Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis.

Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence. Conclusion: Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated. Impact and implications: Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.

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.

Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival.

BACKGROUND AND AIMS: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors. METHOD: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres. RESULTS: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035). CONCLUSION: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.

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.

[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.

Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis.

BACKGROUND & AIMS: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. METHODS: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. RESULTS: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. CONCLUSIONS: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. LAY SUMMARY: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes.

[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.

[Liver transplantation and acute failure in chronic liver disease]. / Transplantation hépatique et défaillance aiguë lors d'hépatopathie chronique.

Acute cirrhotic decompensation is characterized by a rapid and sudden deterioration of hepatocellular function. It may be associated with secondary failure of one or more organs. The definition and understanding of a complex cirrhotic decompensation with multi-organ damage, is still poorly defined. This entity is currently called Acute on Chronic Liver Failure (ACLF). Depending on the number of affected organs, decompensation is classified into 4 stages, from 0 to 4. Mortality is proportional to the number of failed organs, with mortality from 50 % to 80 % at 30 days when 3 or more organs are affected. The interest of liver transplantation in the most severe forms, which has been debated for a long time, seems to be a safe alternative with good results in well selected patients.

La décompensation cirrhotique aiguë est caractérisée par une péjoration rapide et brutale de la fonction hépatocellulaire. Elle peut être associée à une défaillance secondaire d'un ou plusieurs organes. La définition et la compréhension d'une décompensation cirrhotique complexe avec atteinte multi-organes sont encore mal définies. Cette entité est actuellement appelée Acute on Chronic Liver Failure (ACLF). Selon le nombre d'organes affectés, la décompensation est classifiée en 4 stades, de 0 à 4. La mortalité est proportionnelle au nombre d'organes défaillants, avec une mortalité de 50 à 80 % à 30 jours lors d'atteinte de 3 organes ou plus. La transplantation hépatique dans les formes les plus graves, longtemps débattue, semble être une alternative sûre et avec de bons résultats, chez des patients bien sélectionnés.

Human genomics of acute liver failure due to hepatitis B virus infection: An exome sequencing study in liver transplant recipients.

Acute liver failure (ALF) or fulminant hepatitis is a rare, yet severe outcome of infection with hepatitis B virus (HBV) that carries a high mortality rate. The occurrence of a life-threatening condition upon infection with a prevalent virus in individuals without known risk factors is suggestive of pathogen-specific immune dysregulation. In the absence of established differences in HBV virulence, we hypothesized that ALF upon primary infection with HBV could be due to rare deleterious variants in the human genome. To search for such variants, we performed exome sequencing in 21 previously healthy adults who required liver transplantation upon fulminant HBV infection and 172 controls that were positive for anti-HBc and anti-HBs but had no clinical history of jaundice or liver disease. After a series of hypothesis-driven filtering steps, we searched for putatively pathogenic variants that were significantly associated with case-control status. We did not find any causal variant or gene, a result that does not support the hypothesis of a shared monogenic basis for human susceptibility to HBV-related ALF in adults. This study represents a first attempt at deciphering the human genetic contribution to the most severe clinical presentation of acute HBV infection in previously healthy individuals.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates.

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine-preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology-based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch-up immunizations increased the patients' immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology-based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

Hepatic manifestations of Wilson's disease: 12-year experience in a Swiss tertiary referral centre.

BACKGROUND AND AIM: Wilson’s disease is an inherited disorder of hepatic copper metabolism, leading to the accumulation of copper in the liver as well as the brain, cornea and other organs. Here, we describe the adult cases of hepatic Wilson’s disease diagnosed at the Division of Gastroenterology and Hepatology of the University Hospital Lausanne, Switzerland between September 2004 and August 2016. METHODS: Clinical manifestations, results of diagnostic tests, management and outcomes of adult patients with hepatic Wilson’s disease were assessed based on standardised medical records. In addition, liver histology was reviewed and the lesional patterns were recorded. RESULTS: Ten new adult cases of hepatic Wilson’s disease were diagnosed in our centre between September 2004 and August 2016. Male to female ratio was 1:1 and median age at diagnosis was 26 (range 18–56) years. Four patients presented with acute liver failure, four with persistently elevated liver function tests, and two with decompensated cirrhosis; none had neurological manifestations. Only one patient had a Kayser-Fleischer corneal ring. Median ceruloplasmin level at diagnosis was 0.13 (range <0.03–0.30) g/l, median 24-hour urinary copper excretion was 2.8 (range 0.3–77.3) μmol, and median hepatic copper concentration was 789 (range 284–1677) μg/g. At least one mutation in the ATP7B gene was identified in eight patients. Allelic frequency of the common H1069Q mutation was 19%. Leipzig score was ≥5 in all patients. Three patients presenting with acute liver failure and the two with decompensated cirrhosis underwent successful liver transplantation. One patient with acute liver failure recovered under chelation therapy, as predicted by a Dhawan score <11. D-penicillamine was used as first-line chelator treatment, with a subsequent switch to trientine due to adverse effects in three out of six patients. CONCLUSIONS: The clinical presentation of hepatic Wilson’s disease is highly variable. Three out of 10 patients were diagnosed at an age >35 years. A high index of suspicion in clinically compatible situations is key.

A return to harmful alcohol consumption impacts on portal hemodynamic changes following alcoholic hepatitis.

BACKGROUND: Increased hepatic venous pressure gradient (HVPG) plays a role in the clinical manifestations of alcoholic hepatitis (AH). The evolution of HVPG and the influence of alcohol use in the intermediate term are unclear. AIM: The aim of this study was to explore HVPG modifications following AH taking into consideration alcohol use and clinical manifestations. PATIENTS AND METHODS: Patients with AH (n=37; age 52 years; model for end-stage liver disease: 18.5; Maddrey score: 43) and chronic excessive drinkers with compensated cirrhosis (n=19; age: 54 years; model for end-stage liver disease: 9.2) underwent HVPG measurement and liver biopsy. Ten long-standing abstinent alcoholic cirrhotics served as controls. After discharge, patients were monitored for alcohol use and clinical complications, with repeated HVPG after a median duration of 100 days. Inflammation was determined using plasma C-reactive protein. RESULTS: At baseline, compared with chronic excessive drinkers and alcoholic cirrhotics, patients with AH had increased HVPG (18.1±0.6 vs. 13.8±1.4 vs. 15±1.3 mmHg, P<0.05). During follow-up, patients who became abstinent or reported occasional drinking were more likely to achieve a greater than 20% reduction in HVPG compared with those returning to harmful alcohol (45 vs. 0%, P<0.01), and suffered from fewer complications (25 vs. 68%, P<0.03). High baseline C-reactive protein levels correlated to the Maddrey (r=0.38), but no relationship was observed between changes in inflammation and HVPG. CONCLUSION: Elevated HVPG is a feature of AH, with a clinically significant reduction in values in abstinent or occasional drinkers after weeks of follow-up. A return to harmful alcohol has a negative impact on portal hemodynamics and associated clinical complications.

Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. METHODS: This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD. RESULTS: We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined. CONCLUSIONS: At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Geoepidemiology of Primary Biliary Cholangitis: Lessons from Switzerland.

No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers. The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants. The median age at diagnosis was 53 years, 84% were women, and 86% were anti-mitochondrial antibody positive. The median follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients. Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The median transplant-free survival at 10 years was 85%. The following variables were independently associated with poor outcome: low platelet count at baseline (HR = 0.99, p < 0.0001), elevated alkaline phosphatase at baseline (HR = 1.36, p < 0.0001), elevated bilirubin at baseline (HR = 1.11, p = 0.001), and elevated alanine aminotransaminase (HR = 1.35, p = 0.04) after 12 months of UDCA therapy. The AUROC for the UK-PBC risk score at 5, 10, and 15 years was 0.82. The AUROC for the Globe score at 5, 10, and 15 years was 0.77. Patients included in this study are currently being enrolled in a prospective nationwide registry with biobank, taking advantage of the collaboration network generated by this study. Our study provides the first snapshot of PBC in Switzerland, describing a diagnostic delay with one quarter of patients diagnosed when already in the cirrhotic stage. We were also able to externally validate the UK-PBC risk score and the Globe score. The ongoing nationwide prospective registry will be fundamental to improve disease awareness and interdisciplinary collaborations and will serve as a platform for clinical and translational research. TRIAL REGISTRATION NUMBER: clinicaltrials.gov : NCT02846896; SNCTP000001870.

[Paracentesis and cirrhotic patients: should we fear hemorrhages ?] / Ponction d'ascite et patient cirrhotique : faut-il craindre les hémorragies ?

Paracentesis is a frequent procedure, especially in patients with cirrhosis. In these patients, given the fears of severe bleeding associated with coagulation disorders as well as thrombocytopenia, we were interested to review the literature on this subject. Few studies are available and, for the moment, recommendations are of a low level of evidence. Paracentesis seems to be a safe procedure without severe haemorrhagic complications (< 1%), regardless of coagulation disorders and platelet count. Renal insufficiency, Child-Pugh C cirrhosis, thrombocytes < 50 G/L and cirrhosis of alcoholic origin may however increase the risk of bleeding. Caution should be observed in these patients.

La ponction d'ascite est un geste fréquemment pratiqué, surtout chez des patients atteints de cirrhose. Chez ces patients, compte tenu des craintes d'hémorragies sévères, associées aux troubles de la coagulation ainsi qu'à la thrombopénie, nous avons été intéressés par une revue de la littérature sur ce sujet. Peu d'études ont été retrouvées et les recommandations sont, pour le moment, d'un faible niveau de preuve. La ponction d'ascite semble néanmoins être un geste sûr dont les complications hémorragiques sévères sont très rares (< 1 %) et indépendantes des troubles de la coagulation et du taux de plaquettes. Une insuffisance rénale, une cirrhose Child C, des thrombocytes < 50 G/l et une cirrhose d'origine alcoolique pourraient cependant augmenter le risque de saignement. La prudence reste de mise chez ces patients.

[Portal vein thrombosis in patients with cirrhosis]. / Thrombose de la veine porte chez les malades atteints de cirrhose.

Portal vein thrombosis is frequently encountered in patients with cirrhosis. Increased indication for non-invasive imaging in patients with cirrhosis has dramatically increased the recognition of PVT. This has led to a large amount of studies on pathogenesis as well as the prognostic impact of portal vein thrombosis on natural history of cirrhosis. However, in clinical practice, several aspects of the management of portal vein thrombosis remain unclear. This practical review discusses the most recent data toward the management of portal vein thrombosis in cirrhosis, especially regarding : a) the value of etiological workup ; b) the impact of portal vein thrombosis on the natural history of cirrhosis, and c) the indications and modalities of anticoagulation therapy.

La thrombose porte est une complication fréquente au cours de la cirrhose. Sa reconnaissance a largement augmenté, grâce au développement de moyens d'imagerie non invasifs et performants. Au cours des dernières années, la pathogénie de la thrombose porte au cours de la cirrhose, ainsi que sa valeur pronostique ont été largement étudiées. Cependant, en pratique clinique, la prise en charge des malades atteints de cirrhose et de thrombose porte n'est pas établie. Cet article discute les données récentes de la littérature concernant la gestion pratique de la thrombose porte au cours de la cirrhose : a) la nécessité d'un bilan de thrombophilie ; b) l'influence de la thrombose porte sur l'histoire naturelle de la cirrhose et c) les indications et les modalités du traitement anticoagulant.