Publications
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Lemoine M, Thursz MR, 2016, Field battle against hepatitis B infection and HCC in Africa, Journal of Hepatology, Vol: 66, Pages: 645-654, ISSN: 1600-0641
Despite effective and safe HBV vaccine and antiviral therapies, HBV-related hepatocellular carcinoma remains a major cause of deaths in young adults in Africa. Barriers to control the burden of HBV infection and HCC are multiple. In comparison to other major infectious diseases, hepatitis B virus infection and liver diseases have received remarkably little attention from the global health community. Improving birth dose vaccine coverage and implementing screening and treatment interventions are urgently needed. This requires a dramatic simplification of the management of chronic hepatitis B in Africa with access to reliable, robust and inexpensive diagnostic tools but also strong support from the local governments and the international health community. This review analyses 1) the characteristics of HBV viral hepatitis and HCC epidemics in Africa and 2) the barriers and requested solutions to control it.
Lemoine MN, Shimakawa Y, Njie R, et al., 2016, Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study, Lancet Global Health, Vol: 4, Pages: e559-e567, ISSN: 2214-109X
BackgroundDespite the introduction of immunisation for hepatitis B virus (HBV) in the 1990s, HBV-related morbidity and mortality remain high in sub-Saharan Africa. Identification and treatment of asymptomatic people with chronic HBV infection should reduce the disease burden. We therefore assessed the feasibility of a screen-and-treat programme for HBV infection in The Gambia, west Africa, and estimated the proportion of HBV-infected people who had significant liver disease in need of treatment.MethodsBetween Dec 7, 2011, and Jan 24, 2014, individuals living in randomly selected communities in western Gambia were offered hepatitis B surface antigen (HBsAg) screening via a point-of-care test. The test was also offered to potential blood donors attending the central hospital in the capital, Banjul. HBsAg-positive individuals were invited for a comprehensive liver assessment and were offered treatment according to international guidelines. We defined linkage to care as visiting the liver clinic at least once. Eligibility for treatment was judged in accordance with the 2012 European Association for the Study of the Liver guidelines.FindingsHBsAg screening was accepted by 5980 (weighted estimate 68·9%, 95% CI 65·0–72·4) of 8170 adults from 27 rural and 27 urban communities and 5559 (81·4%, 80·4–82·3) of 6832 blood donors. HBsAg was detected in 495 (8·8%, 7·9–9·7) individuals in communities and 721 (13·0%, 12·1–13·9) blood donors. Prevalence was higher in men (239 [10·5%, 8·9–12·1] of 2328 men vs 256 [7·6%, 6·5–8·7] of 3652 women; p=0·004) and middle-aged participants. Linkage to care was high in the communities, with 402 (81·3%) of 495 HBsAg-positive individuals attending the clinic. However, only 300 (41·6%) of 721 HBsAg-positive people screened at the blood bank linked into care. Of those
Nayagam S, Conteh L, Sicuri E, et al., 2016, Cost-effectiveness of community-based screening and treatment for chronic hepatitis B in The Gambia: an economic modelling analysis, Lancet Global Health, Vol: 4, Pages: e568-e578, ISSN: 2214-109X
Background: Despite the high burden of hepatitis B virus (HBV)infection in sub-Saharan Africa (SSA), a lack of access to widespreadscreening or treatment leads to most people remaining undiagnosed untillater stages of disease when prognosis is poor and treatment options arelimited. We evaluated the cost-effectiveness of community-based screeningand early treatment with antiviral therapy for HBV in The Gambia.Methods: An economic evaluation comparing adult community-based screeningusing a Hepatitis B surface antigen (HBsAg) rapid test and subsequent HBVantiviral therapy to a status quo scenario, where no treatment isavailable, was performed by combining a decision tree with a Markov statetransition model. This was parameterised with primary screening and costdata from the PROLIFICA study. A health provider perspective was takenand costs and health outcomes were discounted at 3% per annum.Findings: In The Gambia, where the HBsAg prevalence is 8.8% among thoseaged over 30 years old, adult screening and treatment for HBV, has anIncremental Cost-Effectiveness Ratio (ICER) of $540 per DisabilityAdjusted Life Year (DALY) averted, $645 per Life Year (LY) saved and $511per Quality Adjusted Life Year (QALY) gained, compared to status quo.These ICERs are in line with willingness-to-pay levels of one times thecountry's Gross Domestic Product (GDP) per capita ($487) per DALYaverted, whilst remaining robust, over a wide range of epidemiologicaland cost parameters.Interpretation: Adult community-based screening and treatment for HBV inthe Gambia is likely to be a cost-effective intervention with an ICERthat is comparable with those of HIV screening and treatmentinterventions in SSA. Even higher cost-effectiveness, may be achievablewith targeted facility-based screening, price reductions of drug and diagnostics and integration of HBV screening with other public healthinterventions.
Lemoine M, Shimakawa Y, Nayagam S, et al., 2016, The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa, Gut, Vol: 65, Pages: 1369-1376, ISSN: 1468-3288
BACKGROUND: Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa. METHODS: Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets). RESULTS: Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4. CONCLUSIONS: The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa.
Tam NT, Laureillard D, Lacombe K, et al., 2016, High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262), PLOS One, Vol: 11, ISSN: 1932-6203
Rationale and AimsScreening and treatment for chronic hepatitis C are very limited in Vietnam and clinical data on HCV-related liver disease in HIV-coinfected people are almost inexistent. This study aimed to assess the severity of liver fibrosis and its risk factors in HIV-HCV coinfected patients in Haiphong, Northern Vietnam.MethodsA cross-sectional study was conducted at a HIV outpatient clinic. Consecutive HIV treated adults with positive HCV serology completed a standardised epidemiological questionnaire and had a comprehensive liver assessment including hepatic elastography (Fibroscan®, Echosens).ResultsFrom February to March 2014, 104 HIV-HCV coinfected patients receiving antiretroviral therapy (ART) were prospectively enrolled (99 males, median age: 35.8 (32.7–39.6) years, median CD4 count: 504 (361–624) /mm3. Of them, 93 (89.4%) had detectable HCV RNA (median 6.19 (4.95–6.83 Log10 IU/mL). Patients were mainly infected with genotypes 1a/1b (69%) and genotypes 6a/6e (26%). Forty-three patients (41.3%) had fibrosis ≥F2 including 24 patients (23.1%) with extensive fibrosis (F3) and/or cirrhosis (F4). In univariate analysis, excessive alcohol consumption, estimated time duration from HCV infection, nevirapine and lopinavir-based ARV regimen and CD4 nadir were associated factors of extensive fibrosis/cirrhosis. Alcohol abuse was the only independent factor of extensive fibrosis in multivariate analysis. Using Fibroscan® as a gold standard, the high thresholds of AST-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4) had very good performances for the diagnosis of extensive fibrosis/cirrhosis (Se: 90 and 100%, Sp:84 and 81%, AUROCs = 0.93, 95%CI: 0.86–0.99 and 0.96 (0.92–0.99), respectively).ConclusionIn this study, nearly 25% of HIV-HCV coinfected patients successfully treated with ART have extensive fibrosis or cirrhosis, and therefore require urgently HCV treatment.
Lemoine M, Thursz M, Mallet V, et al., 2016, Diagnostic accuracy of the gamma-glutamyl transpeptidase to platelet ratio (GPR) using transient elastography as a reference, GUT, Vol: 66, Pages: 195-+, ISSN: 0017-5749
Shimakawa Y, Njai HF, Takahashi K, et al., 2016, Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 43, Pages: 375-384, ISSN: 0269-2813
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- Citations: 13
Stockdale AJ, Phillips RO, Geretti AM, 2016, The gamma-glutamyl transpeptidase to platelet ratio (GPR) shows poor correlation with transient elastography measurements of liver fibrosis in HIV-positive patients with chronic hepatitis B in West Africa. Response to: ‘The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa’ by Lemoine et al, Gut, Vol: 65, Pages: 882-884, ISSN: 0017-5749
Shimakawa Y, Toure-Kane C, Mendy M, et al., 2016, Mother-to-child transmission of hepatitis B in sub-Saharan Africa, Lancet Infectious Diseases, Vol: 16, Pages: 19-20, ISSN: 1473-3099
Lemoine M, Chevaliez S, Bastard JP, et al., 2015, Association between <i>IL28B</i> polymorphism, TNF and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance, JOURNAL OF VIRAL HEPATITIS, Vol: 22, Pages: 890-896, ISSN: 1352-0504
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- Citations: 6
Shimakawa Y, Lemoine M, Bottomley C, et al., 2015, Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia, LIVER INTERNATIONAL, Vol: 35, Pages: 2318-2326, ISSN: 1478-3223
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- Citations: 30
Cohn J, Roberts T, Amorosa V, et al., 2015, Simplified diagnostic monitoring for hepatitis C, in the new era of direct-acting antiviral treatment, CURRENT OPINION IN HIV AND AIDS, Vol: 10, Pages: 369-373, ISSN: 1746-630X
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- Citations: 25
Johannessen A, Lemoine M, 2015, Is aspartate aminotransferase-to-platelet ratio index a reliable tool in human immunodeficiency virus patients in Africa?, LIVER INTERNATIONAL, Vol: 35, Pages: 2059-2059, ISSN: 1478-3223
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- Citations: 4
Howell J, Ladep NG, Nayagam S, et al., 2015, PROLIFICA: A story of West African clinical and research collaborations to target hepatitis B-related hepatocellular carcinoma in West Africa, QJM-an International Journal of Medicine, Vol: 109, Pages: 373-375, ISSN: 1460-2725
Shimakawa Y, Lemoine M, Bottomley C, et al., 2015, NATURAL HISTORY OF CHRONIC HEPATITIS B INFECTION IN THE GAMBIA, WEST AFRICA: A LONGITUDINAL POPULATION-BASED STUDY, 50th International Liver Congress of the European-Association-for-the-Study-of-the-Liver, Publisher: ELSEVIER SCIENCE BV, Pages: S540-S541, ISSN: 0168-8278
Lemoine M, Thursz M, 2015, Viral hepatitis: Scaling up HCV treatment in resource-limited countries., Nat Rev Gastroenterol Hepatol, Vol: 12, Pages: 193-194
Njai HF, Shimakawa Y, Sanneh B, et al., 2015, Validation of Rapid Point-of-Care (POC) Tests for Detection of Hepatitis B Surface Antigen in Field and Laboratory Settings in the Gambia, Western Africa, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 53, Pages: 1156-1163, ISSN: 0095-1137
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- Citations: 70
Lemoine M, Thursz M, 2015, VIRAL HEPATITIS Scaling up HCV treatment in resource-limited countries, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 12, Pages: 193-194, ISSN: 1759-5045
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- Citations: 4
Shimakawa Y, Takao Y, Anderson ST, et al., 2015, The prevalence and burden of symptoms in patients with chronic liver diseases in The Gambia, West Africa, PALLIATIVE MEDICINE, Vol: 29, Pages: 184-185, ISSN: 0269-2163
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- Citations: 9
Lemoine M, Eholie S, Lacombe K, 2015, Reducing the neglected burden of viral hepatitis in Africa: Strategies for a global approach, JOURNAL OF HEPATOLOGY, Vol: 62, Pages: 469-476, ISSN: 0168-8278
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- Citations: 79
Howell J, Ladep NG, Lemoine M, et al., 2015, Prevention of Liver Fibrosis and Cancer in Africa: The PROLIFICA project - a collaborative study of hepatitis B-related liver disease in West Africa, SAMJ South African Medical Journal, Vol: 105, Pages: 185-186, ISSN: 0256-9574
Ladep NG, Lesi OA, Mark P, et al., 2014, Problem of hepatocellular carcinoma in West Africa., World J Hepatol, Vol: 6, Pages: 783-792, ISSN: 1948-5182
The incidence of hepatocellular carcinoma (HCC) is known to be high in West Africa with an approximate yearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B (HBV), environmental food contaminants (aflatoxins), poor management of predisposing risk factors and poorly-managed strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include: (1) high rate of risk factors; (2) failure to identify at risk populations; (3) lack of effective treatment; and (4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.
Howell J, Van Gemert C, Lemoine M, et al., 2014, An overview of hepatitis B prevalence, prevention, and management in the Pacific Islands and Territories, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol: 29, Pages: 1854-1866, ISSN: 0815-9319
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- Citations: 15
Ladep NG, Dona AC, Lewis MR, et al., 2014, Discovery and Validation of Urinary Metabotypes for the Diagnosis of Hepatocellular Carcinoma in West Africans, HEPATOLOGY, Vol: 60, Pages: 1291-1301, ISSN: 0270-9139
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- Citations: 59
Howell J, Ladep NG, Lemoine M, et al., 2014, Hepatitis B: A global health dilemma, EuroAsian Journal of Hepato-Gastroenterology, Vol: 1, Pages: v-vi, ISSN: 2231-5047
Howell J, Ladep NG, Lemoine M, et al., 2014, Hepatitis B in sub-Saharan Africa., South Sudan Medical Journal, Vol: 7, Pages: 59-61, ISSN: 2309-4613
Hepatitis B virus (HBV) infection causes a spectrum ofacute and chronic liver disease, ranging from inactivechronic carrier status to progressive chronic hepatitis,leading to end-stage cirrhosis and primary liver cancer.In sub-Saharan Africa, over 8% of the population haschronic HBV carriage with a high risk for progressive liverdisease. HBV-related hepatocellular carcinoma is the mostcommon cancer among men and third most commonamong women. HBV therefore represents a critical threatto health in the African continent.
Shimakawa Y, Lemoine M, Mendy M, et al., 2014, Population-based interventions to reduce the public health burden related with hepatitis B virus infection in the gambia, west Africa., Trop Med Health, Vol: 42, Pages: 59-64, ISSN: 1348-8945
In The Gambia, West Africa, the prevalence of chronic hepatitis B virus (HBV) infection in adults exceeds eight percent and hepatocellular carcinoma (HCC) has been the most frequent type of malignancy. Two population-based intervention studies to control HBV infection, namely, GHIS (Gambia Hepatitis Intervention Study) and PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa), are discussed. The GHIS started in 1986 as a nation-wide trial of the HBV vaccine to evaluate the effectiveness of infant HBV vaccination in preventing HCC in adulthood. The vaccine was progressively introduced into the Expanded Program of Immunization (EPI) of The Gambia over four years in a phased manner, called the "stepped-wedge" design. This was because instantaneous universal vaccination in the country was impossible for logistic and financial reasons. However, this design also allowed the study to have an unvaccinated control group which consisted of the newborns of the areas where HBV vaccine has not yet been incorporated in the EPI. To assess the outcome, a national cancer registry was founded and all HCC patients in this birth cohort are linked with the vaccine trial database. The study is still ongoing to answer whether the HBV vaccine in infancy prevent HCC in adulthood in The Gambia. Although the universal HBV vaccination since 1990 has been successful in reducing the prevalence of chronic HBV infection in young Gambians, the number of HCC cases may not decline over the next decades as people infected prior to the immunization program are likely to continue to develop the diseases. To reduce the HCC incidence through community-based screening of HBV infection and provision of antiviral therapy, the PROLIFICA project started in 2011. Study hypothesis and design of these two studies, GHIS and PROLIFICA, are further discussed.
Howell J, Lemoine M, Thursz M, 2014, Prevention of materno-foetal transmission of hepatitis B in sub-Saharan Africa: the evidence, current practice and future challenges, JOURNAL OF VIRAL HEPATITIS, Vol: 21, Pages: 381-396, ISSN: 1352-0504
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- Citations: 34
Njai HF, Ceesay A, Bayzid N, et al., 2014, Virological profiles of hepatitis B virus (HBV)-infected African patients treated with tenofovir, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 21, Pages: 8-8, ISSN: 1201-9712
Njai HF, Shimakawa Y, Ferguson L, et al., 2014, Validation of hepatitis B surface antigen (HBsAg) rapid test to screen HBV infection in rural Gambia, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 21, Pages: 271-271, ISSN: 1201-9712
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