Après lecture des propositions du comité du GGV, nous relevons plusieurs questions qui nous semblent pertinentes pour leur application pratique et quelques propositions complémentaires qui pourraient venir étoffer ce document.

Background: Inflammatory bowel disease (IBD) needs early interventions and an individual specialist–patient relationship. Distance from a tertiary IBD center might affect patient’s disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods: Patient’s home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: <10 km (group 1); 10–35 km (group 2); >35 km (group 3). Results: Our study included in total 408 IBD patients [234 Crohn’s disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups. Conclusions: Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland.

Background/Aims Extraintestinal manifestations (EIM) involving joints, skin, eyes and liver represent an important problem in the treatment of IBD patients. The aim of this study was to identify factors that are associated with the occurrence of joint EIM and therefore allow an early diagnosis and guide medical treatment. Methods We studied clinical and epidemiological data from 3298 patients included in the Swiss IBD Cohort Study (SIBDCS), 1860 suffered from Crohn’s disease (CD) and 1438 from ulcerative colitis or IBD unclassified (UC/IBDU). Results We found female gender as well as a longer disease duration and activity (specified as CDAI or MTWAI, respectively) to be related to the appearance of arthritis/arthralgia, but also sacroiliitis/ankylosing spondylitis in IBD patients. IBD patients with arthritis/arthralgia or sacroiliitis/ankylosing spondylitis were more often treated with anti-TNF and patients with arthritis/arthralgia underwent more often IBD-related surgeries. We revealed that eye or skin EIM were more frequent in patients with arthritis/arthralgia or sacroiliitis/ankylosing spondylitis. In multivariate analysis, we confirmed female gender, longer disease duration, IBD-related surgery, presence of other EIM and treatment with anti-TNF to be independent risk factors for the onset of arthritis/arthralgia in CD and UC/IBDU patients. Conclusion In this study, we demonstrated that markers for a more severe disease course were associated with the onset of joint EIM in IBD patients. Our data suggest that in particular females under anti-TNF treatment and patients suffering from non-joint and/or IBD-related surgery should be close and carefully monitored for presence of arthritis or sacroiliitis/ankylosing spondylitis.

Background Many inflammatory bowel disease (IBD) patients follow a restrictive diet due to perceived positive effects on their symptoms. We assessed the prevalence of vegetarian (VD) and gluten-free diets (GFDs) in IBD patients, the reasons for following such a diet, and whether nutrition has an impact on disease activity and microbiota composition. Methods We included 1254 patients from the Swiss Inflammatory Bowel Disease Cohort Study with prospective acquisition of clinical data and psychosocial, disease-related and lifestyle factors between 2006 and 2015. Dietary habits were assessed through a self-report questionnaire. In 92 patients, we analysed intestinal mucosa-associated microbial composition using high-throughput sequencing. Results Overall, 4.1% (n = 52) of the patients reported following a VD and 4.7% (n = 54) a GFD. No differences regarding disease activity, fistula, hospitalization or surgery rates were observed. Patients on a VD or GFD had significantly higher levels of post-traumatic stress symptoms. Furthermore, GFD patients had significantly higher anxiety and depression symptom levels. The gut microbiota composition in IBD patients following a VD or GFD was significantly different compared to that of omnivores. Conclusions Although we did not identify a relevant impact of a specific diet on the course of the disease, there was a significant association with lower psychological well-being in VD and GFD patients.

BACKGROUND:Extraintestinal manifestations (EIM) contribute significantly to the burden of disease in inflammatory bowel disease (IBD). Pain is a leading symptom in IBD and could be seen as an EIM itself. Treatment of IBD associated pain is challenging and insufficiently studied. A better knowledge on the association of pain and IBD specific treatment is warranted to improve the management of IBD patients.METHODS:All patients of the Swiss IBD Cohort Study (SIBDCS) (n = 2152) received a questionnaire regarding pain localization, pain character, and the use of IBD specific medication.RESULTS:1263 completed questionnaires were received. Twenty-one out of 184 patients (10%) receiving anti-TNF treatment compared to 142 out of 678 patients (21%) not receiving anti-TNF medication reported elbow pain (p = 0.002) while 28 out of 198 patients (14%) receiving steroid treatment significantly more often reported elbow pain compared to 59 from 696 patients (8%) not receiving steroids (p = 0.021). Furthermore, we found significantly more female patients under anti-TNF treatment to report knee/ lower leg pain and ankle/ foot pain compared to their male counterparts (36% vs. 20% and 22% vs. 10%, respectively, p = 0.015 for both comparisons). The frequency of knee, lower leg, ankle and foot pain was especially low in male patients under anti-TNF treatment, indicating a high benefit of male patients from anti-TNF therapy regarding EIM.CONCLUSIONS:The frequency of elbow pain was lower in IBD patients treated with anti-TNF but higher in patients treated with steroids.

BackgroundThe frequency of upper gastrointestinal [GI] tract involvement in Crohn`s disease [CD] has been reported with a large variation. Risk factors and disease course of patients with upper GI tract involvement remain largely elusive.MethodsData on CD patients in the Swiss Inflammatory Bowel Disease Cohort were analysed. Patients with upper GI tract involvement were compared with controls. Logistic regression models for prediction of upper GI tract involvement and Cox proportional hazard models for occurrence of complications were computed.ResultsWe included 1638 CD patients, of whom 107 [6.5%] presented with upper GI tract involvement at the time of diagnosis and 214 [13.1%] at any time. Prevalence of such involvement at diagnosis increased over time [5.1% for 1955-95 versus 11.3% for 2009-16]. In a multivariate logistic regression model, male sex and diagnosis between 2009 and 2016 [versus before 1995] were independent predictors for presence of upper GI tract involvement at CD diagnosis (odds ratio [OR] 1.600, p = 0.021 and OR 2.686, p < 0.001, respectively), whereas adult age was a negative predictor [OR 0.388, p = 0.001]. Patients with upper GI tract involvement showed a disease course similar to control patients (hazard ratio [HR] for any complications 0.887, (95% confidence interval [CI] 0.409-1.920), and a trend towards occurrence of fewer intestinal fistulas [log-rank test p = 0.054].ConclusionsPrevalence of upper GI tract involvement has been increasing over the past decades. Male sex and young age at diagnosis were identified as the main predictive factors for such involvement at CD diagnosis. Involvement of upper GI tract did not result in a worse outcome.

1) Ajmera V, Perito ER, Bass NM, Terrault NA, Yates KP, Gill R, et al.; NASH Clinical Research Network. Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. HEPATOLOGY 2017;65:65-77. 2) Sookoian S, Castano GO, Burgueno AL, Rosselli MS, Gianotti TF, Mallardi P, et al. Circulating levels and hepatic expression of molecular mediators of atherosclerosis in nonalcoholic fatty liver disease. Atherosclerosis 2010;209:585-591. 3) Rosselli MS, Burgueno AL, Carabelli J, Schuman M, Pirola CJ, Sookoian S. Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model. Atherosclerosis 2009;206:119-126. 4) Takeshita Y, Takamura T, Ando H, Hamaguchi E, Takazakura A, Matsuzawa-Nagata N, et al. Cross talk of tumor necrosis factor-alpha and the renin-angiotensin system in tumor necrosis factor-alpha-induced plasminogen activator inhibitor-1 production from hepatocytes. Eur J Pharmacol 2008;579:426-432. 5) Sookoian S, Pirola CJ. Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis. Obes Surg 2013;23:1815-1825.

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is continuously evolving. Updated data on dual HBV and HCV infection are still needed. Aims: To assess the main characteristics of patients with HBV and HCV dual infection, to compare these with those of patients infected with either HBV or HCV and, among patients with dual infection, to assess fibrosis according to HCV replication. Methods: Data of 23 patients with dual infection were compared to data from 92 age and sex-matched HBV or HCV monoinfected patients. Results: Patients with dual infection were more often immigrants from Africa or Asia than HCV or HBV patients (52% vs. 20% and 22%, respectively, P= 0.01). Intravenous drug use was the route of transmission in 22% of patients with dual infection, which was less frequent than in HCV patients (41%) but more frequent than in HBV patients (0%). Extensive fibrosis or cirrhosis was as frequent among dual-infected patients as among those with HCV or chronic hepatitis B infection (19% vs. 29% vs. 14%, respectively, P=0.4), even when fibrosis stage was reported considering the duration of infection. In dual-infected patients, the prevalence of extensive fibrosis or cirrhosis was similar in patients with and without detectable HCV RNA (18% vs. 20%). Conclusions: Patients with HBV and HCV dual infection were more often immigrants from Africa or Asia and had similar fibrosis stages than HCV or HBV monoinfected patients. In patients with dual infection, extensive fibrosis or cirrhosis was not associated with HCV replication. (C) 2017 Elsevier Masson SAS. All rights reserved.

BackgroundAutochthonous hepatitis E is increasingly recognized as zoonotic infection in western countries. Serological assays have varying sensitivity and specificity. MethodsWe implemented molecular testing to identify and characterize acute hepatitis E acquired in Switzerland. ResultsNinety-three cases of mostly symptomatic acute hepatitis E acquired in Switzerland were documented by PCR between November 2011 and December 2016. Median HEV RNA was 7.5x10(4) IU/mL (range, 5.3 to 4.7x10(7) IU/mL). HEV genotyping was successful in 78 patients, revealing genotype 3 in 75 and genotype 4 in three patients. Phylogenetic analyses revealed a few limited geographical and temporal clusters. Of the 91 patients with available anti-HEV IgM serology, four were negative; three of these were also IgG-negative, likely as a result of immunosuppression, and one was IgG-positive, a constellation compatible with HEV reinfection. Median age of the patients was 58years (range, 20-80years); 71 (76.3%) were men and 49 of these (69.0%) were 50years old. The clinical course was particularly severe in patients with underlying chronic liver disease, with fatal outcome in two patients. Six patients (6.5%) presented with neuralgic amyotrophy. ConclusionsNucleic acid-based diagnosis reveals HEV as a relevant cause of acute hepatitis in Switzerland. Middle-aged and elderly men constitute the majority of symptomatic patients. Testing for HEV should be included early in the diagnostic workup of acute hepatitis and of neuralgic amyotrophy, a typical extrahepatic manifestation of HEV genotype 3 infection.

We thank Deltenre et al. [ [1] Deltenre P. Marot A. Knebel J.-F. Doerig C. Henrion J. Moreno C. Effect of abstinence on the prognosis of patients with alcoholic liver disease: a word of caution. J Hepatol. 2017; 66: 1329-1330 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ] for their interest in our study on long-term prognosis in patients with alcoholic liver disease (ALD) [ [2] Lackner C. Spindelboeck W. Haybaeck J. Douschan P. Rainer F. Terracciano L. et al. J Hepatol. 2017; 66: 610-618 Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar ]. In response to their methodological concerns, we would like to clarify the following points: Effect of abstinence on the prognosis of patients with alcoholic liver disease: A word of cautionJournal of HepatologyVol. 66Issue 6PreviewWe read the article by Lackner and collaborators [1] with great interest. The main goal of this study was to assess factors associated with long-term prognosis in patients with biopsy-proven alcoholic liver disease (ALD). Although this study is of major clinical relevance, we believe it deserves several comments. Full-Text PDF Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver diseaseJournal of HepatologyVol. 66Issue 3PreviewAlcoholic liver disease (ALD) is a substantial burden on public health and is responsible for half of the cases of cirrhosis worldwide [1,2]. Despite its health and socioeconomic burden, there have not been major advances in the management of these patients. There are no widespread programs for early detection and the current therapy for its more severe form (i.e., prednisolone for alcoholic hepatitis) has not evolved since 1971 [3,4]. The complex pathogenesis of ALD, influenced by host and environmental factors, is only partially understood. Full-Text PDF

Introduction: We describe a patient who developed neuralgic amyotrophy (NA) related to hepatitis E virus (HEV) infection. Methods: The patient underwent neurological and electrodiagnostic examinations, high-resolution analysis of serological changes, and HEV load profile, and was treated with intravenous immunoglobulin. Results: There was evidence of bilateral, asymmetric acute inflammatory cervical polyradiculopathy and possible brachial plexopathy. Positive serum anti-HEV IgM was followed by seroconversion to anti-HEV IgG positivity. A calculated anti-HEV antibody index was compatible with intrathecal synthesis, and HEV genotype 3 RNA was found in serum and cerebrospinal fluid (CSF). Liver function tests returned to normal within 6 weeks. Conclusions: Bilateral involvement of cervical nerve roots and/or plexus, elevated liver function tests, and abnormal CSF are typical features of HEV-associated NA. The pathogenesis involves possible immune-mediated mechanisms. However, our findings support the hypothesis that HEV-related NA is associated with direct infection.

Background & Aims: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death.Methods: Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis.Results: 74 patients consumed alcohol (median alcohol intake: 15 g/day); 68 reached viral eradication. During a median follow-up of 58 months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p = 0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p = 0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p = 0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p = 0.004). Alcohol intake did not influence the risk of decompensation or death.Conclusions: Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence.Lay summary: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

ALT and waist circumference are both correlated to insulin resistance (IR).Objective : To determine whether ALT provides information in addition to waist circumference for identifying IR.Methods : IR was defined by HOMA-IR index >= 3. In this Europid population, a waist circumference >= 80 cm in women and >= 94 cm in men was considered excessive. Elevated ALT was defined using either the usual cut-off or updated cut-offs of 19 U/l in women and 30 U/l in men.Results : 288 participants without medication affecting insulin concentration were included. 81 (28%) were insulin resistant, 30 (10%) and 98 (34%) had increased ALT using usual and updated cut-offs, respectively, and 218 (76%) had excessive waist circumference. Among subjects with normal waist circumference, IR was as frequent in participants with normal ALT as in those with increased ALT. Among subjects with excessive waist circumference, IR was less frequent in participants with normal ALT according to the usual cut-off (31% vs. 56%, p=0.01), and tended to be less frequent in participants with normal ALT according to updated cut-offs (29% vs. 41%, p=0.07) than in those with increased ALT.Conclusion : ALT is useful for identifying IR only if waist circumference is excessive. In subjects with excessive waist circumference, IR is present in more than 40% in women with ALT >19 U/l and in men with ALT >30 U/l, and in more than 50% in individuals with ALT >45 U/l.

Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.