Identifying critically ill patients with cirrhosis who benefit from nutrition therapy: the mNUTRIC score study.

Background and Aim: Malnutrition increases risk of mortality in critically ill patients with cirrhosis. Modified Nutrition Risk in Critically ill (mNUTRIC) score is a validated tool to identify at risk patients who may benefit from goal-directed nutrition therapy. We aimed to study the association between mNUTRIC score and 28-day mortality in critically ill patients with cirrhosis. Methods: A prospective study was conducted in the liver intensive care unit of a quaternary teaching institute. Baseline and follow-up data pertaining to mNUTRIC score, clinical, hemodynamic, biochemical, nutritional parameters, mechanical ventilation, length of ICU stay, and development of sepsis were collected. Correlation between mNUTRIC score and its modulation by nutritional adequacy was determined. Results: One hundred and fifty patients were enrolled. Out of these, 116 (77%) had a high NUTRIC score (HNS) and 34 (23%) had a low NUTRIC score (LNS). Patients with HNS had higher mortality (54% vs. 10%; P = 0.008), longer mechanical ventilation (P = 0.02), and high incidence of sepsis (32% vs. 2.6%; P = 0.002) compared to LNS. The probability of survival increased with increase in nutritional adequacy (P < 0.01) in patients with HNS. Conclusion: mNUTRIC score is a useful tool for identifying nutrition risk in critically ill patients with cirrhosis. Goal-directed nutrition therapy in patients with HNS can significantly improve survival. Relevance for Patients: Critically ill patients with cirrhosis who are at a higher nutritional risk as identified by the mNUTRIC score may have a better survival benefit if higher calorie and protein adequacy are achieved in the ICU.

Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure.

Objective: The monocyte-macrophage system is central to the host's innate immune defense and in resolving injury. It is reported to be dysfunctional in acute-on-chronic liver failure (ACLF). The disease-associated alterations in ACLF monocytes are not fully understood. We investigated the mechanism of monocytes' functional exhaustion and the role of umbilical cord mesenchymal stem cells (ucMSCs) in re-energizing monocytes in ACLF. Design: Monocytes were isolated from the peripheral blood of ACLF patients (n = 34) and matched healthy controls (n = 7) and patients with compensated cirrhosis (n = 7); phagocytic function, oxidative burst, and bioenergetics were analyzed. In the ACLF mouse model, ucMSCs were infused intravenously, and animals were sacrificed at 24 h and day 11 to assess changes in monocyte function, liver injury, and regeneration. Results: Patients with ACLF (alcohol 64%) compared with healthy controls and those with compensated cirrhosis had an increased number of peripheral blood monocytes (p < 0.0001) which displayed significant defects in phagocytic (p < 0.0001) and oxidative burst capacity (p < 0.0001). ACLF patients also showed a significant increase in the number of liver macrophages as compared with healthy controls (p < 0.001). Bioenergetic analysis showed markedly reduced oxidative phosphorylation (p < 0.0001) and glycolysis (p < 0.001) in ACLF monocytes. Patients with monocytes having maximum mitochondrial respiration of <37.9 pmol/min [AUC = 0.822, hazard ratio (HR) = 4.5] and baseline glycolysis of ≤42.7 mpH/min (AUC = 0.901, HR = 9.1) showed increased 28-day mortality (p < 0.001). Co-culturing ACLF monocytes with ucMSC showed improved mitochondrial respiration (p < 0.01) and phagocytosis (p < 0.0001). Furthermore, ucMSC therapy increased monocyte energy (p < 0.01) and phagocytosis (p < 0.001), reduced hepatic injury, and enhanced hepatocyte regeneration in ACLF animals. Conclusion: Bioenergetic failure drives the functional exhaustion of monocytes in ACLF. ucMSCs resuscitate monocyte energy and prevent its exhaustion. Restoring monocyte function can ameliorate hepatic injury and promote liver regeneration in the animal model of ACLF.

Effect of long-term aggressive nutrition therapy on survival in patients with alcohol-related cirrhosis: A randomized controlled trial.

BACKGROUND: The aim of this study was to assess the effect of long-term aggressive nutritional therapy on clinical outcomes and survival in patients with alcoholic liver cirrhosis (ALC). METHODS: Malnourished patients assessed by Royal Free Hospital-Subjective Global Assessment (RFH-SGA) were randomized to control group (CG) (35-40 kcal and 1.2 g protein/kg/day; diet alone) or intervention group (IG) (40-45 kcal and 1.5 g protein/kg/day; diet plus polymeric formula) for 3 months. Patients were followed up at 3 and 12 months. RESULTS: Malnourished patients (age 44.0 ± 9 years; M [100%]; Child A:B:C [%] = 11:39:50) were randomized to the CG (n = 50) or IG (n = 54); 21 patients in CG and 27 in IG completed 3 months of follow-up. The RFH-SGA improved in 7 (33.3%; p = 0.016) in IG vs. 3 (14.2%; p = 0.625) in CG. Over 3 months, increments (CG vs. IG) were seen in calories (1554 ± 972 to 1823 ± 398; p = 0.001 vs.1542 ± 603 to 2254 ± 372; p=0.001), protein (53.1 ± 18.4 to 72.5 ± 19.6; p = 0.001 vs. 53 ± 21 to 86.9 ± 18.8; p = 0.00), dry body weight (64 ± 10 to 66 ± 11; p = 0.04 vs. 60.8 ± 9.2 to 63.2 ± 10.7; p = 0.009), and mid-upper arm circumference (MUAC) (24.7 ± 3.3 to 25.5 ± 3.3; p = 0.116 vs. 23.5 ± 2.7 to 24.1 ± 2.9; p = 0.015), with better ascites resolution in IG (53.3%; p = 0.008) vs. CG (44.4%; p = 0.227). Median 12-month survival was comparable in both the groups (p = 0.864). Irrespective of the intervention group, energy intake > 25 kcal and protein > 0.8 g/kg/day significantly improved 12-month survival. CONCLUSION: Aggressive nutritional therapy improves nutritional status and resolves ascites, however fails to show long-term survival benefit, though higher calorie and protein intake has the potential to impact survival. TRIAL REGISTRATION: NCT02140294.

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.

Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey.

BACKGROUND: The pandemic of Corona Virus (COVID-19) hit India recently; and the associated uncertainty is increasingly testing psychological resilience of the masses. When the global focus has mostly been on testing, finding a cure and preventing transmission; people are going through a myriad of psychological problems in adjusting to the current lifestyles and fear of the disease. Since there is a severe dearth of researches on this issue, we decided to conduct an online survey to evaluate its psychological impact. METHODS: From 26th to 29th March an online survey (FEEL-COVID) was conducted using principles of snowballing, and by invitation through text messages to participate. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event-revised (IES-R) scale. RESULTS: There were a total of 1106 responses from around 64 cities in the country. Out of these 453 responses had at least one item missing; and were excluded from the analysis. The mean age of the respondents was around 41 years with a male female ratio of 3:1 and around 22% respondents were health care professionals. Overall approximately one third of respondents had significant psychological impact (IES-R score > 24). Higher psychological impact was predicted with younger age, female gender and comorbid physical illness. Presence of physical symptoms and contact history predicted higher psychological impact, but did not reach statistical significance. CONCLUSION: During the initial stages of COVID-19 in India, almost one-third respondents had a significant psychological impact. This indicates a need for more systematic and longitudinal assessment of psychological needs of the population, which can help the government in formulating holistic interventions for affected individuals.

Safety and Efficacy of Sodium Tetradecyl Sulfate and Lipiodol Foam in Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) for Large Porto-Systemic Shunts.

OBJECTIVE: To evaluate the safety and efficacy sodium tetradecyl sulfate and lipiodol foam (STS foam) in BRTO for large (caliber ≥15 mm) porto-systemic shunt and gastric fundal varices. MATERIALS AND METHODS: It is a retrospective record-based study of patients who underwent BRTO using STS foam at the Institute of Liver and Biliary Sciences, New Delhi, for gastric variceal bleed or refractory hepatic encephalopathy (HE) who had large porto-systemic shunt (diameter ≥15 mm) with or without associated gastric varices. Clinical and laboratory parameters were evaluated before and after the procedure. All patients were followed for minimum of 12 months. RESULTS: Records of 22 patients were analyzed. Technical success was achieved in 22 of 22 sessions. Complete obliteration of shunt with clinical improvement was seen in 20 of 22 cases. Patients with gastric varices had no residual gastric varices on follow-up endoscopy. There were significant reduction in CTP scores and improvement in HE grades following BRTO. Post-procedure complication was encountered in 6 patients (5 minor and 1 major), and 7 patients showed worsening of esophageal varices and underwent endoscopic variceal ligation. One patient had succumbed to septicemia at a follow-up of 34 months. CONCLUSION: Our experience suggests STS foam is a safe and effective agent for patients with large shunt undergoing BRTO.