The rs429358 locus in apolipoprotein E is associated with hepatocellular carcinoma in patients with cirrhosis

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P=2.9×10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P=3.1×10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P=0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P=0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis

Hépatite C: contribution à l'évaluation de l'histoire naturelle et à la prise en charge thérapeutique de l'hépatite chronique

L’hétérogénéité de l’histoire naturelle de l’hépatite C est expliquée par l’existence de facteurs environnementaux ou liés au malade qui influencent l’évolution de la maladie. L’obtention d’une réponse virologique soutenue est l’objectif principal de la prise en charge thérapeutique car c’est la seule façon de réduire l’incidence de la cirrhose et la mortalité liée au virus de l’hépatite C. Pour être efficaces, les stratégies thérapeutiques doivent être élaborées à deux niveaux. A l’échelle individuelle, elles doivent optimaliser les chances de réponse virologique tout en limitant l’exposition aux effets secondaires. A l’échelle d’une population, la meilleure stratégie est celle qui aura l’impact le plus important sur l’incidence de la cirrhose et sur la mortalité liées au virus de l’hépatite C.Les travaux réalisés dans le cadre de cette thèse ont permis d’identifier des critères virologiques autorisant l’arrêt d’un traitement inefficace dès le terme de la 4ème semaine chez les malades présentant des transaminases normales et chez les malades non répondeurs à un premier traitement, de quantifier la perte de chance de réponse virologique lorsque la durée du traitement est limitée à 24 semaines chez les malades infectés par un génotype 1, d’évaluer la place de l’amantadine dans l’arsenal thérapeutique, de quantifier l’impact d’une insulino-résistance sur le taux de réponse virologique, de contribuer à l’élaboration d’une stratégie thérapeutique permettant une meilleure tolérance hématologique chez les malades hémodialysés et de quantifier l’impact des polymorphismes de l’interleukine 28B sur le taux réponse virologique des malades infectés par un génotype 2 ou 3. Nos travaux ont également permis de mesurer l’impact d’une consommation excessive d’alcool sur la morbi-mortalité liée au virus de l’hépatite C à l’échelle d’une population et de quantifier l’impact des mesures thérapeutiques actuelles et de stratégies thérapeutiques alternatives sur cette morbi-mortalité. Au cours de la prochaine décennie, le traitement de l’hépatite chronique C sera articulé autour des molécules antivirales spécifiques agissant directement contre le virus de l’hépatite C. De nouvelles stratégies thérapeutiques intégrant la cinétique virale et les marqueurs génétiques prédictifs de la réponse virologique soutenue devront être élaborées afin d’offrir les meilleures chances d’éradication virologique au plus grand nombre de malades.Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Prognostic value of histologic parameters in alcoholic hepatitis: a word of caution.

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Prise en charge de l'hépatite C chronique en 2012 en Belgique.

Chronic hepatitis C virus infection is a major public health problem. It is estimated that 15 to 35% of infected patients will develop cirrhosis after a period of 30 years. Fibrosis stage must be evaluated in all hepatitis-C-infected patients. Noninvasive methods for the evaluation of liver fibrosis have been developed, mainly serum markers and transient elastography or Fibroscan. The goal of therapy is to achieve a sustained virological response, defined by hepatitis C RNA undetectable in serum 6 months after the end of therapy. This indicates viral eradication. Treatment of chronic hepatitis C has considerably improved. The association of pegylated interferon with ribavirin remains the standard of care for non-genotype-1-infected patients. Genotype-1-infected patients (who represent the majority of cases) are preferentially treated by triple therapy pegylated interferon plus ribavirin plus a first generation protease inhibitor (telaprevir or boceprevir). While triple therapy represents a major advance, by increasing the possibility of viral eradication, such therapy also presents new challenges, including the need for strict compliance, risk of additional side effects and development of resistant variants, drug-drug interactions, etc. which call for first-rate expertise in management of chronic hepatitis C therapy. Several new antiviral compounds are currently in clinical development and might lead to viral eradication in the vast majority of infected patients in the near future.English AbstractJournal ArticleReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

BAEP wave V latency-intensity curve and rarefaction-condensation differential potentials in dogs during maturation of the auditory system

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Progressive cholangiopathy in COVID-19 patients: Other possible diagnoses than ketamine-induced cholangiopathy should be considered

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The concept of MAFLD gathers patients with distinct disease progression trajectories.

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Outcomes after early liver transplantation for patients with severe alcoholic hepatitis: Additional evidence from a meta-analysis.

Dear Editors: We read with interest the article from Lee et al1 about early liver transplantation for severe alcoholic hepatitis. We compliment them for their exhaustive collection of data on patients transplanted for alcoholic hepatitis across the United States in the retrospective ACCELARATE-AH study. We would like to add some comments that may contribute to the debate on this hot topic. [...