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Lemoine M, Assoumou L, Girard P-M, et al., 2023, Screening HIV Patients at Risk for NAFLD Using MRI-PDFF and Transient Elastography: A European Multicenter Prospective Study., Clin Gastroenterol Hepatol, Vol: 21, Pages: 713-722.e3
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m2 (IQR, 23.6-28.7 kg/m2); metabolic syndrome (67%); and CD4 cell count, 630/mm3 (IQR, 510-832/mm3). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF ≥5%). Among them, 11.3% had a liver stiffness ≥9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23 ; 95% CI, 1.07-1.42 ; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operat
Im YR, Jagdish R, Leith D, et al., 2022, Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 7, Pages: 932-942
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Ndow G, Cessay A, Cohen D, et al., 2022, Prevalence and clinical significance of occult hepatitis B infection in The Gambia, West Africa., Journal of Infectious Diseases, Vol: 226, Pages: 862-870, ISSN: 0022-1899
BACKGROUND: Prevalence of occult hepatitis B infection (OBI) and its clinical outcomes have been poorly studied in Africa. METHOD: Using the PROLIFICA cohort, we compared the prevalence of OBI between HBsAg-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases) and estimated the population attributable fraction for the effect of OBI on advanced liver disease. RESULTS: OBI prevalence was significantly higher among the cases (15/82, 18.3%) than in the control group (31/330, 9.4%, p=0.03). Among participants with OBI, pre-S2 mutations were detected in 5/31 (16.1%) controls and 3/14 (21.4%) cases (p=0.7).After adjusting for age, sex, and anti-HCV serology, OBI was significantly associated with advanced liver disease [OR: 2.8 (95% CI: 1.3-6.0), p=0.006]. In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (7.5-18.1%) and 16.9% (15.2-18.6%), respectively. CONCLUSION: OBI is endemic and an independent risk factor of advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg-positivity.
Boyer S, Baudoin M, Nishimwe ML, et al., 2022, Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa, BMC Health Services Research, Vol: 22, Pages: 1-15, ISSN: 1472-6963
BackgroundAlthough direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d’Ivoire and Senegal.MethodsUsing modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country’s predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo ‘no DAA treatment’ as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d’Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves.ResultsWith slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country’s per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to sign
Gill US, Lemoine M, 2022, Making safe sense of an anti-sense!, Cell Reports Medicine, Vol: 3, Pages: 1-2, ISSN: 2666-3791
Mohamed Z, Scott N, Nayagam S, et al., 2022, Cost effectiveness of simplified HCV screening-and-treatment interventions for people who inject drugs in Dar-es-Salaam, Tanzania, International Journal of Drug Policy, Vol: 99, ISSN: 0955-3959
Lemoine M, Ndow G, Shimakawa Y, 2021, Improving disease knowledge is critical to eliminate hepatitis B, JOURNAL OF VIRAL HEPATITIS, Vol: 29, Pages: 231-232, ISSN: 1352-0504
Ingiliz P, Maurice J, Shimakawa Y, et al., 2021, Impact of an add-on strategy of the C-C chemokine receptor 5 (CCR5) antagonist maraviroc on hepatic inflammation in HIV-infected individuals with non-alcoholic steatohepatitis: a paired-liver biopsy proof-of-concept study, 18th European AIDS Conference (EACS 2021), Publisher: Wiley, Pages: 191-191, ISSN: 1464-2662
Introduction. Non-alcoholic steatohepatitis (NASH) is of concern in an agingand antiretroviral therapy (ART)-pretreated HIV-infected population. Notherapeutic agent has yet been licensed for the treatment of NASH in orderto reduce hepatic inflammation, steatosis, or liver fibrosis. The CCR5receptor antagonist maraviroc is an approved HIV drug, but hepatic CCR5inhibition has also been suggested to reduce hepatic inflammation andfibrogenesis in animal models. This study aimed to investigate the impact ofa maraviroc add-on strategy on hepatic inflammation in ART-treated HIVmono-infected individuals with NASH.Methods. The MASH study (Maraviroc-Add on for Steatohepatitis in HIVinfected patients) was a single-arm, open-label trial conducted across 5sites in Germany and the United Kingdom. HIV-infected individuals withbiopsy proven NASH were invited to add maraviroc BID to their existing,suppressive ART regimen for 48 weeks, and undergo a second liver biopsythereafter. Patients had immunologic, cytokine, metabolic, and histologicassessment at baseline and end of treatment (EOT).Results. Overall, 24 subjects were screened, and 13 completed the study and were analyzed. All participants were male,median age 50.5 years [45.5-55.5], baseline BMI 30.66 kg/m2 [27.92-33.63]; 83.3% (10/12) had insulin resistance. Atbaseline, 11/13 patients (85%) had fibrosis >1 (Metavir). At EOT no significant changes in the hepatic immune cell infiltrate(CD4/CD8/CD68) were observed, however, the NAS score decreased non significantly from 4.077 ± 0.76 at baseline to 3.64 ±0.51 at EOT (p = 0.125). At week 48, 7/11 patients (63%) showed significant fibrosis> stage 1, EOT BMI was similar comparedto baseline. Add-on MVC had no significant impact on inflammatory markers or lipid metabolism.
Maurice JB, Goldin R, Hall A, et al., 2021, Increased BMI and Type 2 diabetes are the main predictors of NAFLD and advanced fibrosis in liver biopsies of patients with HIV mono-infection., Clinical Infectious Diseases, Vol: 73, Pages: e2184-e2193, ISSN: 1058-4838
BACKGROUND: Liver disease is an important cause of morbidity and mortality in people living with HIV (PLWH), of which non-alcoholic fatty liver disease (NAFLD) is an increasingly recognised cause. There is limited data investigating NAFLD in HIV mono-infection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD and NASH among PLWH, and explore the diagnostic accuracy of non-invasive markers of fibrosis. METHODS: Retrospective cross-sectional international multicentre study including patients with HIV mono-infection, without chronic viral hepatitis or other known causes of chronic liver disease, who underwent liver biopsy for abnormal liver biochemistry and/or clinical suspicion of liver fibrosis. RESULTS: One hundred and sixteen patients from 5 centres were included. Sixty-three (54%) had NAFLD, of whom 57 (92%) had NASH. Overall, 36 (31%) had advanced fibrosis (≥F3) and 3 (3%) cirrhosis. Of the 53 cases without NAFLD, 15 (28%) had advanced fibrosis. Collagen proportionate area (CPA) was similar between cases with and without NAFLD (3% vs 2%). Body mass index (BMI) was independently associated with NAFLD (aOR 1.2 95% CI 1.08-1.34), and type 2 diabetes was independently associated with advanced fibrosis (aOR 3.42 95% CI 1.00-11.71)). The area under the curve for advanced fibrosis was 0.65 and 0.66 for both NAFLD Fibrosis Score (NFS) and FIB-4. Cut-off values of -1.455 (NFS) and 1.3 (FIB-4) have negative predictive values of 0.80 and 0.82, respectively. CONCLUSION: Advanced fibrosis is strongly associated with type 2 diabetes in PLWH. Serological markers require further optimisation.
Vinh VH, Shimakawa Y, Kim J, et al., 2021, Assessment and Simplification of Treatment Eligibility Among Patients With Chronic Hepatitis B Infection in Vietnam, Clinical Infectious Diseases, Vol: 73, Pages: E1072-E1077, ISSN: 1058-4838
BackgroundTreatment eligibility and the accuracy of its simplified criteria have been poorly documented in patients with chronic hepatitis B virus (HBV) infection worldwide, especially in low- and middle-income countries.MethodsFrom a cohort of HBV-infected patients in Vietnam, we assessed the proportion of patients eligible for treatment using the national guidelines based on reference tests (HBV DNA quantification and FibroScan); and the accuracy of simplified treatment criteria free from HBV DNA and FibroScan (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score and simplified World Health Organization [WHO] criteria) to select patients for antiviral therapy using the national guidelines as a reference.ResultsWe analyzed 400 consecutive treatment-naïve HBV-monoinfected patients: 49% males, median age 38 years (range, 18–86), 32% hepatitis B e antigen-positive, median HBV DNA 4.8 log10 IU/mL (undetectable −8.4), median FibroScan 5.3 kPa (3.0–67.8), and 25% having significant liver fibrosis including 12% with cirrhosis. Of these, 167 (42%) fulfilled treatment criteria according to national guidelines. Using the national criteria as a reference, the performance of TREAT-B to select patients for treatment was high (area under the receiver operating characteristic [AUROC], 0.89 [95% confidence interval 0.87-0.92]) with a sensitivity of 74.3% and a specificity of 88.4%. In a subset of patients with 2 alanine aminotransferase measurements over a 6-month period (n = 89), the AUROC of TREAT-B was significantly higher than that of the simplified WHO criteria (P < .001).ConclusionsOur study suggests that a large proportion of patients with chronic HBV infection require antiviral therapy in Vietnam. Compared with the simplified WHO criteria free from HBV DNA quantification, TREAT-B is a better alternative to easily indicate treatment eligibility and might help scale up treatment intervention in Vietnam.
Alexander JL, Powell N, 2021, SARS-CoV-2 vaccination in immunosuppressed patients with inflammatory bowel disease: should our approach change?, The Lancet Gastroenterology & Hepatology, Vol: 6, Pages: S28-S29, ISSN: 2468-1253
Lemoine M, Cooke GS, Thursz M, et al., 2021, Cuts to UK official development assistance budget jeopardise global viral hepatitis elimination goals., Lancet Gastroenterol Hepatol, Vol: 6, Pages: 527-528
Post G, Howell J, Sow A, et al., 2021, Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B, JOURNAL OF VIRAL HEPATITIS, Vol: 28, Pages: 1003-1010, ISSN: 1352-0504
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Kim JU, Ingiliz P, Shimakawa Y, et al., 2021, Improving care of migrants is key for viral hepatitis elimination in Europe, Bulletin of the World Health Organization, Vol: 99, Pages: 280-286, ISSN: 0042-9686
By 2040, deaths from chronic viral hepatitis worldwide are projected to exceed those from human immunodeficiency virus infection,tuberculosis and malaria combined. The burden of this disease is predominantly carried by low-resource countries in Africa and Asia. Inresource-rich countries, the epidemiological spread of viral hepatitis is partially driven by migrant movements from areas of high endemicity.In the last decade, Member States of the European Union and the European Economic Area have experienced an unprecedented influxof migrants, which has resulted in the polarization of political views about migration. In addition, the coronavirus disease 2019 pandemichas worsened the economic and health conditions of migrants and contributed to hostility to ensuring their health rights. Moreover, theimplementation of hostile laws in some host nations has increased the vulnerability of marginalized migrant subgroups, such as asylumseekers and undocumented individuals. These developments have complicated the historical challenge of identifying high-risk migrantgroups for screening and treatment. However, if European countries can apply the simplified assessment tools and diagnostic tests for viralhepatitis that have been used for decentralized screening and monitoring in resource-poor countries, the uptake of care by migrants couldbe dramatically increased. Given the global calls for the elimination of viral hepatitis, European nations should recognize the importance oftreating this vulnerable migrant population. Political and health strategies need to be adapted to meet this challenge and help eliminateviral hepatitis globally
Cole A, Bashyam M, Nathwani R, et al., 2021, A study evaluating outcomes of cirrhotic patients managed virtually in a specialist liver cirrhosis service due to the COVID crisis, ILC 2021, Publisher: Elsevier, Pages: S534-S534, ISSN: 0168-8278
Scott N, Mohamed Z, Rwegasha J, et al., 2021, Upscaling prevention, testing and treatment to control hepatitis C as a public health threat in Dar es Salaam, Tanzania: A cost-effectiveness model, INTERNATIONAL JOURNAL OF DRUG POLICY, Vol: 88, ISSN: 0955-3959
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- Citations: 9
Toye RM, Cohen D, Pujol FH, et al., 2021, Hepatitis B Virus Genotype Study in West Africa Reveals an Expanding Clade of Subgenotype A4, Microorganisms, Vol: 9, ISSN: 2076-2607
Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences
Nathwani R, Koeckerling D, Mullish BH, et al., 2021, Non-selective beta-blocker use in cirrhosis: the additional benefit in preventing secondary infections, Frontline Gastroenterology, Vol: 13, ISSN: 2041-4137
Yoshida K, Desbiolles A, Feldman SF, et al., 2021, Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants, CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, Vol: 19, Pages: 46-+, ISSN: 1542-3565
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- Citations: 21
McNaughton AL, Lemoine M, van Rensburg C, et al., 2020, Extending treatment eligibility for chronic hepatitis B virus infection, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 18, Pages: 146-147, ISSN: 1759-5045
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- Citations: 13
Shimakawa Y, Lemoine M, 2020, Reply to: "Validation of the TREAT-B score for hepatitis B treatment eligibility in a large Asian cohort: TREAT-B improves with age", JOURNAL OF HEPATOLOGY, Vol: 73, Pages: 1284-1285, ISSN: 0168-8278
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Lemoine M, Kim JU, Ndow G, et al., 2020, Effect of the COVID-19 pandemic on viral hepatitis services in sub-Saharan Africa, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 5, Pages: 966-967
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- Citations: 14
Forlano R, Mullish BH, Mukherjee SK, et al., 2020, In-hospital mortality is associated with inflammatory response in NAFLD patients admitted for COVID-19, PLoS One, Vol: 15, ISSN: 1932-6203
Background & aimsAlthough metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19.MethodsThis study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality.Results561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not.ConclusionThe presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.
Kim JU, Majid A, Judge R, et al., 2020, Effect of COVID-19 lockdown on alcohol consumption in patients with pre-existing alcohol use disorder, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 5, Pages: 886-+
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- Citations: 93
Forlano R, Mullish B, Mukherjee S, et al., 2020, 450 - In-hospital mortality is associated with inflammatory response in NAFLD patients admitted for COVID-19, Hepatology, Vol: 72, Pages: 282A-283A, ISSN: 0270-9139
Baudoin M, Woode ME, Nishimwe ML, et al., 2020, Long-term clinical benefits of Sofosbuvir-based direct antiviral regimens for patients with chronic hepatitis C in Central and West Africa, LIVER INTERNATIONAL, Vol: 40, Pages: 2643-2654, ISSN: 1478-3223
Mohamed Z, Scott N, Al-Kurdi D, et al., 2020, Cost-effectiveness of strategies to improve HCV screening, linkage-to-care and treatment in remand prison settings in England., Liver International, Vol: 40, Pages: 2950-2960, ISSN: 1478-3223
BACKGROUND: A simplified cascade-of-care may improve screening and treatment uptake among incarcerated individuals. We assessed the cost-effectiveness of traditional and simplified screening and treatment in a London remand prison. METHODS: Using empirical data from Her Majesty's Prison (HMP) Wormwood Scrubs, London, we designed a decision tree and Markov transition state model using national average data for HCV screening and treatment for the base-case scenario. This was compared two alternative strategies; (1) general prison population screening and treatment and (2) prioritising screening and treatment among people who inject drugs (PWID) combined with general prison population screening and treatment. Strategies varied the rates of screening (47-90%), linkage-to-care (60-86%) and treatment (21-85%). Cost, utility and disease transition rates were obtained from existing literature. Outcome measures were; screening, treatment and disease-related costs per admitted individual, quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated for each intervention. All costs and utilities were discounted at a rate of 3.5% per annum. Both univariate and probabilistic sensitivity analyses have been conducted. RESULTS: In our cohort of 5,239 incarcerated individuals with an estimated chronic HCV prevalence of 2.6%, all strategy ICER values (£3,565-10,300) fell below the national willingness to pay threshold (£30,000). Increased successful treatment (7-54%) was observed by an optimising cascade-of-care. A robust sensitivity analysis identified treatment cost of, QALY for mild liver disease and probability of completing treatment as important factors that impact the ICER value. CONCLUSION: In our remand setting, optimising adherence to the cascade-of-care is cost-effective. Where universal screening is not practical, a stratified approach focused on intensive screening and treatment of PWID also results in increased treatment
Cox AL, El-Sayed MH, Kao J-H, et al., 2020, Progress towards elimination goals for viral hepatitis, Nature Reviews Gastroenterology and Hepatology, Vol: 17, Pages: 533-542, ISSN: 1759-5045
The global burden of viral hepatitis is substantial; in terms of mortality, hepatitis B virus and hepatitis C virus infections are on a par with HIV, malaria and tuberculosis, among the top four global infectious diseases. In 2016, the 194 Member States of the World Health Organization committed to eliminating viral hepatitis as a public health threat by 2030, with a particular focus on hepatitis B virus and hepatitis C virus infection. With only 10 years to go until the 2030 deadline is reached, and although much progress has been made towards elimination, there are still some important gaps in terms of policy and progress. In this Viewpoint, we asked a selection of scientists and clinicians working in the viral hepatitis field for their opinions on whether elimination of viral hepatitis by 2030 is feasible, what the key areas of progress are and what the focus for the next 10 years and beyond should be for viral hepatitis elimination.
Nathwani R, Mukherjee S, Forlano R, et al., 2020, Letter: liver disease and COVID-19 - not the perfect storm, Alimentary Pharmacology and Therapeutics, Vol: 52, Pages: 572-574, ISSN: 0269-2813
This article is linked to Garrido et al papers. To view these articles, visit https://doi.org/10.1111/apt.15813 and https://doi.org/10.1111/apt.15886.
Cohen D, Ghosh S, Shimakawa Y, et al., 2020, Hepatitis B virus preS2 Delta 38-55 variants: A newly identified risk factor for hepatocellular carcinoma, JHEP Reports, Vol: 2, ISSN: 2589-5559
Background & AimsAlthough HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia.MethodsWe conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Consecutive treatment-naive patients with chronic HBV infection and detectable viral load were recruited: 211 controls with no significant liver disease and 91 cases (56 cirrhosis and 35 HCC cases). HBV genotypes and surface gene variants were determined by Sanger sequencing or next-generation sequencing (NGS) in serum DNA. Aflatoxin B1 (AFB1)-specific codon 249 TP53 mutation was determined by NGS in circulating cell-free plasma DNA.ResultsIn phylogenetic analysis, 85% of individuals carried HBV genotype E, 14% genotype A, and 1% A/E recombinant viruses. Surface gene variants were more frequently observed in cases (43% and 57% in cirrhosis and HCC cases, respectively) than controls (25%; p <0.001), with preS2 deletions between nucleotides 38–55 (preS2Δ38–55) being the main genetic variant detected. In multivariable analysis, HBeAg seropositivity, low HBsAg levels, and HDV seropositivity were significantly associated with cirrhosis and HCC, whilst older age, higher viral load, genotype A, preS2Δ38–55, and AFB1 exposure were only associated with HCC. There was a multiplicative joint effect of preS2Δ38–55 variants with HBeAg seropositivity (odds ratio [OR] 43.1 [10.4–177.7]), high viral load >2,000 IU/ml (OR 22.7 [8.0–64.9]), HBsAg levels <10,000 IU/ml (OR 19.0 [5.5–65.3]), and AFB1 exposure (OR 29.3 [3.7–230.4]) on HCC risk.ConclusionsThis study identified a hotspot for HBV preS2 deletions as a strong independent factor for HCC in The Gambia, with HBV genotypes and AFB1 exposure contributing to the high liver cancer risk.
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