Heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions. (Hepatology 2018;67:1284-1302).

Background and Aims-A greater understanding of cholestatic disease is necessary to advance diagnostic tools and therapeutic options for conditions such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The purpose of this study was to determine and compare the serum metabolomes of patients with PBC (n=18) or PSC (n=21) and healthy controls (n=10) and to identify metabolites that may differentiate these two cholestatic diseases.

Background & Aims Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort: subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex. Methods We compared data from 145 patients with AH cases and 124 controls, based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the time line follow back method, the Alcohol Use Disorders Identification Test, and National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses we to assess effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. Results Cases with AH were older (47 vs 44 years; P=.03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P=.007). Conclusion Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism.

Background & Aims Previous cross-sectional studies have shown that serum keratin 18 (K18) fragment levels predict liver histology in individuals with nonalcoholic fatty liver disease (NAFLD). We conducted a study to examine the relationship between changes in serum K18 levels and changes in liver histology in both adults and children with NAFLD. Methods Serum K18 levels were measured at baseline and at various time points in 231 adults and 152 children with NAFLD who participated in two randomized controlled trials. Liver biopsies from baseline and week 96 were reviewed centrally. Results There was greater decrease in serum K18 levels in adults with histological improvement at week 96 than those without histological improvement at week 16 (-193 ± 293 vs -139 ± 467 U/L, p<0.001), week 48 (-232 ± 360 vs -113 ± 425 U/L, p<0.001), and week 96 (-269 ± 368 vs -97 ± 400 U/L, p<0.001). There was greater decrease in serum K18 levels in children with histological improvement than those without histological improvement at week 48 (-197 ± 467 vs.-47 ± 350 U/L, p=0.005) and week 96 (-206 ± 432 vs. -2 ± 474 U/L, p<0.001). However, decrease in serum K18 was not better than decrease in ALT in identifying histological improvement in adults (AUROC, 0.71 [0.63, 0.80] vs 0.68 [0.61, 0.79], p=0.34) or children (0.72 [0.63-0.81] vs. 0.79 [0.70-0.87], p=0.42). Conclusion Decrease in serum K18 levels is strongly associated with improvement in liver histology in adults or children with NAFLD. However, K18 decrease did not perform better than ALT improvement in identifying histological changes in NAFLD.

Summary:The relationship between exercise tolerance assessed by a conventional exercise stress test using a standard Bruce protocol and quality of life (QoL) was studied in 50 patients with stable angina pectoris (AP). Before the exercise test, patients completed three self-administered QoL questionnaires, the Psychological General WellBeing Index, an Angina-Specific QoL Questionnaire, and Jenkins' Sleep Dysfunction Scale. Total exercise time (r= -0.40) and time until onset ofpain (r= -0.44) were significantly correlated with perceived physical limitations. Somatic symptoms were related to total time (r= -0.38). Apart from a significant correlation between depressed mood and total exercise time (r=0.36), there was no corresponding correlation with well-being and sleep disturbance. These results suggest that exercise stress tests do not rcilect quality of life in patients with AP.