Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial.

BACKGROUND: The global prevalence of ulcerative colitis is increasing, and induction and maintenance of remission is a crucial therapeutic goal. We assessed the efficacy and safety of filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, for treatment of ulcerative colitis. METHODS: This phase 2b/3, double-blind, randomised, placebo-controlled trial including two induction studies and one maintenance study was done in 341 study centres in 40 countries. Eligible patients were aged 18-75 years with moderately to severely active ulcerative colitis for at least 6 months before enrolment (induction study A: inadequate clinical response, loss of response to or intolerance to corticosteroids or immunosuppressants, naive to tumour necrosis factor [TNF] antagonists and vedolizumab [biologic-naive]; induction study B: inadequate clinical response, loss of response to or intolerance to any TNF antagonist or vedolizumab, no TNF antagonist or vedolizumab use within 8 weeks before screening [biologic-experienced]). Patients were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 in either induction study entered the maintenance study. Patients who received induction filgotinib were rerandomised 2:1 to continue their induction filgotinib regimen or to placebo. Patients who received induction placebo continued receiving placebo. The primary endpoint was clinical remission by Mayo endoscopic, rectal bleeding, and stool frequency subscores at weeks 10 and 58. For the induction studies, efficacy was assessed in all randomised patients who received at least one dose of study drug or placebo within that study. For the maintenance study, efficacy was assessed in all patients randomised to any filgotinib treatment group in the induction studies who received at least one dose of study drug or placebo in the maintenance study. Patients who received placebo throughout the induction and maintenance study were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of the study drug or placebo within each study. This trial is registered with ClinicalTrials.gov, NCT02914522. FINDINGS: Between Nov 14, 2016, and March 31, 2020, we screened 2040 patients for eligibility. 659 patients enrolled in induction study A were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). 689 patients enrolled into induction study B were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142). 34 patients in induction study A and 54 patients in induction study B discontinued the study drug before week 10. After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A, 273 from induction study B). 93 patients continued to receive placebo. 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99). 263 patients discontinued treatment in the maintenance study. At week 10, a greater proportion of patients given filgotinib 200 mg had clinical remission than those given placebo (induction study A 26·1% vs 15·3%, difference 10·8%; 95% CI 2·1-19·5, p=0·0157; induction study B 11·5% vs 4·2%, 7·2%; 1·6-12·8, p=0·0103). At week 58, 37·2% of patients given filgotinib 200 mg had clinical remission versus 11·2% in the respective placebo group (difference 26·0%, 95% CI 16·0-35·9; p<0·0001). Clinical remission was not significantly different between filgotinib 100 mg and placebo at week 10, but was significant by week 58 (23·8% vs 13·5%, 10·4%; 0·0-20·7, p=0·0420). The incidence of serious adverse events and adverse events of interest was similar between treatment groups. In the induction studies, serious adverse events occurred in 28 (5·0%) of 562 patients given filgotinib 100 mg, 22 (4·3%) of 507 patients given filgotinib 200 mg, and 13 (4·7%) of 279 patients given placebo. In the maintenance study, serious adverse events were reported in eight (4·5%) of 179 patients given filgotinib 100 mg, seven (7·7%) of 91 patients in the respective placebo group, nine (4·5%) of 202 patients in the filgotinib 200 mg group, and no patients in the respective placebo group. No deaths were reported during either induction study. Two patients died during the maintenance study; neither was related to treatment. INTERPRETATION: Filgotinib 200 mg was well tolerated, and efficacious in inducing and maintaining clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. FUNDING: Gilead Sciences.

Primary Prophylaxis Patterns for Hepatic Encephalopathy in Patients with Liver Cirrhosis: What are the Current Prescribing Trends in Specialty Practice?

INTRODUCTION: Hepatic encephalopathy (HE) is a significant complication of severe chronic liver insufficiency characterized by altered sensorium, motor, and cognitive dysfunction. This was a cross-sectional multicenter, epidemiological study to understand the prescribing pattern for primary prophylaxis of overt HE (OHE) in patients with cirrhosis in India. METHODS: The study was conducted at eight centers across different geographical regions of India. A total of 200 patients (100%) were screened, of which 197 (98.50%) met all the inclusion criteria. The prescribing pattern of the physicians was studied by calculating the percentage (subject to availability of sufficient data) of OHE-naïve patients with cirrhosis who were prescribed with different classes of drugs as primary prophylaxis of HE (such as lactulose, rifaximin, neomycin, sodium benzoate, and L-ornithine L- aspartate). The risk factors responsible for initiation of primary prophylaxis of HE was also determined. RESULTS: All the 197 patients (100%) were prescribed with prophylactic treatment. The factors that were considered by treating physicians to pose a risk for precipitating OHE for which prophylaxis was initiated were constipation in 111 (56.35%), infections in 51 (25.89%) and gastrointestinal bleeding in 35 (17.77%). Of the total 197 patients, 122 (61.93%) patients were prescribed a monotherapy, and 75 (38.07%) were prescribed a combination therapy. Of the patients on combination therapy, 68 (34.52%) patients were prescribed with two primary prophylaxis agents (dual therapy), and seven (3.55%) patients were prescribed with three primary prophylaxis agents (triple therapy). Lactulose was the most commonly prescribed agent for primary prophylaxis, followed by rifaximin. CONCLUSION: These findings may guide recommendations on primary prophylaxis for OHE in patients with liver cirrhosis that may help reduce the occurrence of first episode of overt HE, and thereby prevent subsequent cognitive impairment in these patients.

Sociodemographic and Clinical Profiles of Patients with Irritable Bowel Syndrome: A Cross-sectional, Multi-centric, Epidemiological Study in India.

AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by impaired gut-brain interaction. Considering the paucity of evidence in the Indian setting, the current study was conducted to determine the sociodemographics, clinical profiles, management practices, and patients' perception among newly diagnosed patients with IBS. METHODS: This was a cross-sectional, single-visit, observational, non-interventional, epidemiological study conducted across 12 centres. The primary objective was evaluation of sociodemographic and clinical profiles. The key secondary objective was assessment of gastrointestinal symptom severity including evaluation of anxiety and depression using the hospital anxiety and depression scale (HADS) scores. Knowledge, attitude, and practices (KAP) were evaluated as an exploratory objective. RESULTS: Out of 300 enrolled patients, 120 (40%) were aged 31-45 years (mean age: 38.55±12.45 years), and 204 were men (68%). Overall, 40% of patients belonged to the upper-middle-class, with a Kuppuswamy score of 16-25. Most patients (91%) did not work in night shifts. Only 13% of patients performed more than recommended physical activity. Stress and food were the leading triggers for IBS (29%). Abdominal pain and diarrhoea as cardinal symptoms were reported by 43.3% and 33.0% patients, respectively. Borderline abnormal anxiety and depression were reported by 21.3% and 26.7% of patients, respectively. KAP assessment revealed that 56.0% of patients had poor knowledge, 26.3% had moderate knowledge, and 17.7% had good knowledge about IBS; nevertheless, 43% of patients maintained high levels of precaution towards managing symptoms. CONCLUSION: Given the limited knowledge about IBS in India among newly diagnosed patients, strategies to enhance awareness about the condition are warranted.

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.

Acute-on-chronic liver failure in India: The Indian National Association for Study of the Liver consortium experience.

BACKGROUND AND AIM: The aim of this study was to analyze etiologies and frequency of hepatic and extrahepatic organ failures (OFs) and outcome of acute-on-chronic liver failure (ACLF) at 10 tertiary centers in India. METHODS: In this retrospective study (2011-2014), patients satisfying Asian Pacific Association for the Study of the Liver definition of ACLF were included. Etiology of acute precipitating insult and chronic liver disease and outcomes were assessed. Occurrence and severity of OF were assessed by chronic liver failure-sequential organ failure assessment score. RESULTS: The mean (±SD) age of 1049 consecutive ACLF patients was 44.7 ± 12.2 years; Eighty-two percent were men. Etiology of acute precipitants included alcohol 35.7%, hepatitis viruses (hepatitis A, hepatitis B, and hepatitis E) 21.4%, sepsis 16.6%, variceal bleeding 8.4%, drugs 5.7%, and cryptogenic 9.9%. Among causes of chronic liver disease, alcohol was commonest 56.7%, followed by cryptogenic and hepatitis viruses. Predictors of survival were analyzed for a subset of 381 ACLF patients; OF's liver, renal, coagulation, cerebral, respiratory, and failure were seen in 68%, 32%, 31.5%, 22.6%, 14.5%, and 15%, respectively. Fifty-seven patients had no OF, whereas 1, 2, 3, 4, and 5 OFs were recorded in 126, 86, 72, 28, and 12 patients, respectively. The mortality increased progressively with increasing number of OFs (12.3% with no OF, 83.3% with five OFs). During a median hospital stay of 8 days, 42.6% (447/1049) of patients died. On multivariate analysis by Cox proportional hazard model, elevated serum creatinine (hazard ratio [HR] 1.176), advanced hepatic encephalopathy (HR 2.698), and requirement of ventilator support (HR 2.484) were independent predictors of mortality. CONCLUSIONS: Alcohol was the commonest etiology of ACLF. Within a mean hospital stay of 8 days, 42% patients died. OFs independently predicted survival.

Hypothyroidism Presenting as Multiple Body Cavity Effusions.

Primary hypothyroidism is a common clinical condition in which serous effusions are rare. Isolated cases have been reported in literature about presence of ascites, pleural effusion, pericardial effusion or combination of any two. But combination of all three is extremely rare. We hereby report a case of multiple body cavity effusions (ascites, pleural and pericardial effusions) and tissue edema (pedal and facial) in a hypothyroid male. He responded well to thyroid hormone replacement therapy.

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.

Intravenous versus oral 'L-ornithine-L-aspartate' in overt hepatic encephalopathy: a randomized comparative study.

Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) L-ornithine-L-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

Efficacy and Rationale of Endoscopic Ultrasound-Guided Thrombin Injection in Visceral Artery Pseudoaneurysm Not Amenable to Angioembolization.

BACKGROUND: Pseudoaneurysm usually occurs after vascular injuries or erosions such as in trauma or inflammation like pancreatitis and is associated with high morbidity and mortality. AIM: The aim of study is to assess efficacy and safety of EUS-guided thrombin injection in pseudoaneurysm. MATERIALS AND METHODS: Prospective data collection was done at SMS Hospital, Jaipur, from January 2015 to March 2023. All patients with pseudoaneurysm were consecutively enrolled. RESULTS: Twenty patients (M/F, 18:2) with median age of 41 years (25-58 years), were studied. Underlying etiology of pseudoaneurysm was chronic pancreatitis in 75% of the patients, blunt trauma abdomen in 15% of the patients, recurrent acute pancreatitis in 5%, and idiopathic in 5% of the patients. At the time of admission, mean hemoglobin was 6.7 g/dL (3.4-8.2), with median blood transfusion requirement was 2 units (0-6 units). Hemoglobin values after 4-6 weeks showed a significant improvement ( t = 9.21, P < 0.05).Mean dose of human thrombin required for complete obliteration of pseudoaneurysm was 520 ± 188.6 IU per patient (300-800 IU). Amount of thrombin (IU) dose needed to achieve complete obliteration correlated well significantly with the dimension of pseudoaneurysm, P value less than 0.05 ( R = 0.80). Median follow-up duration in this study was 44 months (3-84 months), which was the longest follow-up period by far. CONCLUSIONS: Endoscopic ultrasound-guided thrombin injection in visceral artery pseudoaneurysm is a safe and effective alternative for patients not amenable for digital subtraction angiography-guided angioembolization.

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.

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.

A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1,000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED).

OBJECTIVES: In the largest head-to-head comparison between an oral and an intravenous (IV) iron compound in patients with inflammatory bowel disease (IBD) so far, we strived to determine whether IV iron isomaltoside 1,000 is non-inferior to oral iron sulfate in the treatment of iron deficiency anemia (IDA). METHODS: This prospective, randomized, comparative, open-label, non-inferiority study was conducted at 36 sites in Europe and India. Patients with known intolerance to oral iron were excluded. A total of 338 IBD patients in clinical remission or with mild disease, a hemoglobin (Hb) <12 g/dl, and a transferrin saturation (TSAT) <20% were randomized 2:1 to receive either IV iron isomaltoside 1,000 according to the Ganzoni formula (225 patients) or oral iron sulfate 200 mg daily (equivalent to 200 mg elemental iron; 113 patients). An interactive web response system method was used to randomize the eligible patient to the treatment groups. The primary end point was change in Hb from baseline to week 8. Iron isomaltoside 1,000 and iron sulfate was compared by a non-inferiority assessment with a margin of -0.5 g/dl. The secondary end points, which tested for superiority, included change in Hb from baseline to weeks 2 and 4, change in s-ferritin, and TSAT to week 8, number of patients who discontinued study because of lack of response or intolerance of investigational drugs, change in total quality of life (QoL) score to weeks 4 and 8, and safety. Exploratory analyses included a responder analysis (proportion of patients with an increase in Hb ≥2 g/dl after 8 weeks), the effect of regional differences and total iron dose level, and other potential predictors of the treatment response. RESULTS: Non-inferiority in change of Hb to week 8 could not be demonstrated. There was a trend for oral iron sulfate being more effective in increasing Hb than iron isomaltoside 1,000. The estimated treatment effect was -0.37 (95% confidence interval (CI): -0.80, 0.06) with P=0.09 in the full analysis set (N=327) and -0.45 (95% CI: -0.88, -0.03) with P=0.04 in the per protocol analysis set (N=299). In patients treated with IV iron isomaltoside 1,000, the mean change in s-ferritin concentration was higher with an estimated treatment effect of 48.7 (95% CI: 18.6, 78.8) with P=0.002, whereas the mean change in TSAT was lower with an estimated treatment effect of -4.4 (95% CI: -7.4, -1.4) with P=0.005, compared with patients treated with oral iron. No differences in changes of QoL were observed. The safety profile was similar between the groups. The proportion of responders with Hb ≥2 g/dl (IV group: 67%; oral group: 61%) were comparable between the groups (P=0.32). Iron isomaltoside 1,000 was more efficacious with higher cumulative doses of >1,000 mg IV. Significant predictors of Hb response to IV iron treatment were baseline Hb and C-reactive protein (CRP). CONCLUSIONS: We could not demonstrate non-inferiority of IV iron isomaltoside 1,000 compared with oral iron in this study. Based on the dose-response relationship observed with the IV iron compound, we suggest that the true iron demand of IV iron was underestimated by the Ganzoni formula in our study. Alternative calculations including Hb and CRP should be explored to gauge iron stores in patients with IBD.

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%).

Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Redefining Celiac Iceberg in Children in North India-Do Asymptomatic Subjects Need Screening?

The prevalence of celiac disease (CD) in Indian children is not well documented, with most of the studies focusing on high-risk groups and not the general population. This study was conducted to determine the prevalence of CD in asymptomatic school children of Jaipur, Rajasthan. A cross- sectional study was conducted among healthy school children of Jaipur. Demographic data, symptoms, and signs including dermatological examination were recorded. The screening for CD was done by ELISA-based anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibody testing. Children with high IgA anti-tTG underwent upper gastrointestinal endoscopy for small bowel biopsy from the second part of the duodenum. This study involved 575 subjects, out of which, 6 (1.04%) were found to be IgA tissue transglutaminase antibody (IgA-tTG) positive. All 6 subjects were found to be having changes consistent with celiac disease on duodenal biopsy. To conclude, the calculated prevalence of celiac disease was 1 in 96 subjects.

Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease.

Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.

Comparative evaluation of efficacy and safety of drotaverine versus mebeverine in irritable bowel syndrome: A randomized double-blind controlled study.

BACKGROUND: Drotaverine and Mebeverine are used for alleviating the pain of IBS, but the evidence for their efficacy is scarce. In this randomised control study, we evaluated and compared their efficacy in improving severity, frequency of pain and its associated symptoms. METHODS: Patients fulfilling the ROME III criteria of IBS were evaluated in this randomised control trial during 4 weeks of treatment. Group A (n = 100) received 80 mg Drotaverine and Group B (n = 100) received 135 mg Mebeverine three times a day, 1 hour before meals. Primary outcome measure was, the reduction in severity of pain (>30% reduction) assessed by VAS (0 to 10 scale) & PSS (patient symptoms scores). RESULTS: The pain severity score fell from 6.02 to 4.8 on day 3 in Group A as compared to decrease from 6.72 to 6.62 in Group B (p < 0.01). This significant reduction in pain severity was observed till the end of the study, reducing from 6.02 to 1.78 (74% reduction) in Group A compared to 6.72 to 3.62 (46.1% reduction) in Group B (p < 0.05). There was a significant reduction in pain frequency, straining on stool, a change in one score in Bristol stool chart (BSC), achievement of complete spontaneous smooth bowel movement in Group A, compared to Group B patients. A significant improvement in Patient's evaluation of Global Assessment of Symptoms (p < 0.05) and Patient Assessment of Constipation - Quality Of Life (PAC-QOL) (p < 0.01) was observed in Group A compared to Group B. CONCLUSION: Drotaverine was significantly superior in efficacy as compared to Mebeverine in alleviating pain severity (starting from day 3), frequency and stools-elated symptoms of IBS.

Levels of Aminotransferases Among Schoolchildren in Jaipur, Rajasthan.

We did cross-sectional study for normal values of amino-transferases in school children aged 2- 18 years. Median (IQR) AST and ALT values in study subjects were 30 (27- 34) U/L and 23 (19-29) U/L. We also provided age-and sex-related percentiles of aminotransferases of children. We observed a peak of median AST serum values in the age group 6-8 years followed by continuous decline with increasing age. While in ALT, we observed maximum values in age group 2-5 years followed by continuous decline. There was a statistically significant difference in values of amino-transferases between sexes.