Impact of inflammatory bowel disease on the outcome of liver transplantation for primary sclerosing cholangitis: A multicenter comparative study

La cholangite sclérosante primitive (CSP) représente 4 % des indications de transplantations hépatiques (TH) en Europe. Elle est associée aux maladies inflammatoires chroniques intestinales (MICI) dans 70 % des cas. L’influence d’une MICI sur les suites d’une TH des patients atteints de CSP a rarement été étudiée. L’objectif de notre étude était d’évaluer l’impact des MICI sur la survie et les complications après TH pour CSP. Cette étude multicentrique rétrospective a été menée dans quatre centres français de TH et a inclus tous les patients transplantés hépatiques pour CSP ou syndrome de chevauchement entre 1989 et 2017. Les patients retransplantés ont été exclus. Les caractéristiques cliniques, endoscopiques et thérapeutiques des MICI avant et après TH ont été collectées. L’objectif était de comparer, au sein des patients transplantés pour CSP, la survie globale et la survie du greffon entre ceux avec MICI associée avant TH (groupe 1) et ceux sans MICI (groupe 2). Les complications post-TH ont secondairement été analysées. Les facteurs associés à la survie ont été recherchés à l’aide d’un modèle de régression logistique. Les paramètres de survie ont été analysés comparativement à un groupe contrôle de patients transplantés pour cirrhose éthylique (groupe 3) avec appariement sur l’âge du receveur et l’année de TH. Résultats : Quatre-vingt-sept patients ont reçu une TH pour CSP incluant 52 patients avec MICI (groupe 1) et 35 patients sans MICI (groupe 2). 86 patients étaient dans le groupe contrôle (groupe 3). La durée médiane de suivi était de 89 mois (36-160 mois) dans l’ensemble de la population. Concernant les patients avec CSP, les scores de MELD du groupe 2 étaient plus élevés que ceux du groupe 1 lors de la TH (17 versus 10, p=0,010). La majorité des patients avec MICI étaient en rémission clinique, 75% étaient en rémission endoscopique. Les protocoles d’immunosuppression per-TH étaient similaires entre les 2 groupes de CSP mais la corticothérapie a été poursuivie plus de 3 mois dans le groupe 1 (96,2% versus 82,9% p=0,035). Les taux de survie globale et de survie du greffon à 10 ans n’étaient pas différents : 92,6% [IC 95% 0,843-1] et 77,1% [IC 95% 0,538-0,853] dans le groupe 1 et, 97,1% [IC 95% 0,914-1] (p=0,441) et 83,2% [IC 95% 0,696 0,969] (p=0,! 433) dans le groupe 2 respectivement. Comparativement au groupe 3, la survie globale à 10 ans des patients avec CSP était plus élevée (94,5% [IC 95% 0,891- 0,998] versus 77,9% [0,673-0,884], p=0,032). Il n’y avait pas de différence sur la récidive de la CSP (21,2% versus 11,4%, p=0,239). Les taux de rejets, d’infections et de cancers après TH étaient similaires dans les deux groupes. Cependant, les infections à CMV étaient significativement plus fréquentes dans le groupe 1 (36,5% versus 17,1%, p=0,050). L’exposition à un traitement immunosuppresseur par Azathioprine après TH et une courte durée d’évolution de la CSP avant TH étaient les facteurs associés au décès en analyse multivariée et à la perte du greffon en analyse univariée. Conclusion : La présence d’une MICI associée à une CSP avant TH ne modifie ni la survie globale ni la survie du greffon. Elle est associée à un risque plus important d’infections à CMV.Primary sclerosing cholangitis (PSC) accounts for 4% of indications for liver transplantations (LT) in Europe. It is usually associated with inflammatory bowel diseases (IBD). LT is the only effective treatment for patients with end-stage liver disease. When associated with PSC, the impact of IBD on LT outcome remains poorly known. Aims: to assess the impact of IBD on the survival and complications following LT for PSC. This retrospective study was conducted in four French liver transplantation centers recruiting consecutive adult patients who underwent LT for PSC from 1989 to 2017. Clinical, endoscopic and therapeutic features of IBD were collected. The primary objective was to compare overall and graft survivals in grafted PSC patients having an associated IBD before LT (group 1) to those without IBD (group 2). Then, we studied the complications post-LT. Survival data were analyzed comparatively to a control-matched group of transplanted alcoholic cirrhotic patients (group 3). A logistic regression multivariate model identified predictive survival factors. Results: Eighty-seven patients underwent LT for PSC, including 52 patients with IBD (group 1) and 35 patients without (group 2), and 86 patients in the control group (group 3). The median follow-up duration was 88.9 months (range, 36-160 months). Regarding PSC patients, MELD scores from group 2 was higher than those from group 1 (17 versus 10, p=0.010). Most patients with IBD were in clinical remission and 75% of patients were in endoscopic remission. The immunosuppressive protocols per-OLT were similar between the two PSC groups, but steroids were continued more than 3 months in group 1 (96.2% versus 82.9% p=0.035). The ten-year overall survival and graft survival rates were not significantly different: 92.6% [95% CI 84.3-100] and 77.1% [95% CI 53.8-85.3] in group 1 and, 97.1% [95% CI 91.4-100] (p=0.441) and 83.2% [95% CI 69.6-96.9] (p=0.433) in group 2, respectively. Comparatively to the group 3, the ten-year overall survival rate of patients with PSC was higher (94.5% [89! .1- 99.8] versus 77.9% [67.3-88.4], p=0.032). More than 50% of patients had at least one infectious event after LT without significant difference in both groups (58% versus 63% in group 1 and in group 2 respectively). PSC recurrence rates were not different in both groups (21% versus 11%, p=0.239). Rates of graft rejection (35% versus 46%, p=0.298) and rates of cancer (17% vs 14%, p=0.54) were also similar. Two colonic cancers occurred in group 1 only. CMV infections occurred more frequently in group 1 (36.5% versus 17.1% p=0.050). A preexisting IBD before LT, an active IBD post-LT and an extended exposition or with high doses of steroids after LT were not factors associated with death and graft loss. Use of azathioprine after LT (OR IC95% 19.08 [2.22-163.7], p=0.007) and a shorter duration of PSC pre-LT (0.57 [0.34-0.93], p=0.026) were associated with death in multivariate analysis (with graft loss in univariate analysis only). Conclusion: Preexisting IBD before LT for PSC has no impact on overall and graft survivals. The presence of IBD increases the rate of CMV infection

Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients

International audienceBackground & aims: Two-dimensional shear wave elastography (2D-SWE) is an accurate method for the non-invasive evaluation of liver fibrosis. We aimed to determine the reliability criteria and the number of necessary reliable measurements for 2D-SWE.Methods: 788 patients with chronic liver disease underwent liver biopsy and 2D-SWE examination in three centers. The 4277 2D-SWE measurements performed were 2:1 randomly divided into derivation (n = 2851) and validation (n = 1426) sets. Reliability criteria for a 2D-SWE measurement were defined in the derivation set from the intrinsic characteristics given by the device (mean liver stiffness, standard deviation, diameter of the region of interest), with further evaluation in the validation set.Results: In the whole population of 4277 measurements, AUROC for bridging fibrosis was 0.825 ± 0.006 and AUROC for cirrhosis was 0.880 ± 0.006. Mean stiffness and coefficient of variation (CV) were independent predictors of bridging fibrosis or cirrhosis. From these two parameters, new criteria were derived to define a reliable 2D-SWE measurement: stiffness <8.8 kPa, or stiffness between 8.8-11.9 kPa with CV <0.25, or stiffness ≥12.0 kPa with CV <0.10. In the validation set, AUROC for bridging fibrosis was 0.830 ± 0.013 in reliable measurements vs 0.667 ± 0.031 in unreliable measurements (P < .001). AUROC for cirrhosis was 0.918±0.014 vs 0.714 ± 0.027, respectively (P < .001). The best diagnostic accuracy for a 2D-SWE examination was achieved from three reliable measurements.Conclusions: Reliability of a 2D-SWE measurement relies on the coefficient of variation and the liver stiffness level. A 2D-SWE examination should include three reliable measurements according to our new criteria

New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD

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Similar 5-year HCC occurrence in Tenofovir- and Entecavir-treated HBV chronic infection in the French AFEF/ANRS CO22 Hepather cohort.

International audienceBackground: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications.Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort.Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co-infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW).Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow-up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir- (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person-years) and entecavir-treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person-years, respectively.Conclusion: The risk of liver-related events or death was not different between tenofovir- and entecavir-treated patients in this large prospective cohort of predominantly non-cirrhotic French patients.Trial registration number: NCT019553458

Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

International audienceBackground: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients.Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively.Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population

Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

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Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort

International audienceBackground: Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models.Results: Among the 6348 participants in the study population, 55% had central obesity, 13.7% had obesity according to their BMI, and 12.4% were current cannabis users. After multivariable adjustment, current cannabis use was associated with lower risk of central obesity (adjusted odds ratio, aOR [95% confidence interval, CI]: 0.45 [0.37-0.55]), BMI-based obesity (adjusted relative risk ratio (aRRR) [95% CI]: 0.27 [0.19-0.39]), and overweight (aRRR [95% CI]: 0.47 [0.38-0.59]). This was also true for former use, but to a lesser extent. Former and current cannabis use were inversely associated with waist circumference and BMI.Conclusions: We found that former and, to a greater extent, current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity in patients with chronic HCV infection. Longitudinal studies are needed to confirm these relationships and to assess the effect of cannabis use on corpulence and liver outcomes after HCV cure.Trial registration: ClinicalTrials.gov identifier: NCT01953458