[Liver transplantation in adults : choosing the appropriate candidate and timing]. / Quel patient adresser à un centre de transplantation hépatique ?

Liver transplantation is the best treatment option for patients with end-stage liver failure, as well as for various oncological (hepatic or extrahepatic), metabolic and genetic indications. Cirrhosis and its complications represent the most frequent indication for transplantation. This treatment option should be considered for cirrhotic patients with significant liver failure, the development of hepatocellular carcinoma or when complications linked to portal hypertension appear. In view of the limited availability of organs and a waiting time on the list estimated at around one year in Switzerland, careful assessment of the risk-benefit ratio and correct timing of evaluation in a transplant center are crucial to optimize the benefits of this procedure.

La transplantation du foie est la meilleure option thérapeutique pour les patients atteints d'une insuffisance hépatique terminale ainsi que pour différentes indications oncologiques (hépatiques ou extrahépatiques), métaboliques et génétiques. La cirrhose et ses complications représentent l'indication la plus fréquente à la transplantation. Celle-ci doit être évoquée chez un patient cirrhotique en cas d'insuffisance hépatique marquée, d'apparition d'un carcinome hépatocellulaire ou lors de complications liées à l'hypertension portale. Vu la disponibilité limitée des organes et d'un temps d'attente en liste de transplantation pouvant être supérieur à un an en Suisse, l'évaluation du rapport bénéfices-risques de la transplantation ainsi que du meilleur moment pour un bilan pré-greffe permet d'optimiser les bénéfices de cette intervention.

[Updated recommandations for the follow-up of a patient with cirrhosis]. / Actualisation du suivi d'un patient atteint de cirrhose.

A close collaboration between the general practitioner and the gastroenterologist is necessary to optimize the management of a patient with cirrhosis, a frequent and serious complication of chronic liver diseases. Both the treatment of the etiological factor of liver disease and the surveillance of potential complications of cirrhosis are key issues in the proper management of cirrhosis. Preventive measures aim at keeping the patient in a compensated form of cirrhosis which is associated with a better survival. We address here the updated management strategies regarding the most frequent complications of cirrhosis.

La prise en charge d'un patient atteint de cirrhose implique une collaboration étroite entre le médecin généraliste et le spécialiste, combine le traitement de la maladie causale ainsi que la mise en place d'une surveillance des complications pouvant occasionner une décompensation avec un impact pronostique négatif. Nous passons en revue les principales situations cliniques de la cirrhose pour lesquelles des recommandations actualisées ont pour but d'améliorer la prise en charge de cette maladie fréquente grevée d'une importante morbimortalité.

Discontinuation of immunosuppression in patients with immune-mediated drug-induced liver injury or idiopathic autoimmune hepatitis: A case-control study.

Background and Aim: Drug-induced liver injury (DILI) may present with autoimmune features and require immunosuppressive therapy (IST) to reach biochemical response. Discontinuation of IST without hepatitis relapse may be more frequent in these patients as compared to patients with classical autoimmune hepatitis (AIH). We aimed to determine baseline characteristics and outcome of patients with immune-mediated drug induced liver injury (IMDILI) with particular emphasis on IST during follow-up. Methods: We performed a single-center retrospective study of consecutive patients presenting at a tertiary care center between January 2005 and December 2019 either with IMDILI or with classical AIH, for whom full baseline characteristics and a close follow-up were available over a 12-month period. Results: Overall, 31 patients (IMDILI n = 16, mean age 59 [34-74] years; AIH n = 15, mean age 47 [15-61] years) were included, showing similar biochemical, serological, and histological characteristics. Incriminating drugs in IMDILI patients were mostly represented by nonsteroidal antiinflammatory drugs and sartans. Initial corticosteroids combined with IST led to biochemical response in all patients. Compared to idiopathic AIH, more patients with IMDILI were weaned off corticosteroids at the end of follow-up (11/16 [68.7%] vs 4/15 [26.6%], P < 0.02). At 1 year of follow-up, more patients in the IMDILI group compared to the classical AIH group were off any type of IST (13/16 [81%] vs 15/15 [100%], P = 0.08). Conclusions: Although presenting with similar baseline biochemical and histological characteristics as idiopathic AIH, patients with IMDILI may not require long-term IST.

Evaluation of 30-day mortality in patients undergoing gastrointestinal endoscopy in a tertiary hospital: a 3-year retrospective survey.

OBJECTIVE: Despite international guidelines recommendations to use mortality as a quality criterion for gastrointestinal (GI) procedures, recent studies reporting these data are lacking. Our objective was to report death causes and rate following GI endoscopies in a tertiary university hospital. DESIGN: We retrospectively reviewed all GI procedures made between January 2017 and December 2019 in our tertiary hospital in Switzerland. Data from patients who died within 30 days of the procedure were recorded. RESULTS: Of 18 233 procedures, 251 patients died within 30 days following 345 (1.89%) procedures (244/9180 gastroscopies, 53/5826 colonoscopies, 23/2119 endoscopic ultrasound, 19/911 endoscopic retrograde cholangiopancreatography, 6/197 percutaneous endoscopic gastrostomies). Median age was 70 years (IQR 61-79) and 173/251 (68.92%) were male. Median Charlson Comorbidity Index was 5 (IQR 3-7), and 305/345 procedures (88.4%) were undertaken on patients with an ASA score ≥3. Most frequent indications were suspected GI bleeding (162/345; 46.96%) and suspected cancer or tumourous staging (50/345; 14.49%). Major causes of death were oncological progression (72/251; 28.68%), cardiopulmonary failure or cardiac arrest of unkown origin (62/251; 24,7%) and liver failure (20/251; 7.96%). No deaths were caused by complications such as perforation or bleeding. CONCLUSIONS: Progression of malignancies unrelated to the procedure was the leading cause of short-term death following a GI procedure. After improvements in periprocedural care in the last decades, we should focus on patient selection in this era of new oncological and intensive care therapies. Death rate as a quality criterion is subject to caution as it depends on indication, setting and risk benefit ratio.

[Polycystic liver disease]. / Polykystoses hépatiques.

Polycystic liver disease (PLD) includes three entities in adults : biliary hamartomas which develop as a result of ductal plate malformation, autosomal dominant polycystic liver disease (ADPLD) and autosomal dominant polycystic kidney disease (ADPKD) which occur in the setting of genetic disorders. Hamartomas are asymptomatic and benign. PLD are marked by a steady growth of cysts over time, clinically silent in the majority of cases. Symptomatic forms mainly affect women due to the influence of estrogens on the growth of cysts therefore estrogen treatments are contraindicated in this setting. Diagnosis is based on imaging. Complications are rare but must be identified early in order to offer appropriate care in an expert center.

Les polykystoses hépatiques (PKH) de l'adulte regroupent les hamartomes biliaires, conséquence d'une malformation congénitale de la plaque ductale, la polykystose hépatorénale autosomique dominante (PKHRAD) et la polykystose hépatique isolée (PKHI), de cause génétique. Les hamartomes sont asymptomatiques et bénins. Les PKH sont marquées par une croissance régulière des kystes au fil du temps, silencieuse dans la majorité des cas. Les formes symptomatiques concernent majoritairement les femmes, la croissance des kystes étant influencée par les œstrogènes. De ce fait, les traitements œstrogéniques doivent être proscrits. Le diagnostic repose sur l'imagerie. Les complications sont rares mais doivent être identifiées précocement afin de proposer une prise en charge adaptée en centre expert.

Final safety and efficacy results from a 106 real-world patients registry with an ascites-mobilizing pump.

BACKGROUND AND AIMS: Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump® is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real-world cohort with cirrhotic refractory ascites and contraindications for TIPSS. METHODS: A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively. RESULTS: Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up. The most frequent causes of on-study death and complication-related explant were progression of liver disease and infection. The device reduced the requirement for large-volume paracentesis significantly, with more than half of patients not having required any post-implant. Survival benefits were not observed. Device-related reinterventions were predominantly caused by device deficiencies. A post-hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications. CONCLUSIONS: The device reduced paracentesis frequency in a real-world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427).

[Advances in gastroenterology and hepatology 2021]. / Gastroentérologie et hépatologie.

Among the recent advances in gastroenterology, colonoscopy with artificial intelligence is associated with a better quality of screening. In refractory UC, Ozanimod seems to be an interesting salvage treatment, which still needs to be validated by Swissmedic. Among the direct-acting anticoagulants, Rivaroxaban is more frequently associated with GI bleeding. The classification of oesophageal motor disorders has been recently revised, the Chicago v4.0 classification should be applied in diagnostic management. The use of Semaglutide seems to show very promising results in the management of metabolic steatosis. SARS-CoV-2 infection can be complicated by biliary tract disease, which can progress to hepatocellular failure.

Parmi les récentes avancées en gastroentérologie, la coloscopie couplée à une intelligence artificielle est associée à un dépistage de meilleure qualité. Lors de rectocolite hémorragique réfractaire, l'ozanimod semble être un traitement de sauvetage intéressant, qui doit encore être validé par Swissmedic. Parmi les anticoagulants à action directe, le rivaroxaban est plus fréquemment associé aux hémorragies digestives. La classification des troubles moteurs de l'œsophage a fait l'objet d'une révision récente, la classification de Chicago v4.0 doit être appliquée dans la prise en charge diagnostique. L'utilisation du sémaglutide semble montrer des résultats très prometteurs dans la prise en charge de la stéatose métabolique. L'infection par le virus à SARS-CoV-2 peut se compliquer d'une atteinte des voies biliaires, pouvant évoluer jusqu'à l'insuffisance hépatocellulaire.

Impact of Nonalcoholic Steatohepatitis on the Outcome of Patients Undergoing Roux-en-Y Gastric Bypass Surgery: a Propensity Score-Matched Analysis.

PURPOSE: It is currently unknown whether NASH (nonalcoholic steatohepatitis), as compared to simple steatosis, is associated with impaired postoperative weight loss and metabolic outcomes after RYGB surgery. To compare the effectiveness of Roux-en-Y gastric bypass (RYGB) on patients with NASH versus those with simple nonalcoholic fatty liver (NAFL). MATERIALS AND METHODS: We retrospectively retrieved data from 515 patients undergoing RYGB surgery with concomitant liver biopsy. Clinical follow-up and metabolic assessment were performed prior to surgery and 12 months after surgery. We used multivariate analysis of variance (MANOVA) and propensity score matching and we assessed for changes in markers of hepatocellular injury and metabolic outcomes. RESULTS: There were 421 patients with simple NAFL, and 94 with NASH. Baseline alanine and aspartate aminotransferases were significantly higher in patients with NASH (p < 0.01). Twelve months after the RYGB surgery, as determined by both MANOVA and propensity score matching, patients with NASH exhibited a significantly greater reduction in alanine aminotransferase (ß-coefficient - 12 iU/l [- 22 to - 1.83], 95% CI, adjusted p = 0.021) compared to their NAFL counterparts (31 matched patients in each group with no loss to follow-up at 12 months). Excess weight loss was similar in both groups (ß-coefficient 4.54% [- 3.12 to 12.21], 95% CI, adjusted p = 0.244). Change in BMI was comparable in both groups (- 14 (- 16.6 to - 12.5) versus - 14.3 (- 17.3 to - 11.9), p = 0.784). CONCLUSION: After RYGB surgery, patients with NASH experience a greater reduction in markers for hepatocellular injury and similar weight loss compared to patients with simple steatosis.

[Update on cystic echinococcosis of the liver]. / Actualités sur l'échinococcose kystique hépatique.

Hepatic cystic echinococcosis (HCE), is a cosmopolitan parasitic zoonosis. Autochtonous HCE cases are rare and the majority of cases are imported from endemic areas. It induces the development in the liver of Echinococcus granulosus larvae. Extrahepatic localizations are also possible. Cyst development is slow with an often-late diagnosis. In Switzerland, HCE discovery is usually fortuitous, during an abdominal radiological examination. More rarely, an acute clinical picture reveals a complication that can be severe or even fatal. The diagnosis is based on ultrasound findings that allows cyst characterization according to the WHO classification. This guides the therapeutic choice: simple monitoring, albendazole therapy, percutaneous procedures or surgery.

L'échinococcose kystique hépatique (EKH) est une zoonose parasitaire cosmopolite. Les cas d'EKH autochtones sont rares et la majorité est importée par des patients originaires de zones d'endémie. L'EKH est due au développement dans le foie de la larve d'Echinococcus granulosus. Des localisations extrahépatiques sont également possibles. Son évolution est lente avec un diagnostic fréquemment tardif. En Suisse, celui-ci est souvent fortuit, à l'occasion d'un examen radiologique abdominal. Plus rarement, un tableau clinique aigu et bruyant révèle une complication qui peut être sévère, voire mortelle. Le diagnostic basé sur l'échographie permet la caractérisation du kyste selon la classification de l'OMS. Celle-ci guide le choix thérapeutique: surveillance simple, traitement par albendazole, gestes percutanés ou chirurgie.

Hepatic Alveolar Echinococcosis.

Hepatic alveolar echinococcosis (HAE) is a rare but severe zoonosis caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. HAE is present only in the Northern Hemisphere, predominantly in China. Currently, there is a significant resurgence of cases in historically endemic areas associated with emergence of HAE in countries not previously concerned. Today, in European countries, HAE is often discovered by chance; however, clinicians should be made aware of opportunistic infections that progressively emerged recently as a result of therapeutic or pathological immunosuppression. Ultrasonography is the key first-line diagnostic procedure, with specific serology providing confirmation in 95% of the cases. Albendazole, only parasitostatic, is the mainstay for treatment. Surgical resection, if feasible, is the gold standard for treatment, and more patients are currently eligible for this option because of an earlier diagnosis. The prognosis has considerably improved but remains poor in countries where access to care is less favorable.

Management of Acute Wilsonian Hepatitis with Severe Hemolysis: A Successful Combination of Chelation and MARS Dialysis.

Wilson's disease is a rare hereditary disorder of copper metabolism leading to progressive accumulation of copper in several organs including the brain and the liver. Acute liver failure is a relatively rare hepatic manifestation of WD which may require urgent liver transplantation if medical treatment fails. We report here the case of a young woman who presented with classic acute Wilsonian hepatitis complicated by liver and renal failure and a severe hemolysis related to massive nonceruloplasmin bound copper accumulation requiring repeated blood transfusions. The early initiation of a combined treatment including conventional chelation therapy and repeated MARS dialysis sessions allowed a rapid control of hemolysis, a progressive decrease of free copper overload, and clinical recompensation without liver transplantation.

Clinical Presentation and Gene Expression of Acute Alcohol-Induced Microvesicular Steatosis Mimicking Alcoholic Hepatitis.

Acute alcoholic microvesicular steatosis (MIC) may complicate heavy alcohol intake and present as alcoholic hepatitis (AH) syndrome. However, detailed clinical, biological, and histologic data associated with MIC are scarce. We compared the clinical presentation, histologic features, and hepatic transcriptomic of patients presenting with AH due to either MIC or severe alcoholic steatohepatitis (ASH). In this case-control study, patients who drank heavily (>100 g/day) with the AH syndrome were included either in the MIC group (>50% severe microvesicular steatosis, no inflammation) or in the severe ASH group (polynuclear neutrophil infiltration, macrosteatosis, ballooned hepatocytes). All patients received standard supportive care plus steroids for those with severe ASH and were followed up for 3 months. Whole-liver transcriptome profiling was performed on liver snap-frozen biopsies. Compared to ASH (n = 24, mean age 49.3 years), patients in the MIC group (n = 12, mean age 49.1 years) had a higher reported alcohol intake (P < 0.01), lower Model for End-Stage Liver Disease score (P < 0.05), lower hepatic venous pressure gradient (P < 0.01), higher alanine aminotransferase (P < 0.02) and gamma-glutamyltransferase (P < 0.001), higher triglycerides (P < 0.001) and total cholesterol (P < 0.002), but similar bilirubin levels (P = 0.54). At histology, patients with MIC had a lower fibrotic stage compared to those with ASH (P < 0.001). A higher density of megamitochondria was seen in MIC compared to ASH (P < 0.05). During follow-up, death or transplantation occurred in 4/12 (33%) patients with MIC and 7/24 (29%) patients with severe ASH. Differential hepatic gene expression in MIC compared to ASH included down-regulation of genes related to inflammation and fibrosis and up-regulation of genes involved in lipid metabolism and mitochondrial function. Conclusion: MIC is an acute, noninflammatory, potentially severe alcoholic liver injury mimicking ASH, is associated with a lower fibrosis stage, and has a distinct gene expression profile.

NAFLD and MAFLD as emerging causes of HCC: A populational study.

BACKGROUND & AIMS: There are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014. METHODS: We identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. RESULTS: A total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990-1994 and 2010-2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08-3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85-1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0-29%, p = 0.037) than in men (2-12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women (p <0.001). From 2000-2004 to 2010-2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77-5.08) for men and 12.7 (95% CI 1.63-545) in women, whereas it decreased or remained stable for other major aetiologies of HCC. CONCLUSIONS: In a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women. LAY SUMMARY: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.

Disulfiram-Induced Acute Liver Injury.

Disulfiram is a drug used to treat alcohol dependence since many years. It interferes with the metabolism of alcohol, may be associated with neurological and dermatological symptoms, and can be hepatotoxic. Due to the frequent coexistent liver test alterations due to alcohol, the true incidence of disulfiram-associated liver injury is unclear and severity of injury may vary from mildly elevated liver enzymes to fulminant hepatitis leading to death. There are several reported cases of disulfiram hepatitis in the literature. Liver histology, when available, demonstrates some degree of portal inflammation with eosinophils and hepatocyte necrosis. We present here a well-documented case of acute hepatitis due to disulfiram with typical histological lesions, favorable outcome following drug withdrawal, and a brief steroid course. The risk of hepatotoxicity should be kept in mind when prescribing disulfiram.

[Efficacy of new therapies]. / Hépatite D†: efficacité des nouvelles thérapies.

Hepatitis D virus causes chronic hepatitis D. The virus is defective, meaning it requires simultaneous presence of hepatitis B virus within the hepatocytes to complete its viral cycle. Globally, 15 to 20 millions people are estimated to be chronically co-infected by hepatitis B and D viruses. Current therapy remains limited to pegylated interferon alfa, which has an unsatisfactory success rate, several contraindications and many side effects. Drugs directly targeting the hepatitis D virus life cycle are being developed with promising results. These drugs target viral entry into hepatocytes, virion assembly or secretion from infected hepatocytes. This article provides an overview of the newly developed therapies and their efficacy.

L'hépatite D chronique est une infection causée par le virus de l'hépatite D, un virus défectueux nécessitant l'infection concomitante des hépatocytes par le virus de l'hépatite B. On estime que 15 à 20 millions d'individus dans le monde pourraient être co-infectés chroniquement par ces deux virus. Le seul traitement disponible est l'interféron alfa pégylé dont l'efficacité est encore insatisfaisante avec des effets indésirables fréquents. Des thérapies ciblant le virus de l'hépatite D sont en développement avec des résultats prometteurs. Parmi eux, les inhibiteurs de l'entrée du virus dans l'hépatocyte, de son assemblage ou encore de sa sécrétion. Cet article fait le point sur les thérapies en développement et leur efficacité.

[NASH: new terminology and what else is new in 2020]. / NASH†: nouvelle terminologie et nouveautés en 2020.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of hepatic pathology ranging from non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH) occasionally complicated with hepatic fibrosis or even cirrhosis. In order to propose a diagnosis with positive criteria, a panel of experts recently proposed the use of an alternative nomenclature, metabolic-dysfunction-associated fatty liver disease (MAFLD) whose use remains debated. In addition, in Switzerland and elsewhere, there is strong epidemiological growth of NAFLD. The next years will probably see the approval of new therapies for NAFLD/NASH but, at present, management remains focused on lifestyle interventions and joint monitoring by the primary care physician and, when necessary, the specialist.

La stéatopathie non alcoolique (NAFLD) comprend un spectre de pathologies allant de la stéatose hépatique non alcoolique à la stéatohépatite non alcoolique (NASH) parfois compliquée d'une fibrose hépatique, voire d'une cirrhose. Afin de proposer un diagnostic avec des critères positifs, un panel d'experts a récemment proposé l'utilisation d'une nomenclature alternative, la stéatopathie associée à la dysfonction métabolique (Metabolic-Dysfunction-Associated Fatty Liver Disease, MAFLD) dont l'utilisation reste discutée. D'autre part, la NAFLD est en pleine croissance épidémiologique en Suisse comme ailleurs. Les prochaines années vont probablement voir l'approbation de nouvelles thérapeutiques pour la NAFLD/NASH mais, à l'heure actuelle, la prise en charge reste centrée sur les mesures hygiéno-diététiques et le suivi conjoint par le médecin de premier recours et, si nécessaire, par le spécialiste.