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.

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.

Motorized Power Spiral Enteroscopy (MSE): Is Routine Bougienage of the Upper Esophageal Sphincter (UES) Necessary?

Introduction Wire-guided bougienage of the upper esophageal sphincter (UES) was performed routinely before per-oral motorized power spiral enteroscopy (MSE). In the present study, we aimed to answer the clinical question of whether routine bougienage of UES is required. Methods This was a retrospective study that included 20 patients who underwent antegrade spiral enteroscopy for various indications. The feasibility and safety of anterograde MSE without prior bougie dilatation of the upper esophageal sphincter were assessed. The technical success rate (TSR), diagnostic yield, and adverse events (AEs) were also assessed. Results In 16 out of the 20 patients, a spiral enteroscope was taken directly across UES into the esophagus without a prior bougie dilatation. The spiral enteroscope could not be negotiated across UES only in one patient, and bougie dilatation was done. The technical success rate was 100%. The diagnostic yield was 80%. Four patients reported AEs. Conclusions MSE had a good technical success rate and diagnostic yield. Routine dilatation of the UES before the procedure may be unnecessary.

Efficacy and safety of self-expandable metallic stents for management of benign gastric outlet obstruction-A prospective study.

INTRODUCTION: We aimed at evaluating the safety and efficacy of self-expandable metallic stent (SEMS) insertion for managing patients with benign gastric outlet obstruction (GOO). METHODS: This prospective interventional study included 23 patients. All consecutive treatment-naïve symptomatic patients with benign GOO were recruited. Fully covered SEMS were deployed across the stricture under fluoroscopic and endoscopic guidance. Technical success, clinical success and sustained treatment response (STR) were assessed. Technical success was defined as the successful deployment of SEMS at the desired anatomic location. Clinical success was defined as the resolution of symptoms and an increase in Gastric Outlet Obstruction Scoring System (GOOSS) of at least 1 point from the baseline score on Day 7. STR was assessed at four and eight weeks post stent removal in patients who had a response at week four. Factors associated with stent migration and non-response at week four were also assessed. RESULTS: The median age of the study population was 30 years (range 19-65 years). Males constituted 65.22%. Most patients presented with vomiting (100%) and abdominal pain (95.65%). Peptic stricture was most common etiology for GOO (60.9%) followed by tubercular (26.1%) and corrosive (13%). Most common site of obstruction was junction of first and second part of duodenum (69.57%) followed by pyloric (30.43%). Median length of stricture was 2 cm (range 1.5-4). Technical success was achieved in all 23 patients (100%). Clinical success was achieved in 21 patients (91.3%). Response at Day 28 was seen in 20 patients (86.95%). Eighteen of 20 (90%) patients who had a response at week four had STR at week four and week eight after stent removal. Stent migration occurred in five (21.7%) patients. On univariate analysis, stricture length, calibre and stent length were found to predict migration. CONCLUSIONS: Fully covered SEMS was an effective and safe management modality in patients with benign GOO. Stent migration remains a troublesome disadvantage.

Clinical Profile and Outcome of Patients Presenting With Acute-on-Chronic Liver Failure: A Single-Center Experience.

BACKGROUND AND AIM: We aimed to study the etiologies and clinical profile and to describe the factors associated with mortality in acute-on-chronic liver failure (ACLF) patients at our center. METHODS: Patients meeting the Asian Pacific Association for the Study of the Liver (APASL) definition of ACLF were included. We studied etiologies and clinical profile and analyzed the factors associated with mortality in patients with ACLF. We also analyzed the mortality rates based on the number of organ failures and the grade of ACLF. RESULTS: 114 patients were included. Alcohol (82, 71.9%), drugs (22, 19.3%), and viral hepatitis (17, 14.9%) were the commonest precipitating factors of ACLF. The commonest cause of chronic disease was alcohol (83, 72.8%). Fifty-three (46.5%), 60 (52.6%), 44 (38.6%), 32 (28.1%), and 24 (21.1%) experienced renal, coagulation, cerebral, respiratory, and circulation failures, respectively. Overall, the in-hospital mortality rate stood at 54 (48.6%), with a median stay of eight days. Advanced hepatic encephalopathy and ventilator support independently predicted mortality. The Sequential Organ Failure Assessment (SOFA) score outperformed all other prognostic scores in predicting mortality in ACLF. CONCLUSION: Alcohol was the most common precipitating factor for ACLF. The in-hospital mortality rate was 48.6%. Advanced hepatic encephalopathy and ventilator support independently predicted mortality. The SOFA score is a more accurate predictor of mortality in ACLF when compared to other prognostic scores.

Natural History of Asymptomatic Walled-off Necrosis in Patients With Acute Pancreatitis.

Background and objectives Studies on the natural history of asymptomatic walled-off necrosis (WON) in acute pancreatitis (AP) are scarce. We conducted a prospective observational study to look for the incidence of infection in WON. Material and methods In this study, we included 30 consecutive AP patients with asymptomatic WON. Their baseline clinical, laboratory, and radiological parameters were recorded and followed up for three months. Mann Whitney U test and unpaired t-tests were used for quantitative data and chi-square and Fisher's exact tests were used for qualitative data analysis. A p-value <0.05 was considered significant. Receiver operating characteristic curve (ROC) analysis was done to identify the appropriate cutoffs for the significant variables. Results Of the 30 patients enrolled, 25 (83.3%) were males. Alcohol was the most common etiology. Eight patients (26.6%) developed an infection on follow-up. All were managed by drainage either percutaneously (n=4, 50%) or endoscopically (n=3, 37.5%). One patient required both. No patient required surgery and there was no mortality. Median baseline C-reactive protein (CRP) was higher in infection group 76 (IQR=34.8) mg/L vs asymptomatic group, 9.5 mg/dl (IQR=13.6), p<0.001. IL-6 and tumor necrosis factor (TNF)-alpha was also higher in the infection group. The size of the largest collection (157.50±33.59 mm vs 81.95±26.22 mm, P<0.001) and CT severity index (CTSI) (9.50±0.93 vs 7.82±1.37, p<0.01) were also higher in infection group as compared to the asymptomatic group. ROC curve analysis of baseline CRP (cutoff 49.5mg/dl), size of WON (cutoff 127mm) and CTSI (cutoff of 9) showed AUROC (area under ROC) of 1, 0.97, and 0.81 respectively for the future development of infection in WON. Conclusion Around one-fourth of asymptomatic WON patients developed an infection during three-months follow-up. Most patients with infected WON can be managed conservatively.

Diagnostic utility of urine neutrophil gelatinase-associated lipocalin and renal resistive index in patients of decompensated cirrhosis with acute kidney injury.

BACKGROUND: The differentiation between types of acute kidney injury(AKI) in decompensated cirrhosis(DC) patients in clinical practice is done by clinical adjudication. Biomarkers have good diagnostic accuracy for predicting acute tubular necrosis(ATN), however they are not available routinely. AIMS: We compared the diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin(UNGAL) and renal resistive index(RRI) in predicting type of AKI among DC patients. METHODS: Consecutive DC patients with AKI stage≥1B seen between June/2020 to May/2021 were evaluated. UNGAL levels and RRI were measured at diagnosis of AKI(Day 0) and 48hrs(Day 3) after volume expansion. Diagnostic accuracy of UGNAL and RRI was compared for differentiating ATN and non-ATN AKI by area under receiver operating characteristic curve(AUROC), using clinical adjudication as gold standard. RESULTS: 388 DC patients were screened, 86 patients(Pre-renal AKI[PRA] n=47,55%; Hepatorenal syndrome[HRS] n=25,29%;ATN n= 14,16%) were included. The AUROC of UNGAL for differentiating ATN-AKI and non-ATN AKI at day 0 was 0.97(95%CI, 0.95-1.0) and on day 3 was 0.97(95%CI, 0.94-1.0). The AUROC of RRI for differentiating ATN and non-ATN AKI at day 0 was 0.68(95%CI, 0.55-0.80) and on day 3 was 0.74(95%CI, 0.63-0.84). CONCLUSION: UNGAL has an excellent diagnostic accuracy in predicting ATN-AKI in DC patients both at day 0 and 3.

Validity and Reliability of the European Organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 in Indian Patients With Corrosive-Induced Benign Refractory Esophageal Strictures.

Background The European organization Research and Treatment of Cancer Quality of Life Questionnaire-Oesophagogastric 25 (EORTC QLQ-OG 25) is designed for patients with esophagogastric cancer. Its performance has never been tested with benign disorders. A health-related quality-of-life questionnaire does not exist for patients with benign corrosive-induced esophageal strictures. Hence, we evaluated the EORTC QLQ-OG 25 in Indian patients with corrosive strictures. Methods The English or Hindi version of QLQ-OG 25 was administered to 31 adult patients undergoing outpatient esophageal dilation at GB Pant hospital, New Delhi. These patients had refractory or recurrent esophageal strictures due to corrosive ingestion and had not undergone reconstructive surgery. Score distribution was analyzed, and item performance was determined based on floor and ceiling effects. Convergent validity, discriminant validity, and internal consistency were checked. Results The average time to finish the questionnaire was 6.70 minutes. Most scales fulfilled convergent validity (corrected item-total correlation >0.4), barring the Odynophagia scale and one item of the Dysphagia scale. Most scales exhibited divergent validity except for odynophagia and one item of dysphagia. Cronbach's alpha was >0.70 for all scales except odynophagia. Responses to questions evaluating taste, cough, swallowing saliva, and talking were highly skewed and had prominent floor effects. Overall, the questionnaire demonstrated good internal consistency, convergent validity, and divergent validity in benign corrosive-induced refractory esophageal strictures patients. Conclusion The EORTC QLQ-OG 25 can be satisfactorily used in patients with benign esophageal strictures to assess health-related quality of life.

Comparing Myelosuppression Frequency in Indian Inflammatory Bowel Disease Patients: A Randomized Trial of Full Dose Versus Gradual Escalation of Thiopurines.

INTRODUCTION: We aimed to compare the frequency of myelosuppression in patients initiating azathioprine (AZA) at full dose versus those undergoing gradual dose escalation. METHODS: Forty patients with inflammatory bowel disease were recruited over one year and randomized into two groups of 20. Group A initiated AZA at a full dose of 2 mg/kg, while group B started at 1 mg/kg with subsequent dose increases at regular intervals. RESULTS: Seventeen patients from each group were included in the final analysis. During follow-up, two patients (11.8%) from group A and four patients (23.5%) from group B experienced relapses (p=0.65). Myelosuppression occurred in two patients (11.8%) from each group. Absolute neutrophil counts in group A tended to have lower median values than those in group B, particularly four weeks after AZA initiation. Univariate analysis identified serum proteins, albumin, and bilirubin as significantly associated with leukopenia, but these factors were not significant according to multivariate analysis. CONCLUSIONS: The incidence of myelosuppression was similar between the groups. Patients with full-dose initiation of AZA had numerically fewer relapses during the follow-up period.

Efficacy of hepatitis B vaccination in patients with ulcerative colitis: a prospective cohort study.

BACKGROUND/AIMS: Response to vaccine in patients with inflammatory bowel disease is lower than in the general population. We aimed to evaluate the efficacy of hepatitis B virus (HBV) vaccination in patients with ulcerative colitis (UC) versus controls. METHODS: We prospectively compared antibody response to HBV vaccination in 100 patients with UC versus controls. HBV vaccination was given to all the cases and controls at 0, 1 and 6 months. Anti-hepatitis B surface (anti-HBs) titers were then measured 4 weeks after the first and the third dose. Adequate immune response (AIR) was considered if the anti-HBs titer was >10 IU/L and effective immune response (EIR) if the anti-HBs titer was >100 IU/L. RESULTS: Median anti-HBs titer was lower in patients with UC than controls (67 IU/L vs. 105 IU/L, P<0.01). AIR and EIR were significantly lower in patients than in controls (82% vs. 96%, P=0.001; 41% vs. 66%, P<0.001, respectively). Univariate analysis showed that age <30 years, mild to moderate severity of disease, disease duration <5 years, male sex, post first dose anti-HBs titer >2 IU/L and non-exposure to corticosteroids, azathioprine and biologicals were predictors of AIR in patients with UC (P<0.05). Multivariate analysis revealed that only non-exposure to corticosteroids, azathioprine and biologicals, male sex, and disease duration <5 years were independent predictors of AIR. CONCLUSIONS: Response rate to the HBV vaccination in patients with UC was significantly lower as compared to the controls. Male sex, shorter disease duration, and non-exposure to immunomodulators were independent predictors of AIR.

Enhanced Liver Fibrosis Score: Is It Useful for Evaluation of Fibrosis Severity in Chronic Hepatitis C Infection?

INTRODUCTION: The assessment of liver fibrosis is important in patients with chronic hepatitis C (CHC). In recent years, non-invasive tests like enhanced liver fibrosis (ELF) have been developed as an alternative to liver biopsy for estimating the severity of liver fibrosis. Therefore, we aimed to assess whether the ELF score can be used for fibrosis severity estimation using liver biopsy as the gold standard. MATERIALS AND METHODS: Forty-nine patients with CHC were enrolled in this study. Liver biopsy, ELF assessment, and transient elastography (TE) were performed in all patients, and severity of fibrosis on histopathology was assessed by meta-analysis of histological data in viral hepatitis (METAVIR) score. In addition, the diagnostic performance of ELF was evaluated by receiver operator characteristic curve (ROC) analyses, and liver biopsy histopathology was taken as the gold standard for the severity of liver fibrosis. RESULTS: The area under receiver operator characteristic curve (AUROC) for significant fibrosis of ELF score was 0.64 (95% confidence interval {CI}, 0.48-0.79) and of TE was 0.85 (95% CI, 0.73-0.96). The AUROC for advance fibrosis of ELF was 0.77 (95% CI, 0.57-0.97) and TE was 0.98 (95% CI, 0.94-1.0). The calculated cut-offs of ELF overestimated fibrosis in 53.06% (26/49) of patients and underestimated fibrosis in 6.12% (3/49) patients. AUROC of TE was significantly better than ELF for diagnosis of significant fibrosis (p=0.004) and advanced fibrosis (p=0.034). CONCLUSION: The ELF score can be used for estimating the severity of fibrosis but it is inferior to TE in estimating liver fibrosis severity.

Mucin-filled CBD, difficult to manage cholangitis.

Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the pancreas but occasionally can involve surrounding structures (1.9%-6.6%), like bile duct and duodenum, and are labelled as IPMN with invasion. Jaundice as a manifestation of IPMN is not common (4.5%). It can present as jaundice as a result of invasion of common bile duct (CBD) resulting in stricture formation or uncommonly as a result of fistulising to CBD with resultant obstruction of CBD by thick mucin secreted by this tumour. As only few cases (around 23) of mucin-filled CBD are reported in the literature. We are presenting our experience in dealing a rare case of obstructive jaundice caused by IPMN fistulising into CBD, highlighting the difficulties faced in managing such case, especially with regards to biliary drainage and what can be the optimum management in such cases.

Kaposiform haemangioendothelioma of duodenum in a neonate.

Kaposiform haemangioendothelioma, an endothelial borderline tumour, is typically seen in childhood involving extremities. It has been closely associated with a consumptive coagulopathy state, Kasabach-Merritt phenomenon (KMP). Extracutaneous involvement is uncommon. Intestinal involvement is quite uncommon and can masquerade as an acute abdomen. A 24-day-old neonate presented with bilious vomiting and fever for 5 days. Sections from the resected gangrenous duodenum contained a submucosal tumour composed of infiltrating nodules of slit-like or crescentic CD34-positive spindled-to-flattened endothelial-lined vascular spaces along with zones of fibrosis. No nuclear pleomorphism or necrosis identified. The findings were classic example of kaposiform haemangioendothelioma with an absence of any deranged coagulation profile. The index case raises interest given its congenital incidental presentation at an uncommon site, like duodenum, and absence of coexistent KMP.