Showing papers by "Fabien Zoulim published in 2019"
TL;DR: Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.
412 citations
University of Messina1, Lyon College2, University of Michigan3, University of Cambridge4, University of Pavia5, National Taiwan University6, Hannover Medical School7, University of Hamburg8, University of Parma9, University of Giessen10, University of the Witwatersrand11, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico12, Southern Medical University13, National Institutes of Health14, St. John's University15, University of Paris-Est16, French Institute of Health and Medical Research17, University of Hong Kong18
TL;DR: The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both the existing controversial and newly emerging aspects, and ultimately to update the statements previously agreed in 2008.
312 citations
TL;DR: Advances in hepatitis B therapies and challenges for their development are reviewed, including antiviral and immune-boosting strategies that could be part of combination strategies to achieve functional cure.
Abstract: Chronic hepatitis B virus (HBV) infection is a common cause of liver disease globally, with a disproportionately high burden in South-East Asia. Vaccines and nucleoside or nucleotide drugs are available and reduce both new infection rates and the development of liver disease in HBV-positive persons who adhere to long-term suppressive treatment. Although there is still considerable value in optimizing access to virus-suppressing regimens, the scientific and medical communities have embarked on a concerted journey to identify new antiviral drugs and immune interventions aimed at curing infection. The mechanisms and drug targets being explored are diverse; however, the field universally recognizes the importance of addressing the persistence of episomal covalently closed circular DNA, the existence of integrated HBV DNA in the host genome and the large antigen load, particularly of hepatitis B surface antigen. Another major challenge is to reinvigorate the exhausted immune response within the liver microenvironment. Ultimately, combinations of new drugs will be required to cure infection. Here we critically review the recent literature that describes the rationale for curative therapies and the resulting compounds that are being tested in clinical trials for hepatitis B.
306 citations
Royal Melbourne Hospital1, Scripps Research Institute2, University of Hamburg3, University of Toronto4, Indiana University5, Pennsylvania State University6, University of the Witwatersrand7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Istituto Italiano di Tecnologia9, Tsinghua University10, National Institutes of Health11, National University of Singapore12, Peking University13, Saint Louis University14, University of Freiburg15, French Institute of Health and Medical Research16
TL;DR: The International Coalition to Eliminate HBV (ICE-HBV) as mentioned in this paper is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, they have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure.
280 citations
TL;DR: It is demonstrated that quantification of hepatitis B core-related antigen in serum correlates with cccDNA amount and activity and could be used to monitor disease progression and develop new antiviral treatments directly targeting the intrahepatic pool of ccc DNA.
192 citations
TL;DR: The results demonstrate that tenofovir-resistant HBV mutants can emerge, although the genetic barrier is high, and reveal that the quadruple (CYEI) mutation increases the amount of ten ofovir required to inhibit HBV by 15.3-fold in IC50 and 26.3% in IC90.
102 citations
TL;DR: In an analysis of data from a large cohort of patients with HBV- or HCV-associated cirrhosis in France, the Baveno VI guidelines on screening and surveillance of PHT were validated, even for patients who achieved a sustained response to antiviral therapy.
101 citations
Stanford University1, Xi'an Jiaotong University2, Kyushu University3, Osaka City University4, Nagoya City University5, Monash University6, Kurume University7, University of Bologna8, University of Tokyo9, University of Hasselt10, University of Bari11, University of Bern12, Keio University13, Charité14, Lyon College15, Veterans Health Administration16
TL;DR: Overall, SVR was lower in HCC compared to non-HCC patients, especially in those with active HCC though heterogeneity was high, and Continued efforts are needed to aggressively screen, diagnose and treat HCC to ensure higher CHC cure rates.
62 citations
TL;DR: In patients with cirrhosis, CD8+T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID, and in comparison to their HLA-DR− counterparts, Hla-DR+CD8-T cells promoted less proliferation of PBMCs and induced phenotypesic and functional dysfunctions in monocytes and neutrophils in vitro.
47 citations
TL;DR: HBV modulates liver macrophage functions to favour its establishment and likely its maintenance, and can be recapitulated in naive liver Macrophages or monocytes-derived-macrophages ex vivo by short exposure to the virus or cells replicating the virus, thus suggesting an "easy to implement" mechanism of inhibition.
46 citations
TL;DR: In this article, the authors discuss surrogate non-invasive biomarkers for evaluating intrahepatic covalently closed circular (ccc)DNA abundance and transcriptional activity, and present their relevance for improving the classification of patients with regards to their natural history and for evaluating novel compounds to assess target engagement and to define new virological endpoints.
TL;DR: Novel treatments both targeting directly and indirectly ccc DNA, and newer technologies emerge that could potentially allow the destruction of cccDNA, exciting new possibilities for curative therapies are discussed.
Abstract: Chronic hepatitis B (CHB) infection affects over 250 millon people worldwide and 800000 are expected to die yearly due to the development of hepatocellular carcinoma (HCC). Current antiviral therapies include nucleoside analogs (NAs) that target the viral retrotranscriptase inhibiting de novo viral production. Pegylated interferon (Peg-IFN) is also effective in reducing the viral DNA load in serum. However, both treatments remain limited to control the infection, aiming for viral suppression and improving the quality of life of the infected patients. Complete cure is not possible due to the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Attempts to achieve a functional cure are thus ongoing and novel targets and molecules, together with different combination therapies are currently in the pipeline for early clinical trials. In this review we discuss novel treatments both targeting directly and indirectly cccDNA. As we gain knowledge in the Hepatitis B virus (HBV) transcriptional control, and newer technologies emerge that could potentially allow the destruction of cccDNA, exciting new possibilities for curative therapies are discussed.
TL;DR: Important advances towards a cure are being made, both in the development of a multitude of new therapeutic agents currently undergoing clinical trials, and through the establishment of a new global initiative dedicated to an HBV cure, ICE-HBV, that is working together with existing organisations to fast-track anHBV cure available to all.
Abstract: Over 257 million people live with chronic hepatitis B virus (HBV) infection and there is no known cure. The effective preventative vaccine has no impact on existing infection. Despite the existence of drugs which efficiently suppress viral replication, treatment is usually life-long and finite therapies that cure HBV infection are urgently required. However, even if such therapies were available today, it is unlikely they would reach all of those who need it most, due to chronic hepatitis B (CHB) being largely undiagnosed across the globe and to the dire need for health systems promoting access to therapy. Considerable challenges to developing and implementing an effective HBV cure remain. Nonetheless, important advances towards a cure are being made, both in the development of a multitude of new therapeutic agents currently undergoing clinical trials, and through the establishment of a new global initiative dedicated to an HBV cure, ICE-HBV, that is working together with existing organisations to fast-track an HBV cure available to all.
TL;DR: Clinical and experimental data support rtL180M+A181C+M204V as a novel non-classical ETV-resistance mutation pattern and undetectable serum HBV DNA was achieved in two of five longitudinally followed patients who received switching-to TDF therapy, but not in the other three who received add-on adefovir therapy during observation.
Abstract: Background and Aims: Entecavir (ETV) resistance of hepatitis B virus (HBV) conventionally requires rt184, 202, or 250 mutations plus lamivudine-resistance mutation (rtM204V/I ± L180M). This study a...
TL;DR: In French patients with HBV cirrhotic patients mostly virally suppressed, independent HCC risk factors were host‐related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE‐B score was the most accurate risk score.
Abstract: Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy-proven Child-Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2-year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan-Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2-year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow-up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 103 /mm3 and body mass index ≥ 30 kg/m2 . Two out of five risk scores were validated, and the most accurate was PAGE-B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host-related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE-B score was the most accurate risk score.
TL;DR: Light is shed on the ultrastructural organization of HBc aggregates to provide insight into the mechanisms of action of BAY 41-4109 against HBV and will serve as a basis for comparison with other HBV capsid assembly inhibitors.
TL;DR: HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels, in Rio Branco, Brazil.
Abstract: The clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse-transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort ( P < 0.01). Women were significantly younger (39.8 years; 8-77 years) than males (44.7 years; 12-79 years; P < 0.01). Sixty-eight (18%) patients were infected with HBV-F genotype and 264 (69.8%) with HBV/non-F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94; P = 0.015). HDV-3 was the most prevalent (88.9%) genotype. Almost 70% of HDV-3 coinfected patients were infected with HBV/non-F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV-3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.
TL;DR: Infection with hepatitis B virus genotype G has been associated with increased liver fibrosis levels compared with other genotypes in cross‐sectional studies, yet its role in fibrosis evolution remains to be established.
Abstract: INTRODUCTION Infection with hepatitis B virus (HBV) genotype G has been associated with increased liver fibrosis levels compared with other genotypes in cross-sectional studies, yet its role in fibrosis evolution remains to be established. METHODS In this prospective cohort study, 158 human immunodeficiency virus (HIV)-HBV coinfected patients had available HBV genotyping at baseline. Liver fibrosis was assessed at baseline and every 6 to 12 months by the FibroTest (BioPredictive, Paris, France). Risk factors for fibrosis regression (F3-F4 to F0-F1-F2) and progression (F0-F1-F2 to F3-F4) between baseline and end of follow-up were evaluated. RESULTS Most patients were male (88.6%) with a median age of 39 years. HBV genotype A was more prevalent compared with other HBV genotypes (62.7% vs D = 10.8%, E = 10.8%, and G = 15.8%). Patients were followed up for a median of 83 months (IQR = 37-97). In the 43 (27.2%) patients with F3-F4 baseline liver fibrosis, 7 (16.2%) regressed to F0-F1-F2 fibrosis at the last follow-up visit. In the 115 (72.8%) with F0-F1-F2 fibrosis at baseline, 19 (16.5%) progressed to F3-F4 fibrosis at last visit. In multivariable analysis, fibrosis progression was independently associated with older age (P <0.005), baseline CD4+ cell count less than 350/mm 3 ( P <0.01), longer antiretroviral therapy duration ( P <0.03), and HBV genotype G infection (vs non-G, P <0.01). When examining averages over time, the rate of FibroTest increase was faster in genotype G vs non-G-infected patients with baseline F0-F1-F2 fibrosis ( P for interaction = 0.002). CONCLUSION In HIV-HBV coinfected patients, HBV genotype G is an independent risk factor for liver fibrosis progression as determined by noninvasive markers. HBV genotype G-infected patients with low initial liver fibrosis levels may require more careful monitoring.
TL;DR: In this article, the authors present a survey on the caracteristiques des patients inclus dans ce dispositif au sein de deux centers and les results of l'enquete nationale sur la contribution des centres de soins, d'accompagnement et de prevention en addictologie (CSAPA) a ce nouvel outil de reduction des risques.
Abstract: Resume Introduction La France a autorise temporairement aux structures d’addictologie l’utilisation de la naloxone intranasale (Nalscue®) pour prevenir les deces par overdose aux opiaces. Les objectifs de ce travail sont de presenter a la fois les caracteristiques des patients inclus dans ce dispositif au sein de deux centres et les resultats de l’enquete nationale sur la contribution des centres de soins, d’accompagnement et de prevention en addictologie (CSAPA) a ce nouvel outil de reduction des risques. Methode Les donnees patients sont celles demandees dans le cadre du protocole lors de la periode d’inclusion (juillet 2016–janvier 2018). L’enquete est un questionnaire en ligne diffuse a tous les CSAPA par mail. Resultats Sur cette periode, dans les deux CSAPA, 370 kits (35 % du total national) ont ete distribues a 330 personnes dont 312 usagers dependants aux opiaces. Quinze pour cent declarent s’injecter et 85 % sont poly-consommateurs. Quatorze pour cent de l’entourage a pu etre forme a l’utilisation du Nalscue®. Quarante kits (30 donnes, 6 egares, 4 administres) ont ete renouveles a 35 usagers. Sur les 462 CSAPA contactes, 82 (18 %) ont repondu. Parmi les 76 structures prenant en charge des usagers dependants aux opiaces, deux ne se sentaient pas concernees et une ne connaissait pas l’antidote. Cinquante-cinq structures ont ete formees par le laboratoire exploitant. Trente-sept centres ont inclus un total de 947 patients (58 % de la totalite). Quarante-quatre centres ont commande 2458 boites et dispense 1116 (y compris hors autorisation temporaire d’utilisation [ATU]). Treize structures ont rapporte une utilisation du Nalscue®. Conclusion L’interet de la naloxone par voie intranasale n’est aujourd’hui plus a demontrer dans un contexte d’overdose aux opioides, mais le cadre de l’ATU n’a pas permis une diffusion majeure de l’antidote au sein de la population la plus a risque. Esperons que la mise a disposition en officine puisse favoriser sa diffusion et ainsi reduire le nombre de deces.
TL;DR: All patients with RASs detectable by next‐generation sequencing at baseline who were treatment‐eligible and treated with currently recommended drugs achieved a virological response, and the presence of pre‐existing HBV R ASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.
Abstract: Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naive patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naive patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.
TL;DR: HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication, and wider dispersion in ALT over time was associated with higher baseline HIV RNA and higher baseline HBV DNA levels.
Abstract: BACKGROUND In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent. METHODS A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Cote d'Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as 'infection' (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or 'hepatitis' (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression. RESULTS During a median 25 months (IQR 19-31), 17 (40%) patients consistently had 'infection', 5 (12%) consistently had 'hepatitis' and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p 4.0 log10 IU/mL (p=0.02). CONCLUSIONS HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.
TL;DR: A novel research approach may identify as yet unsuspected HCC risk factors that lie at the interface between neurobehavioral traits of the patient and the pathology of the organ, and may improve prediction of disease prognosis and response to personalized therapy.
Abstract: iver cancer casualties are increasing worldwide Ldespite the recent advent of adequate hepatitis B virus and hepatitis C virus therapies. Though extensive effort has been made in the past 20 years to study the effects of nonviral comorbidities on hepatocellular carcinoma (HCC), the unexplained heterogeneity of clinical evolution among patients in terms of traits and speed remains problematic for clinicians. After almost two decades of intense molecular profiling, the overall understanding of HCC development at the level of cells and tissues remains incomplete. Despite many potential therapeutic options, several drugs have failed to exceed the efficacy of the currently available compounds in phase III trials, indicating a need for novel targets and renewed approaches for studying the disease. Indeed, although the major contribution of hepatocytes, and the implication of activated hepatic stellate cells and immune cells, is well documented in HCC, other cell types including intrahepatic neurons have seldom been studied. These latter lie at the interface between neurobehavioral traits of the patient and the pathology of the organ, and may thus improve prediction of disease prognosis and response to personalized (ie, tailor-made) therapy. Furthermore, keeping in mind that, in general oncology, 60% of patients develop cancers for reasons as yet unknown, once likely risk factors (eg, predisposing congenital mutations, smoking, alcohol consumption) have been considered, this novel research approach may identify as yet unsuspected HCC risk factors.
TL;DR: The Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC, and uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies.
Abstract: Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016 From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies
Paris Descartes University1, University of Paris2, French Institute of Health and Medical Research3, University of Lyon4, Paris Diderot University5, Pierre-and-Marie-Curie University6, Sorbonne7, University of Lorraine8, Metz9, Centre national de la recherche scientifique10, University of Rennes11, University of Paris-Sud12
TL;DR: In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/−ribavirin combination appears to be efficient and safe.
Abstract: Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients. Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician. Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naive for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported. In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/−ribavirin combination appears to be efficient and safe. Trial registration with ClinicalTrials.gov NCT01953458
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TL;DR: Results indicate that LARP1 binds to HCV, an event associated with retention of intracellular infectivity, which is unrelated to changes in the hepatocyte secretory pathway.
TL;DR: This work aimed to identify S‐gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa.
Abstract: Background & aims Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Methods Seventy-three antiretroviral treatment (ART)-naive human immunodeficiency virus (HIV)-HBV co-infected patients from Cote d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Results Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Conclusion Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.
TL;DR: Prolifica as discussed by the authors is a program europeen Prolifica, which mettre en place les approches de depistage et traitement des patients porteurs du HBV for en prevenir les complications, en particulier le CHC.
Abstract: Malgre l’existence d’un vaccin efficace, le virus de l’hepatite B infecte 257 millions de personnes a travers le monde et engendre la majorite des cas de carcinome hepatocellulaire (le deuxieme cancer le plus meurtrier). Les pays a faibles ressources sont les plus atteints comme ceux d’Afrique subsaharienne ou l’acces a un systeme de sante est restreint. Pour pallier cela, le programme europeen Prolifica a contribue a mettre en place les approches de depistage et de traitement des patients porteurs du HBV pour en prevenir les complications, en particulier le CHC. Ces travaux ont permis de demontrer la faisabilite et l’aspect « cout efficace » d’un tel programme. Prolifica a genere des donnees d’une importance cruciale pour mieux connaitre les infections HBV en Afrique de l’Ouest et fournir les bases d’une meilleure prise en charge des patients.
TL;DR: Le programme europeen Prolifica a contribue a mettre en place les approches de depistage and de traitement des patients porteurs du HBV pour en prevenir les complications, en particulier le CHC.
Abstract: Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC. With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest. Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare. To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC. Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016. From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies.