The incidence of OAC in non-dysplastic BO is around 1 per 300 patients per year. The incidence of OAC in short-segment BO is under 1 per 500 patients per year.

SSI is associated with detriment to patient and graft survival following renal transplantation. The prevalence of SSI is higher among obese recipients, but those who avoid SSI have comparable outcomes to nonobese recipients. These findings redemonstrate the importance of SSI prevention following renal transplantation.

No abstract

Background and Aims The effects of diet quality (DQ), physical activity (PA), and socioeconomic status (SES) on the risk of NAFLD are unclear. We examined the association among DQ, PA, SES, and NAFLD risk. Approach and Results This is a cross‐sectional analysis of the National Health and Nutrition Examination Surveys, 2017–2018, which included 3589 participants with reliable information on vibration‐controlled transient elastography (VCTE) measurements, 24‐h dietary recalls, PA, and SES. DQ was assessed by the Healthy Eating Index (HEI)‐2015. PA was determined by the Global Physical Activity Questionnaire. SES was assessed by the educational attainment and family poverty income ratio (PIR). Risk of NAFLD was considered by means of a composite outcome using VCTE measurements: non‐NAFLD versus NAFLD without clinically significant fibrosis (CSF) versus NAFLD with CSF. The NAFLD risk was lower in physically active (≥600 metabolic equivalent of task [MET] min/week) versus inactive participants (<600 MET min/week) (OR: 0.71, p = 0.043). A high‐quality diet (HQD) (HEI > 56.64) was associated with a lower risk of NAFLD (OR: 0.58, p < 0.01) compared with a non‐HQD. The lowest NAFLD risk was observed in those physically active with HQD (OR: 0.43, p < 0.01). Body mass index and waist circumference significantly mediated the effect of DQ and PA on NAFLD risk. Education (college or above) (OR: 0.65, p = 0.034), but not PIR, was associated with a reduced NAFLD risk. HQD and increased PA partially mediated the effect of education on NAFLD risk. The total effect of education on NAFLD risk mediated by DQ was 29% and by PA was 8%. Conclusions HQD, increased physical activity, and college education were associated with lower NAFLD risk in the US population.

Background and Aims Human NAFLD is characterized at early stages by hepatic steatosis, which may progress to NASH when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through down‐regulation of miR‐125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR‐125b signaling on hepatic steatosis, biliary senescence, and liver fibrosis in NAFLD/NASH. Approach and Results In vivo, 4‐week‐old male wild‐type, Sct−/− and Sctr−/− mice were fed a control diet or high‐fat diet (HFD) for 16 weeks. The expression of SCT/SCTR/miR‐125b axis was measured in human NAFLD/NASH liver samples and HFD mouse livers by immunohistochemistry and quantitative PCR. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were evaluated in mouse liver and human NAFLD/NASH liver samples. miR‐125b target lipogenesis genes in hepatocytes were screened and validated by custom RT2 Profiler PCR array and luciferase assay. Biliary SCT/SCTR expression was increased in human NAFLD/NASH samples and in livers of HFD mice, whereas the expression of miR‐125b was decreased. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were observed in human NAFLD/NASH samples as well as HFD mice, which were decreased in Sct−/− and Sctr−/− HFD mice. Elovl1 is a lipogenesis gene targeted by miR‐125b, and its expression was also decreased in HFD mouse hepatocytes following Sct or Sctr knockout. Bile acid profile in fecal samples have the greatest changes between wild‐type mice and Sct−/−/Sctr−/− mice. Conclusion The biliary SCT/SCTR/miR‐125b axis promotes liver steatosis by up‐regulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR‐125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.

Background The American Association for the Study of Liver Diseases (AASLD) practice guidelines provide recommendations in diagnosing and managing patients with liver disease from available scientific evidence in combination with expert consensus opinions. Aim To systematically review the evolution of recommendations from AASLD guidelines and identify gaps limiting the evidence-based foundations of these guidelines. Methods Initial and current AASLD guidelines published from January 1998 to August 2012 were reviewed. The AGREE II instrument was used to evaluate rigour and transparency of guideline development. The number of recommendations, distribution of grades (strength or certainty), classes (benefit versus risk) and types of recommendations were evaluated. Whenever possible, multiple versions were evaluated for evolving scientific evidence. Results A total of 991 recommendations from 28 guidelines on 17 topics were evaluated. From initial to current guidelines, the total number of recommendations increased by 36%(512 to 699). The largest increases were from chronic hepatitis B (HBV) (+71), liver transplantation (+53) and autoimmune hepatitis (AIH) (+27). Most current recommendations are grade II (44%) and less than 20% are grade I. The AGREE II evaluation showed global improvement in guideline quality. Both HBV and chronic hepatitis C guidelines had greatest increases in grade I recommendations (+383% and +67%, respectively). The greatest increases in treatment recommendations were from HBV (grade I, +1150%), liver transplantation (grade II, +112%) and AIH (grade III, +105%). Conclusions Despite significant increases in the numbers of recommendations within AASLD practice guidelines over time, only a minority are supported by grade I evidence, highlighting the need for developing well-designed investigations to provide evidence for areas of uncertainty and improving the quality of future guidelines in hepatobiliary diseases.

Oxidative stress (OS) in non-alcoholic fatty liver disease (NAFLD) promotes liver injury and inflammation. Treatment with vitamin E (α-tocopherol, αT), a lipid-soluble antioxidant, improves liver injury but also decreases steatosis, thought to be upstream of OS, through an unknown mechanism. To elucidate the mechanism, we combined a mechanistic human trial interrogating pathways of intrahepatic triglyceride (IHTG) accumulation and in vitro experiments. 50% of NAFLD patients (n = 20) treated with αT (200–800 IU/d) for 24 weeks had a ≥ 25% relative decrease in IHTG by magnetic resonance spectroscopy. Paired liver biopsies at baseline and week 4 of treatment revealed a decrease in markers of hepatic de novo lipogenesis (DNL) that strongly predicted week 24 response. In vitro, using HepG2 cells and primary human hepatocytes, αT inhibited glucose-induced DNL by decreasing SREBP-1 processing and lipogenic gene expression. This mechanism is dependent on the antioxidant capacity of αT, as redox-silenced methoxy-αT is unable to inhibit DNL in vitro . OS by itself was sufficient to increase S2P expression in vitro , and S2P is upregulated in NAFLD livers. In summary, we utilized αT to demonstrate a vicious cycle in which NAFLD generates OS, which feeds back to augment DNL and increases steatosis. Clinicaltrials.gov : NCT01792115.

BACKGROUND & AIMS: We studied impaired quality of life (QOL) and its determinants among individuals with nonalcoholic fatty liver disease (NAFLD). METHODS: We collected data from 341 patients with NAFLD who completed the short form 36 (SF-36) questionnaire. Body composition and liver fibrosis were assessed in patients with NAFLD using bioelectrical impedance and transient elastography, respectively. Advanced fibrosis was defined as liver stiffness measurements (LSMs) of 12.1 kPa or greater. SF-36 scores of patients with NAFLD were compared with SF36 scores of individuals with chronic medical illnesses and the general population obtained from the published literature. RESULTS: Among patients with NAFLD, percent body fat was negatively associated with scores from all 8 SF-36 scales, whereas lean body mass was positively associated with scores from 5 of 8 SF-36 scales. On multivariable analysis, SF-36 PF scores were negatively associated with type 2 diabetes, body mass index, and LSM and positively associated with lean body mass and level of alanine aminotransferase. Patients with NAFLD, and even those without advanced fibrosis, had significantly lower mean QOL scores than the control group or the general population. CONCLUSIONS: Individuals with NAFLD, even those without advanced fibrosis, have lower QOL than controls. Body composition associates with QOL in patients with NAFLD; both of the modifiable factors independently associated with QOL are related to body composition. Further studies are needed to investigate if interventions to improve body composition can increase QOL for patients with NAFLD.