Background This cross-sectional study aims to investigate the association between subclinical atherosclerosis and metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD), and a synergistic effect of diabetes mellitus (DM) and MAFLD on subclinical atherosclerosis. Methods Of 977 subjects who underwent health checkups with coronary artery calcification (CAC), carotid intima-media thickness, and brachial-ankle pulse wave velocity (ba-PWV), 890 were included in this study. They were classified as MAFLD, NAFLD, or Neither-FLD, and MAFLD was further categorized into three groups by three metabolic disorders (obesity, lean with metabolic dysregulation, DM), according to its new definition: Obesity-MAFLD, Lean-MAFLD and DM-MAFLD. Results In a multivariable analysis, MAFLD and NAFLD were significantly associated with subclinical atherosclerosis, except for an association between ba-PWV and NAFLD. MAFLD had higher odds for CAC than NAFLD (for CAC score > 100, odds ratio (OR) = 2.599, 95% confidence interval (CI) = 1.625–4.157; OR = 1.795, 95%CI = 1.145–2.814, respectively). In a sub-analysis, DM-MAFLD had higher odds for CAC (for CAC score > 100, OR = 5.833, 95%CI = 3.047–11.164) than the other groups of MAFLD, when compared to Neither FLD as a reference. Moreover, DM-MAFLD had a higher level of homeostasis model assessment of insulin resistance and high sensitive C-reactive protein, compared to the other groups of MAFLD. Conclusions MAFLD was significantly associated with subclinical atherosclerosis in the general population. Additionally, DM-MAFLD could be a significant risk factor for cardiovascular disease through insulin resistance and low-grade inflammation and requires careful follow-up or appropriate intervention.

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Background: Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated. Tolvaptan, an orally available, selective vasopressin V2-receptor antagonist approved for hyponatremia in the United States and European Union. It is also used for cirrhotic ascites at a relatively low dose (3.75 mg to 7.5 mg) in Japan, exerts its diuretic function by excreting electrolyte-free water. We hypothesized that bioimpedancedefined dynamic changes in fluid status allow prediction of response of V2 antagonism and survival in cirrhotic patients. Methods: In this prospective observational study, 30 patients with decompensated liver cirrhosis who were unresponsive to conventional diuretics were enrolled. Detailed serial changes of body composition that were assessed by using non-invasive bioimpedance analysis (BIA) devices, along with biochemical studies, were monitored at 5 time points. Results: Sixteen patients were classified as short-term responders (53%). Rapid and early decrease of BIA-defined intracellular water, as soon as 6 h after the first dose (ΔICW BIA %-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ΔICW BIA %-6 h was highly correlated with the change of BIA-derived phase angle of trunk, e.g. reduced body reactance operated at 50 kHz after 24 h of the first dose of tolvaptan. Lower baseline blood urea nitrogen and lower serum aldosterone were predictive of a rapid and early decrease of ICW BIA. A rapid and early decrease of ICW BIA in response to tolvaptan was also predictive of a better transplant-free survival. Conclusions: BIA-defined water compartment monitoring may help predict short-term efficacy and survival in decompensated cirrhotic patients treated with tolvaptan.

Background Acute decompensation (AD) of liver cirrhosis (LC) and subsequent acute-on-chronic liver failure (ACLF) are fatal and impair quality of life. Insufficient knowledge of the highly heterogeneous natural history of LC, including decompensation, re-compensation, and possible recurrent decompensation, hinders the development and application of novel therapeutics. Approximately 10%-50% of AD/ACLF is reported to be precipitated by any indeterminate (unidentifiable, cryptogenic, or unknown) acute insults; however, its clinical characteristics are unclear. Methods We conducted a single-center observational study of 2165 consecutively admitted patients with LC from January 2012 to December 2019. A total of 466 episodes of AD/ACLF in 285 patients, including their 285 first indexed AD/ACLF, were extracted for analysis. Stratified analyses of different acute precipitants, classified as indeterminate (AD/ACLFIND), bacterial infection (AD/ACLFBAC), gastrointestinal bleeding, active alcoholism, and miscellaneous, were performed. Results AD/ACLFIND was the leading acute precipitant (28%), followed by AD/ACLFBAC (23%). AD/ACLFIND showed better survival outcomes than AD/ACLFBAC (P = 0.03); however, hyperbilirubinemia, hyponatremia, or leukocytosis significantly and uniquely characterized subgroups of AD/ACLFIND with comparable or even worse survival outcomes than those of AD/ACLFBAC. Patients with subsequent AD/ACLF significantly tended to suffer from AD/ACLF with any organ failure in AD/ACLFIND but not in AD/ACLFBAC (P = 0.004, for trend). In competing risk analysis, patients with AD/ACLFIND were significantly more vulnerable to suffer from recurrent episodes of AD/ACLF within 180 days, compared to those triggered by other precipitants (P = 0.04). Conclusions AD/ACLFIND, the leading acute precipitant, also plays a role in subsequent AD/ACLF. An abruptly exacerbating, remitting, and relapsing nature of systemic inflammation underlying AD/ACLF may also be useful for risk estimation.

Controversies and debates remain regarding the best management of severe acute-onset autoimmune hepatitis (SA-AIH) due to the lack of useful outcome or complication prediction systems. We conducted this clinical practice-based observational study to clarify whether Chronic Liver Failure Consortium Organ Failure scores (CLIF-C OFs) and the computed tomography-derived liver volume to standard liver volume (CTLV/SLV) ratio at admission to a tertiary transplant center can predict outcomes and complications due to infection. Thirty-four consecutive corticosteroid-treated patients with SA-AIH from 2007 to 2018 were included. Severe hepatitis was defined as an international normalized ratio (of prothrombin time) over 1.3 any time before admission. Of the 34 corticosteroid-treated patients with SA-AIH inclusive of 25 (73.5%) acute liver failure cases, transplant-free survival was observed in 24 patients (70.6%). Any infection was noticed in 10 patients (29.4%). CLIF-C OFs, at the cutoff of 9, significantly predicted survival (P = 0.0002, log-rank test), outperformed the Model for End-stage Liver Disease system in predicting outcome (P = 0.0325), and significantly discriminated between liver transplant and death in a competing risk analysis. SA-AIH was characterized as having decreased CTLV/SLV, which was also predictive of survival (P < 0.0001). Interestingly, CLIF-C OFs, especially the subscores for respiratory dysfunction, also predicted infection (P = 0.007). Conclusion: In corticosteroid-treated patients with SA-AIH, CLIF-C OFs and CTLV/SLV ratios predicted both survival outcome and complications due to infection. Further investigation is warranted to determine whether making decisions based on CLIF-C OFs or CTLV/SLV ratios is useful. (Hepatology Communications 2020;4:1019-1033).