Bariatric surgery, obesity and liver transplantation.

The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.

Low Thyroid Function in Nonalcoholic Fatty Liver Disease Is an Independent Predictor of All-Cause and Cardiovascular Mortality.

INTRODUCTION: Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status. METHODS: The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality. RESULTS: In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group. DISCUSSION: In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.

Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking. APPROACH AND RESULTS: We performed a serial, cross-sectional analysis among adults by using the 2007-2016 US National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure-time PA, occupation-related PA, transportation-related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age, 47.4 years; 47.9% males), leisure-time PA (≥150 minutes per week) demonstrated 40% lower odds of NAFLD, whereas transportation-related PA was associated with a 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose-response association between sitting time and NAFLD (P for trend < 0.001). Compliance with the PA Guidelines was lower in individuals with NAFLD versus those without NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in individuals with NAFLD except for a downtrend in transportation-related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure time was noted in the cohort without NAFLD. Although PA demonstrated a 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA Guidelines. Trends in total sitting time increased significantly regardless of NAFLD status. CONCLUSIONS: Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the cohort with NAFLD, with sex- and ethnicity-based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.

Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD.