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.

Early precut versus primary precut sphincterotomy to reduce post-ERCP pancreatitis: randomized controlled trial (with videos).

BACKGROUND AND AIMS: Precut sphincterotomy, usually performed after prolonged and failed cannulation, is considered a risk factor for post-ERCP pancreatitis (PEP). There are limited studies on primary needle-knife precut for the prevention of PEP. The aim of this study was to assess the safety and efficacy of primary precut. METHODS: A randomized controlled trial was conducted in a tertiary care setting on patients who underwent ERCP. Patients were randomized to very early precut (group A, precut after 2 failed attempts of wire-guided sphincterotome cannulation) and primary precut (group B, direct needle-knife precut). All procedures were done by an experienced endoscopist. The primary outcome of the study was to compare the incidence of PEP between the 2 groups. RESULTS: Three hundred three patients were randomized to group A (n = 152, age 48.2 ± 15.4 years, 61 men) and group B (n = 151, age 46.7 ± 13.8 years, 65 men). There was no significant difference in baseline characteristics and indications for ERCP between the 2 groups. Development of PEP (5.2% vs .67%; P = .04) and asymptomatic hyperamylasemia (12.5% vs 2.6%; P = .01) were lower in group B compared with group A. The bile duct cannulation time (13.8 ± 2.2 vs 7.2 ± 1.7 minutes; P = .001) was lower in group B, whereas the overall cannulation success rate (98% vs 98.6%; P = 1.0) was similar in both the groups. CONCLUSIONS: Primary precut by an experienced endoscopist results in low risk of PEP. (Clinical trial registration number: CTRI/2017/08/009510.).

Efficacy and Safety of Direct Acting Antiviral Therapy for Chronic Hepatitis C in Thalassemic Children.

OBJECTIVES: There is limited data on the efficacy and safety of directly acting antiviral therapy (DAA) for chronic hepatitis C in pediatric population. The aim was to assess the efficacy and safety of DAA in chronic hepatitis C ß-thalassemic major pediatric patients. METHODS: Prospective study was conducted from September 2015 to January 2017. All ß-thalassemic major chronic hepatitis C pediatric patients with age between 5 and 14 years were included in this study. Data related to demography, laboratory parameters, hepatitis C viral load, genotype and outcome of antiviral therapy was analyzed. DAA was planned according to EASL guidelines 2015 for chronic hepatitis C therapy in adults. OBSERVATIONS: Fourteen ß-thalassemic major patients (median age was 9.5 y, 12 male) were studied. All patients were of genotype 3, received DAA (sofosbuvir 400 mg+daclatasvir 80 mg) for 12 weeks. The median viral load was 2.5×10 IU/mL. End of treatment response and sustained virological response at 12 weeks was achieved in all the patients. Serum alanine aminotransferase, aspartate aminotransferase, ferritin, and albumin significantly reduced after DAA. CONCLUSIONS: DAA in adult dosage are safe and effective for treatment of chronic hepatitis C (genotype 3) in pediatric ß-thalassemic major population.

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.

Spectral electroencephalogram in liver cirrhosis with minimal hepatic encephalopathy before and after lactulose therapy.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy. Spectral electroencephalogram (sEEG) analysis improves the recognition of MHE by decreasing inter-operator variability and providing quantitative parameters of brain dysfunction. We compared sEEG in patients with cirrhosis with and without MHE and the effects of lactulose on sEEG in patients with MHE. METHODS: One hundred patients with cirrhosis (50 with and 50 without MHE) were enrolled. Diagnosis of MHE was based on psychometric hepatic encephalopathy score (PHES) of ≤ -5. Critical flicker frequency, model of end-stage liver disease score, and sEEG were performed at baseline in all patients. The spectral variables considered were the mean dominant frequency (MDF) and relative power in beta, alpha, theta, and delta bands. Patients with MHE were given 3 months of lactulose, and all parameters were repeated. RESULTS: Spectral electroencephalogram analysis showed lower MDF (7.8 ± 1.7 vs 8.7 ± 1.3 Hz, P < 0.05) and higher theta relative power (34.29 ± 4.8 vs 24 ± 6.7%, P = 001) while lower alpha relative power (28.6 ± 4.0 vs 33.5 ± 5.3%, P = .001) in patients with MHE than in patients without MHE. With theta relative power, sensitivity 96%, specificity 84%, and accuracy of 90% were obtained for diagnosis of MHE. After lactulose treatment, MHE improved in 21 patients, and significant changes were seen in MDF (7.8 ± 0.5 vs 8.5 ± 0.6), theta (34.2 ± 4.8 vs 23.3 ± 4.1%), alpha (28.6 ± 4.0 vs 35.5 ± 4.5%), and delta relative power (13.7 ± 3.5 vs 17.0 ± 3.3%) after treatment (P ≤ 0.05). CONCLUSIONS: Spectral EEG is a useful objective and quantitative tool for diagnosis and to assess the response to treatment in patients with cirrhosis with MHE.

Malnutrition in cirrhosis increases morbidity and mortality.

BACKGROUND AND AIMS: Malnutrition is frequent in patients with cirrhosis and is associated with complications like ascites, hepatic encephalopathy, infections, and death. We determined the prevalence of malnutrition by various methods and its clinical importance in patients with cirrhosis. METHODS: Consecutive patients of cirrhosis from August 2013 to February 2015 were assessed. Nutritional status was assessed by traditional model (mid-arm circumference, triceps skinfold thickness, serum albumin, creatinine height index, total lymphocyte count), handgrip, and body composition analysis measuring skeletal muscle mass and body fat mass. All patients were followed up for 12 months to assess the outcome. RESULTS: 247 patients (age 42.10 ± 10.14 years, 81% male) were included in the study. Etiology of cirrhosis was alcohol in 53% patients. Prevalence of malnutrition was 59.5% according to traditional model, 66.8% by body composition analysis and 71.4% by handgrip. Nutritional status was poor in alcoholic cirrhotics versus nonalcoholics as assessed by triceps skinfold thickness (9.33 ± 2.9 vs 11.64 ± 3.5 mm; P = 0.001), serum albumin (25.1 ± 4 vs 28.1 ± 4 g/L; P = 0.001), and body fat mass (7.6 ± 3.1 vs 8.7 ± 3.3 kg; P = 0.008). Prevalence of malnutrition was 12/27 (44.5%), 96/131 (73.3%) and 84/89 (94.4%) in Child's class A, B, and C respectively. Complications requiring hospitalization (71.3% vs 38.2%; 0.002) and mortality (41.1% vs 18.2%; P = 0.001) were more in malnourished patients compared to well nourished. Nutritional assessment parameters significantly correlated with the liver disease severity (P < 0.05). CONCLUSIONS: Prevalence of malnutrition is high in patients with cirrhosis. It is associated with increased complications and mortality.

Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

Outcome of forgotten biliary stents for more than five years-A two-decade experience.

BACKGROUND AND OBJECTIVES: Prolonged biliary stenting may lead to complications such as cholangitis, stentolith and stent migration. There is limited data on forgotten biliary stents for more than five years in literature. The aim of this retrospective study was to analyze the complications and outcomes in patients who forgot to get their biliary stents removed or exchanged for more than five years. METHODS: The study population included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and plastic biliary stent placements in a tertiary care center from 1990 to 2022 for benign biliary diseases. Loss to follow-up and subsequent forgotten stent for more than five years were observed in 40 patients who underwent ERCP during this study period. We retrospectively analyzed the indications of stenting, present status of stent, complications and outcomes in the study patients. RESULTS: The mean age of the study patients was 51.5 ± 11.5 years with 27 females. Indications of biliary stent placement were choledocholithiasis (33, 82.5%), bile leak (3, 7.5%), benign biliary stricture (2, 5%) and choledochal cyst (2, 5%). The mean duration of forgotten stent was 5.9 ± 3.6 years. Presenting symptoms were abdominal pain (37, 92.5%), fever (26, 65%) and jaundice (32, 80%). Most commonly placed stent was 7 French double pigtail of 10 cm length. Complications in the study patients were cholangitis (35, 87.5%), internal migration (2, 5%), pancreatitis (1, 2.5%) and portal hypertension (1, 2.5%). The outcomes were stone removal (30, 90.9%), stent removal (31, 77.5%), stent reinsertion (19, 47.5%), broken stent (3, 7.5%) and surgery (2, 5%). CONCLUSIONS: Prolonged duration (> 5 years) of forgotten stent is uncommon and is observed most commonly in patients with choledocholithiasis. The most common complication of long duration of forgotten stents was cholangitis followed by internal migration, pancreatitis and portal hypertension. Stone and stent removal was successful in a majority of patents, while surgery was required in less number of patients.

Scrub Typhus: An Acute Precipitant for Acute on Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high mortality. Many acute precipitating factors have been implicated in triggering the acute event of ACLF, with bacterial infections being a common precipitant. However, many other precipitants can cause ACLF; therefore, identification of these factors early in the golden window and their treatment can result in improved prognosis. Scrub typhus usually presents as uncomplicated acute febrile illness but rarely as complicated. Few case reports of scrub-typhus-induced acute liver failure have been reported but none with scrub-typhus-precipitating ACLF so far. Therefore, we are reporting a case of scrub-typhus-precipitating ACLF, where timely intervention with antibiotics results in improved outcome.

Changing etiological spectrum of acute liver failure.

BACKGROUND AND OBJECTIVES: Acute liver failure (ALF) is an uncommon but potentially dramatic syndrome characterized by massive hepatic necrosis and has a very high mortality rate of 50% to 75% without liver transplantation. This study is aimed at analyzing the etiological spectrum of ALF patients and compare these with ALF mimics such as malaria, dengue fever and other tropical infectious diseases. METHODS: The study population included patients who presented with ALF and ALF mimics in a tertiary care center over two years. We retrospectively analyzed the patient case files and a comparison was made concerning the baseline demographic details, clinical profile, laboratory values and outcomes. RESULTS: Sixty-three patients were assessed, with 32 in ALF and 31 in ALF mimics group. The most common cause for ALF was hepatitis A virus (25%), followed by hepatitis B virus (18.7%), drug-induced liver injury (12.7%), autoimmune hepatitis (12.5%), hepatitis E virus (9.3%) and Wilson's disease (6.25%). In the ALF mimics group, malaria (58.06%) was the most common cause, followed by dengue fever (16.1%), leptospirosis (12.9%) and scrub typhus (12.9%). Patients in the ALF mimics group had significantly higher incidence of fever (p = 0.001), hepatosplenomegaly (p = 0.01), anemia (p = 0.02) and shorter jaundice to encephalopathy duration (p = 0.032) as compared to the ALF group, while higher transaminase levels (p = 0.03), bilirubin (p = 0.01), prothrombin time (p = 0.01), serum ammonia (p = 0.02) and mortality (p = 0.02) were observed in ALF patients. CONCLUSIONS: The most common cause for ALF was hepatitis A virus, followed by hepatitis B virus, while in ALF mimics it was malaria followed by dengue fever, in our study. Patients of ALF mimics can have similar presentation, but a high index of suspicion and awareness is required to identify the common infectious ALF mimics for early diagnosis.

Aetiology and clinical spectrum of gastric outlet obstruction in North West India.

Our study to evaluate the aetiological and clinical spectrum of gastric outlet obstruction (GOO) in North-west India showed malignant cause (54.9%) was more common than benign (45.1%). Common causes of malignancy were gall bladder (37.5%), gastric (31.8%) and pancreatic carcinoma (19.6%); commonest benign causes were opioid abuse (29%), peptic ulcer disease (21.6%), ingestion of corrosives (20.2%) and chronic pancreatitis (12.3%).

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. METHODS: Prospectively collected data from the AARC database were analyzed. RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. CONCLUSION: Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Management of walled-off necrosis with nasocystic irrigation with hydrogen peroxide versus biflanged metal stent: randomized controlled trial.

Background and study aims Walled-off necrosis (WON) is a known complication of acute necrotizing pancreatitis (ANP). There is no study comparing nasocystic irrigation with hydrogen peroxide (H 2 O 2 ) versus biflanged metal stent (BMS) in the management of WON. The aim of this study was to compare the clinical efficacy of both the treatment strategies. Patients and methods This study was conducted on patients with symptomatic WON who were randomized to nasocystic irrigation with H 2 O 2 (Group A) and BMS placement (Group B). Primary outcomes were clinical and technical success while secondary outcomes were procedure time, adverse events, need for additional procedures, duration of hospitalization, and mortality. Results Fifty patients were randomized into two groups. Group A (n = 25, age 37.8 ±â€Š17.6 years, 16 men) and Group B (n = 25, age 41.8 ±â€Š15.2 years, 17 men). There were no significant differences in baseline characteristics between the two groups. The most common etiology of pancreatitis was alcohol, observed in 27 (54 %) patients. Technical success (100 % vs 96 %, P  = 0.98), clinical success (84 % vs 76 %, P  = 0.76), requirement of additional procedures (16 % vs 24 %, P  = 0.70) and adverse events (4 vs 7, P  = 0.06) were comparable in both the groups. The duration to clinical success (34.4 ±â€Š12 vs 14.8 ±â€Š10.8 days, P  = 0.001) and procedure time (36 ±â€Š15 vs 18 ±â€Š12 minutes, P  = 0.01) were longer in Group A compared to Group B. Conclusions Nasocystic irrigation with H 2 O 2 and BMS are equally effective in the management of WON but time to clinical success and procedure time is longer with nasocystic irrigation.

Seronegative Celiac Disease; Frequently Encountered Yet Undiagnosed Clinical Entity.

BACKGROUND There are limited studies on the seronegative celiac disease from the Indian subcontinent. The aim of this study was to assess the prevalence, pathological, genetic, and clinical profile of patients with seronegative celiac disease. METHODS This prospective observational study was conducted in the Department of Gastroenterology, SMS Hospital, Jaipur, between October 2017 to March 2019. Consecutive patients with seronegative celiac disease with age ≥ 3 years were enrolled for the assessment of demography, clinical features, histological findings, celiac serology, genetic analysis, and response to gluten-free diet. RESULTS Out of total of 312 patients with celiac disease, 13 (4.16 %) patients (median age 25 years [range 5-46 years], 10 female) were diagnosed as having seronegative celiac disease. Presenting symptoms were chronic diarrhea in nine (69.23%), abdominal pain in six (46.15%), weight loss in five (38.46%), and short stature in two (15.38 %) patients. On histological analysis, Marsh stage 2 was seen in five (38.46%), Marsh 3c in two (15.38%), Marsh 3a in three (23.07%), and Marsh 3b in three (23.07%) patients. On HLA analysis, HLA-DQ2.5 was seen in six (46.15%) patients, HLA-DQ2.2 in five (38.46%), and HLA-DQ8 in two (15.38%) patients. CONCLUSION The prevalence of seronegative celiac disease in our study was 4.16%. The most common symptoms were chronic diarrhea and abdominal pain, and the histological grade was Marsh stage 2.

Endoscopic ultrasound-guided thrombin injection, a management approach for visceral artery pseudoaneurysms.

Background and study aims Pseudoaneurysms are usually associated with high rates of morbidity and mortality. There are limited data in the literature on endoscopic ultrasound (EUS)-guided thrombin injection for pseudoaneurysms. The aim of this study is to assess the efficacy and safety of EUS-guided thrombin injection for pseudoaneurysms. Patients and methods This prospective study was conducted in our department between January and December 2018. All patients with symptomatic visceral artery pseudoaneurysms, who were unable to undergo angioembolization, were enrolled consecutively. Data related to demography, laboratory parameters, radiological imaging, pseudoaneurysms, and endotherapy were analyzed. Results Eight patients with median age 34 years (27-58 years), all men, were studied. The vessel involved was the splenic artery in 5 patients (62.5 %), the left hepatic artery in 2 (25 %), and the gastroduodenal artery in 1 patient (12.5%). The median size of the pseudoaneurysms was 2.9 cm × 2.6 cm (range, 1.8 × 1.9-4 × 5 cm). The median thrombin requirement was 400 IU (range, 200-500 IU) for loss of Doppler flow signals. EUS after 3 months showed obliterated pseudoaneurysms in 7 patients (87.5 %), while recurrence was observed in 1 patient (12.5 %) after 6 weeks. Conclusions EUS-guided thrombin injection may be a new option for the management of pseudoaneurysms.