1.Sarcopenia: Ammonia metabolism and hepatic encephalopathy
Ankur JINDAL ; Rakesh Kumar JAGDISH
Clinical and Molecular Hepatology 2019;25(3):270-279
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.
Ammonia
;
Aspartic Acid
;
Fibrosis
;
Hepatic Encephalopathy
;
Hyperammonemia
;
Liver
;
Liver Cirrhosis
;
Metabolism
;
Motor Activity
;
Myostatin
;
Peptide Initiation Factors
;
Phosphorylation
;
Proteolysis
;
Quality of Life
;
Reactive Oxygen Species
;
Sarcopenia
;
Testosterone
2.Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients
Priyanka JAIN ; Saggere Muralikrishna SHASTHRY ; Ashok Kumar CHOUDHURY ; Rakhi MAIWALL ; Guresh KUMAR ; Ankit BHARADWAJ ; Vinod ARORA ; Rajan VIJAYARAGHAVAN ; Ankur JINDAL ; Manoj Kumar SHARMA ; Vikram BHATIA ; Shiv Kumar SARIN
Clinical and Molecular Hepatology 2021;27(1):175-185
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<0.001) male (97.7% vs. 67.7%), younger (40–50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC.
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.
3.Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial
Manoj Kumar SHARMA ; Sumeet KAINTH ; Sachin KUMAR ; Ankit BHARDWAJ ; Hemant Kumar AGARWAL ; Rakhi MAIWALL ; Kapil Dev JAMWAL ; Saggere Muralikrishna SHASTHRY ; Ankur JINDAL ; Ashok CHOUDHARY ; Lovkesh ANAND ; Rajender Mal DHAMIJA ; Guresh KUMAR ; Barjesh Chander SHARMA ; Shiv Kumar SARIN
Clinical and Molecular Hepatology 2019;25(2):199-209
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.
Arousal
;
Cytidine Triphosphate
;
Extremities
;
Fibrosis
;
Humans
;
Sleep Initiation and Maintenance Disorders