Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients

Background/Aims@#Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC. @*Methods@#Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included. @*Results@#Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2–10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P @*Conclusions@#One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.

Sarcopenia: Ammonia metabolism and hepatic encephalopathy

Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.

Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial

BACKGROUND/AIMS: The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis. METHODS: Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks. RESULTS: The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture. CONCLUSIONS: Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.

Anxiolytic-like effect of etazolate, a type 4 phosphodiesterase inhibitor in experimental models of anxiety.

Etazolate is a selective inhibitor of type 4 phosphodiesterase (PDE4) class enzyme. Antidepressant-like effect of etazolate has been previously demonstrated in the rodent models of depression. The present study was designed to investigate the anxiolytic-like activity of etazolate in experimental mouse models of anxiety. The putative anxiolytic effect of etazolate (0.25-1 mg/kg, ip) was studied in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark (L/D) aversion, hole board (HB) and open field (OFT) with diazepam (2 mg/kg, ip) as reference anxiolytic. Like diazepam (2 mg/kg, ip), etazolate (0.5 and 1 mg/kg, ip) significantly increased the percentage of both time spent and entries into open arms in the EPM test. In the L/D test etazolate (0.5 and 1 mg/kg, ip) increased the both total time spent in and latency time to leave the light compartment. Etazolate (0.5 and 1 mg/kg, ip) also significantly increased head dipping scores and time spent in head dipping, whereas significantly decreased the head dipping latency in HB test. In addition, etazolate (0.5 and 1 mg/kg, ip) significantly increased the ambulation scores (square crossed) and number of rearing in OFT. In conclusion, these findings indicated that etazolate exhibited an anxiolytic-like effect in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.