Long-term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real-world experience.

Background and Aim: Azathioprine (AZA) forms the cornerstone for maintenance of sustained remission in inflammatory bowel disease (IBD). There is apprehension regarding the long-term effectiveness and safety of AZA in IBD. We present our experience with AZA use and outcomes in a cohort of IBD patients followed up over a long period of time. Methods: Records of 507 IBD patients under treatment at a single, tertiary care center in south India between 2013 and 2022 were evaluated retrospectively. Long-term compliance, tolerance, clinical outcome at the point of last follow-up, type and duration to the onset of adverse events, and subsequent amendment to treatment with regard to AZA were analyzed. Results: Of 507 patients with IBD, 320 patients (207 Crohn's disease [CD], 113 ulcerative colitis [UC]) who received AZA were included. The median follow-up was 41 months (interquartile range 15.5-77.5). Total duration of exposure was 1359 patient-years with median usage of 33 months. Of the patients, 26.9% received AZA for >5 years. Mean initiation and maximum doses of AZA were 0.97 and 1.72 mg/kg/day. Among the participants, 20.6% experienced side effects, including myelotoxicity (7.2%) and gastrointestinal intolerance (5.6%). Six patients developed malignancy. Among the side effects, 39.4% of side effects were dose-dependent. Among the patients, 38.1% had relapses requiring pulse corticosteroid therapy, and 16.2% had more than one relapse after commencement of AZA. AZA was continued till the last follow-up in 76.5%. Among the patients, 49.7% (UC 51.3, CD 48.8) attained durable remission without biologics, and 5.3% continued to have active disease. Conclusion: AZA is safe and effective in the long-term in IBD. Effectiveness, tolerance, and compliance with AZA are well sustained beyond 5 years of usage and comparable between UC and CD.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

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.

Inflammatory bowel disease: An Indian perspective.

Inflammatory bowel disease (IBD) in recent times is causing a significant healthcare burden as both ulcerative colitis and Crohn's disease (CD) require lifelong therapy and constant monitoring. The current review highlights the concerns in a country like India with special reference to the changing trends of IBD, risk attribution and the financial issues. Indian immigrants behave like residential Indians, whereas their children show IBD prevalence similar to the West, highlighting the role of environmental triggers. However, the environmental and genetic factors in Indians with IBD are not well understood. Men appear to be more frequently affected than women in India. The disease severity is milder in the patients, both males and females, but the risk for colorectal cancer (CRC) is similar to the West. The incidence of paediatric IBD is on the rise. The major burden of IBD in the Indian subcontinent at present is in children, adolescents and teens. Cost towards the management of complications, non-adherence to treatment, differentiating tuberculosis from CD and finally screening for CRC in patients with IBD are the points to ponder in the Indian scenario.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Rodenticide ingestion is an important cause of acute hepatotoxicity in Tamil Nadu, southern India.

BACKGROUND AND AIM: Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India. METHODS: We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases. RESULTS: Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15-34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265-6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%. CONCLUSION: Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this.

The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Role of N-acetyl Cysteine in Post-transarterial Chemoembolization Transaminitis in Hepatocellular Carcinoma: A Single-center Experience.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common locoregional therapy for hepatocellular carcinoma (HCC). Postembolization syndrome is not an uncommon complication. At present, there is no specific treatment for management of this complication. We aimed to study the role of N-acetyl cysteine (NAC), an antioxidant, in management of this complication. METHODS: In a prospective observational study, consecutive patients with HCC undergoing TACE from January 2016 to January 2017 were included. Patients with postembolization syndrome, defined as an elevation of transaminase levels more than 3-4 times the upper limit of normal, were administered intravenous NAC for 72 h (150 mg/kg for 1 h, then 12.5 mg/kg/h for 4 h, and continuous infusion 6.25 mg/h for the remaining 67 h). The other group received only supportive standard of care. The primary end point was reduction in post-TACE transaminitis. RESULTS: Of 112 patients with HCC, 53 (47.3%) received NAC. The majority were cirrhotics in both the groups. Both groups were well matched in demographic, laboratory, and tumor characteristics. In the NAC group, there was significant reduction in Aspartate transaminase (AST) and Alanine transaminase (ALT) levels from day 1 to day 3 (p = 0.000) compared with the non-NAC group, with no significant change in bilirubin or international normalized ratio levels. The duration of hospital stay was similar in both the groups. None had any major adverse events to NAC. CONCLUSION: This is a prospective, single-center experience, showing that early initiation of N-acetyl cysteine in those with post-TACE embolization syndrome reduces the transaminase level significantly.

Serum C-reactive protein and neutrophil-to-lymphocyte ratio as predictors of survival in cirrhotic patients with systemic inflammatory response syndrome and bacterial infection.

BACKGROUND: Cirrhotic patients are prone to infections due to underlying immune dysfunction in them. We aimed to study the role of inflammatory markers, serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), in predicting infection, blood culture positivity, and short-term (1 month) mortality in hospitalized cirrhotic patients. METHODS: This prospective study was done over a period of 14 months (October 2017 to November 2018). Patient data included age, gender, etiology of cirrhosis, reason for admission, and comorbidity. Laboratory tests included blood chemistry and blood cell counts, and blood and urine culture. The specific tests included were CRP and NLR. Survival of patients in the following 1 month was noted. Area under receiver operating characteristic curve (AUROC), sensitivity, specificity, predictive values, diagnostic accuracy were calculated and logistic regression analysis performed. A p-value < 0.05 was considered significant. RESULTS: Two hundred and eight patients formed the study cohort. The median age was 51.5 years and male predominance was noted. Alcohol-related liver disease (49%) was the commonest etiology. The infection rate was 62%, culture positivity was 58.5%, and mortality was 30.8%. NLR and CRP were significantly higher in those with documented infection (culture positive or negative) and among nonsurvivors. Optimal cutoffs for NLR and CRP to predict infection were 5.86 and 33.7, respectively. The risk of having an infection was 7.5 times and about 15 times if NLR and CRP were above the cutoffs. The risk of 1-month mortality was 2-3 times higher if patients had NLR and CRP above the cutoffs. The combination of NLR and CRP (≥ 5.86 and ≥ 33.7, respectively) increased specificity and diagnostic accuracy for infection. CONCLUSION: NLR and CRP were independently good predictors of infection and 1-month survival among the patients with cirrhosis of liver included in this study.

Defaecation disorders among information technology personnel: A cross-sectional study.

Background Individuals working in the information technology (IT) industry are likely to develop lifestyle disorders. We aimed to determine the presence of defaecation-related disorders in IT personnel in Chennai. Methods This cross-sectional, questionnaire-based study was done from June to December 2018. We included employees between 18 and 60 years of age and excluded those with <1 year stay in Chennai, pregnancy and those who sent incomplete responses. The cohort was classified as normal, irritable bowel syndrome (IBS), faecal evacuation disorder (FED) and a combination of the latter two. Results The overall response rate was 95.6%. The study included 54.7% of men, and the median age was 31 years. The majority of respondents used an Indian toilet (554; 58%). Almost all (96.2%) passed stools daily, and stool consistency was soft in 59%. Based on the study criteria, 180 (18.8%) had FED, 56 (5.9%) had IBS and a small group had a combination of symptoms of IBS and FED (20; 2.1%). Respondents with symptoms of IBS had a higher proportion of comorbid states (p<0.0001), lesser stool frequency (p<0.0001) and required more toilet time (p<0.00001). Conclusion Over one-fourth (26.7%) of the respondents had defaecation-related issues, 18.8% had symptoms suggestive of FED and 5.6% that of IBS, often above 30 years of age.

Oral melatonin improves the detection of parasitemia in malaria.

INTRODUCTION: Malaria is a growing global threat and a major cause of mortality in the tropics. The gold standard diagnosis is peripheral blood smear examination. It has been demonstrated that melatonin acts as messenger molecule in malaria pathophysiology. This concept was used to evolve a clinical study wherein use of exogenous melatonin could improve the chance of detection of the parasite. METHODOLOGY: In a prospective study, 80 consecutive patients seen in the Department of Medicine at Kasturba Hospital, Manipal, suspected to have malarial fever were enrolled with proper informed consent, and randomly assigned to the groups given oral melatonin 3mg (melatonin group, n = 40) or placebo (control group, n = 40). Blood samples were collected for peripheral smear examination at baseline and then at two, three, four and five hours after drug administration. The primary end point was the parasite detection index. RESULTS: Baseline characteristics of patients were comparable. In the melatonin group, there was a significant increase of 0.0943 ± 0.22 in the mean parasite index from 0.217 ± 0.42 pre-melatonin to 0.3114 ± 0.5 post-melatonin (p = 0.001), compared to a difference of 0.0025 ± 0.22 in mean parasite index before and after placebo in the control group (p = 0.95). The maximum rise in parasite detection was seen at five hours after melatonin. CONCLUSIONS: In a single centre study, for the first time, it has been shown that a significantly higher proportion of patients was diagnosed with malaria on peripheral smear after oral melatonin administration, maximal at five hours after administration of melatonin.

Retrospective study on symptoms and treatment modalities used and short-term follow up of achalasia cardia in Indian setting.

BACKGROUND: Achalasia cardia is a rare esophageal motor disorder that is frequently diagnosed late. AIM: The aim of this study was to study the symptoms, treatment given, and response to treatment in patients with achalasia cardia in an Indian setting. MATERIALS AND METHODS: This retrospective study included all patients diagnosed with achalasia cardia on high-resolution esophageal manometry, using Chicago Classification v 3.0. On follow up, patients were contacted by telephone, and details of the treatment given and response were recorded in a predesigned pro forma. We excluded overseas patients, postoperative cases of achalasia, and those in whom the manometry catheter could not be passed across the gastroesophageal junction. RESULTS: A total of 452 patients (260 males, median age 44.5 years) were included in the study cohort. The major symptoms included dysphagia for solids and liquids (428, 94.7%), regurgitation (360, 79.6%), naso-oral regurgitation (182, 40.3%), weight loss (322, 71.3%), and chest pain (158, 35%). Type 2 achalasia (229, 50.6%) was the most common subtype, followed by type 3 (154, 34.1%). Chest pain was more common in type 3, and weight loss and naso-oral regurgitation were more common in type 2 achalasia. A majority of patients underwent Heller's myotomy and pneumatic dilatation. Of 280 patients for whom treatment details were available, 98% reported good response to endoscopic/surgical management. CONCLUSION: The predominant symptoms of achalasia cardia vary per the manometric subtype. Heller's myotomy and pneumatic dilatation are the most commonly used treatment options. Response to treatment is good. The choice of treatment modality was likely influenced by financial reasons and availability of local expertise.

Predictors of immediate and short-term mortality in spontaneous bacterial peritonitis.

BACKGROUND: There is scarce data from the Indian subcontinent on the outcomes following spontaneous bacterial peritonitis (SBP). AIM: To study the immediate (within 30 days) and short-term mortality (31-90 days) associated with SBP and to determine the predictors of the same. METHODS: This prospective observational study was done among patients with liver cirrhosis who underwent paracentesis. Patient data included age, gender, co-morbidity, cirrhosis-related complications, model of end-stage liver disease (MELD), and Child-Turcotte-Pugh (CTP) scores. SBP was diagnosed based on ascitic fluid polymorphonuclear leukocyte count > 250/mm3 with or without ascitic fluid culture positivity. RESULTS: Of the 870 patients with cirrhosis and ascites registered during the study period, 610 fulfilled the criteria for inclusion. Altogether, 122 patients with SBP were identified: 52 (42.6%) died, 40 (32.8%) survived without liver transplant, and 30 (24.6%) underwent liver transplantation within 3 months. Thirty-two patients (26.2%) were blood culture posi tive for bacteria and 7 (5.7%) demonstrable bacterial growth in ascitic fluid. Blood culture positivity was significantly higher in the group with immediate mortality (p < 0.0001) and was also significantly associated (p 0.005) with mortality at 3 months. CONCLUSION: Nearly two-fifths (42.6%) of the study cohort died within 3 months of an episode of SBP. Four-fifths of these patients died within 30 days. Blood culture positivity was significantly associated with immediate and short-term mortality.

Explant liver evaluation decodes the mystery of cryptogenic cirrhosis!

BACKGROUND AND AIM: To determine the concordance of liver explants with the pretransplant diagnosis. METHODS: This was a retrospective analysis of 251 liver explants. Patient information included demography, comorbidity, and etiological diagnosis. Final diagnosis was based on morphological and histological findings. For non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis, we investigated comorbid states such as obesity, hypertension, and diabetes. Chi square test and Cohen's Kappa value were used. A P value of <0.05 was considered significant. RESULTS: A total of 192 patients (76.5%) were males. A significant concordance of explant diagnosis with pretransplant diagnosis was present in 225 (89.6%) patients. It was 100% for alcohol-related disease, hepatitis B, hepatitis C, autoimmune (AI) liver disease, biliary cirrhosis, and Budd-Chiari syndrome. Of 37 patients with a pretransplant diagnosis of cryptogenic cirrhosis, major discordance was observed in 23 (62.1%). On explant, seven patients each had hemochromatosis 5 (13.5%), AI hepatitis, and NASH (18.9%); two had noncirrhotic fibrosis (5.4%); and one each had Wilson's disease and congenital hepatic fibrosis (2.7%). Of the 20 explants, 3 with pretransplant diagnosis of NASH had a diagnosis of cryptogenic cirrhosis on explant specimens. Cohen's Kappa for the concordance of pretransplant diagnosis and explant diagnosis in NASH and cryptogenic cirrhosis patients was 0.75 and 0.47, respectively. An incidental hepatocellular carcinoma was picked up in 16 explants, and 18 had granulomas. CONCLUSION: Concordance between pretransplant and explant diagnosis is lower for NASH and cryptogenic cirrhosis. The true prevalence of cryptogenic cirrhosis in our study was 5.6%.