Lifestyle Optimization Leads to Superior Liver Regeneration in Live Liver Donors and Decreases Early Allograft Dysfunction in Recipients: A Randomized Control Trial.

INTRODUCTION: The aim of the current randomized control trial was to assess the efficacy of donor lifestyle optimization on liver regeneration and outcome following live donor liver transplantation. METHODS: Live liver donors (LLDs) who were fit with no or minimal steatosis were randomized to receive either a customized low-calorie diet with calorie intake equalling their basal requirement along with exercise for 2 weeks before surgery versus to continue their normal routine lifestyle. Primary objectives were the difference in the day of normalization of serum bilirubin and PT-International normalized ratio and the percentage growth of the liver at postoperative day 7 and 14. Secondary objectives were differences in intraoperative liver biopsy, liver-regeneration markers, blood loss, hospital stay, the complication rate in LLDs, and rates of early graft dysfunction (EGD) in recipients. RESULTS: Sixty-two consecutive LLDs were randomized (28 in intervention vs. 34 in control). Baseline parameters and graft parameters were similar in both groups. LLDs in the intervention arm had significantly decreased calorie intake ( P <0.005), abdominal girth ( P <0.005), BMI ( P =0.05), and weight ( P <0.0005). The mean blood loss ( P =0.038), day of normalization of bilirubin ( P =0.005) and International normalized ratio ( P =0.061), postoperative peak aspartate transaminase ( P =0.003), Alanine transaminase ( P =0.025), and steatosis ( P <0.005) were significantly less in the intervention group. There was significantly higher volume regeneration ( P =0.03) in donors in the intervention arm. The levels of TNF-α, IL-6, and IL-10 levels were significantly higher, while the TGF-ß level was lower in donors in the intervention group. The rate of EGD was significantly higher in recipients in the control group ( P =0.043). CONCLUSION: Lifestyle optimization of LLD is simple to comply with, improves liver regeneration in LLDs, and decreases EGD in recipients, thus can enhance donor safety and outcomes in live donor liver transplantation.

Intragastric Balloon in Obese Compensated Nonalcoholic Steatohepatitis Cirrhosis Patients Is Safe and Achieves Significant Weight Reduction at 6-Months.

BACKGROUND AND STUDY AIMS: Weight reduction is the mainstay treatment for Nonalcoholic steatohepatitis (NASH). intragastric balloon (IGB) placement has proven benefit in terms of weight reduction. The aim of the present study is to assess the safety and efficacy of IGB placement in compensated NASH cirrhosis. PATIENTS AND METHODS: Nonalcoholic steatohepatitis cirrhosis patients with CTP ≤ 7, BMI of > 30, and who were unable to achieve weight reduction with lifestyle modification in past 3 months were prospectively enrolled. Spatz3™ adjustable gastric balloon was placed endoscopically. Primary objective was to determine efficacy in weight loss at 6 months, with secondary objectives of reduction in hepatic venous pressure gradient (HVPG), liver fat (controlled attenuation parameter, CAP), liver stiffness measurement (LSM) and clinical events as well as the tolerability and adverse events due to IGB placement. RESULTS: Altogether 56 cirrhosis patients, with a baseline BMI of 35.24 ± 3.92 and a CTP score of 6.27 ± 1.28 underwent IGB placement. The absolute weight reduction achieved was 15.88 kg (- 16.46%) and reduction in BMI was - 10.1% at 6 months. The percentage total body weight loss of ≥ 10% was achieved in 31 (55.35%) patients. The reduction in HVPG at 6-months was 11.12% (n = 16, 14.18 ± 2.12 to 12.60 ± 1.67 mmHg). The mean reduction in LSM was 28.6% and in CAP was 10.09%. Three (5.36%) patients required removal of IGB before 6-months due to persisting vomiting. No patient developed new-onset decompensation or any serious adverse event. CONCLUSION: IGB placement is a safe, well tolerated and effective option for reduction in weight and portal pressure in compensated obese cirrhosis patients. TRIAL REGISTRY: Clinicaltrails.gov identifier no: NCT03753438.

Vitamin D status & bone health in patients with liver cirrhosis.

Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.

Subjective global nutritional assessment as a nutritional tool in childhood chronic liver disease.

Objective of the study was to assess subjective global nutritional assessment (SGNA) in children with chronic liver diseases (CLD). Children aged 3 months to 18 years with CLD were prospectively enrolled (January 2016 to October 2018). SGNA was performed as per validated pro forma for children. Nutritional categories were categorised into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). Agreement between SGNA and anthropometric measures, prediction of morbidity and death or liver transplantation (LT) at 1-year post-enrolment by SGNA and inter-observer reliability of SGNA were assessed. Ninety-two subjects were enrolled, median age 23·5 (3-216) months. SGNA classified 47 patients (51·1 %) in group A, 26 (28·3 %) in group B and 19 (20·6 %) in group C. Kendall coefficients disclosed significant association of SGNA with all anthropometric measurements, greatest with weight for age (r = -0·637), height for age (r = -0·581) and mid-arm fat area (r = -0·449). At 12 months follow-up, twenty children died and four received LT. A significantly higher number of children with malnutrition (groups B and C) had poor outcome (OR 6·74 (95 % CI 2·21, 20·55), P = 0·001), increased risk of hospital readmission (OR 12·2 (95 % CI 4·60, 35·88), P = 0·001), higher rate of infectious complications (OR 22·68 (95 % CI 7·29, 70·53), P < 0·0001) and lower median survival with native liver (Log Rank < 0·001) as compared with group A. Inter-observer agreement in assessment of SGNA was good (90·2 %). SGNA, in contrast to anthropometric measures, is a better nutritional assessment tool. It is reliable, comprehensive and predicts poor outcome in childhood CLD.

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

BACKGROUND AND AIMS: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Effect of Vitamin D Supplementation on Vitamin D Level and Bone Mineral Density in Patients With Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: In patients with cirrhosis, highly prevalent vitamin D deficiency and low bone mineral density (BMD) increase the burden of disease, and role of vitamin D supplementation is not clear. So, our aim was to determine the effect of vitamin D supplementation on vitamin D level and BMD in patients with cirrhosis. METHODS: Patients with cirrhosis (18-60 years) of any etiology were enrolled. We measured serum 25(OH)D, parathyroid hormone, thyroid-stimulating hormone, free T4, bone-specific alkaline phosphatase, insulin-like growth factor (IGF)-1, and health-related quality of life at entry and at 1 year; however, serum calcium was measured at 3-month interval. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine and left hip neck at entry and after 1 year. Statistical analysis was performed according to intention-to-treat analysis. RESULTS: Of 390 screened patients with cirrhosis, 164 participants (82 in each group) were randomized. There was significant increase in 25(OH)D levels in intervention group after 1 year (33.7 [24.3-45.7] ng/mL vs 23.1 [17-28.2] ng/mL; P < 0.001) when compared with placebo. The mean difference in BMD at lumbar spine and left hip neck was not significantly changed after 1 year of intervention with vitamin D between both groups. There was no significant change in both the groups in levels of calcium, thyroid-stimulating hormone, parathyroid hormone, free T4, IGF-1, and bone-specific alkaline phosphatase and quality of life. DISCUSSION: Supplementation with vitamin D for 1 year improves vitamin D levels but did not result in improvement in BMD at lumbar spine and left hip neck in patients with cirrhosis.

Omega-3 fatty acid lipid emulsions are safe and effective in reducing endotoxemia and sepsis in acute-on-chronic liver failure: An open-label randomized controlled trial.

BACKGROUND AND AIM: Sepsis is an important determinant of the outcome of acute-on-chronic liver failure (ACLF) patients. Omega-3 fatty acids (FAs) are known to suppress inflammation, reduce morbidity, and mortality in postoperative and critically ill patients. We aimed to evaluate the effect of intravenous omega-6 and omega-3 FA lipid emulsions in ACLF patients. METHODS: Ninety ACLF patients were randomly allocated to three groups: Gr. A received no lipid emulsions, Gr. B received omega-6 FAs, and Gr. C received omega-3 FAs. The primary and secondary aims were to compare the effects of lipid emulsions on immune modulation, the incidence of bacterial sepsis, and mortality at day 28. RESULTS: The baseline characteristics of the patients were comparable. Serum endotoxin levels remained suppressed by 22% in Gr. C compared with a 4% and 12% rise in Gr. B and A (P < 0.001). Omega-3 FAs also suppressed C-reactive protein levels and neutrophil-to-lymphocyte ratio in Gr. C. Compared with Gr. A, omega-3 FAs reduced sepsis by 86% (HR, 0.14; 95% CI 0.04-0.43; P < 0.001). Omega-3 FAs significantly increased the expression of TLR2 and TLR4 on both CD14+ and CD16+ monocytes, and TLR4, on macrophages and neutrophils. There were no serious adverse events, except transient flushing in 20% and 16.6% of patients receiving omega-6 FAs and omega-3 FAs, respectively. CONCLUSION: Omega-3 FAs are safe and effective in reducing systemic inflammation, endotoxemia, and sepsis in patients with ACLF. These lipid emulsions could also be considered as effective sources of immunonutrition in such sick patients.

Positive familial history for metabolic traits predisposes to early and more severe alcoholic cirrhosis: A cross-sectional study.

BACKGROUND & AIMS: Familial aggregation of metabolic traits in NAFLD is well documented. However, relevance of these traits in alcoholic cirrhosis is not well studied. We aimed to explore the association of family history of metabolic traits with age at diagnosis, severity and complications of alcoholic cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with alcoholic cirrhosis presenting to our tertiary care centre were included. Family and personal history, demographic characteristics, medical history, anthropometric measurements and laboratory data were recorded. The amount and duration of alcohol consumption were also carefully recorded. RESULTS: Out of 1084 alcoholic cirrhotics (age 48.5 ± 10.1 years, all males), family history for metabolic traits was documented in 688 (63.5%) patients. These patients had younger age at diagnosis, increased incidence of jaundice, ascites, variceal bleed and hepatic encephalopathy with consequently higher MELD and CTP score. These patients developed cirrhosis despite shorter median duration (13 years, IQR 7-20 vs 21, IQR 18-25) and lesser amount of alcohol consumption (74 g/d, IQR 24-96 vs 144, IQR 100-148). Patients with both family and personal history of metabolic traits had a higher risk by 3.3 times (95% CI 2.2-4.8) of an early age at diagnosis, 13.2 times (95% CI 8.7-20.1) of progression to cirrhosis with lesser amount of alcohol consumption and 4.6 times (95% CI 3.1-6.9) with lesser duration of alcohol consumption. CONCLUSIONS: Positive family and personal history of metabolic traits predispose to alcoholic cirrhosis with an earlier age at onset and more severity despite lesser exposure to alcohol.

Impact of family history of metabolic traits on severity of non-alcoholic steatohepatitis related cirrhosis: A cross-sectional study.

BACKGROUND & AIMS: Familial aggregation of metabolic traits with fatty liver disease is well documented. However, there is scarcity of data regarding such association with non-alcoholic steatohepatitis (NASH)-related cirrhosis. This study was aimed to explore the association of family history of metabolic traits with severity of cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with NASH-related cirrhosis presenting to our tertiary care centre were included. Family history, personal history, demographic characteristics, medical history, anthropometric measurements and laboratory data were recorded. RESULTS: Of the 1133 cirrhotics (68.1% males, age 51.4±10.9 years); 779 (68.8%) had family history for metabolic traits. These patients had lower age at diagnosis (45.4±10.6 vs 49.6±11.2 years), higher Child-Turcotte-Pugh (CTP) score (7.8±1.9 vs 6.6±1.5), higher model for end stage liver disease (MELD) score (12.9±6.1 vs 10.9±4.1) and more incidence of decompensation in the form of ascites (46.3% vs 25.7%), jaundice (12.1% vs 6.2%) and hepatic encephalopathy (26.1% vs 11.0%). Patients with family and personal history of metabolic traits, had an increased risk of an early diagnosis of cirrhosis at<45 years of age (OR: 3.1, 95% CI 2.1-4.4), CTP≥10 (OR: 4.6, 95% CI 2.3-9.1), MELD>15 (OR: 6.6, 95% CI 3.8-11.5) with ≥1 features of decompensation (OR: 4.2, 95% CI 2.9-6.1). Family history of diabetes alone, also had higher risk of cirrhosis with MELD>15 (OR: 4.3, 95% CI 2.4-5.3, P<.001). CONCLUSION: Family and personal history of metabolic traits are associated with early age at diagnosis of cirrhosis with more severity and decompensation and so, has a prognostic importance in NASH-related cirrhotics.

Characterization of body composition and definition of sarcopenia in patients with alcoholic cirrhosis: A computed tomography based study.

BACKGROUND: Alterations in body composition (BC) as loss of fat and muscle mass (sarcopenia) are associated with poor outcome in alcoholic cirrhosis (ALC). Prevalence of sarcopenia depends upon the method of assessment. Computed Tomography (CT) is a gold standard tool for assessing BC. AIM: To characterize BC and define sarcopenia in ALC patients using CT. METHODS: Single slice CT images at L3 vertebrae of healthy controls (HC) - organ transplant donors and ALC patients were analysed to give cross-sectional area of five skeletal muscles normalized for height -skeletal muscle index (SMI; cm2 /m2 ), area of subcutaneous (SAT;cm2 ) and visceral adipose tissue (VAT;cm2 ). Cut-offs for defining sarcopenia was established at 2SD below the mean of HC. HC were compared with Child A-compensated (C) and Child B+C-decompensated (DC) patients. RESULTS: Cut-offs of SMI derived from HC (n = 275; M: 50%; age 32.2 ± 9.8 years; BMI 24.2 ± 3.2 Kg/m2 ) were 36.54 in males and 30.21 in females. Sarcopenia was found in 12.8% of ALC patients [n = 148; C (31.8%): DC (68.2%); M: 100%; age 46.6 ± 9.7 years; BMI 24.5 ± 4.4]. Compared to HC, compensated patients had higher adiposity and comparable muscularity; decompensated patients had significantly lower muscle and also fat mass compared to both HC and compensated patients. HC vs C vs DC: SAT (140 ± 82 vs 177.3 ± 11 vs 112 ± 8.2); VAT (96.5 ± 6.5 vs 154.9 ± 8.7 vs 87.5 ± 6.5) and SMI (52.1 ± 0.9 vs 49.6 ± 1.2 vs 46 ± 0.9). CONCLUSIONS: Compensated ALC have increased adiposity and relatively preserved muscularity but decompensation leads to loss of both muscle and fat mass. Prevalence of sarcopenia, based on derived ethnic cut-offs was 12.8%.

Translation and validation of the Hindi version of chronic liver disease questionnaire (CLDQ) for the assessment of health related quality of life in patient with chronic liver disease in India.

Background: Chronic liver disease questionnaire (CLDQ) is an established disease specific tool to assess the health related quality of life (HRQOL) in patients with CLD irrespective of the etiology and severity. The objective of the study was to develop the Hindi language version of CLDQ and to assess the validity of the Hindi CLDQ. Methods: CLDQ was adapted into Hindi language by following a standard method of forward and back-translation by two bilingual translators, revision by expert panel and formulation of a consensual version followed by pilot testing and appropriate modifications before final administration. Hindi CLDQ along with short form 36 (SF-36) were administered in 494 patients with chronic liver disease (CLD) and 103 healthy controls (HC). To assess reproducibility, Hindi CLDQ was re-administered in a subsample of 20 patients. Internal consistency was assessed by Cronbach's alpha coefficient. Structural validity was assessed by exploratory factor analysis and construct validity was assessed with help of correlation of SF-36 scores and CLDQ pattern across disease severity groups. Results: The Cronbach's alpha coefficient was 0.93 and intra class coefficient correlation was 0.88 for the average CLDQ score, suggestive of good reliability. An inverse relationship of the average CLDQ score with the disease severity (CLDQ score of Child A vs. B vs. C = 5.2±1.10 vs. 4.73±1.24 vs. 4.15±1.19 respectively; p<0.001) and good correlation with SF-36 scores (average CLDQ score with PCS & MCS; r=0.63 & 0.55; p<0.001) was suggestive of good validity of Hindi CLDQ. The factor analysis identified 6 domains accounting for 62% of variability. The derived cut-off of 6 for the average CLDQ had the AUC of 0.826 with a sensitivity of 76.7. Conclusion: Hindi version of CLDQ is found to be a reliable and a valid tool comparable to the original English version. The HRQOL of patients with CLD is lower than healthy controls and HRQOL decreases with increase in disease severity.

Effect of probiotic VSL#3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial.

AIM: Minimal hepatic encephalopathy (MHE) impairs daily functioning and health-related quality of life in chronic liver disease (CLD). Lactulose is the standard treatment but has side-effects. Probiotics have an encouraging role in MHE. The aim of the present study was to test whether probiotics are non-inferior to lactulose in improving MHE. METHODS: Patients with CLD (n = 227) were screened for MHE using neuropsychometric tests (number connection tests A and B [or figure connection tests A and B]) and/or neurophysiological test (P-300 auditory event-related potential), and 120 (53%) were diagnosed with MHE by abnormal tests. MHE patients were randomized to lactulose (30-60 mL/day) or probiotic (four capsules of VSL#3; total of 450 billion CFU/day) for 2 months. Response was defined as normalization of tests. Serum ammonia was measured by commercial kit. RESULTS: Of 120 patients randomized, 40 in the lactulose arm and 33 in the probiotic arm completed 2 months of intervention. MHE improved in 25 (62.5%) patients taking lactulose and 23 (69.7%) taking probiotics. The effect size of difference of improvement in MHE between lactulose and probiotic was 0.072 per per-protocol analysis and 0.040 as per intention to treat analysis (within -20% of non-inferiority margin). Serum ammonia was comparable between groups at baseline and 2 months; it decreased in patients in whom MHE improved, while increased in patients with no improvement in MHE. CONCLUSION: The probiotic VSL#3 was non-inferior to the standard therapy, lactulose in the treatment of MHE. Improvement in MHE correlated with reduction of ammonia levels.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Intestinal permeability and complications in liver cirrhosis: A prospective cohort study.

AIM: Increased intestinal permeability (IP) has been implicated as an important factor for bacterial translocation (BT), leading to bacteremia and endotoxemia, resulting in various septic complications, variceal bleeding (VB), hepatic encephalopathy (HE), hepatorenal syndrome (HRS) and death in patients with liver cirrhosis (LC). This study was planned to assess IP in patients with LC and follow them for the occurrence of complications. METHODS: Patients with Child B and C cirrhosis without a history of disease-related complications were followed up for 6 months. IP was measured by lactulose and mannitol excretion ratio (LMR) in patients and 50 healthy controls (HC). Serum endotoxin levels were also assessed in 48 patients and 20 HC. RESULTS: Eighty patients (74 male), 41 (51.3%) Child B and 56 (70%) Child C, with a mean age of 40.7 ± 9.8 years were enrolled. IP was increased in 28 (35%) patients. LMR of patients was higher than HC (patients vs HC = 0.0238 [0.0010-1.557] vs 0.0166 [0.0018-0.720]; P = 0.007]. No significant difference was seen in the LMR of patients among various Child classes and etiologies. Serum endotoxin levels (GMU/mL) were higher in patients than HC (patients vs HC = 1.42 [0.68-2.13] vs 0.994 [0.067-1.382]; P = 0.001), but comparable between patients with abnormal and normal IP. At follow up, there was no significant difference in the incidence of complications like spontaneous bacterial peritonitis, HRS, VB, HE and death between patients with abnormal and normal IP. CONCLUSION: IP was increased in 35% of patients with LC; however, it was not associated with a higher incidence of disease-related complications.

Post-transjugular Intrahepatic Portosystemic Shunt Hepatic Encephalopathy: Sarcopenia Adds Insult to Injury.

BACKGROUND: Hepatic encephalopathy, which is a serious complication, and sarcopenia are undesirable consequences in cirrhosis. Transjugular intrahepatic portosystemic shunt increases the risk of hepatic encephalopathy. We investigated the effect of sarcopenia on the incidence of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. METHODS: Clinical data of patients who underwent transjugular intrahepatic portosystemic shunt were extracted retrospectively. Computed tomography images at L3 level of scans performed prior to transjugular intrahepatic portosystemic shunt were analyzed to assess skeletal muscle index-expressed as skeletal muscle area (cm2)/ height (m2). RESULTS: Of 210 patients who underwent transjugular intrahepatic portosystemic shunt, complete information was available in 79 [male: 68 (86%); age: 50.5 ± 11.2 years; Child-Turcotte-Pugh score: 8.81 ± 1.23; etiology-alcohol: 44 (56%), non-alcoholic steatohepatitis: 16 (20%), others: 19 (24%); transjugular intrahepatic portosystemic shunt indication-ascites: 56 (71%); bleed: 23 (29%); sarcopenics: 42 (53%)]. Post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy developed in 29 (37%) patients. In patients who developed hepatic encephalopathy, both serum ammonia [177.6 ± 82.5 vs. 115.5 ± 40.5 µg/dL, P =.008] and prevalence of sarcopenia [69% vs. 44%; P =.02; odds ratio (95% CI): 2.8 (1.08-7.4), P =.02] were higher, with sarcopenics having 3 times higher risk of hepatic encephalopathy and 8 times higher risk of multiple episode of hepatic encephalopathy [31% vs. 5.4%; odds ratio (95% CI): 8.2 (1.68- 40.5), P =.009]. In multivariate analysis, age [odds ratio (95% CI): 1.05 (1.001-1.11), P =.047], serum albumin [odds ratio (95% CI): 0.162 (0.05-0.56), P =.004], and skeletal muscle index [odds ratio (95% CI): 0.925 (0.89-0.99), P =.017] were independently associated with post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy. CONCLUSIONS: Sarcopenia is present in nearly half of the cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt, which increases the risk of a single episode of hepatic encephalopathy by 3-fold and that of multiple episodes of hepatic encephalopathy by 8-fold after transjugular intrahepatic portosystemic shunt procedure. Increased skeletal muscle index is associated with decreased risk of hepatic encephalopathy.

Tadalafil improves erectile dysfunction and quality of life in men with cirrhosis: a randomized double blind placebo controlled trial.

BACKGROUND AND AIMS: Patients with cirrhosis have high prevalence of erectile dysfunction (ED). The aim of this study was to study the efficacy and safety of tadalafil for ED in patients with cirrhosis. METHODS: 140 cirrhotic males with ED were randomized into tadalafil 10 mg daily (n = 70) or placebo (n = 70) for 12 weeks. ED was diagnosed if erectile function (EF) domain score was < 25 in International Index of Erectile Function (IIEF) questionnaire. The erectile function domain consists of six questions concerning erection frequency, erection firmness, frequency of partner penetration, frequency of maintaining erection after penetration, ability to maintain erection to completion of intercourse and confidence in achieving and maintaining erection. Primary outcome was proportion of patients having an increase in > 5 points in EF domain of the IIEF. Generalized Anxiety Disorder 7 (GAD-7) questionnaire was used for screening and severity measuring of GAD. The presence of depression was screened using the Patient Health Questionnaire (PHQ-9) and the assessment of health related quality of life was done using the Short Form (36) Health Survey. RESULTS: At the end of 12 weeks, more patients in tadalafil group achieved > 5 points increase in the EF domain of the IIEF when compared with the placebo group [44(62.9%) vs. 21(30%), p < 0.001]. At the end of 12 weeks, patients receiving tadalafil had significantly more change in scores on the erectile function domain, orgasmic function domain, intercourse satisfaction domain, overall satisfaction domain, erection vaginal penetration rates and successful intercourse; significantly more decline in the GAD-7 and PHQ-9 scores; significantly more improvement in scores of five of the eight domains of SF-36 (general health perception, vitality score, social functioning, role emotional and mental health) and the mental component summary rates when compared with placebo. The development of side effects and the changes in HVPG were not significantly different between the two groups. CONCLUSIONS: Tadalafil therapy may enhance erectile function, improve anxiety, depression and quality of life; and is well tolerated by men with cirrhosis (CTP score < 10) and ED. However, further larger and long-term studies are needed to confirm these results and look for rarer side effects of using tadalafil in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT03566914; first posted date: June 25, 2018.

Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial.

BACKGROUND: Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn's disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP. AIM: We evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD. METHODS: In a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5 g/kg ideal body weight/day for 2 months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system. RESULTS: Patients (age 34.5 ± 10.5 years; 20 males) were assigned to the GG (n = 15) or ACG (n = 15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2 months was 0.029 (0.006-0.090) and 0.033 (0.009-0.077), respectively, with P = 0.6133. IP normalized in 8 (57.1%) patients in each group (P = 1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2 months was 2.68 (1.02) and 2.49 (0.67), respectively, (P = 0.347). At the end of 2 months LMR improved significantly in GG from 0.071 (0.041-0.254) to 0.029 (0.006-0.090) (P = 0.0012) and in ACG from 0.067 (0.040-0.136) to 0.033 (0.009-0.077) (P = 0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P = 0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P = 0.009). CONCLUSIONS: Intestinal permeability and morphology improved significantly in both glutamine and ACG.

Handgrip strength: Best practice for a rapid nutrition screening and risk stratification in male patients with alcoholic liver cirrhosis, a classification and regression tree analysis study.

BACKGROUND: Rapid nutrition screening (NS) is vital for apt management in patients with alcoholic liver cirrhosis (ALC). AIM: To identify a quick method of NS having high reliability and prognostic significance. METHODS: NS of patients with ALC was assessed using mid-upper arm circumference (MUAC), handgrip strength (HGS), fat-free mass index (FFMI), and the Royal Free Hospital-Global Assessment (RFH-GA). Baseline clinical and biochemical information were recorded along with 90-day survival data. The classification and regression tree method was used to classify HGS, MUAC, and FFMI values as well nourished (WN), moderately malnourished (MM), and severely malnourished (SM), and their concordance with RFH-GA categories was assessed using Kendall tau-b coefficient. The prognostic proficiency of each method was tested by Cox regression analysis. RESULTS: According to the RFH-GA, of 140 male patients with ALC, 13 of 140 (9.3%) were WN, 93 of 140 (66.4%) were MM, and 34 of 140 (26.8%) were SM. HGS has the strongest association with the RFH-GA (Kendall tau-b = 0.772; diagnostic accuracy -81.4%). HGS was found to be the independent predictor of 90-day mortality (26 of 140 [18.6%]; hazard ratio, 0.93; 95% CI, 0.88-0.98; P = 0.002) after adjusting for age, body mass index, and disease severity. The hazard of mortality was 8.5-times higher in patients with ALC with HGS < 22 kg as compared with those with HGS > 29. CONCLUSION: HGS is a reliable tool for rapid NS. HGS < 22 kg suggests a high risk for severe malnutrition and is strongly associated with short-term mortality in male patients with ALC.

Sarcopenia is the independent predictor of mortality in critically ill patients with cirrhosis.

Background: Sarcopenia is strongly associated with poor outcome in cirrhosis. There are little prospective data that sarcopenia influences outcomes in critically ill cirrhotics (CICs). Computed tomography (CT) is the gold standard for sarcopenia assessment in the intensive care unit (ICU), as it is independent of hydration status. Aim: This study aims to assess the prevalence of sarcopenia and study its impact on clinical outcomes in CICs. Methods: In this prospective observational study, CICs admitted to the liver ICU were enrolled, if meeting inclusion (age 18-70 years, abdominal CT scan within three months before ICU admission) and exclusion criteria (survival likely to be <24 h, coexisting chronic diseases). Clinical, hemodynamic, biochemical, and nutritional parameters, including length of stay (LOS), duration of mechanical ventilation (MV), development of new-onset infections (NOI), incidence of new-onset acute kidney injury (AKI), and overall survival, were recorded. CT images at the L3 level were analyzed using Slice-O-Matic V4.3 software to assess the skeletal muscle index (SMI) expressed as skeletal muscle area (cm2)/height (m2). Sarcopenia was defined if SMI was <50 cm2/m2 - males and <39 cm2/m2 - females. Data were analyzed using SPSS version 22. Results: Altogether 111 patients (M-83.8%; age 48.4±11.3 years; etiology: Alcohol - 56 [50.5%], non-alcoholic steatohepatitis - 27 [24.3%], viral - 12 [10.8%], and others - 16 [14.4%]; Child-Turcotte-Pugh - 11.9±1.8; model for end-stage liver disease - 27.8±7.3; sequential organ failure assessment - 10.5±4.1; APACHE - 23±8; and MV - 54 [48.6%]) were enrolled. Of these, 76 (68.5%) were sarcopenic and 35 (31.5%) non-sarcopenic. Sarcopenic CICs had higher overall mortality (72.4%) compared to non-sarcopenics (40%) (P=0.001, OR [95% CI] - 3.93 [1.69-9.12]), and higher prevalence of sepsis at ICU admission (53.9% vs. 31.4%, P=0.027, OR [95% CI] - 1.7 [1.0-2.92]) than non-sarcopenics. LOS, duration of MV, incidence of NOI, and development of new-onset AKI were comparable between groups. Multivariate binary logistic regression showed that sarcopenia, sepsis, and APACHE II score were independently associated with mortality. Conclusion: Two-thirds of CICs have sarcopenia at ICU admission, making them 1.7 times more susceptible to sepsis and increasing the risk of mortality by almost 4-fold in the ICU. Relevance for Patients: Almost 70% of patients with chronic liver disease admitted to the ICU have low muscle mass (sarcopenia). The presence of sarcopenia per se makes them highly prone to infections and increases the chances of death by almost 4-fold; thus, highlighting the importance of nutrition optimization in this patient group.