Recurrence of primary sclerosing cholangitis after liver transplantation - analysing the European Liver Transplant Registry and beyond.

Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant - a pilot study.

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn's disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.

Nonalcoholic Fatty Liver Disease in The Rotterdam Study: About Muscle Mass, Sarcopenia, Fat Mass, and Fat Distribution.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Obesity is a major risk factor for NAFLD and recently, low skeletal muscle mass emerged as additional risk factor for NAFLD. However, the different contributions of body mass index (BMI) to the risk of NAFLD are not yet well-known. We therefore studied body composition and muscle function with NAFLD in an elderly population-based study. Participants of European descent underwent dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography. NAFLD was defined as liver steatosis in absence of secondary causes for steatosis. Skeletal muscle index (SMI) was defined as appendicular lean mass/height2 and (pre)sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus guidelines. All analyses were stratified by sex and BMI (cut point: 25 kg/m2 ) and adjusted for age, weight, height, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and android-fat-to-gynoid-fat ratio (AGR). We included 4609 participants, of whom 1623 had NAFLD (n = 161 normal-weight and n = 1462 overweight). Presarcopenia and sarcopenia prevalence was low (5.9% and 4.5%, respectively) and both were not associated with NAFLD. SMI was associated with less NAFLD in normal-weight women (OR, 0.48; 95% CI, 0.29 to 0.80). A similar association for SMI and NAFLD was seen in normal-weight men, but significance dissipated after adjustment for AGR (OR, 0.63; 95% CI, 0.39 to 1.02). Generally, fat mass was a better predictor for NAFLD than lean mass. In particular, android fat mass was associated with all NAFLD subgroups (OR from 1.77 in overweight men to 8.34 in normal-weight women, pmax = 0.001), whereas substitution of gynoid fat mass for other body components had a significant protective association with NAFLD in every subgroup, but normal-weight men. Likewise, AGR was the best performing predictor for NAFLD prevalence (OR from 1.97 in normal-weight men to 4.81 in normal-weight women, pmax < 0.001). In conclusion, both high fat mass and low SMI were associated with normal-weight NAFLD. However, fat distribution (as assessed by AGR) could best predict NAFLD prevalence. © 2019 American Society for Bone and Mineral Research.