Nutritional therapy for persistent cognitive impairment after resolution of overt hepatic encephalopathy in patients with cirrhosis: A double-blind randomized controlled trial.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) reflects cognitive impairment in patients with liver cirrhosis and is associated with poor prognosis. We assessed the effects of nutritional therapy on cognitive functions, health-related quality of life (HRQOL), anthropometry, endotoxins, and inflammatory markers in cirrhotic patients with MHE. METHODS: In a double-blind randomized controlled trial, cirrhotic patients with MHE were randomized to nutritional therapy (group I: 30-35 kcal/kg/day and 1.0-1.5 g of protein/kg/day) and no nutritional therapy (group II: diet as patients were taking before) for 6 months. MHE was diagnosed based on psychometric hepatic encephalopathy score (PHES). Anthropometry, ammonia, endotoxins, inflammatory markers, myostatin, and HRQOL were assessed at baseline and after 6 months. Primary endpoints were improvement or worsening in MHE and HRQOL. RESULTS: A total of 150 patients were randomized to group I (n = 75, age 46.3 ± 12.5 years, 58 men) and group II (n = 75, age 45.2 ± 9.3 years, 56 men). Baseline PHES (-8.16 ± 1.42 vs -8.24 ± 1.43; P = 0.54) was comparable in both groups. Reversal of MHE was higher in group I (73.2% vs 21.4%; P = 0.001) than group II. Improvement in PHES (Δ PHES 4.0 ± 0.60 vs -4.18 ± 0.40; P = 0.001), HRQOL (Δ Sickness Impact Profile 3.24 ± 3.63 vs 0.54 ± 3.58; P = 0.001), anthropometry, ammonia, endotoxins, cytokines, and myostatin levels was also significantly higher in group I than group II. Overt hepatic encephalopathy developed in 6 patients in group I and 13 in group II (P = 0.04). CONCLUSIONS: Nutritional therapy is effective in treatment of MHE and associated with improvement in nutritional status, HRQOL, ammonia, endotoxins, inflammatory markers, and myostatin levels.

A double blind randomized controlled trial to assess efficacy of nutritional therapy for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis.

BACKGROUND AND AIM: Overt hepatic encephalopathy (OHE) has high risk of recurrence and is associated with poor survival. The role of nutrition therapy is well documented in cirrhosis, but its efficacy in preventing the recurrence of OHE has not been studied. METHODS: In double blind RCT, we randomly assigned 150 patients with liver cirrhosis, with history of OHE in recent past to receive nutrition therapy (group I) or no nutrition therapy (group II) and followed up for 6 months. The primary efficacy end points were occurrence of breakthrough episodes and time to breakthrough episode of OHE. Secondary end points were OHE related hospitalizations and time to hospitalization involving OHE. Other parameters included anthropometry, changes in serum cytokines (IL-1, IL-6, IL-10, and TNF-α), endotoxin and myostatin. RESULTS: There was significant reduction in occurrence of breakthrough episodes of OHE in group I [10 vs 36, hazard ratio 0.20; P < 0.001], OHE-related hospitalization [8 vs 24, hazard ratio 0.27; P < 0.001)]. Times to breakthrough episode of OHE and OHE-related hospitalization were longer in group I. At the end of 6 months, inflammatory and anthropometry parameters showed significant improvement in group I compared with worsening of serum albumin, anthropometric parameters, IL-6, IL-10 and TNF-α in group II. At the end of 6 months, ascites (50 vs 66, P = 0.01), gastrointestinal bleed (2 vs 11, P = 0.007), and jaundice (16 vs 41, P < 0.001) were lower in group I. CONCLUSIONS: Treatment with nutrition therapy prevented recurrence of OHE and decreased OHE-related hospitalizations as compared with no nutrition therapy.

Angle of His Accentuation Is a Viable Alternative to Dor Fundoplication as an Adjunct to Laparoscopic Heller Cardiomyotomy: Results of a Randomized Clinical Study.

BACKGROUND: There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM. METHODS: A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL. RESULTS: Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups. CONCLUSION: AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time. CLINICAL REGISTRATION NUMBER: CTRI: REF/2014/06/007146.

Efficacy of Nutritional Therapy for Patients With Cirrhosis and Minimal Hepatic Encephalopathy in a Randomized Trial.

BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) impairs health-related quality of life (HRQOL), leads to the development of overt HE, and is associated with poor outcome. We performed a randomized controlled trial to assess the effects of nutritional therapy on cognitive functions and HRQOL in patients with cirrhosis with MHE. METHODS: In a tertiary care setting in New Delhi, India, patients with cirrhosis with MHE were assigned randomly to groups given nutritional therapy (30-35 kcal/kg/d, 1.0-1.5 g vegetable protein/kg/d; n = 60; age, 42.1 ± 10.3 y; 48 men) or no nutritional therapy (patients continued on their same diet; n = 60; age, 42.4 ± 9.6 y; 47 men) for 6 months in 2014. MHE was diagnosed based on their psychometry hepatic encephalopathy score (PHES). HRQOL was assessed by a sickness impact profile (SIP) questionnaire. Primary end points were improvement or worsening in MHE and improvement in HRQOL. RESULTS: There was no significant difference in baseline PHES (-8.12 ± 1.32 vs -8.53 ± 1.38; P = .08) or SIP (14.25 ± 5.8 vs 15.44 ± 5.03; P = .85) scores. After the 6-month study period, a higher proportion of patients in the nutritional therapy group had reversal of MHE (71.1% vs 22.8%; P = .001). Patients in the nutritional therapy group also had larger increases in PHES (3.86 ± 3.58 vs 0.52 ± 4.09; P = .001) and HRQOL (improvement in SIP score of 3.24 ± 3.63 vs 0.54 ± 3.58; P = .001). Overt HE developed in 10% of patients in the nutritional therapy group vs 21.7% of the control group (P = .04). CONCLUSIONS: Based on a randomized controlled trial performed in India, nutritional therapy is effective in the treatment of MHE and is associated with improvement in HRQOL. Clinical Trial Registry-India registration no: CTRI/2013/07/003851.