Prospective Analysis of Transjugular Portosystemic Shunt in Difficult-to-manage Hepatic Hydrothorax

( Ankur Jindal ),( Amar Mukund ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Pleural effusions complicate end-stage liver disease in 5% of patients. Early and careful identification of cause and related complications is imperative for appropriate management and patient survival. Unlike refractory ascites, data is limited on safety and efficacy of TIPS in cirrhotic patients with refractory refilling pleural effusion. Methods: We analyzed a consecutive cohort of hospitalized cirrhotic patients having pleural effusion (PE) at admission. Baseline HVPG and PE tap was done to determine etiology and presence of infection. We determined the rate and predictors of PE resolution with standard medical treatment (SMT), need for intercostal drainage (ICD) for repeated pleurocentesis, and efficacy and safety of TIPS in hepatic hydrothorax. Results: Of 1149 admissions involving 762 cirrhotics (mean CTP- 10.6±1.8) with PE, 967(84.2%) had hepatic hydrothorax (HH), 181(15.8%) had tubercular PE (TBPE) and despite comparable HVPG, CTP and MELD scores at baseline, patients with HH in comparison to TBPE developed more complications (HE-41.6% vs. 30.2%, AKI- 48.6% vs. 37%, pneumonia- 16.1% vs. 7.2%, bacteremia-11.7% vs. 6.1% and septic shock-14.1% vs. 8.3%; all P< 0.01) on follow up. Among admissions with HH, 475(49.2%) were symptomatic (mainly dyspnea-30.1%, cough-24% and chest pain-16.9%), 24.7% were isolated left sided and PE tap revealed SBE in 219(22.9%). Presence of co-existing SBP (52.5%; Odd’s ratio, OR: 5.2) and ICD placement (24.2%; OR: 3.1) were independent predictors for SBE. Baseline HVPG (16.6 ± 4.4 vs. 16.4 ± 5.1; P-0.6) and MELD scores (22.3 ± 6.9 vs. 21.9 ± 7.3; P-0.1) were comparable in SBE versus no SBE. In 43% of admissions, HH responded to SMT alone and 133(13.8%) required ICD for repeated pleurocentesis. 41 patients were carefully selected for TIPS [based on lower CTP score (TIPS vs no TIPS- 9.9 ± 1.6 vs 10.7 ± 1.8; P-0.02), lower MELD (18.7 ± 5.5 vs. 21.5 ± 7.5; P-0.03) and higher HVPG (19 ± 4.7 vs. 16.4 ± 4.8; P-0.08)]. Despite reduction in pressure gradient (mean portal venous - mean right atrial pressure) from 23.1 ± 3.8 mm Hg to 7.2 ± 2.5 mm Hg), only 20(48.2%) had complete resolution of HH, with no difference in mortality rates. Main complications of TIPS in HH were post TIPS encephalopathy (8 patients, 6 resolved) and ischemic hepatitis (4 patients, 2 resolved). 321(35.9%) patients with HH had in-hospital mortality and independent predictors were MELD >25, SBE non-response to SMT and septic shock requiring vasopressors. Conclusions: Only one-half of hepatic hydrothorax resolve with standard medical therapy and need for any intervention including TIPS generally herald poor outcome. Role of hepatic hemodynamics in predicting complications and resolution of hydrothorax is limited. Early referral for liver transplantation is imperative.

Sarcopenia: Ammonia Metabolism and Hepatic Encephalopathy

( Ankur Jindal ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Sarcopenia: Ammonia metabolism and hepatic encephalopathy

Ankur Jindal,Rakesh Kumar Jagdish 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.3

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.

Natural History of Patients with Compensated Cirrhosis and a Hepatic Venous Pressure Gradient >20 mm Hg: A Prospective Longitudinal Cohort Study

( Aditi Gupta ),( Ankit Bhardwaj ),( Ankur Jindal ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: HVPG >10 mm Hg predicts clinical decompensation (CD) in compensated cirrhotics. A few cirrhotics exhibit high HVPG (>20mm Hg) despite no CD. Their natural history, pattern of CD (ascites, hepatic encephalopathy, variceal bleed) and complications (HCC, mortality) is largely unknown. Methods: Consecutive compensated cirrhosis patients with HVPG >5 mm Hg (n=747) were followed up every 3-6 monthly for CD. They were sub-classified at baseline based on HVPG (< 12 mmHg (low HVPG group), 12-20 mmHg (Intermediate HVPG group) and >20 mmHg (High HVPG group). We analyzed only the low and high HVPG groups. Multivariate Logistic regression was used to identify predictors Results: 295(39.4%) patients developed clinical decompensation (CD) at mean follow up of 1.9 ± 0.3 years. In comparison to low HVPG group, first CD in high HVPG group developed early (1.4 ± 0.3 years vs 2 ± 0.3 years, P=0.02), more frequently (ascites- 27.1% vs 13.2%, variceal bleed- 31.9% vs 7.9%, AKI- 31% vs 12.8%, HCC- 12.4% vs. 3.9%; all P<0.05) with higher mortality (15.9% vs 1.9%; P<0.05). There was no significant correlation between baseline HVPG level and grade of esophageal varices (P=0.457). All patients in high HVPG group received carvedilol (maximum dose-25 mg/d, divided) and a repeat HVPG measured after a mean duration of 1.8 ± 0.4 years showed suboptimal HVPG response (≥20% reduction in HVPG or < 12 mmHg) in 26.6% patients (mean HVPG reduction, 3.3± 1.3 mm Hg). Etiology of cirrhosis and grade of varices were not significantly associated with CD or HVPG response. On multivariate analysis, baseline HVPG >20 mm Hg (hazard ratio [HR], 5.09; 95% confidence interval [CI], 2.909-8.926, P=0.001) and high MELD score (HR, 1.125; 95% CI, 1.066- 1.187, P=0.001) were independent predictors of CD. Conclusions: An HVPG of >20mm Hg independently predicts early and more frequent CD in compensated cirrhotics. Only a quarter of these patients respond to carvedilol and hence mandates us for careful HVPG monitoring and low threshold for additional drugs or interventions.

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 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

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. (Clin Mol Hepatol 2021;27:175-185)

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 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.2

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.