Background Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long‐term mortality in cirrhosis. Methods A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X‐tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C‐index), calibration curve, and decision curve analysis (DCA). Results Stratifying by X‐tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3‐year mortality. A sex‐stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C‐index of 0.787 (95% CI, 0.736–0.838) and 0.789 (95% CI, 0.727–0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram. Conclusions Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long‐term mortality in cirrhosis.

Bicyclol, a novel synthetic antihepatitis drug, has been shown to protect against liver injury via various pharmacological activities. The purpose of the current study was to further investigate the protective effect of bicyclol against carbon tetrachloride (CCl 4)-induced acute liver injury (ALI) and its underlying molecular mechanism, particularly autophagic machinery, antioxidative, and anti-inflammatory potentials. Our results found that treatment with bicyclol significantly reduced CCl 4-induced hepatotoxicity by alleviating histopathological liver changes, decreasing the alanine transaminase levels, promoting autophagic flux, attenuating the expression of inflammatory cytokines, and modulating oxidative markers. Furthermore, bicyclol efficiently induced the conversion of LC3 and enhanced the liver expressions of ATG7 and Beclin-1. Meanwhile, bicyclol induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and p62. These protective effects may be mediated by activation of AMP-activated protein kinase and inhibition of mTOR or MAPK signaling pathways. Taken together, our study firstly suggests that bicyclol has protective potential against CCl 4-induced hepatotoxicity, which might be closely associated with induction of autophagy, concomitant anti-oxidative stress, and anti-inflammatory response.

Background: Frailty is a syndrome that diminishes the potential for functional recovery in liver cirrhosis (LC). However, its utility is limited due to sole reliance on physical performance, especially in hospitalized patients. We investigate the predictive value of a modified self-reported Frailty Index in cirrhotics, and identify which health deficits play more important roles. Methods: Consecutive LC patients were assessed by our frailty scale. Outcomes of interest were mortality for 90-day, 1-year and 2-year. Independent predictors were identified by multivariate Cox regression. Receiver operating characteristic curve (ROC) was performed to evaluate discriminative ability. We used a combination of stepwise selection, best subset selection, and Akaike information criteria (AIC) to identify pivotal frailty components. Results: The study cohort consisted of 158 patients, in which 37 expired during follow-up. Compared with non-frail groups, the frail group had higher 1-and 2-year mortality. The area under ROC of the Child-Turcotte-Pugh classification (CTP) and Frailty Index were 0.66 and 0.68, while 0.72 for CTP + Frailty Index (P=0.034), respectively. The optimal predictors comprised instrumental activities of daily living (IADL) limitation, falls and loss of weight (AIC =170, C-statistic =0.67). Conclusions: It is plausible for incorporating Frailty Index to improve prognostication in cirrhotics. IADL limitation, falls and loss of weight play more crucial roles on mortality determination.

Background & Aims An elevated neutrophil‐to‐lymphocyte ratio (NLR) has received attention as a prognostic surrogate across chronic liver diseases. However, an exact threshold has not been fully elucidated. Methods A total number of 589 patients with cirrhosis (LC) were included. The value of NLR was calculated and its optimal cut‐off was initially determined by X‐tile program. Independent predictors of 90‐day mortality were identified with Cox regression model. The Kaplan‐Meier method was used to generate survival curves. To reduce influences of selection bias and possible confounders, a 1:2 propensity score matching (PSM) was performed. Results The X‐tile indicated that the difference in survival was most significant for NLR more than 8.9. Serum NLR > 8.9 was an independent indicator in the entire cohort and PSM subset (HR 4.268, 95% CI 2.211‐8.238, P < .001; HR 4.209, 95% CI 1.448‐12.238, P = .008 respectively). Subgroup analysis showed that NLR > 8.9 was an independent risk factor of 90‐day mortality regardless of age, gender, CTP or MELD score. Conclusions The value of NLR more than 8.9 is a feasible cut‐off across clinical settings among applicable population. The adding of NLR to other conventional predictive systems has the potential to provide incremental value without extra economic cost.

Background: To develop a nomogram incorporating indicator of muscle waste to prognosticate long-term mortality in liver cirrhosis (LC), and identify the prognostic impact of psoas muscle index (PMI).Methods: A total of 251 LC patients who underwent computed tomography were included in this study.Multiple Cox regression was performed, and sex-specific nomogram models incorporating PMI were developed. The utility of the proposed models were evaluated by Harrell's concordance index (C-index), calibration curve and decision curve analysis. X-tile was used to determine optimal cutpoint for stratifying subjects with distinct outcomes. Subgroup analysis was implemented in terms of age and MELD score. The correlation between PMI and gait speed was also evaluated.Results: On multiple analysis, independent predictors for 3-year all-cause mortality were age, BMI, PMI and MELD for males, and age, PMI and MELD for females. Both nomogram models gave rise to moderately strong discrimination, with a C-index of 0.792 (95% CI: 0.723-0.861) in males and 0.715 (95% CI: 0.637-0.793) in females, respectively. The calibration curve implied predicted survival corresponding optimally with the actual outcomes. The proposed models were feasible in clinical settings based on decision curve analysis. On subgroup analysis, PMI might confer valid predictive value on LC patients with MELD <15. Moreover, a definitely positive correlation between PMI and gait speed was revealed.Conclusions: Our proposed nomogram embedding PMI rendered an individualized predictive tool for long-term mortality in LC. The diminishing value of PMI is likely indicative of muscle dysfunction.

Genipin, as the most effective ingredient of various traditional medications, encompasses antioxidative, anti-inflammatory, and antibacterial capacities. More recently, it is suggested that genipin protects against septic liver damage by restoring autophagy. The purpose of the current study was to explore the protective effect of genipin against carbon tetrachloride- (CCl4-) induced acute liver injury (ALI) and its underlying molecular machinery. Our results indicated that treatment with genipin significantly reduced CCl4-induced hepatotoxicity by ameliorating histological liver changes, decreasing the aspartate aminotransferase and alanine transaminase levels, alleviating the secretion of inflammatory cytokines, and promoting autophagic flux. Moreover, genipin effectively induced the conversion of LC3 and inhibition of p62 accumulation. The liver expressions of ATG5, ATG7, and ATG12 were significantly increased by genipin pretreatment in the ALI mice model. This protective effect may be mediated by the inhibition of mTOR and the activation of p38 MAPK signaling pathways. Meanwhile, genipin attenuated CCl4-induced inflammatory response by inhibiting the NF-κB and STAT3 signaling pathway. In addition, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or inhibition of p38 MAPK by SB203580 abolished the hepatoprotective effect of genipin. Taken together, our study implicates that genipin has a protective potential against CCl4-induced hepatotoxicity, which might be strongly associated with the induction of autophagy and the attenuation of inflammatory response.

Background: The 5 m gait speed (5MGS), a simple and reliable performance metric and surrogate indicator of frailty, consistently predicts adverse events in elders. Additionally, MELD-Na (model for end-stage liver disease-sodium) scores fail to capture nutritional and functional decline of cirrhotic patients that may confer excess mortality. We hypothesized that 5MGS might be associated with all-cause mortality, and that inclusion of frailty assessment within MELD-Na could improve the prediction of mortality in cirrhosis. Methods: 5MGS was measured at baseline in 113 hospitalized cirrhotic patients. Survival status over 2 years and cirrhosis-related complications were recorded. We evaluated the prognostic value of 5MGS (as a continuous variable and as a dichotomous variable). The definition of slow versus preserved 5MGS was 0.8 ms−1 based on previous publication. Using Cox proportional hazards regression, a novel MELDNa-5MGS score was derived. Receiver operating characteristics (ROC) curves estimated discrimination between the new score model and established prognostic indices. Results: The continuous 5MGS and slow 5MGS were independent predictors of all-cause mortality [5MGS: hazard ratio (HR) 0.133 (0.047–0.347), p < 0.001; slow 5MGS: HR 4.805 (1.536–15.026), p < 0.007]. The equation derived from Cox regression analysis was as follows: MELDNa-5MGS: MELD-Na score + 11 × slow 5MGS. The 2-year mortality in patients with high MELDNa-5MGS score was significantly higher ( p < 0.001). Discriminatory power was significantly better for MELDNa-5MGS than MELD-Na score (AUC: 0.802 versus 0.724, p = 0.014 for 1 year; 0.773 versus 0.709, p = 0.044 for 2 years). Conclusion: In cirrhotic patients, 5GMS is an independent risk factor of mortality. Modification of MELD-Na to include frailty estimated by low 5GMS is related to improved prognostication of mortality.

Aim It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2RA) and SBP through meta‐analysis. Methods We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random‐effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non‐parametric “trim‐and‐fill” tests were conducted for sensitivity analysis. Results A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta‐analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49–2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75–1.48). Conclusions In conclusion, PPI use, but not H2RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2RA might be beneficial for patients who require long‐term acid suppression therapy.