L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial.

BACKGROUND AND AIMS: Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. APPROACH AND RESULTS: In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n = 70) or placebo, lactulose, and rifaximin (n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. CONCLUSIONS: Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.

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.

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.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

The outcome of 100 patients with achalasia cardia following laparoscopic Heller myotomy with blunt dissection technique.

Background: Laparoscopic Heller myotomy (LHM) can be performed by blunt dissection technique (BDT). Only a few studies have assessed long-term outcomes and relief of dysphagia following LHM. The study reviews our long-term experience following LHM by BDT. Methods: This retrospective study was analysed from a prospectively maintained database (from 2013 to 2021) of a single unit of the Department of Gastrointestinal Surgery at G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi. The myotomy was performed by BDT in all patients. A fundoplication was added in selected patients. Post-operative Eckardt score >3 was considered treatment failure. Results: A total of 100 patients underwent surgery during the study period. Of them, 66 patients underwent LHM, 27 underwent LHM with Dor fundoplication and 7 underwent LHM with Toupet fundoplication. The median length of myotomy was 7 cm. The mean operative time was 77 ± 29.27 min and the mean blood loss of 28.05 ± 16.06 ml. Five patients had intraoperative oesophageal perforation. The median length of hospital stay was 2 days. There was no hospital mortality. The post-operative integrated relaxation pressure (IRP) was significantly lower than the mean pre-operative IRP (9.78 vs. 24.77). Eleven patients developed treatment failure, of which ten patients presented with recurrence of dysphagia. There was no difference in symptom-free survival amongst various types of achalasia cardia (P = 0.816). Conclusion: LHM performed by BDT has a 90% success rate. Complication using this technique is rare, and recurrence post-surgery can be managed with endoscopic dilatation.

Endoscopic retrograde cholangiopancreaticography-related complications - Experience from tertiary care teaching centre over half a decade.

Introduction: Endoscopic retrograde cholangiopancreaticography (ERCP) is an essential therapeutic procedure with a significant risk of complications. Data regarding the complications and predictors of adverse outcomes such as mortality are scarce, especially from India and Asia. We aimed to look at the incidence and outcome of complications in ERCP patients. Materials and Methods: This study is a retrospective analysis of prospectively collected data of all the patients who underwent ERCP and had a complication from January 2012 to December 2018. Data were recorded in predesigned pro forma. The data analysis was done by appropriate statistical tests. Results: : A total of 17,163 ERCP were done. A total of 570 patients (3.3%) had complications; perforation (n = 275, 1.6%) was most common followed by pancreatitis (n = 177, 1.03%) and bleeding (n = 60, 0.35%). The majorities of perforations were managed conservatively (n = 205, 74.5%), and 53 (19%) required surgery. Overall, 69 (0.4%) patients died. Of these, 30 (10.9%) patients died with perforation. Age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.005-1.07) and need of surgery (OR: 5.11, 95% CI: 1.66-15.77) were the predictors of mortality in patients with perforation. The majority pancreatitis were mild (n = 125, 70.6%) and overall mortality was 5.6% (n = 10). Conclusion: ERCP complications have been remained static over the years, with perforation and pancreatitis contributing the most. Most perforations can be managed conservatively with good clinical outcomes.

Management of Obscurely Dilated Common Bile Duct with Normal Liver Function Tests: A Pragmatic Approach.

OBJECTIVE: Dilated common bile duct (CBD) (8-15 mm) with normal liver function tests is seen not infrequently, while management of such patients is ambiguous. We propose a treatment algorithm for this cohort of patients after observing them over a period of 8 years. METHODS: Seventy-eight such patients were managed from 2009 to 2017 and categorized as: Group A-dilated CBD with post-cholecystectomy status (n = 15); B-dilated CBD with cholelithiasis (n = 34); C-dilated CBD without cholelithiasis (n = 16); D-dilated CBD with no cause identified and underwent CBD excision (n = 13). Causes for CBD dilatation were evaluated. The outcome of patients in Group B + C without any cause (n = 33) was compared with Group D. RESULT: Median age, CBD diameter, bilirubin and alkaline phosphatase were 51 years (13-79), 10 mm (8-20), 0.6 mg/dl (0.2-2.5) and 126 IU (60-214), respectively. Group-A patients who did not manifest any cause of CBD dilatation were managed conservatively. The aetiology was identified in 17/50 patients in Group B & C [acute pancreatitis (n = 6), passed CBD calculi (n = 3), perivaterian diverticulum (n = 3), viral aetiology (n = 4) and tumour (n-1)]. In Group-C, 7 patients with no obvious cause underwent endoscopic sphincterotomy, pancreatoduodenectomy (n = 1), and the rest were managed conservatively (n = 8). There was no significant difference in the complication between Group B + C (without any cause) and Group D (3/33 vs. 1/13; p = 0.58) at a median follow-up of 72 months (30-90). CONCLUSION: Dilated CBD with normal LFT's without apparent cause is mostly benign and of no consequence. Excision of the CBD is not required for most of these patients.

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.

Infliximab-induced tuberculosis in patients with UC: Experience from India-a country with high prevalence of tuberculosis.

BACKGROUND AND AIM: Tuberculosis (TB) is a well-recognized iatrogenic adverse event following administration of biologic therapy given for a variety of clinical indications. There is paucity of data on the development of TB following the use of biologics from countries with a high prevalence of TB. The aim of this study was to determine the risk of development of TB following biological therapy in a country, which is highly endemic for TB. METHODS: The article retrospectively analyse data from three referral inflammatory bowel disease centers to evaluate the risk of development of TB following biological therapy for patients with ulcerative colitis. RESULTS: Of the 79 patients with ulcerative colitis treated with infliximab, seven (8.8%) developed TB at a median interval of 8 weeks after the first exposure despite screening for latent TB. Three of the seven (42%) patients developed disseminated disease, whereas pulmonary disease was documented in four patients (57%). All patients were successfully treated with anti-tuberculous drugs for a period of 6-13 months. In contrast to data from the West, none of the patients in our study had a fatal outcome. None of the patients required a colectomy after a median follow up of 2 years following cessation of the infliximab therapy. CONCLUSIONS: These data suggest that despite the significantly higher prevalence, the outcome of TB after infliximab therapy is quite sanguine in the Indian subcontinent.

Celiac disease and Helicobacter pylori infection in children: Is there any Association?

BACKGROUND AND AIM: Helicobacter pylori (HP) infection can influence the inflammatory and immune responses in the gut and may therefore play a role in the development of gluten-related enteropathy in genetically susceptible individuals. Our objective was to assess the relationship between celiac disease and HP infection in children. METHODS: Children (1-18 years) diagnosed as celiac disease (CD) (n = 324) with submission of gastric and duodenal biopsies and duodenal histology having Marsh grade III features were eligible for the study. Non-celiac patients referred for endoscopy were selected as controls. We studied proportion of HP prevalence in children with confirmed CD as compared with HP prevalence in reference group comprising non-celiac children referred for endoscopy. We also evaluated predictors of HP infection in children with celiac disease. RESULTS: Of the 324 participants with CD, gastric HP was seen in 37 (11.4%) patients. The prevalence of HP in patients without CD (50%, P < 0.001) was significantly higher. Among patients with CD, HP infection was most frequent in patients with Marsh IIIa. In the stepwise regression analysis for risk factors of HP infection in CD patients: presence of gastritis, hemoglobin, and absence of scalloping were found to be independent predictors in a multivariate setup. CONCLUSION: Celiac disease and gastric HP infection have inverse relationship that raises the question whether development of HP infection confers protection against CD.

Sleep disturbances in patients of liver cirrhosis with minimal hepatic encephalopathy before and after lactulose therapy.

Sleep disturbances are common in patients of cirrhosis with minimal hepatic encephalopathy (MHE) and affect health related quality of life (HRQOL). No study has evaluated effect of lactulose on sleep disturbances and correlation with HRQOL in patients with MHE. We assessed sleep disturbances in cirrhosis with MHE and effect of lactulose on sleep disturbances and HRQOL. One hundred patients of cirrhosis [MHE; (n = 50, age 45.3 ± 11.2 years, 45 males) no-MHE (n = 50, age 46.3 ± 10.4 years, 44 males)] were included. MHE was diagnosed with psychometric hepatic encephalopathy score (PHES) ≤ -5. All patients underwent laboratory parameters including arterial ammonia and critical flicker frequency (CFF) Sleep disturbances were measured with Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and polysomnography. HRQOL was measured with SF-36(v2) questionnaire. Patients with MHE were given lactulose therapy for 3 months and all the parameters were repeated. Poor quality of sleep and excessive day time sleepiness were more common in patients with MHE, compared to without MHE. With lactulose therapy there was improvement in MHE in 21 patients and arterial ammonia levels (93.74 ± 14.8 vs. 71.44 ± 18.8 µmol/L: p < 0.001), CFF (34.83 ± 3.54 vs. 39.44 ± 4.95 Hz: p < 0.001), PHES (-7.64 ± 2.1 vs. -5.58 ± 2.09: p < 0.001), PSQI (8.6 ± 3.3 vs. 5.2 ± 1.5: p < 0.001), ESS (12.52 ± 3.01 vs. 9.24 ± 2.27: p < 0.001) and HRQOL (p = 0.01). Excessive day time sleepiness and impaired sleep quality are common in patients with MHE and correlate with neuropsychiatric impairment. Improvement in MHE with lactulose also leads to improvement in sleep disturbances and HRQOL.

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.

Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is associated with a poor prognosis in patients with advanced liver disease. Probiotics alter the intestinal microbiota with non-urease-producing organisms that reduce production of ammonia. We investigated the efficacy of probiotics for the primary prophylaxis of HE. METHODS: We conducted a prospective trial at a tertiary care referral institute in New Delhi, India, from January 2012 through March 2013, of patients with cirrhosis without overt HE (age, 48.6 ± 11.1 y; 96 men and 64 women); 25 were Child-Turcotte-Pugh (CTP) class A, 51 were CTP class B, and 84 were CTP class C. Subjects were assigned randomly to groups given probiotics (1 × 10(8) colony-forming units, 3 times daily; n = 86, 42 with minimal HE) or no test article (control, n = 74; 33 with minimal HE). All subjects underwent psychometric analyses, critical flicker fusion (CFF) threshold assessments, glucose hydrogen breath tests to identify small intestinal bacterial overgrowth (SIBO), and lactulose hydrogen breath tests to measure orocecal transit time (OCTT). The primary end point was the development of overt HE. RESULTS: At baseline, subjects in each group had comparable CTP score, model for end-stage liver disease scores, CFF assessments, psychometric hepatic encephalopathy scores, and OCTT. After a mean follow-up period of 38.6 ± 8.80 weeks for patients given probiotics and 40.3 ± 9.8 weeks for controls, 6 patients given probiotics and 7 controls died (P = .81). Three months of probiotic administration significantly reduced levels of arterial ammonia, SIBO, and OCTT; increased psychometric hepatic encephalopathy scores; and increased CFF thresholds, compared with baseline. Seven subjects in the probiotic group and 14 controls developed overt HE (P < .05; hazard ratio for controls vs probiotic group, 2.1; 95% confidence interval, 1.31-6.53). Psychometric hepatic encephalopathy scores, CTP scores, and SIBO correlated with the development of overt HE. CONCLUSIONS: In a prospective, randomized controlled trial, probiotics were found to be effective in preventing HE in patients with cirrhosis. Trial registration No: CTRI/2012/07/002807.

Jejunal strongyloidiasis mimicking crohn's colitis: A diagnostic dilemma!

ABSTRACT: We report an unusual case of jejunal strongyloidiasis presenting as chronic malabsorption and intractable small bowel diarrhea in an immunocompetent adolescent boy who posed a diagnostic challenge for pathologists, radiologists, and gastroenterologists. Histopathology revealed chronic active colitis and was consistent with the clinicoradiological diagnosis of Crohn's colitis but nonresponse to immunomodulators warranted full-thickness jejunal biopsy through laparotomy which showed numerous larvae and eggs of Strongyloides. There is a need to increase the awareness of Strongyloides colitis given its high rate of misdiagnosis and mortality as the correct diagnosis can avoid a fatal outcome of this curable disease.