamid
Subjects: HBV, hepatitis B virus, transmission, prevention, PMTCT, vertical transmission, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Summary: Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.
Published: 2023
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9. Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017)

Author: Andrew Scheibe, Katherine Young, Anna Versfeld, C. Wendy Spearman, Mark W. Sonderup, Nishi Prabdial-Sing, Adrian Puren, and Harry Hausler
Subjects: Hepatitis B, Hepatitis C, HIV, HBV, HCV, People who use drugs, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. Methods We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. Results Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). Conclusions HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.
Published: 2020
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10. Motivations, facilitators and barriers to accessing hepatitis C treatment among people who inject drugs in two South African cities

Author: Anna Versfeld, Angela McBride, Andrew Scheibe, and C. Wendy Spearman
Subjects: Hepatitis C treatment, HCV, People who inject drugs, Motivators, Facilitators, Barriers, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Treatment of hepatitis C (HCV) among people who inject drugs (PWID) is a critical component of efforts to eliminate viral hepatitis. A recent study found high HCV prevalence among PWID in two cities, Pretoria (84%) and Cape Town (44%). Very few (< 5%) HCV-infected individuals attended follow-up appointments. This sub-study explores differences between stated desire for cure and appointment attendance in light of perceived facilitators and barriers to HCV treatment and care access among PWID. Method Two sets of semi-structured interviews were implemented in a group of HCV-infected participants opportunistically sampled and recruited at harm reduction service sites. Initial interviews, conducted before the planned hospital appointment date, asked participants (N = 17, 9 in Pretoria and 8 in Cape Town) about past experiences of healthcare provision, plans to attend their referral appointment and perceived barriers and facilitators to seeking hepatitis treatment. Second interviews (n = 9, 4 in Pretoria, 5 in Cape Town), conducted after the planned referral appointment date, asked about appointment attendance and treatment experience. Trained social scientists with experience with PWID conducted the interviews which were recorded in detailed written notes. Data was thematically analysed in NVivo 11. Results Despite routine experiences of being stigmatised by the healthcare system in the past, most participants (n = 16, 94%) indicated a desire to attend their appointments. Attendance motivators included the desire to be cured, fear of dying and the wish to assist the research project. Perceived barriers to appointment attendance included fear of again experiencing stigmatisation and concerns about waiting periods and drug withdrawal. Perceived facilitators included the knowledge they would be treated quickly, and with respect and access to opioid substitution therapy. In the end, very few participants (n = 5) went to their appointment. Actual barriers to attendance included lack of finances, lack of urgency and forgetting and fatalism about dying. Conclusions South Africa can learn from other countries implementing HCV treatment for PWID. Successful linkage to care will require accessible, sensitive services where waiting time is limited. Psychosocial support prior to initiating referrals that focuses on building and maintaining a sense of self-worth and emphasising that delayed treatment hampers health outcomes is needed.
Published: 2020
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11. Understanding hepatitis B, hepatitis C and HIV among people who inject drugs in South Africa: findings from a three-city cross-sectional survey

Author: Andrew Scheibe, Katherine Young, Lorraine Moses, Rudolph L. Basson, Anna Versfeld, C. Wendy Spearman, Mark W. Sonderup, Nishi Prabdial-Sing, Jack Manamela, Adrian J. Puren, Kevin Rebe, and Harry Hausler
Subjects: Hepatitis C, Hepatitis B, HIV, HBV, HCV, People who inject drugs, Public aspects of medicine, RA1-1270
Abstract: Abstract Background People who inject drugs (PWID) are at high risk for hepatitis C (HCV), hepatitis B (HBV) and HIV without accessible harm reduction programmes. Coverage of needle and syringe and opioid substitution therapy (OST) services in South Africa is below global recommendations and no hepatitis services exist for PWID. We assessed HCV, HBV and HIV prevalence and risk factors among PWID accessing harm reduction services in Cape Town, Durban and Pretoria to inform policy and programming. Methods We conducted a cross-sectional survey among PWID in these cities between August 2016 and October 2017. Participants were opportunistically sampled while accessing services. Study team members administered a questionnaire that assessed sociodemographic characteristics, drug use and sexual risk practices. We tested for HCV (antibody, viral load and genotype), HBV surface antigen (HBsAg) and HIV. Bivariate and multivariate analyses assessed associations with HCV serostatus. Results Nine hundred and forty-three PWID were included in the per protocol analysis. The majority (87%, 819/943) were male, the overall median age was 29 and most lived on the street (66%, 626/943). At last injection, 77% (722/943) reported using a new needle and syringe and 17% (163/943) shared equipment. HIV prevalence was 21% (196/926), HBsAg positivity 5% (47/936), HCV seroprevalence 55% (513/937), HCV viraemic prevalence (proportion tested with detectable HCV) 43% (404/937) and HCV viraemic rate (proportion HCV antibody positive with detectable HCV) 79% (404/513). HCV genotype 1a (73%, 270/368) was the most prevalent. In multivariate analysis, HCV infection was positively associated with residing in Pretoria (adjusted odds ratio (aOR) 1.27, 95% CI 1.21–1.34), living on the street (aOR 1.90, 95% CI 1.38–2.60), frequent injecting (aOR 1.58, 95% CI 1.15–2.16) and HIV infection (aOR 1.69, 95% CI 1.15–2.47), and negatively associated with black race (aOR 0.52, 95% CI 0.36–0.74) and sexual activity in the previous month (aOR 0.61, 95% CI 0.42–0.88). Conclusions HCV and HIV are major health threats affecting PWID in these cities. Access to OST and needle and syringe services needs to be increased and integrated with HCV services. Social and structural factors affecting PWID who live on the street need to be addressed.
Published: 2019
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12. The performance of hepatitis C virus (HCV) antibody point‐of‐care tests on oral fluid or whole blood and dried blood spot testing for HCV serology and viral load among individuals at higher risk for HCV in South Africa

Author: Nishi Prabdial‐Sing, Lucinda Gaelejwe, Lillian Makhathini, Jayendrie Thaver, Morubula Jack Manamela, Susan Malfeld, C. Wendy Spearman, Mark Sonderup, Andrew Scheibe, Katherine Young, Harry Hausler, and Adrian J. Puren
Subjects: dried blood spot, HCV, high risk, point‐of‐care, screening, Medicine
Abstract: Abstract Background and Aims To enhance screening and diagnosis in those at‐risk of hepatitis C virus (HCV), efficient and improved sampling and testing is required. We investigated the performance of point‐of‐care (POC) tests and dried blood spots (DBS) for HCV antibody and HCV RNA quantification in individuals at higher risk for HCV (people who use and inject drugs, sex workers and men who have sex with men) in seven South African cities. Methods Samples were screened on the OraQuick HCV POC test (471 whole blood and 218 oral fluid); 218 whole blood and DBS paired samples were evaluated on the ARCHITECT HCV antibody (Abbott) and HCV viral load (COBAS Ampliprep/COBAS TaqMan version 2) assays. For HCV RNA quantification, 107 dB were analyzed with and without normalization coefficients. Results POC on either whole blood or oral fluid showed an overall sensitivity of 98.5% (95% CI 97.4‐99.5), specificity of 98.2% (95% CI 98.8‐100) and accuracy of 98.4% (95% CI 96.5‐99.3). On the antibody immunoassay, DBS showed a sensitivity of 96.0% (95% CI 93.4‐98.6), specificity of 97% (95% CI 94.8‐99.3) and accuracy of 96.3% (95% CI 93.8‐98.8). A strong correlation (R2 = 0.90) between viral load measurements for DBS and plasma samples was observed. After normalization, DBS viral load results showed an improved bias from 0.5 to 0.16 log10 IU/mL. Conclusion The POC test performed sufficiently well to be used for HCV screening in at‐risk populations. DBS for diagnosis and quantification was accurate and should be considered as an alternative sample to test. POC and DBS can help scale up hepatitis services in the country, in light of our elimination goals.
Published: 2021
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13. Global Disparities in Hepatitis B Elimination—A Focus on Africa

Author: Mark W. Sonderup and C. Wendy Spearman
Subjects: disparities, viral hepatitis, elimination, Hep B birth dose, vaccination, integration, Microbiology, QR1-502
Abstract: In 2016, WHO member states at the World Health Assembly adopted a Global Health Sector Strategy that included a policy of eliminating viral hepatitis. Clear targets were established to assist in achieving this by 2030. The strategy, while achievable, has exposed existing global disparities in healthcare systems and their ability to implement such policies. Compounding this, the regions with most disparity are also those where the hepatitis B prevalence and disease burden are the greatest. Foundational to hepatitis B elimination is the identification of both those with chronic infection and crucially pregnant women, and primary prevention through vaccination. Vaccination, including the birth dose and full three-dose coverage, is key, but complete mother-to-child transmission prevention includes reducing the maternal hepatitis B viral load in the third trimester where appropriate. Innovations and simplified tools exist in order to achieve elimination, but what is desperately required is the will to implement these strategies through the support of appropriate investment and funding. Without this, disparities will continue.
Published: 2022
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14. Disseminated Emmonsia in an HIV-HBV co-infected man

Author: Arthur Mutyaba, Mark W. Sonderup, Michael Locketz, Ikechi Okpechi, C. Wendy Spearman, and Alan Tooke
Subjects: HIV, Hepatitis B, Fungal infection, Maculopapular rash, Infectious and parasitic diseases, RC109-216
Abstract: The differential diagnoses in patients with advanced HIV/AIDS presenting with fever and systemic illness is wide and warrants both infectious and non-infectious considerations. The need to make an early and accurate diagnosis is important to effect correct therapy and thus improve outcome. We describe a patient with several co-morbidities and an unusual disseminated fungal infection.
Published: 2015
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15. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa

Author: C Wendy Spearman, Geoffrey Dusheiko, Eduard Jonas, Abdelmounem Abdo, Mary Afihene, Lina Cunha, Hailemichael Desalegn, Chris Kassianides, Leolin Katsidzira, Anna Kramvis, Philip Lam, Olufunmilayo A Lesi, Eileen A Micah, Emmanuel Musabeyezu, Gibril Ndow, Chidi V Nnabuchi, Ponsiano Ocama, Edith Okeke, John Rwegasha, Abate B Shewaye, Fatuma F Some, Christian Tzeuton, and Mark W Sonderup
Subjects: Aflatoxin B1, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Gastroenterology, Humans, Hepatitis C, Africa South of the Sahara
Abstract: Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.
Published: 2022
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16. Treatment of hepatocellular carcinoma in sub-Saharan Africa: challenges and solutions

Author: Eduard, Jonas, Marc, Bernon, Barbara, Robertson, Chris, Kassianides, Elie, Keli, Kwaku Offei, Asare, Isaac Olusegun, Alatise, Michael, Okello, Nana Oumarou, Blondel, Kenedy Ondede, Mulehane, Zeki Abdurahman, Abubeker, Alaaeldin Awad, Nogoud, Pueya Rashid, Nashidengo, Onesai, Chihaka, Christian, Tzeuton, Geoffrey, Dusheiko, Mark, Sonderup, and C Wendy, Spearman
Subjects: Carcinoma, Hepatocellular, Ethanol, Hepatology, Incidence, Liver Neoplasms, Gastroenterology, Humans, Africa South of the Sahara
Abstract: Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.
Published: 2022
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17. Epidemiology, risk factors, social determinants of health, and current management for non-alcoholic fatty liver disease in sub-Saharan Africa

Author: O S Ojo, C Wendy Spearman, Chris Kassianides, Ponsiano Ocama, Omolade Betiku, Christian Tzeuton, Bilal Bobat, Mary Afihene, Hailemichael Desalegn Mekonnen, Leolin Katsidzira, Imran Paruk, Mark W. Sonderup, and Lina Cunha
Subjects: Adult, Male, medicine.medical_specialty, Social Determinants of Health, Population, Disease, Chronic liver disease, Cost of Illness, Non-alcoholic Fatty Liver Disease, Risk Factors, Environmental health, Epidemiology, Prevalence, Humans, Medicine, Obesity, Social determinants of health, Renal Insufficiency, Chronic, Noncommunicable Diseases, education, Africa South of the Sahara, Dyslipidemias, Metabolic Syndrome, education.field_of_study, Hepatology, business.industry, Incidence, Fatty liver, Gastroenterology, Disease Management, Health Care Costs, Awareness, Middle Aged, Prognosis, medicine.disease, Gastrointestinal Microbiome, Diabetes Mellitus, Type 2, Hypertension, Female, Metabolic syndrome, business, Polycystic Ovary Syndrome
Abstract: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.
Published: 2021
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18. Health-care provision and policy for non-alcoholic fatty liver disease in sub-Saharan Africa

Author: Aggrey Ambali, Olufunmilayo A. Lesi, Yaw Asante Awuku, Margareth Ndomondo-Sigonda, Charles A Onyekwere, C Wendy Spearman, Abdelmounem Abdo, Chris Kassianides, Abate B Shewaye, John Rwegasha, and Mark W. Sonderup
Subjects: medicine.medical_specialty, Population, Disease, Health Services Accessibility, Global Burden of Disease, Patient Education as Topic, Non-alcoholic Fatty Liver Disease, Risk Factors, Environmental health, parasitic diseases, Epidemiology, Health care, Diabetes Mellitus, Prevalence, medicine, Humans, Obesity, Noncommunicable Diseases, education, Africa South of the Sahara, Aged, Metabolic Syndrome, education.field_of_study, Primary Health Care, Hepatology, SARS-CoV-2, business.industry, Health Policy, Fatty liver, Gastroenterology, COVID-19, Middle Aged, medicine.disease, Social Class, Metabolic syndrome, business, Delivery of Health Care, Risk Reduction Behavior, Malaria
Abstract: Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and diabetes, enhance the risk of non-alcoholic fatty liver disease (NAFLD), yet this remains an unrecognised complication of metabolic syndrome. There are no guidance documents on NAFLD from sub-Saharan Africa, and non-communicable disease (NCD) guidance documents do not include the associated burden of fatty liver disease. Combating the health and socioeconomic burden of NAFLD requires an integrated liver health approach, with task-shifting to primary health care. Using clear guidance documents to link education and management of HIV, viral hepatitis, NAFLD, and associated NCDs is also crucial to an integrated approach to infectious diseases and NCDs, which requires targeted funding from both governments and international development agencies.
Published: 2021
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19. Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author: Luca Valenti, Elena Corradini, Leon A. Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagström, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Lainé, Koji Miyanishi, Martina U. Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John D. Ryan, Laura Silvestri, C. Wendy Spearman, Per Stål, Emmanuel A. Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller, Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), The University of Western Australia (UWA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Johns Hopkins University (JHU), Pontificia Universidad Católica de Chile (UC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), Universitat de Girona [Girona], Universitat de Girona (UdG), Università degli studi di Verona = University of Verona (UNIVR), Karolinska University Hospital [Stockholm], Leopold Franzens Universität Innsbruck - University of Innsbruck, Washington State University (WSU), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Sapporo Medical University School of Medicine, Sapporo Medical University, Heidelberg University, IRCCS Ospedale San Raffaele [Milan, Italy], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Royal College of Surgeons in Ireland (RCSI), University of Cape Town, University College of London [London] (UCL), Weill Cornell Medicine [New York], The First Affiliated Hospital of Wenzhou Medical University [Wenzhou, China], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ministero della Salute, Ricerca Finalizzata RF-2016-02364358, RC Rete cardiologica ‘CV PREVITAL’, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ‘Liver BIBLE’ (PR-0391), Innovative Medicines Initiative 2 joint undertaking of European Union’s Horizon 2020 research and innovation programme and EFPIA European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS, H2020 under grant agreement ‘101016726’, the European Union, programme ‘Photonics’ under grant agreement ‘101016726’ for L.V. Fondo Nacional de Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and from the Agencia Nacional de Investigación y Desarrollo, ANID through ANID ACE 210009 grant for M.A. NIH (P30DK124723), and Veterans Administration (2I01 BX001140) for D.M. SFB1036, SFB1118 and DFG (FerrOs — FOR5146, SPP2306) as well as Marsilius Kolleg for M.U.M. National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) for M.-H.Z. Swedish Cancer Society (170690) and Stockholm County Council (K2017-4579) for P.S., Jonchère, Laurent, Weill Cornell Medicine [Cornell University], and Cornell University [New York]
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, iron, Endocrinology, iron, hyperferritinemia, metabolic syndrome, Endocrinology, Diabetes and Metabolism, hyperferritinemia, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, metabolic syndrome
Abstract: International audience; Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
Published: 2023
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20. Hepatitis C elimination in Africa: Seizing the moment for hepatitis-C free future

Author: Gamal Esmat, Rahma Mohamed, Hailemichael Desalegn, Mark W. Sonderup, C Wendy Spearman, Nabil Debzi, Ahmed Cordie, and Mohammed A Medhat
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, Hepacivirus, Hepatitis C, medicine.disease, Antiviral Agents, Virology, Africa, medicine, Humans, business, Disease Elimination
Published: 2021
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21. Low prevalence of Hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: Implications for oral pre-exposure prophylaxis roll out

Author: Dvora, Joseph Davey, Nei-Yuan, Hsiao, C, Wendy Spearman, Mark, Sonderup, Nai-Chung, Hu, Nyiko, Mashele, Rufaro, Mvududu, and Landon, Myer
Subjects: Adult, Hepatitis B virus, Chronic Liver Disease and Cirrhosis, Clinical Sciences, HIV Infections, Reproductive health and childbirth, Pregnant, Microbiology, Hepatitis, Cohort Studies, Vaccine Related, Hepatitis - B, South Africa, Pregnancy, Clinical Research, Prevalence, Humans, Emtricitabine, Tenofovir, Hepatitis B Surface Antigens, Liver Disease, Prevention, Infant, HIV, Pre-exposure prophylaxis, Hepatitis B, Cross-Sectional Studies, Infectious Diseases, Good Health and Well Being, Medical Microbiology, HIV/AIDS, Pre-Exposure Prophylaxis, Female, Immunization, Pregnant Women, Digestive Diseases, Infection
Abstract: Background Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use. Methods We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV. Results We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%). Conclusion The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.
Published: 2022
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22. Diagnostic performance of non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan Africa: a Bayesian individual patient data meta-analysis

Author: Asgeir Johannessen, Alexander J. Stockdale, Marc Y.R. Henrion, Edith Okeke, Moussa Seydi, Gilles Wandeler, Mark Sonderup, C. Wendy Spearman, Michael Vinikoor, Edford Sinkala, Hailemichael Desalegn, Fatou Fall, Nicholas Riches, Pantong Davwar, Mary Duguru, Tongai Maponga, Jantjie Taljaard, Philippa C. Matthews, Monique Andersson, Roger Sombie, Yusuke Shimakawa, and Maud Lemoine
Abstract: ObjectiveIn sub-Saharan Africa, hepatitis B is the principal cause of liver disease. Non-invasive biomarkers of liver fibrosis are needed to identify patients requiring antiviral treatment. We assessed aspartate aminotransferase-to-platelet ratio index (APRI), gamma-glutamyl transferase-to-platelet ratio (GPR) and FIB-4 to diagnose significant fibrosis and cirrhosis in an individual patient data (IPD) meta-analysis.DesignIn total, 3,549 patients from 12 cohorts of HBsAg positive individuals in 8 sub-Saharan African countries were included. Transient elastography was used as a reference test for cirrhosis (>12.2 kPa), excluding patients who were pregnant, had hepatitis C, D, or HIV co-infection, were on hepatitis B therapy, or had acute hepatitis. A bivariate Bayesian IPD model was fitted with patient-level covariates and study-level random effects.ResultsAPRI and GPR had the best discriminant performance (area under receiver operating curve 0.81 and 0.82) relative to FIB-4 (0.77) for cirrhosis. The World Health Organization (WHO) recommended APRI threshold of ≥2.0 was associated with a sensitivity and specificity (95% credible interval) of 16.5% (12.5-20.5) and 99.5% (99.2-99.7) for cirrhosis. For APRI, we identified an optimised rule-in threshold for cirrhosis (cut-off 0.65) with a sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (cut-off 0.36) with a sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8).ConclusionsThe WHO recommended APRI threshold of 2.0 is too high to diagnose cirrhosis in sub-Saharan Africa. We identified new and optimised rule-in and rule-out thresholds for cirrhosis, with direct consequences for treatment guidelines in this setting.
Published: 2022
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23. Global multi-stakeholder endorsement of the MAFLD definition

Author: Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. 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Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. 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Neuman, M, Ng'Wanasayi, M, Ni, Y, Nicoll, A, Niizeki, T, Nikolova, D, Ningning, W, Niriella, M, Nogoibaeva, K, Nordien, R, O Sullivan, C, O'Beirne, J, Obekpa, S, Ocama, P, Ochwoto, M, Ogolodom, M, Ojo, O, Okrostsvaridze, N, Oliveira, C, Omana, R, Omar, O, Omar, H, Omar, M, Omran, S, Omran, R, Osman, M, Owise, N, Owusu-Ansah, T, Padilla- Machaca, P, Palle, S, Pan, Z, Pan, X, Pan, Q, Papaefthymiou, A, Paquissi, F, Par, G, Parkash, A, Payawal, D, Peltekian, K, Peng, X, Peng, L, Peng, Y, Pengoria, R, Perez, M, Perez, J, Perez, N, Persico, M, Pessoa, M, Petta, S, Philip, M, Plaz Torres, M, Polavarapu, N, Poniachik, J, Portincasa, P, Pu, C, Purnak, T, Purwanto, E, Qi, X, Qian, Z, Qiang, Z, Qiao, Z, Qiao, L, Queiroz, A, Rabiee, A, Radwan, M, Rahetilahy, A, Ramadan, Y, Ramadan, D, Ramli, A, Ramm, G, Ran, A, Rankovic, I, Rao, H, Raouf, S, Ray, S, Reau, N, Refaat, A, Reiberger, T, Remes-Troche, J, Reyes, E, Richardson, B, Ridruejo, E, Riestra Jimenez, S, Rizk, I, Roberts, S, Roblero, J, Robles, J, Rockey, D, Rodriguez, M, Rodriguez Hernandez, H, Roman, E, Romeiro, F, Romeo, S, Rosales-Zabal, J, Roshdi, G, Rosso, N, Ruf, A, Ruiz, P, Runes, N, Ruzzenente, A, Ryan, M, Saad, A, Sabbagh, E, Sabbah, M, Saber, S, Sabrey, R, Sabry, R, Saeed, M, Said, D, Said, E, Sakr, M, Salah, Y, Salama, R, Salama, A, Saleh, H, Saleh, A, Salem, A, Salifou, A, Salih, A, Salman, A, Samouda, H, Sanai, F, Sanchez-Avila, J, Sanker, L, Sano, T, Sanz, M, Saparbu, T, Sawhney, R, Sayed, F, Sayed, S, Sayed, A, Sayed, M, Sebastiani, G, Secadas, L, Sediqi, K, Seif, S, Semida, N, Senates, E, Serban, E, Serfaty, L, Seto, W, Sghaier, I, Sha, M, Shabaan, H, Shalaby, L, Shaltout, I, Sharara, A, Sharma, V, Shawa, I, Shawkat, A, Shawky, N, Shehata, O, Sheils, S, Shewaye, A, Shi, G, Shi, J, Shimose, S, Shirono, T, Shou, L, Shrestha, A, Shui, G, Sievert, W, Sigurdardottir, S, Sira, M, Siradj, R, Sison, C, Smyth, L, Soliman, R, Sollano, J, Sombie, R, Sonderup, M, Sood, S, Soriano, G, Stedman, C, Stefanyuk, O, Stimac, D, Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease
Subjects: Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract: Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)
Published: 2022
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24. The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?

Author: Jeffrey V. Lazarus, Henry E. Mark, Marcela Villota-Rivas, Adam Palayew, Patrizia Carrieri, Massimo Colombo, Mattias Ekstedt, Gamal Esmat, Jacob George, Giulio Marchesini, Katja Novak, Ponsiano Ocama, Vlad Ratziu, Homie Razavi, Manuel Romero-Gómez, Marcelo Silva, C. Wendy Spearman, Frank Tacke, Emmanuel A. Tsochatzis, Yusuf Yilmaz, Zobair M. Younossi, Vincent W.-S. Wong, Shira Zelber-Sagi, Helena Cortez-Pinto, Quentin M. Anstee, Samir Rouabhia, Hasmik Ghazinyan, Natacha Jreige Iskandar, Michael Trauner, Gulnara Aghayeva, Flloyd Carter, Kannan Sridharan, Mamun Al Mahtab, Sven Francque, Nicolas Kodjoh, Ruben Muñoz Camacho, Motswedi Anderson, Claudia Pinto Marques Souza de Oliveira, Lyudmila Mateva, Abdel Karim Serme, Antonieta A. Soares Martins, Mark G. Swain, Narcisse Patrice Komas, Ming-Hua Zheng, Patricio Lopez Jaramillo, Omar Alfaro Murillo, Ivana Mikolasevic, Emmelia Vounou, Radan Brůha, Charles Mbendi Nlombi, Maja Thiele, Marlene Perez, Juan José Suárez M, Imam Waked, Riina Salupere, Hailemichael Desalegn, Hannele Yki-Järvinen, Tengiz Tsertsvadze, Lali Sharvadze, Maia Butsashvili, Yaw Asante Awuku, Georgios Papatheodoridis, Bela Hunyady, Einar Stefan Bjornsson, Ajay Duseja, Cosmas Rinaldi A. Lesmana, Reza Malekzadeh, Suzanne Norris, Kazuhiko Koike, Alexander V. Nersesov, Missiani Ochwoto, Mohammad Jamal, Tobokalova Saparbu, Ieva Tolmane, Raymond Sayegh, Dhastagir Sultan Sheriff, Jonas Valantinas, Joseph Weber, Isaac Thom Shawa, Soek-Siam Tan, Sophia E. Martínez Vázquez, Oidov Baatarkhuu, Undram Lkhagvaa, Tsolmon Jadamba, Tahiri Mohammed, K.C Sudhamshu, Kirsten Coppell, Charles Onyekwere, Dafina Nikolova, Mette Vesterhus, Khalid Al-Naamani, Saeed Hamid, Juan Paredes Méndez, María Cecilia Cabrera Cabrejos, Robert Flisiak, Esther A. Torres, Shahrad Taheri, Ki-Chul Sung, Turcanu Adela, Liana Gheorghe, Faisal M. Sanai, Tamara Milovanovic, George Boon Bee Goh, Marek Rac, Anuradha Dassanayake, Shahinaz Bedri Osama, M. Elsanousi, Jean-François Dufour, Jia-Horng Kao, Dilshod Saidi, Sombat Treeprasertsuk, Ger Koek, Asma Labidi, Igor Skrypnyk, Maryam Salem AlKhatry, Shakhlo Sadirova, Shokhista Bakieva, Edford Sinkala, Repositório da Universidade de Lisboa, Lazarus, Jeffrey V., Mark, Henry E., Villota-Rivas, Marcela, Palayew, Adam, Carrieri, Patrizia, Colombo, Massimo, Ekstedt, Mattias, Esmat, Gamal, George, Jacob, Marchesini, Giulio, Novak, Katja, Ocama, Ponsiano, Ratziu, Vlad, Razavi, Homie, Romero-Gómez, Manuel, Silva, Marcelo, Spearman, C. Wendy, Tacke, Frank, Tsochatzis, Emmanuel A., Yilmaz, Yusuf, Younossi, Zobair M., Wong, Vincent W.-S., Zelber-Sagi, Shira, Cortez-Pinto, Helena, Anstee, Quentin M., NAFLD policy review collaborators, University of Barcelona, EASL International Liver Foundation [Geneva, Switzerland] (ILF), University of Washington [Seattle], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), IRCCS San Raffaele Hospital, Linköping University (LIU), Cairo University, The University of Sydney, University of Bologna/Università di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Makerere University [Kampala, Ouganda] (MAK), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Center for Disease Analysis Foundation [Lafayette, CO, États-Unis], Biomedicine Institute of Sevilla [Seville, Spain], Hospital Universitario Austral, University of Cape Town, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institute for Liver & Digestive Health [London, UK], Marmara University [Kadıköy - İstanbul], Inova Medicine [Falls Church, Virginia, USA] (IM), The Chinese University of Hong Kong [Hong Kong], University of Haifa [Haifa], Tel Aviv Sourasky Medical Center [Te Aviv], Universidade de Lisboa = University of Lisbon (ULISBOA), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, EASL International Liver Foundation, Bristol-Myers Squibb, Genfit, MSD, Gilead Sciences, Allergan Foundation, Pfizer, Resoundant, Wong, Vincent Wai-Sun, and Malbec, Odile
Subjects: policy preparedness, Adult, [SDV]Life Sciences [q-bio], non-alcoholic steatohepatitis (NASH), multiple correspondence analysis, Global Health, digestive system, Policy preparednesss, Non-alcoholic fatty liver disease (NAFLD), liver health, Non-alcoholic Fatty Liver Disease, Humans, Obesity, Non-alcoholic steatohepatitis (NASH), BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, global public health, Hepatology, Liver health, nutritional and metabolic diseases, health policy, digestive system diseases, Health policy, Multiple correspondence analysis, [SDV] Life Sciences [q-bio], Policy, Policy preparedness, Public Health, Global public health
Abstract: [Background & Aims]: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas., [Methods]: We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied., [Results]: The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and, [Conclusions]: Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels., The data collection and analysis were funded by the EASL International Liver Foundation with support from, Intercept, Bristol-Myers-Squibb Company, Genfit, and MSD. Data collection for the original European data was funded by the EASL International Liver Foundation supported by Gilead Sciences Europe Ltd., Allergan Pharmaceutical International Ltd., Bristol-Myers-Squibb Company, Pfizer Inc., and Resoundant Inc.
Published: 2021
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25. The sub-Saharan Africa position statement on the redefinition of fatty liver disease: From NAFLD to MAFLD

Author: C Wendy Spearman, Reda Elwakil, Abdulmunem A. Abdo, Hailemichael Desalegn, Dennis A Ndububa, Medhat Elsahhar, Reidwan Ally, Musa M. Borodo, O S Ojo, Yasser Fouad, Masolwa Ng'wanasayi, Ponsiano Ocama, and Yaw Asante Awuku
Subjects: Position statement, Sub saharan, Hepatology, business.industry, Environmental health, Fatty liver, Medicine, Disease, business, medicine.disease
Published: 2021
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26. Chronic hepatitis B: identifying who needs to be treated and improving linkage to care

Author: C Wendy Spearman
Subjects: Linkage (software), Hepatology, Chronic hepatitis, business.industry, Gastroenterology, Medicine, business, Bioinformatics
Published: 2021
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27. Hepatitis C

Author: C Wendy, Spearman, Geoffrey M, Dusheiko, Margaret, Hellard, and Mark, Sonderup
Subjects: Editorial, Humans, General Medicine, Hepatitis C
Abstract: Hepatitis C is a global health problem, and an estimated 71·1 million individuals are chronically infected with hepatitis C virus (HCV). The global incidence of HCV was 23·7 cases per 100 000 population (95% uncertainty interval 21·3-28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). HCV transmission is most commonly associated with direct percutaneous exposure to blood, via blood transfusions, health-care-related injections, and injecting drug use. Key high-risk populations include people who inject drugs, men who have sex with men, and prisoners. Approximately 10-20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, liver failure, and hepatocellular carcinoma over a period of 20-30 years. Direct-acting antiviral therapy is now curative, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.
Published: 2019
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28. The case for simplifying and using absolute targets for viral hepatitis elimination goals

Author: Tsendsuren S. Oyunsuren, Chari Cohen, Waseem Hamoudi, Yao‐Chun Hsu, Harry L.A. Janssen, Hisham El Khayat, Manal H El-Sayed, Wan-Long Chuang, Young-Suk Lim, Mohamed Hassany, Fernando Passos Cupertino de Barros, Faisal Abaalkhail, Stefan Zeuzem, Samual S Lee, Miriam T. Levy, Imam Waked, Vassiliki Papaevangelou, James Fung, Erika Castro Batänjer, Kathryn Razavi-Shearer, Boatemaa Ntiri‐ Reid, Rosmawati Mohamed, Pagbajabyn Nymadawa, Robert Flisiak, Alnoor Ramji, Carole Seguin-Devaux, Sherif Mogawer, Béla Hunyady, Huma Qureshi, Mojca Matičič, Martin Lagging, Mark W. Sonderup, Xiaoguang Dou, Anne Oevrehus, William Sievert, Ezequiel Ridruejo, Ann-Sofi Duberg, Ahad Eshraghian, R. P. Shanmugam, Arif Nawaz, Qing Xie, Rick Dunn, Sayed Himatt, Daniel Shouval, Mendez Sanchez Nahum, Sabahattin Kaymakoglu, Vincent Wai-Sun Wong, Soek-Siam Tan, Willis Maddrey, Papu Prasad, Amjad Salamat, Stephanie Popping, Alice Lee, Maurizia Rossana Brunetto, Khalid Alswat, Peyton Thompson, Dong Joon Kim, Henry Chang, Amir Ali Sohrabpour, Ellen Dugan, Peer Brehm Christensen, David A. M. C. van de Vijver, Joaquín Cabezas, Su Wang, Ala I. Sharara, Peter Jarcuska, Karine Lacombe, Danjuma Adda, Sammy Saab, Chien-Jen Chen, Hwai I. Yang, Sanaa Said, Raymond F. Schinazi, Shyamasundaran Kottilil, Graham R. Foster, Qing Ning, Mehlika Toy, Ira M. Jacobson, Ayat R. Abdallah, Laura Cisneros, Dhondup Tashi, Naveed Z. Janjua, Moutaz Derbala, Marcelo Kugelmas, Steven L. Flamm, Angelos Hatzakis, Yusuf Yilmaz, Mark S. Sulkowski, Eugene R. Schiff, Kakharman Yesmembetov, John F. Dillon, Rittoo Prithiviputh, Carlos Eduardo Brandão-Mello, Rajender Reddy, Françoise Roudot-Thoraval, Lewis R. Roberts, Javier Crespo, Massimo Colombo, Nancy Steinfurth, I. M. Hoepelman, Kosh Agarwal, Faisal M. Sanai, Waleed Al-Hamoudi, Shuang Liu, Beat Muellhaupt, Sonjelle Shilton, Curtis Cooper, Calvin Q. Pan, Aijaz Ahmed, Wai-cheung C Lao, Alejandro Soza, Patricia Vélez‐Möller, Ibrahim Altraif, Tarik Asselah, Junko Tanaka, Badr Aljarallah, Adriana Vince, Faryal Khamis, Juan Francisco Sánchez-Ávila, Rafael Esteban Mur, Kimberly A. Brown, Saad Al-Kaabi, Ming-Lung Yu, Jonas Valantinas, Marieta Simonova, Javier García-Samaniego, Do Young Kim, Ieva Tolmane, Valentina Liakina, Antonio Craxì, Devin Razavi-Shearer, Waldemar Halota, Stuart K. Roberts, Donna Cryer, Kenneth Kabagambe, William Remak, Jeffrey V. Lazarus, Brian Conway, Sameera Ezzat, C Wendy Spearman, Karolin Falconer, Maria C Mendes Correa, Poonam Mathur, Ferruccio Bonino, Jose Luis Calleja, Said A. Al-Busafi, E. A. Croes, Tim Block, Shahin Merat, Francesco Negro, Reza Malekzadeh, Fernando L. Gonçales, Amany Zekry, Wahid Doss, Michael Ninburg, Philip Bruggmann, Man-Fung Yuen, George V. Papatheodoridis, Aasim Yusuf, David Kershenobich, Bruce R. Bacon, Abdul Rahman Bizri, Gamal Esmat, Sarah Blach, Hamad Al-Romaihi, Tatsuya Kanto, Ibrahim Mostafa, Homie Razavi, Alessio Aghemo, Mauricio Orrego, Jia-Horng Kao, Daniel Lavanchy, Zobair M. Younossi, Henry Lik-Yuen Chan, Anna Kramvis, David H. Muljono, Clemens Richter, Hla-Hla Thein, Fernando Bessone, Paulo Roberto Abrão Ferreira, Geoffrey Dusheiko, Susan Hay, Geert Robaeys, Eduardo Fassio, Loreta A. Kondili, Jorge Mera, Khalid Al-Naamani, Alaa Osman, Saleh A. Alqahtani, Joseph Doyle, Necati Örmeci, Yee Tak Hui, Heiner Wedemeyer, Laith Jamal Abu Raddad, Masayuki Kurosaki, Rui Tato Marinho, Robert G. Gish, Zaigham Abbas, Seiji Yamada, Giada Sebastiani, Cihan Yurdaydin, Maria Buti, Paulo Ferrinho, Razavi H., Blach S., Razavi-Shearer D., Abaalkhail F., Abbas Z., Abdallah A., Abrao Ferreira P., Abu Raddad L.J., Adda D., Agarwal K., Aghemo A., Ahmed A., Al-Busafi S.A., Al-hamoudi W., Al-Kaabi S., Al-Romaihi H., Aljarallah B., AlNaamani K., Alqahtani S., Alswat K., Altraif I., Asselah T., Bacon B., Bessone F., Bizri A.R., Block T., Bonino F., Brandao-Mello C.E., Brown K., Bruggmann P., Brunetto M.R., Buti M., Cabezas J., Calleja J.L., Castro Batanjer E., Chan H.L.-Y., Chang H., Chen C.-J., Christensen P.B., Chuang W.-L., Cisneros L., Cohen C., Colombo M., Conway B., Cooper C., Craxi A., Crespo J., Croes E., Cryer D., Cupertino de Barros F.P., Derbala M., Dillon J., Doss W., Dou X., Doyle J., Duberg A.-S., Dugan E., Dunn R., Dusheiko G., El Khayat H., El-Sayed M.H., Eshraghian A., Esmat G., Esteban Mur R., Ezzat S., Falconer K., Fassio E., Ferrinho P., Flamm S., Flisiak R., Foster G., Fung J., Garcia-Samaniego J., Gish R.G., Goncales F., Halota W., Hamoudi W., Hassany M., Hatzakis A., Hay S., Himatt S., Hoepelman I.M., Hsu Y.-C., Hui Y.T., Hunyady B., Jacobson I., Janjua N., Janssen H., Jarcuska P., Kabagambe K., Kanto T., Kao J.-H., Kaymakoglu S., Kershenobich D., Khamis F., Kim D.J., Kim D.Y., Kondili L.A., Kottilil S., Kramvis A., Kugelmas M., Kurosaki M., Lacombe K., Lagging M., Lao W.-C., Lavanchy D., Lazarus J.V., Lee A., Lee S.S., Levy M., Liakina V., Lim Y.-S., Liu S., Maddrey W., Malekzadeh R., Marinho R.T., Mathur P., Maticic M., Mendes Correa M.C., Mera J., Merat S., Mogawer S., Mohamed R., Muellhaupt B., Muljono D., Mostafa I., Nahum M.S., Nawaz A., Negro F., Ninburg M., Ning Q., Ntiri- Reid B., Nymadawa P., Oevrehus A., Ormeci N., Orrego M., Osman A., Oyunsuren T., Pan C., Papaevangelou V., Papatheodoridis G., Popping S., Prasad P., Prithiviputh R., Qureshi H., Ramji A., Razavi-Shearer K., Reddy R., Remak W., Richter C., Ridruejo E., Robaeys G., Roberts S., Roberts L., Roudot-Thoraval F., Saab S., Said S., Salamat A., Sanai F., Sanchez-Avila J.F., Schiff E., Schinazi R., Sebastiani G., Seguin-Devaux C., Shanmugam R.P., Sharara A., Shilton S., Shouval D., Sievert W., Simonova M., Sohrabpour A.A., Sonderup M., Soza A., Wendy Spearman C., Steinfurth N., Sulkowski M., Tan S.-S., Tanaka J., Tashi D., Thein H.-H., Thompson P., Tolmane I., Toy M., Valantinas J., Van de Vijver D., Velez-Moller P., Vince A., Waked I., Wang S., Wedemeyer H., Wong V., Xie Q., Yamada S., Yang H.-I., Yesmembetov K., Yilmaz Y., Younossi Z., Yu M.-L., Yuen M.-F., Yurdaydin C., Yusuf A., Zekry A., Zeuzem S., Medical Microbiology & Infectious Diseases, Virology, and Negro, Francesco
Subjects: ddc:616, Carcinoma, Hepatocellular, Hepatology, Hepatitis, Viral, Human, business.industry, Liver Neoplasms, ddc:616.07, medicine.disease, World Health Organization, Virology, digestive system diseases, Goal, Infectious Diseases, Absolute (philosophy), SDG 3 - Good Health and Well-being, medicine, Humans, Viral hepatitis, business, Goals, Human
Abstract: The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
Published: 2021
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29. Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017)

Author: Mark W. Sonderup, Nishi Prabdial-Sing, Anna Versfeld, C Wendy Spearman, Katherine Young, Andrew Scheibe, Harry Hausler, and Adrian Puren
Subjects: Male, HBsAg, Cross-sectional study, 030508 substance abuse, HIV Infections, Hepacivirus, HIV Antibodies, Men who have sex with men, law.invention, South Africa, Sexual and Gender Minorities, 0302 clinical medicine, law, Risk Factors, HBV, Prevalence, 030212 general & internal medicine, Prospective Studies, Substance Abuse, Intravenous, virus diseases, Hepatitis C, Hepatitis B, Viral Load, Infectious Diseases, HCV, Female, 0305 other medical science, Viral hepatitis, Viral load, People who inject drugs, psychological phenomena and processes, Research Article, Adult, Hepatitis B virus, Genotype, Sex workers, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Young Adult, Condom, Environmental health, medicine, Humans, lcsh:RC109-216, MSM, Homosexuality, Male, Hepatitis B Surface Antigens, business.industry, HIV, Key populations, Hepatitis C Antibodies, medicine.disease, Cross-Sectional Studies, business, People who use drugs
Abstract: Background People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. Methods We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. Results Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). Conclusions HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.
Published: 2020

30. Converging pandemics: implications of COVID-19 for the viral hepatitis response in sub-Saharan Africa

Author: Lina Cunha, Karine Lacombe, C Wendy Spearman, Neil Gupta, Richard Njouom, Hailemichael Desalegn, Mark W. Sonderup, Fredrick Kateera, Mary Afihene, and Ponsiano Ocama
Subjects: 2019-20 coronavirus outbreak, Sub saharan, Coronavirus disease 2019 (COVID-19), Hepatitis, Viral, Human, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Article, Betacoronavirus, COVID-19 Testing, Pandemic, Medicine, Humans, Pandemics, Africa South of the Sahara, biology, Hepatology, business.industry, Clinical Laboratory Techniques, Coinfection, SARS-CoV-2, Gastroenterology, COVID-19, biology.organism_classification, medicine.disease, Virology, business, Viral hepatitis, Coronavirus Infections
Published: 2020
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31. Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030

Author: Mark W. Sonderup, Olufunmilayo A. Lesi, C Wendy Spearman, Chris Kassianides, Lina Cunha, Christian Tzeuton, John Rwegasha, Papa Saliou Mbaye, Emmanuel Musabeyezu, Betty S. Apica, Geoffrey Dusheiko, Mary Afihene, Reidwaan Ally, Marie-Jeanne Lohouès-Kouacou, Phillip Lam, Yaw Asante Awuku, Neliswa Gogela, Olesegun Ojo, Betty Musau, Abate B. Shewaye, and Barbara Scholz
Subjects: Economic growth, Sub saharan, Hepatology, Operations research, business.industry, media_common.quotation_subject, Hepatitis C virus, Gastroenterology, Psychological intervention, Hepatitis C, medicine.disease, medicine.disease_cause, Scarcity, 03 medical and health sciences, 0302 clinical medicine, Work (electrical), parasitic diseases, medicine, Coinfection, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business, Viral hepatitis, media_common
Abstract: In 2016, WHO adopted a strategy for the elimination of viral hepatitis by 2030. Africa, and more specifically, sub-Saharan Africa, carries a substantial portion of the global burden of viral hepatitis, especially chronic hepatitis B and hepatitis C virus infections. The task that lies ahead for sub-Saharan Africa to achieve elimination is substantial, but not insurmountable. Major developments in the management of hepatitis C have put elimination within reach, but several difficulties will need to be navigated on the path to elimination. Many of the challenges faced are unique to sub-Saharan Africa and the development of strategies is complicated by a scarcity of good data from countries and regions within sub-Saharan Africa. However, this hindrance should not act as a barrier to delay interventions in screening, detection, and linkage to care. Moreover, by sharing experiences from across sub-Saharan Africa, countries can create supranational synergies to develop their programmes and work together in a more cohesive manner to tackle the burden of hepatitis C in sub-Saharan Africa. In this Series paper, several issues related to hepatitis C in sub-Saharan Africa are addressed, including prevalence, risk factors, and fibrosis assessment, and recommendations are given by experts from across the region. Simplified diagnostic algorithms and treatment regimens for both HIV co-infected and hepatitis C mono-infected patients are suggested. The recommendations are consensus based and provided to guide the development of programmes in sub-Saharan Africa. Political will and appropriate funding will be required to provide impetus to implement these recommendations.
Published: 2017
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32. Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets

Author: Philip Lam, Reidwaan Ally, Chris Kassianides, John Rwegasha, Olufunmilayo A. Lesi, Emmanuel Musabeyezu, Christian Tzeuton, Mark W. Sonderup, Michael C. Kew, Neliswa Gogela, Geoffrey Dusheiko, Yaw Asante Awuku, Lina Cunha, Betty Musau, Abate B. Shewaye, Barbara Scholz, O S Ojo, Papa Saliou Mbaye, C Wendy Spearman, Marie Jeanne Lohouès-Kouacou, Betty S. Apica, and Mary Afihene
Subjects: medicine.medical_specialty, HIV Infections, medicine.disease_cause, Antiviral Agents, Mass Vaccination, Health Services Accessibility, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Epidemiology, Prevalence, medicine, Global health, Humans, Mass Screening, 030212 general & internal medicine, Intensive care medicine, Africa South of the Sahara, Mass screening, Hepatitis B virus, Hepatitis B Surface Antigens, Hepatology, Coinfection, business.industry, Gastroenterology, Hepatitis B, medicine.disease, Virology, Infectious Disease Transmission, Vertical, 030211 gastroenterology & hepatology, Viral hepatitis, business
Abstract: The WHO global health sector strategy on viral hepatitis, created in May, 2016, aims to achieve a 90% reduction in new cases of chronic hepatitis B and C and a 65% reduction in mortality due to hepatitis B and C by 2030. Hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and despite the introduction of universal hepatitis B vaccination and effective antiviral therapy, the estimated overall seroprevalence of hepatitis B surface antigen remains high at 6·1% (95% uncertainty interval 4·6-8·5). In this Series paper, we have reviewed the literature to examine the epidemiology, burden of liver disease, and elimination strategies of hepatitis B in sub-Saharan Africa. This paper reflects a supranational perspective of sub-Saharan Africa, and recommends several priority elimination strategies that address the need both to prevent new infections and to diagnose and treat chronic infections. The key to achieving these elimination goals in sub-Saharan Africa is the effective prevention of new infections via universal implementation of the HBV birth-dose vaccine, full vaccine coverage, access to affordable diagnostics to identify HBV-infected individuals, and to enable linkage to care and antiviral therapy.
Published: 2017
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33. Use of controlled temperature chain and compact prefilled auto-disable devices to reach 2030 hepatitis B birth dose vaccination targets in LMICs: a modelling and cost-optimisation study

Author: C Wendy Spearman, Christopher Morgan, Mark W. Sonderup, Yinzong Xiao, Olufunmilayo A. Lesi, Nick Scott, Monique Andersson, Margaret Hellard, Christopher P Seaman, and J. Howell
Subjects: Vaccination Coverage, Birth dose, Drug Storage, 030231 tropical medicine, Psychological intervention, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Environmental health, Medicine, Humans, Hepatitis B Vaccines, 030212 general & internal medicine, Developing Countries, Syringe, Transmission (medicine), business.industry, Disease progression, Infant, Newborn, Temperature, General Medicine, Hepatitis B, Models, Theoretical, medicine.disease, Infectious Disease Transmission, Vertical, Cost savings, Vaccination, Healthy People Programs, Costs and Cost Analysis, Female, business, Goals
Abstract: Summary Background Hepatitis B causes more than 800 000 deaths globally each year. Perinatal infections are a major driver of this burden but can be prevented by vaccination within 24 h of birth. Currently, only 44% of newborn babies in low-income and middle-income countries (LMICs) receive a timely birth dose. We investigated the effects and cost-effectiveness of implementing ambient storage of hepatitis B vaccines under a controlled temperature chain (CTC) protocol and the use of compact prefilled auto-disable (CPAD) devices for community births. Methods In this mathematical modelling study of perinatal hepatitis B transmission and disease progression, we estimated the coverage impact and cost-effectiveness of implementing CTC and CPAD interventions in the six Global Burden of Disease (GBD) regions containing LMICs. Combinations of four different scenarios of birth dose delivery strategies (cold chain, CTC) and interventions (needle and syringe, CPAD) were modelled across facility or community birth locations. We also estimated the minimum cost and most cost-effective strategy to achieve the WHO 90% hepatitis B birth dose coverage target in GBD regions and in 46 LMICs with a reported coverage of less than 90%. Findings Current delivery protocols achieved a maximum coverage of 65% (IQR 64–65) across GBD regions. Reaching 90% hepatitis B birth dose coverage across all GBD regions was estimated to cost a minimum of US$687·5 million per annum ($494·0 million more than the estimated current expenditure), of which $516·5 million (75%) was required for CTC and CPAD interventions. Reaching 90% coverage in this way was estimated to be cost saving in five of the six regions (and in 40 of 46 LMICs individually assessed) due to the disease costs averted, with the cost per disability-adjusted life-years averted being less than $83·27 otherwise. Interpretation Hepatitis B birth dose coverage of 90% is unlikely to be reached under current protocols. CTC and CPAD vaccine strategies present cost-effective solutions to overcome coverage barriers. Funding The Burnet Institute.
Published: 2020

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

Author: Mark W. Sonderup, Geoffrey Dusheiko, C Wendy Spearman, Maud Lemoine, Simon D. Taylor-Robinson, Hailemichael Desalegn, and Christian Tzeuton
Subjects: GENOTYPE-A, medicine.medical_specialty, Vaccination Coverage, Sub saharan, Birth dose, TRANSMISSION, C INFECTION, VIRUS-INFECTION, Diagnostic tools, 03 medical and health sciences, 0302 clinical medicine, elimination, HBSAG, 1108 Medical Microbiology, Virology, medicine, MANAGEMENT, Humans, EPIDEMIOLOGY, Hepatitis B Vaccines, 030212 general & internal medicine, LIVER-CANCER, Intensive care medicine, Africa South of the Sahara, WEST-AFRICA, Science & Technology, Hepatology, Gastroenterology & Hepatology, Sub-Saharan Africa, treatment, business.industry, 1103 Clinical Sciences, Hepatitis B, medicine.disease, PREVALENCE, Vaccination, Infectious Diseases, 030211 gastroenterology & hepatology, hepatitis B, business, Life Sciences & Biomedicine, 0605 Microbiology
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.
Published: 2019

35. Hepatitis B, hepatitis C and HIV prevalence and related risk practices among key populations in South Africa: findings from a seven-city cross-sectional survey

Author: Mark W. Sonderup, Harry Hausler, Anna Versfeld, Andrew Scheibe, C Wendy Spearman, Nishi Prabdial Sing, Adrian Puren, and Katherine Young
Subjects: Cross-sectional study, business.industry, Environmental health, medicine, virus diseases, Key (lock), Hepatitis C, Hepatitis B, medicine.disease, Hiv prevalence, business
Abstract: Background: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk for HIV and viral hepatitis infection. Limited data exists on the epidemiology of these infections among these key population groups (KPs) in South Africa. We aimed to describe the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and related risk factors among these KPs to inform effective responses. Methods: We aimed to recruit 3 500 KPs across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) for participation in a cross-sectional survey. We used an interviewer administered questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices. We tested for HCV (antibody, viral load and genotype), HBV surface antigen (HBsAg) and HIV antibody. We used descriptive statistics to explore data, which was stratified by KP. Results: Among the 3 439 included in the study (1 528 SWs, 746 MSM, 1 165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence of 16% (highest among PWUD/ID at 46%). Conclusions: HCV, HBV and HIV are major health threats for KPs in South Africa. While HIV is an important condition for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behaviour change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services and access to HCV treatment for PWUD/ID need to be expanded.
Published: 2019
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36. Molecular characterisation of acute intermittent porphyria in a cohort of South African patients and kinetic analysis of two expressed mutants

Author: Philip H. Fortgens, P.N. Meissner, Mark W. Sonderup, Elaine Pienaar, C Wendy Spearman, and Anne V. Corrigall
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Hydroxymethylbilane Synthase, Mutant, Black People, Gene mutation, Biology, medicine.disease_cause, Pathology and Forensic Medicine, Cohort Studies, South Africa, 03 medical and health sciences, Molecular genetics, medicine, Humans, Gene, Acute intermittent porphyria, Genetics, Mutation, General Medicine, medicine.disease, Molecular biology, 030104 developmental biology, Porphyria, Acute Intermittent, Mutation testing, Female
Abstract: Aims Acute intermittent porphyria (AIP) is a disorder of the haem biosynthetic pathway caused by mutations in the hydroxymethylbilane synthase ( HMBS ) gene. Knowledge of the spectrum of mutations present in South Africa is limited. This study presents the molecular profile of 20 South African patients with AIP, and the kinetic analysis of one novel expressed mutated HMBS enzyme and a previously identified mutation at the same position. Methods Genomic DNA was isolated from affected probands and selected family members, the HMBS gene amplified and mutations characterised by direct sequencing and restriction enzyme analysis. One of the novel mutations (p.Lys98Glu), a previously characterised mutation at the same position (p.Lys98Arg), and the wild-type enzyme were expressed, purified and subjected to partial kinetic characterisation. Results Four new mutations, p.Lys98Glu, p.Asp230Aspfs * 20, c.161-1G>A and c.422+3_6delAAGT, are described. Seven previously described mutations were found, while four patients revealed no mutations. Mutation analysis of five offspring of one of the probands carrying the p.Trp283X mutation revealed two asymptomatic carriers. Kinetic analysis showed that the p.Lys98Glu mutation results in loss of substrate affinity, whereas the previously described p.Lys98Arg mutation causes the loss of binding between the enzyme and its dipyrromethane cofactor, rendering the enzyme inactive. Conclusions This study comprises the most comprehensive characterisation of HMBS gene mutations in patients with AIP in South Africa. The biochemical characterisation of expressed HMBS mutants reveals insight into the mechanism of catalytic activity loss, which may inspire investigation into individualised therapy based on the molecular lesion identified.
Published: 2016
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37. N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review

Author: Mahmoud Werfalli, Mohamed Farouk Chughlay, C Wendy Spearman, Nicole Kramer, and Karen Cohen
Subjects: Pharmacology, Hepatitis, medicine.medical_specialty, business.industry, Subgroup analysis, Odds ratio, medicine.disease, Placebo, law.invention, Surgery, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), 030212 general & internal medicine, Prospective cohort study, Adverse effect, business
Abstract: Aims N-acetylcysteine (NAC) may be useful in the management of non-paracetamol drug-induced liver injury (DILI). Our objective was to review systematically evidence for the use of NAC as a therapeutic option for non-paracetamol DILI. Methods We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases, grey literature sources, conference proceedings and ongoing trials. Our pre-specified primary outcomes were all cause and DILI related mortality, time to normalization of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant-free survival and hospitalization duration. Results We identified one RCT of NAC vs. placebo in patients with non-paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3 weeks between NAC [70%, 95% confidence interval (CI) = 60%, 81%, n = 81] and placebo (66%, 95% CI = 56%, 77%, n = 92). NAC significantly improved the secondary outcomes of transplant-free survival compared with placebo: 40% NAC (95% CI = 28%, 51%) vs. 27% placebo (95% CI = 18%, 37%). A subgroup analysis according to aetiology found improved transplant-free survival in patients with non-paracetamol DILI, NAC (58%, n = 19) vs. placebo (27%, n = 26), odds ratio (OR) 0.27 (95% CI = 0.076, 0.942). Overall survival was similar, NAC (79%) vs. placebo (65%);, OR 0.50 (95% CI = 0.13, 1.98). Conclusion Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non-paracetamol DILI. We therefore highlight the need for further research in this area.
Published: 2016
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38. Contributors

Author: Monique Andersson, J.W.S. Devar, Suliman Salih Fedail, Alan Karstaedt, M.K. Kgomo, T.E. Madiba, F. Makumbi, Hazel M. Mitchell, O. Mwantembe, S.R. Rutherford Thomson, Isidor Segal, Mashiko Setshedi, M.D. Smith, Mark W. Sonderup, Frank Tovey, Hester H. Vorster, and C. Wendy Spearman
Published: 2019
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39. Aspects of Viral Hepatitis in Sub-Saharan Africa in the 21st Century

Author: C Wendy Spearman and Mark W. Sonderup
Subjects: Geography, Sub saharan, medicine, Viral hepatitis, medicine.disease, Virology
Published: 2019
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40. Direct-acting antiviral therapy in sub-Saharan Africa

Author: Mark W. Sonderup and C Wendy Spearman
Subjects: Fluorenes, Sub saharan, Hepatology, business.industry, Gastroenterology, Antiviral therapy, Rwanda, Hepatitis C, Chronic, Virology, Antiviral Agents, Medicine, Humans, Benzimidazoles, Sofosbuvir, business, Direct acting, Africa South of the Sahara
Published: 2018

41. Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling study

Author: Margaret Hellard, Nick Scott, Olufunmilayo A. Lesi, C Wendy Spearman, Anna Palmer, Mark W. Sonderup, and Christopher Morgan
Subjects: Cost effectiveness, Cost-Benefit Analysis, Drug Storage, 030231 tropical medicine, medicine.disease_cause, Global Health, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Pregnancy, Environmental health, Prevalence, Medicine, Humans, Hepatitis B Vaccines, 030212 general & internal medicine, Cold chain, health care economics and organizations, Hepatitis B virus, Cost–benefit analysis, business.industry, lcsh:Public aspects of medicine, Infant, Newborn, Temperature, lcsh:RA1-1270, General Medicine, Models, Theoretical, Hepatitis B, Infectious Disease Transmission, Vertical, digestive system diseases, Quality-adjusted life year, Vaccination, Transmission (mechanics), Female, Quality-Adjusted Life Years, Rural area, business
Abstract: Summary Background The controlled temperature chain (CTC) strategy allows vaccines to be kept outside the cold chain for a short period of time. In remote rural areas, the CTC strategy for the hepatitis B virus (HBV) birth dose vaccination could improve its geographical coverage and timeliness of delivery, but with additional outreach costs. We assessed the cost-effectiveness of the CTC strategy for the HBV birth dose across six world regions and 72 countries according to their HBV prevalence, delivery costs, and birth dose coverage and timing. Methods By use of a mathematical model of perinatal HBV transmission and disease progression, we calculated per 1000 births the total HBV-related disability-adjusted life-years (DALYs) and costs, including vaccine delivery costs and costs associated with HBV-related disease, with and without the CTC strategy. Findings A CTC strategy produced health benefits in all regions and was cost-saving in the regions of east Asia and Pacific, Latin America and Caribbean, sub-Saharan Africa, and north Africa and Middle East. The CTC strategy cost US$0·15 (IQR −7·11 to 4·75) per DALY averted in the central and eastern Europe and central Asia region and $79·72 (66·47 to 94·47) in the south Asia region. Within individual countries, more savings were achieved and more DALYs averted in areas with above average HBV prevalence, below average birth dose coverage, or later than average birth dose delivery. Interpretation A CTC outreach strategy that improves the timing and coverage of the HBV birth dose vaccination is likely to be cost-saving and reduce the burden of HBV infection associated with perinatal transmission. Funding Burnet Institute.
Published: 2018

42. Health disparities in liver disease in sub-Saharan Africa

Author: Mark W. Sonderup and C Wendy Spearman
Subjects: Pathology, medicine.medical_specialty, Population, Acquired immunodeficiency syndrome (AIDS), Environmental health, parasitic diseases, Health care, medicine, Humans, Health Workforce, Healthcare Disparities, education, Africa South of the Sahara, Disease burden, education.field_of_study, Hepatology, business.industry, Liver Diseases, Disease Management, Health Status Disparities, Hepatitis C, Hepatitis B, medicine.disease, Health equity, business, Viral hepatitis
Abstract: Disparities in health reflect the differences in the incidence, prevalence, burden of disease and access to care determined by socio-economic and environmental factors. With liver disease, these disparities are exacerbated by a combination of limited awareness and preventable causes of morbidity and mortality in addition to the diagnostic and management costs. Sub-Saharan Africa, comprising 11% of the world's population, disproportionately has 24% of the global disease burden, yet allocates
Published: 2015
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43. A clinicopathological cohort study of liver pathology in 301 patients with human immunodeficiency virus/acquired immune deficiency syndrome

Author: Helen Wainwright, Pauline de la M. Hall, C Wendy Spearman, Henry Norman Hairwadzi, and Mark W. Sonderup
Subjects: Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Opportunistic infection, HIV Infections, Gastroenterology, Cohort Studies, Liver disease, Internal medicine, medicine, Humans, Acquired Immunodeficiency Syndrome, Hepatology, medicine.diagnostic_test, business.industry, Liver Diseases, Hepatitis C, Hepatitis B, medicine.disease, Liver biopsy, Immunology, Coinfection, Female, Chemical and Drug Induced Liver Injury, Steatohepatitis, business
Abstract: Liver disease complicates human immunodeficiency virus (HIV)/acquired immune deficiency syndrome; however, liver pathology data are limited, particularly from high HIV prevalence countries. We investigated the spectrum and clinicopathological correlates of liver pathology in a high HIV burden setting. In a single-center study, all HIV/acquired immune deficiency syndrome patients with complete clinical and demographic data who underwent liver biopsy were analyzed and clinicopathologically assessed by hepatologists and one of two experienced liver pathologists. We evaluated 301 patients, with a median age of 34 (interquartile range 29-40) years. Women (n = 143) were younger than men (n = 158), with a median age of 33 (interquartile range 28-37) versus 35 (interquartile range 31-41) years, P = 0.001. The majority, 76.1%, were black African. Median CD4 at time of biopsy was 127 (52-260) cells/mm(3) . Drug-induced liver injury was the predominant finding (42.2%), followed by granulomatous inflammation (29%), steatosis/steatohepatitis (19.3%), hepatitis B (19%), and hepatitis C coinfection (3.3%), with more than one pathology in 16.2%. With granulomatous inflammation, 52% met the criteria for tuberculosis immune reconstitution syndrome. By univariate analysis, cotrimoxazole and antiretroviral therapy conferred risk for drug injury (odds ratio [OR] = 2.78 [1.72-4.48], P 0.001; OR = 1.69 [1.06-2.68], P = 0.027). In multivariate analysis, cotrimoxazole was associated with a cholestatic or ductopenic injury (OR = 7.05 [2.50-19.89], P 0.001; OR = 17.6 [3.26-95.3], P 0.0001); efavirenz was associated with nonspecific hepatitis or submassive necrosis (OR = 4.3 [1.92-9.83], P 0.001; OR = 10.46 [2.7-40.5], P 0.001). Cholestatic injury was associated with female gender and a CD4 of200 cells/mm(3) , and submassive necrosis was associated with younger age. Hepatitis B demonstrated no association.In a high HIV burden area, drug-induced liver injury due to antiretroviral therapy and cotrimoxazole was a frequent clinicopathological finding; Mycobacterium tuberculosis was the leading opportunistic infection, with more than half of patients fulfilling criteria for tuberculosis immune reconstitution syndrome; liver biopsy remains a useful diagnostic procedure in this setting.
Published: 2015
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44. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population

Author: Peter Gohl, Pham Thi Thu Thuy, Dionysios Neofytos, Wolfgang E. Kaminski, Teresa Santantonio, Giovanni Battista Gaeta, Mark W. Sonderup, Bui Huu Hoang, Gaston Westergaard, Stephan Pabinger, Mikael Gencay, Anja Seffner, Michael Weizenegger, Markus Nauck, Giuseppina Brancaccio, Massimo Fasano, Kirsten Hübner, Eva Brill, Richard Batrla, Jérémie Gautier, Hyon Suk Kim, Christine Reinsch, C Wendy Spearman, Andreas Woeste, Gencay, Mikael, Hübner, Kirsten, Gohl, Peter, Seffner, Anja, Weizenegger, Michael, Neofytos, Dionysio, Batrla, Richard, Woeste, Andrea, Kim, Hyon-Suk, Westergaard, Gaston, Reinsch, Christine, Brill, Eva, Thu Thuy, Pham Thi, Hoang, Bui Huu, Sonderup, Mark, Spearman, C Wendy, Pabinger, Stephan, Gautier, Jérémie, Brancaccio, Giuseppina, Fasano, Massimo, Santantonio, Teresa, Gaeta, Giovanni B, Nauck, Marku, and Kaminski, Wolfgang E
Subjects: 0301 basic medicine, Genetics and Molecular Biology (all), HBsAg, Gene Identification and Analysis, lcsh:Medicine, Hepatitis B Surface Antigen, Artificial Gene Amplification and Extension, medicine.disease_cause, Global Health, Biochemistry, Polymerase Chain Reaction, Database and Informatics Methods, 0302 clinical medicine, Genotype, lcsh:Science, Pathology and laboratory medicine, Genetics, Mutation, Multidisciplinary, Geography, High-Throughput Nucleotide Sequencing, Hepatitis B viru, Gene Pool, Medical microbiology, Phylogeography, Biogeography, Viruses, 030211 gastroenterology & hepatology, Gene pool, Antibody, Pathogens, Hydrophobic and Hydrophilic Interactions, Human, Research Article, Hepatitis B virus, Genotyping, Substitution Mutation, Biology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Hydrophobic and Hydrophilic Interaction, medicine, Amino Acid Substitution, Hepatitis B Surface Antigens, Humans, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Molecular Biology Techniques, Mutation Detection, Molecular Biology, Medicine and health sciences, Evolutionary Biology, Population Biology, Point mutation, lcsh:R, Ecology and Environmental Sciences, Viral pathogens, Organisms, Biology and Life Sciences, Virology, Hepatitis viruses, Microbial pathogens, 030104 developmental biology, Biological Databases, Mutation Databases, biology.protein, Earth Sciences, lcsh:Q, Population Genetics
Abstract: The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.
Published: 2017

45. Highlights from the 3rd international HIV/viral hepatitis Co-infection meeting - HIV/viral hepatitis: improving diagnosis, antiviral therapy and access

Author: Tracy Swan, Rachel Matteau Matsha, C Wendy Spearman, Isabelle Andrieux-Meyer, Andrew Scheibe, Marina B. Klein, Sébastien Morin, Tongai Maponga, Jürgen K. Rockstroh, Division of Hepatology, and Faculty of Health Sciences
Subjects: medicine.medical_specialty, Debate, Epidemiology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), medicine, Global health, 030212 general & internal medicine, lcsh:RC799-869, Hepatitis B virus, Hepatitis, Transmission (medicine), business.industry, Prevention, Hepatitis C, Hepatitis B, medicine.disease, 3. Good health, HIV/viral hepatitis co-infection, Family medicine, Immunology, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Access and equity of treatment, business, Viral hepatitis, 21st International AIDS Conference
Abstract: The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings. The objectives of the meeting were:i.To review the latest therapeutic developments in viral hepatitis;ii.To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis;iii.To advance the agenda for elimination of viral hepatitis as a public health problem. Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016–2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure. This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat.
Published: 2017

46. Hepatitis C treatment: where are we now?

Author: Nicholas J, Burstow, Zameer, Mohamed, Asmaa I, Gomaa, Mark W, Sonderup, Nicola A, Cook, Imam, Waked, C Wendy, Spearman, and Simon D, Taylor-Robinson
Subjects: ribavirin-free regimens, directly acting antivirals, protease inhibitors, interferon-free regimens, hepatitis C eradication, Review, hepatitis C
Abstract: Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin (RBV) regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct-acting antiviral (DAA) therapies began with the development of first-generation NS3/4A protease inhibitors in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then, a multitude of DAAs have been licensed for use, and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, RBV-free, and involve a combination of DAA agents. This review summarizes the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C.
Published: 2017

47. Viral Hepatitis

Author: C. Wendy Spearman, Ronalda de Lacy, and Elizabeth Goddard
Published: 2017
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48. Hepatitis E virus: Western Cape, South Africa

Author: Nathan English, Annemiek A. van der Eijk, Stephen Korsman, Suzan D Pas, Bronwyn Gavine, Mark W. Sonderup, Aniefiok Edem, Odelia Lutchman, C Wendy Spearman, Harry R. Dalton, Joanne Palmer, Sean Wasserman, Christy Kaiyamo, R.G. Madden, Tawanda Chivese, Sebastian Wallace, Glynn W Webb, Elizabeth Goddard, Roxy Govender, and Virology
Subjects: Male, Veterinary medicine, Ethnic group, Seroprevalence, medicine.disease_cause, South Africa, 0302 clinical medicine, Hepatitis E virus, Risk Factors, Seroepidemiologic Studies, Odds Ratio, Prospective Studies, 030212 general & internal medicine, Young adult, Child, Aged, 80 and over, Gastroenterology, General Medicine, Middle Aged, Hepatitis E, Child, Preschool, Female, Adult, Genotype, Adolescent, 030231 tropical medicine, Young Adult, 03 medical and health sciences, Age Distribution, SDG 3 - Good Health and Well-being, Predictive Value of Tests, medicine, Humans, Serologic Tests, Hepatitis Antibodies, Risk factor, Aged, Pork consumption, Hepatitis, business.industry, Infant, Newborn, Odds ratio, medicine.disease, Logistic Models, Case-Control Studies, Immunoglobulin G, Multivariate Analysis, Prospective Study, business, Biomarkers, Demography
Abstract: textabstractAIM To conduct a prospective assessment of anti-hepatitis E virus (HEV) IgG seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure. METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children's Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic/race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus (HIV) status was self-disclosed. HEV IgG testing was performed using the Wantai assay. RESULTS HEV is endemic in the region with a seroprevalence of 27.9% (n = 324/1161) 95%CI: 25.3%-30.5% (21.9% when age-adjusted) with no significant differences between ethnic groups or HIV status. Seroprevalence in children is low but rapidly increases in early adulthood. With univariate analysis, age ? 30 years old, pork and bacon/ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV IgG seropositivity (OR = 7.679, 95%CI: 5.38-10.96, p < 0.001) was being 30 years or older followed by pork consumption (OR = 2.052, 95%CI: 1.39-3.03, p < 0.001). A recent clinical case demonstrates that HEV genotype 3 may be currently circulating in the Western Cape. CONCLUSION Hepatitis E seroprevalence was considerably higher than previously thought suggesting that hepatitis E warrants consideration in any patient presenting with an unexplained hepatitis in the Western Cape, irrespective of travel history, age or ethnicity.
Published: 2016

49. Hepatitis B in rugby: is it time to revisit policy?

Author: Mark W, Sonderup, Jason, Suter, and C Wendy, Spearman
Subjects: Male, Risk, Athletes, Football, Humans, Hepatitis B Vaccines, Hepatitis B, Tenofovir, Antiviral Agents
Published: 2015

50. N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review

Author: Mohamed Farouk, Chughlay, Nicole, Kramer, C Wendy, Spearman, Mahmoud, Werfalli, and Karen, Cohen
Subjects: Humans, Free Radical Scavengers, Systematic Review, Chemical and Drug Induced Liver Injury, Acetylcysteine
Abstract: N-acetylcysteine (NAC) may be useful in the management of non-paracetamol drug-induced liver injury (DILI). Our objective was to review systematically evidence for the use of NAC as a therapeutic option for non-paracetamol DILI.We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases, grey literature sources, conference proceedings and ongoing trials. Our pre-specified primary outcomes were all cause and DILI related mortality, time to normalization of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant-free survival and hospitalization duration.We identified one RCT of NAC vs. placebo in patients with non-paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3 weeks between NAC [70%, 95% confidence interval (CI) = 60%, 81%, n = 81] and placebo (66%, 95% CI = 56%, 77%, n = 92). NAC significantly improved the secondary outcomes of transplant-free survival compared with placebo: 40% NAC (95% CI = 28%, 51%) vs. 27% placebo (95% CI = 18%, 37%). A subgroup analysis according to aetiology found improved transplant-free survival in patients with non-paracetamol DILI, NAC (58%, n = 19) vs. placebo (27%, n = 26), odds ratio (OR) 0.27 (95% CI = 0.076, 0.942). Overall survival was similar, NAC (79%) vs. placebo (65%);, OR 0.50 (95% CI = 0.13, 1.98).Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non-paracetamol DILI. We therefore highlight the need for further research in this area.
Published: 2015

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