Inborn errors of type I interferon immunity in patients with symptomatic acute hepatitis E.

BACKGROUND AND AIMS: The clinical spectrum of human infection by HEV ranges from asymptomatic to severe acute hepatitis. Furthermore, HEV can cause diverse neurological manifestations, especially Parsonage-Turner syndrome. Here, we used a large-scale human genomic approach to search for genetic determinants of severe clinical presentations of HEV infection. APPROACH AND RESULTS: We performed whole genome sequencing in 3 groups of study participants with PCR-proven acute HEV infection: (1) 24 patients with symptomatic acute hepatitis E; (2) 12 patients with HEV-associated Parsonage-Turner syndrome; and (3) 16 asymptomatic blood donors (controls). For variant calling and annotation, we used GATK4 best practices followed by Variant Effect Predictor (VEP) and Annovar. For variant classification, we implemented the American College of Medical Genetics and Genomics/Association for Molecular Pathology Bayesian classification framework in R. Variants with a probability of pathogenicity >0.9 were considered damaging. We used all genes with at least 1 damaging variant as input for pathway enrichment analyses.We observed a significant enrichment of type I interferon response pathways in the symptomatic hepatitis group: 10 out of 24 patients carried a damaging variant in one of 9 genes encoding either intracellular viral sensors ( IFIH1 , DDX58 , TLR3 , POLR3B , POLR3C ) or other molecules involved in type I interferon response [interferon regulatory factor 7 ( IRF7 ), MYD88 , OAS3 , GAPDH ]. We did not find any enriched pathway in the Parsonage-Turner syndrome group or in the controls. CONCLUSIONS: Our results highlight the essential role of type I interferon in preventing symptomatic acute hepatitis E.

[Gastroenterology and hepatology: what's new in 2023]. / Gastroentérologie et hépatologie: ce qui a changé en 2023.

2023 has been marked by numerous advancements in the fields of hepatology, liver transplantation, gastroenterology, and interventional endoscopy. These developments hold the promise of changing our daily practice while enhancing the diagnosis and treatment of various hepatic and gastroenterological conditions. Additionally, the European Association for the Study of the Liver (EASL) has issued recommendations for the management of hepatitis delta, acute-on-chronic liver failure, liver diseases of pregnancy, and intrahepatic cholangiocarcinoma. Risankizumab was approved by Swiss Authorities for patients with Crohn's disease and dupilumab was approved for patients with eosinophilic esophagitis. The European Society of Gastrointestinal Endoscopy (ESGE) has revised its recommendations regarding Barrett's esophagus.

2023 a été marquée par de nombreuses avancées dans le domaine de l'hépatologie, de la transplantation hépatique, de la gastroentérologie et de l'endoscopie interventionnelle. Ces développements promettent de changer notre pratique quotidienne dans le but d'améliorer le diagnostic et le traitement de nombreuses affections hépatiques et gastroentérologiques. En outre, la Société européenne d'hépatologie (EASL) a émis des recommandations pour la prise en charge de l'hépatite delta, de l'insuffisance hépatique aiguë sur chronique, des complications hépatiques de la grossesse et du cholangiocarcinome intrahépatique. Le risankizumab a été approuvé par Swissmedic pour le traitement de la maladie de Crohn et le dupilumab pour les patients avec œsophagite à éosinophiles. La Société européenne d'endoscopie a mis à jour ses recommandations concernant l'œsophage de Barrett.

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening.

OBJECTIVES: This study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha foetoprotein (AFP) and dynamic contrast-enhanced (Dyn)-AMRI. METHODS: This retrospective single-center study included 351 patients (M/F: 264/87, mean age: 57y) with chronic liver disease, who underwent MRI for HCC surveillance between 2014 and 2020. Two reconstructed AMRI sets were obtained based on complete MRI: NC-AMRI (T2-weighted imaging (WI) + diffusion-WI) and Dyn-AMRI (T2-WI + dynamic T1-WI) and were assessed by 2 radiologists who reported all suspicious lesions, using LI-RADS/adapted LI-RADS classification. The reference standard was based on all available patient data. Inter-reader agreement was assessed and MRI diagnostic performance was compared to the reference standard. RESULTS: The reference standard demonstrated 83/351 HCC-positive patients (prevalence: 23.6%, median size: 22 mm, and positive MRIs: 83/631). Inter-reader agreement was substantial for all sets. Sensitivities of Dyn-AMRI and complete MRI (both 92.8%) were similar, higher than NC-AMRI (72.3%, p < 0.001). Specificities were not different between sets. NC-AMRI + AFP (92.8%) had similar sensitivity to Dyn-AMRI and complete MRI. In patients with small size HCCs (≤ 2 cm), sensitivities of Dyn-AMRI (85.3%) and complete MRI (88.2%) remained similar (p = 0.564), also outperforming NC-AMRI (52.9%, p < 0.05). NC-AMRI + AFP had similar sensitivity (88.2%) to Dyn-AMRI and complete MRI (p = 0.706 and p = 1, respectively). CONCLUSIONS: Dyn-AMRI has similar diagnostic performance to complete MRI for HCC detection, while both outperform NC-AMRI, especially for small size HCCs. NC-AMRI + AFP demonstrates similar sensitivity to Dyn-AMRI and complete MRI. CLINICAL RELEVANCE STATEMENT: Due to the low sensitivity of ultrasound for hepatocellular screening, new screening methods are needed. Abbreviated MRI (AMRI) is a candidate, especially non-contrast AMRI with serum alpha foetoprotein as the acquisition time is low, without the need for contrast medium injection. KEY POINTS: • Dynamic contrast-enhanced abbreviated MRI using extracellular gadolinium-based contrast agent and complete MRI have similar diagnostic performance for hepatocellular carcinoma detection in an at-risk population. • Non-contrast abbreviated MRI with alpha foetoprotein has similar diagnostic performance to dynamic contrast-enhanced abbreviated MRI and complete MRI, including when considering small size hepatocellular carcinoma ≤ 2 cm. • Non-contrast abbreviated MRI and dynamic contrast-enhanced abbreviated MRI can be performed in 7 and 10 min, excluding patient setup time.

[Gastroenterology and hepatology: what's new in 2022]. / Gastroentérologie et hépatologie : ce qui a changé en 2022.

The field of gastroenterology and hepatology is evolving constantly. In 2022, numerous landmark studies have been published in all its subspecialities including hepatology, functional diseases, interventional endoscopy, and inflammatory bowel disease. Among the most significant advances are the antiviral treatment for hepatitis D, the new Chicago classification version 4 for esophageal motility disorders, the first biological treatment for eosinophilic esophagitis, a randomized controlled trial about the efficacy of screening colonoscopy, novel endoscopic techniques such as G-POEM or endoscopic sleeve gastrectomy, and emerging IBD therapies such as ozanimod, upadacitinib or anti-IL23 antibodies.

La gastroentérologie et l'hépatologie sont des disciplines variées et en pleine évolution. Durant l'année 2022, plusieurs études marquantes ont été publiées dans les domaines de l'hépatologie, des maladies fonctionnelles, de l'endoscopie et des maladies inflammatoires chroniques de l'intestin (MICI). Les avancées les plus importantes sont le traitement antiviral contre l'hépatite D, la nouvelle classification de Chicago version 4 pour les troubles moteurs œsophagiens, le traitement biologique de l'œsophagite à éosinophiles, l'efficacité de la coloscopie de dépistage, de nouvelles techniques endoscopiques comme le G-POEM ou la gastrectomie endoscopique et des nouveaux médicaments pour les MICI comme l'ozanimod, l'upadacitinib ou les anticorps anti-IL-23.

Humoral response to SARS-CoV-2 infection among liver transplant recipients.

OBJECTIVE: Immunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19. DESIGN: Prospective multicentre case-control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT). RESULTS: Overall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024). CONCLUSIONS: Our findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

[Short telomere syndrome in adults: a rare entity that should be evoked]. / Syndrome des télomères courts chez l'adulte†: une entité rare qu'il faut savoir évoquer.

Short telomere syndrome (STS) is a group of rare, often underrecognized, diseases caused by defects in telomere-maintenance genes, leading to abnormal telomere shortening and associated with diverse multi-organ manifestations. In pediatric patients, STS typically presents with mucocutaneous or gastrointestinal lesions, bone marrow failure and neoplasia. In adulthood, aplastic bone marrow disease, liver disease and pulmonary fibrosis are classic clinical manifestations. At present, medical treatment options for STS remain limited. Danazol, a synthetic androgenic hormone, can slow down telomere shortening and thus limit the progression of the disease. Finally, hematopoietic, hepatic and pulmonary transplantation, sometimes combined, may be discussed in a multidisciplinary setting in certain situations.

Le syndrome des télomères courts (STC) est un groupe de maladies rares dues à un défaut dans les gènes de maintenance des télomères, provoquant leur raccourcissement anormal et des manifestations cliniques multiorganiques. Dans l'enfance, le STC se présente par des lésions mucocutanées et gastro-intestinales, une insuffisance médullaire et des néoplasies. À l'âge adulte, une atteinte médullaire aplasiante, hépatique, et une fibrose pulmonaire sont des manifestations cliniques classiques. Les options thérapeutiques pour le STC restent limitées. Le danazol, une hormone androgène synthétique, permet, parfois, de freiner le raccourcissement télomérique et de limiter la progression de la maladie. Finalement, les transplantations hématopoïétique, hépatique et pulmonaire sont discutées dans certaines situations de manière multidisciplinaire.

The histologic presentation of hepatitis E reflects patients' immune status and pre-existing liver condition.

Infection with the hepatitis E virus (HEV) is one of the main causes of acute hepatitis worldwide. Given that, the histopathology of hepatitis E is relatively poorly characterized, and it is unclear what exactly determines its remarkable variability. The aim of our study was a systematic analysis of hepatitis E histology, especially with regard to the clinical setting. Fifty-two liver samples (48 biopsies, 1 liver explant, 3 autopsy livers) from 41 patients with molecularly proven hepatitis E (28 HEV genotype (gt) 3, three gt 1, one gt 4 and 9 undetermined gt) were systematically evaluated for 33 histopathologic features. Following one approach, the biopsies were assigned to one of five generic histologic patterns. In another approach, they were subjected to hierarchical clustering. We found that 23/41 (56%) patients were immunocompromised, whereas 18 (44%) had no known immunosuppression. Five patients (12%) had pre-existing liver disease (LD). The histopathologic spectrum ranged from almost normal to acute, chronic, and steato-hepatitis to subtotal necrosis, and was thus distributed across all five generic patterns. Hierarchical clustering, however, identified three histopathologic clusters (C1-C3), which segregated along the immune status and pre-existing LD: C1 comprised mostly patients with pre-existing LD; histology mainly reflected the respective LD without pointing to the additional hepatitis E. C2 comprised mostly immunocompetent patients; histology mainly displayed florid hepatitis. C3 comprised mostly immunocompromised patients; histology mainly displayed smoldering hepatitis. Accordingly, C1-C3 differed markedly with respect to their clinical and histopathologic differential diagnoses. Hierarchical clustering suggests three groups with distinct histopathologies, indicating biologically different manifestations of hepatitis E. The association of histopathologic changes with the patient's immune status and pre-existing LD plausibly explains the diversity of hepatitis E histopathology, and suggests that these factors are the crucial underlying determinants. We expect our results to improve patient management by guiding the clinico-pathologic diagnosis of hepatitis E.

Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis.

In the setting of liver cirrhosis (LC), profound hemostatic changes occur, which affect primary hemostasis, coagulation, and fibrinolysis. They involve prohemorrhagic and prothrombotic alterations at each of these steps. Patients with cirrhosis exhibit multifactorial thrombocytopenia and in vitro thrombocytopathy, counterbalanced by increased von Willebrand factor. The resultant shift is difficult to assess, but overall these changes probably result in a rebalanced primary hemostasis. Concerning coagulation, the reduced activity of coagulation factors is counterbalanced by an increase in factor VIII (produced by liver sinusoidal endothelial cells), a decrease of the natural anticoagulants, and complex changes, including changes in circulating microparticles, cell-free DNA, and neutrophil extracellular traps. Overall, these alterations result in a procoagulant state. As for fibrinolysis, increased tissue-type and urokinase-type plasminogen activators, a relatively decreased plasminogen activator inhibitor 1, and decreased levels of thrombin-activatable fibrinolysis inhibitor and α2-antiplasmin are counterbalanced by decreased plasminogen and a decreased fibrin clot permeability. Whether and how these changes shift fibrinolysis remains to be determined. Overall, the current consensus is that in patients with cirrhosis, the hemostasis is shifted toward a procoagulant state. We review the published evidence for the concept of LC as a prothrombotic state, discuss discordant data, and highlight the impact of the underlying cause of LC on the resultant imbalance.

[Advances in gastroenterology and hepatology 2020]. / Gastroentérologie et hépatologie.

The year 2020 has been dominated by the coronavirus disease 2019 (COVID-19) pandemic, with important lessons learned also in gastroenterology and hepatology. Major advances, however, have also been made in other areas, a selection of which is highlighted in this article.

L'année 2020 a été marquée par la pandémie de Covid-19. Un certain nombre d'enseignements de cette pandémie ont pu être tirés également en gastroentérologie et en hépatologie. D'autre part, des progrès importants ont aussi été réalisés en dehors du Covid-19, dont une sélection est présentée dans cet article.

[Autoimmune hepatitis: 2021 update]. / Hépatite autoimmune : mise au point 2021.

Autoimmune hepatitis is a rare disease which can present as acute or chronic forms and can be difficult to diagnose due to its variable clinical presentation. The disease arises in genetically susceptible individuals and several triggers have been identified. The diagnosis is based on the presence of autoantibodies, elevated transaminases and serum immunoglobulin G levels as well as a compatible histology. First-line immunosuppressive treatment strategies lead to clinical remission in most patients. In case of non-response, second-line therapies can be used and in case of hepatocellular insufficiency, liver transplantation remains an excellent option.

L'hépatite autoimmune est une maladie rare, pouvant se présenter sous forme aiguë ou chronique et dont le diagnostic peut être difficile à poser en raison d'une présentation clinique variable. La maladie se développe chez des personnes génétiquement prédisposées et plusieurs événements déclencheurs ont été identifiés. Le diagnostic repose sur la présence d'autoanticorps spécifiques, d'une élévation des transaminases et des immunoglobulines G, ainsi que sur une histologie compatible. Les traitements de première ligne, immunosuppresseurs, permettent dans la plupart des cas d'obtenir une rémission clinique. En cas de non-réponse, des traitements de deuxième ligne sont disponibles et lors d'insuffisance hépatocellulaire, la transplantation hépatique reste une excellente option.

COVID-19 in an international European liver transplant recipient cohort.

OBJECTIVE: Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. DESIGN: We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. RESULTS: 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. CONCLUSION: In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.

[New trends in non-alcoholic fatty liver diseases (NAFLD)]. / Nouveautés dans la stéatose non alcoolique du foie (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases with an epidemiology correlated to obesity and metabolic syndrome. The last decade was rich of significant advances in understanding the pathophysiology of the disease, linking environmental elements, genetic factors and microbiota modifications, as well as in staging, screening and therapeutic development. The purpose of this article is to summarize recent advances in the field of NAFLD, on her way to become the first cause of cirrhosis and liver transplantation worldwide.

La maladie stéatosique non alcoolique du foie (NAFLD) est l'une des atteintes hépatiques les plus prévalentes dans le monde avec une épidémiologie corrélée à celles de l'obésité et du syndrome métabolique. La dernière décennie a connu des avancées importantes dans la compréhension de la physiopathologie en mettant en lien des facteurs environnementaux, génétiques et microbiotiques, ainsi que dans la terminologie de la maladie, ses classifications et ses moyens diagnostiques et thérapeutiques. Le but de cet article est de résumer les avancées récentes dans le domaine de la NAFLD, sur le point de devenir la première cause de cirrhose et de transplantation hépatique dans le monde.

[Adequacy of intensive care admission in cirrhotic patients not eligible for transplantation]. / Patients cirrhotiques sans projet de transplantation: qui admettre aux soins intensifs ?

Decompensated cirrhosis corresponds to the end stage of chronic liver disease. It is associated with poor outcomes, in particular, in patients who are not candidate for a liver transplantation. Those patients require frequent hospital admissions to manage complications. In those situations, the adequacy of a potential intensive care unit admission is regularly discussed among care providers. This article reviews elements to be considered in such situations: available tools, decision timing and modulating factors such as trigger for admission.

La cirrhose décompensée correspond au stade terminal de la maladie hépatique chronique. En dehors d'une transplantation hépatique, son pronostic est sombre. Malheureusement, seule une fraction des patients cirrhotiques est éligible pour une telle procédure. Pour les autres, la survenue inexorable de complications justifie des admissions régulières en milieu hospitalier aigu. Dans ce contexte, en cas de défaillance sévère, la question de la pertinence d'une admission dans un service de soins intensifs se pose régulièrement. Cet article propose les éléments objectifs à considérer dans ce type de situation: les outils disponibles, le timing de la décision et les éléments modulateurs comme le motif d'admission.

[Early TIPS: a practical review after 15 years of scientific evidence]. / Early TIPS†: une revue pratique après 15 ans d'évidence scientifique.

Gastrointestinal bleeding related to portal hypertension of cirrhosis is associated with a significant mortality risk (10-20 %). The transjugular intrahepatic portosystemic shunt (TIPS) reduces the hepatic venous pressure gradient. Several studies have evaluated early TIPS insertion (within 72h from diagnostic endoscopy) with the aim of improving outcomes in selected patients at high risk of failure to control bleeding and/or rebleeding. The majority reported an improvement of 6-week and 1-year survival rates and a decrease in failure to control bleeding and rebleeding. Here, we review the available data and discuss the limits of early TIPS in terms of patient identification and access to the procedure.

Les patients hospitalisés pour hémorragie digestive sur hypertension portale ont un risque élevé de mortalité (10-20%). La création d'un shunt portosystémique par voie transjugulaire (TIPS) permet de diminuer le gradient de pression entre le système porte et la circulation systémique (gradient portosystémique) réduisant ainsi le risque hémorragique. Chez des patients sélectionnés à haut risque de non-contrôle et/ou de récidive hémorragique, plusieurs études ont évalué l'intérêt de l'insertion précoce d'un TIPS (early TIPS) dans les 72 heures suivant l'endoscopie diagnostique. Elles observent en majorité une amélioration de la survie à 6 semaines et 1 an et une diminution du non-contrôle ou de la récidive hémorragique. Nous proposons ici une revue des études disponibles et discutons des limites de cette stratégie en termes d'accessibilité à la technique et d'identification des patients nécessitant encore régulièrement une discussion collégiale au cas par cas.

New therapeutic perspectives to manage refractory immune checkpoint-related toxicities.

Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.

Sofosbuvir add-on to ribavirin for chronic hepatitis E in a cirrhotic liver transplant recipient: a case report.

BACKGROUND: Chronic hepatitis E represents an emerging challenge in organ transplantation, as there are currently no established treatment options for patients who fail to clear hepatitis E virus (HEV) following reduction of immunosuppressive therapy and/or treatment with ribavirin. Sofosbuvir has shown antiviral activity against HEV in vitro but clinical utility in vivo is unknown. CASE PRESENTATION: We describe a 57-year-old liver transplant recipient with decompensated graft cirrhosis due to chronic hepatitis E. Reduction of immunosuppressive treatment as well ribavirin alone for 4 months did not result in viral clearance. Add-on of sofosbuvir for 6 months was associated with HEV RNA becoming undetectable in plasma. However, sustained viral clearance could not be achieved. CONCLUSIONS: Sofosbuvir may have some antiviral activity against HEV when added to ribavirin. However, this did not suffice to yield sustained viral clearance. Our well-characterized observation emphasizes the need for new treatment options to cure chronic hepatitis E in the setting of organ transplantation.

[Alagille Syndrome]. / Syndrome d'Alagille.

Alagille syndrome is a rare disorder with low physician awareness. It affects multiple organs and thus patient management involves several medical specialties. It is an autosomal dominant disorder with significant intrafamilial variability. The most frequent clinical manifestations are neonatal jaundice, chronic cholestasis as well as cardiac, ocular and skeletal malformations associated with characteristic facial features. Inherited mutations affect the Notch pathway. Although the molecular basis of Alagille syndrome is well defined, no specific targeted therapy exists.

Le syndrome d'Alagille est une pathologie rare et peu connue dans la pratique médicale. Il s'agit d'une affection multisystémique dont la prise en charge implique plusieurs spécialités médicales. Sa transmission se fait sur un mode autosomique dominant avec néanmoins une expression clinique très variable, au sein d'une même famille chez des sujets présentant une même mutation. Ses manifestations cliniques principales sont un ictère néonatal, une cholestase chronique, une atteinte cardiaque, oculaire, squelettique ainsi qu'un faciès caractéristique. Les diverses mutations identifiées et héritées affectent la voie de signalisation Notch. Bien que la physiopathologie soit actuellement relativement bien définie, aucune thérapie ciblée n'est à l'heure actuelle disponible.

[Outpatient follow-up of liver transplant recipients: the essential role of the general practitioner]. / Suivi ambulatoire du patient transplanté hépatique: le rôle essentiel du médecin généraliste.

The population of liver transplant recipients has increased in Switzerland over the last few years. Morbidity and mortality after liver transplantation are due, in the early post-transplant period, to surgical and infectious complications as well as to rejection, whereas cardiovascular, metabolic, renal and oncologic complications are the most frequent complications in the late post-transplant period. The role of the general practitioner in the long-term follow-up of liver transplant recipients is of the highest importance and can represent the first-line care of these patients as soon as 6 to 12 months post-transplantation, while maintaining a close and regular collaboration with the transplant center. Multidisciplinary and structured follow-up, along with some specific screening tests, is warranted in order to refine patient management in a timely manner and to optimize outcomes.

Les patients greffés hépatiques représentent une population croissante en Suisse. La morbidité et la mortalité après cette procédure sont liées, dans la phase précoce, aux complications chirurgicales et infectieuses ainsi que, dans une moindre mesure, au rejet, puis surviennent dans la phase tardive les complications cardiovasculaires, métaboliques, rénales et oncologiques, liées en grande partie aux traitements immunosuppresseurs. Le rôle du médecin généraliste dans le suivi médical du patient greffé hépatique est essentiel et peut être de premier recours dès 6 à 12 mois après la transplantation, tout en gardant une collaboration étroite et régulière avec le centre de transplantation. Un suivi multidisciplinaire, régulier et structuré, associé à certaines mesures de dépistage, est indispensable, afin d'adapter précocement la prise en charge et ainsi d'optimaliser le devenir des patients après la greffe.