Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

Burden of Anxiety, Depression and Perceived Stress in Patients with Inflammatory Bowel Disease: A Cohort Study from North India.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

APASL-ACLF Research Consortium-Artificial Intelligence (AARC-AI) model precisely predicts outcomes in acute-on-chronic liver failure patients.

BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF). METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision. RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p < .001) and 12.8% and 10.6% higher than the day 7 MELD for 30-day predictions in validation set (p < .001). The XGB model had the highest AUC for 7- and 90-day predictions as well (p < .001). Day-7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions. CONCLUSIONS: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.

Evaluation of Nutritional Characteristics Reveals Similar Prevalence of Malnutrition in Patients with Ulcerative Colitis and Crohn's Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of malnutrition and sarcopenia. AIMS: To evaluate the nutritional status of patients with IBD and determine the threshold values of different parameters of nutritional assessment to identify malnutrition. METHODS: This was a single-centre cross-sectional analysis of adult patients with IBD [ulcerative colitis (UC) and Crohn's disease (CD)] who underwent anthropometry [body mass index (BMI), mid upper arm circumference (MUAC) and triceps-fold thickness (TSF)], body composition analysis and assessment for sarcopenia [hand-grip strength and skeletal muscle index (SMI) at L3 vertebral level)]. Age- and gender-matched healthy adults served as controls. Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. RESULTS: A total of 406 patients [336 (82.76%) UC and 70 (17.24%) CD; mean age 40.56 ± 13.67 years; 215 (52.95%) males] with IBD and 100 healthy controls (mean age 38.69 ± 10.90 years; 56 (56%) males) were enrolled. The mean BMI, MUAC, TSF thickness, fat and lean mass, hand-grip strength, and SMI at L3 vertebral level were lower in patients with IBD compared to controls. The prevalence of malnutrition was similar in UC and CD [24.40% (n = 82) and 28.57% (n = 20), respectively (p = 0.46)]. Thresholds for fat mass in females (15.8 kg) and visceral fat index in males (0.26) were both sensitive and specific to detect malnutrition. The cutoff values of MUAC and TSF thickness to identify malnutrition were 23.25 cm and 25.25 cm, and 16.50 mm and 8.50 mm, in females and males, respectively. CONCLUSION: Malnutrition and sarcopenia were common in patients with IBD, with the prevalence being similar in patients with both UC and CD.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet versus traditional dietary advice for functional dyspepsia: a randomized controlled trial.

BACKGROUND AND AIM: Prospective trials evaluating efficacy of specific diet restriction in functional dyspepsia (FD) are scarce. We aimed to assess efficacy of low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in FD, compared with traditional dietary advice (TDA). METHODS: In this prospective, single-blind trial, patients with FD (Rome IV) were randomized into low FODMAP diet (LFD) and TDA groups, for 4 weeks (phase I). In phase II (4-12 weeks), LFD group was advised systematic re-introduction of FODMAPs. Symptom severity and quality of life were assessed using "Short-Form Nepean Dyspepsia Index (SF-NDI)." Primary outcome was symptomatic response (symptom score reduction of ≥ 50%), at 4 weeks. Study was registered with CTRI (2019/06/019852). RESULTS: Of 184 patients screened, 105 were randomized to LFD (n = 54) and TDA (n = 51) groups. At 4 weeks, both groups showed significant reduction in SF-NDI symptom scores compared with baseline, with no significant difference in inter-group response rates [LFD: 66.7% (36/54); TDA: 56.9% (29/51); P = 0.32]. On sub-group analysis, patients with postprandial distress syndrome or bloating had significantly better symptomatic response with LFD (P = 0.04). SF-NDI quality of life scores improved significantly in both groups. On multivariate analysis, factors predicting response to LFD were bloating and male gender. Incidences of adverse events (minor) were similar in both groups. CONCLUSIONS: In patients with FD, LFD and TDA lead to significant symptomatic and quality of life improvement. Patients with postprandial distress syndrome or bloating respond significantly better to LFD. Therefore, dietary advice for FD should be individualized according to FD subtype.

Construction and benchmarking of a multi-ethnic reference panel for the imputation of HLA class I and II alleles.

Genotype imputation of the human leukocyte antigen (HLA) region is a cost-effective means to infer classical HLA alleles from inexpensive and dense SNP array data. In the research setting, imputation helps avoid costs for wet lab-based HLA typing and thus renders association analyses of the HLA in large cohorts feasible. Yet, most HLA imputation reference panels target Caucasian ethnicities and multi-ethnic panels are scarce. We compiled a high-quality multi-ethnic reference panel based on genotypes measured with Illumina's Immunochip genotyping array and HLA types established using a high-resolution next generation sequencing approach. Our reference panel includes more than 1,300 samples from Germany, Malta, China, India, Iran, Japan and Korea and samples of African American ancestry for all classical HLA class I and II alleles including HLA-DRB3/4/5. Applying extensive cross-validation, we benchmarked the imputation using the HLA imputation tool HIBAG, our multi-ethnic reference and an independent, previously published data set compiled of subpopulations of the 1000 Genomes project. We achieved average imputation accuracies higher than 0.924 for the commonly studied HLA-A, -B, -C, -DQB1 and -DRB1 genes across all ethnicities. We investigated allele-specific imputation challenges in regard to geographic origin of the samples using sensitivity and specificity measurements as well as allele frequencies and identified HLA alleles that are challenging to impute for each of the populations separately. In conclusion, our new multi-ethnic reference data set allows for high resolution HLA imputation of genotypes at all classical HLA class I and II genes including the HLA-DRB3/4/5 loci based on diverse ancestry populations.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Primary Hyperparathyroidism Masquerading as Acute Pancreatitis.

Acute pancreatitis as an initial manifestation of primary hyperparathyroidism (PHPT) is a rare occurrence and timely diagnosis of PHPT is crucial in preventing repeat attack of pancreatitis. The study aimed at evaluating the clinico-radiological profile of patients admitted with acute pancreatitis as the index presentation of PHPT and to determine the factors associated with development of severe pancreatitis. This series included retrospective analysis of medical records of 30 patients admitted with acute pancreatitis as initial manifestation of PHPT. Additionally, we analyzed the data of another 30 patients admitted with PHPT but without any evidence of pancreatitis, to serve as control group. The mean age of the subjects was 44.9±13.9 years with male to female ratio of 1.30. The mean serum calcium level was 12.24±2.79 mg/dl and five (16.6%) patients had normocalcemia at time of presentation. Presence of nephrolithiasis was significantly associated with severe pancreatitis. One patient had refractory hypercalcemia associated with renal failure and was successfully managed with denosumab. Patients with PHPT associated with acute pancreatitis had significantly higher calcium levels and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis. PHPT masquerading as acute pancreatitis is rare and high index of suspicion is required to diagnose this condition especially in the presence of normocalcemia at presentation. Patients with PHPT associated pancreatitis had male preponderance, higher calcium levels, and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis.

Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet in patients with diarrhea-predominant irritable bowel syndrome: A prospective, randomized trial.

BACKGROUND AND AIM: Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet improves irritable bowel syndrome (IBS) symptoms. Data on long-term "modified" FODMAP diet are emerging. We aimed to assess efficacy and acceptability of short-term "strict" low FODMAP diet (LFD) and long-term "modified" FODMAP diet in patients with diarrhea-predominant IBS (IBS-D). METHODS: This prospective randomized trial included patients with IBS-D (Rome IV) and IBS severity scoring system (IBS-SSS) ≥ 175. In phase I (4 weeks), patients were randomized to strict LFD and traditional dietary advice (TDA) groups. From 4 to 16 weeks, LFD group was advised systematic reintroduction of FODMAPs ("modified" FODMAP diet). Response was defined as > 50-point reduction in IBS-SSS. RESULTS: Of the total 166 patients with IBS-D screened, 101 (mean age 41.9 ± 17.1 years, 58% male) were randomized to LFD (n = 52) and TDA (n = 49) groups. Both at 4 and 16 weeks, total IBS-SSS and IBS quality of life score reduced significantly in both groups, but there was significantly greater reduction in LFD group. By intention-to-treat analysis, responders in LFD group were significantly higher than TDA group (4 weeks-62.7% [32/51] vs 40.8% [20/49], respectively, P = 0.0448; 16 weeks-52.9% [27/51] vs 30.6% [15/49], respectively; P = 0.0274). Compliance to LFD was 93% at 4 weeks and 64% at 16 weeks. Energy, carbohydrate, fat, and fiber intake showed reduction in LFD group at 4 weeks, which improved till 16 weeks. CONCLUSIONS: Strict LFD for short-term and "modified" LFD for long term in IBS-D patients is acceptable and leads to significant improvement in symptoms and quality of life.

Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE).

OBJECTIVE: The underlying microbial basis, predictors of therapeutic outcome and active constituent(s) of faecal microbiota transplantation (FMT) mediating benefit remain unknown. An international panel of experts presented key elements that will shape forthcoming FMT research and practice. DESIGN: Systematic search was performed, FMT literature was critically appraised and a 1-day round-table discussion was conducted to derive expert consensus on key issues in FMT research. RESULTS: 16 experts convened and discussed five questions regarding (1) the role of donor and recipient microbial (bacteria, viruses, fungi) parameters in FMT; (2) methods to assess microbiota alterations; (3) concept of keystone species and microbial predictors of FMT, (4) influence of recipient profile and antibiotics pretreatment on FMT engraftment and maintenance and (5) new developments in FMT formulations and delivery. The panel considered that variable outcomes of FMT relate to compositional and functional differences in recipient's microbiota, and likely donor-associated and recipient-associated physiological and genetic factors. Taxonomic composition of donor intestinal microbiota may influence the efficacy of FMT in recurrent Clostridioides difficile infections and UC. FMT not only alters bacteria composition but also establishes trans-kingdom equilibrium between gut fungi, viruses and bacteria to promote the recovery of microbial homeostasis. FMT is not a one size fits all and studies are required to identify microbial components that have specific effects in patients with different diseases. CONCLUSION: FMT requires optimisation before their therapeutic promise can be evaluated for different diseases. This summary will guide future directions and priorities in advancement of the science and practice of FMT.

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant. METHODS: A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed. RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events. CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Role of interventional inflammatory bowel disease in the era of biologic therapy: a position statement from the Global Interventional IBD Group.

Interventional (or therapeutic) inflammatory bowel disease (IBD) endoscopy has an expanding role in the treatment of disease and surgical adverse events. Endoscopic therapy has been explored and used in the management of strictures, fistulas/abscesses, colitis-associated neoplasia, postsurgical acute or chronic leaks, and obstructions. The endoscopic therapeutic modalities include balloon dilation, stricturotomy, stent placement, fistulotomy, fistula injection and clipping, sinusotomy, EMR, and endoscopic submucosal dissection. With a better understanding of the disease course of IBD, improved long-term impact of medical therapy, and advances in endoscopic technology, we can foresee interventional IBD becoming an integrated part of the multidisciplinary approach to patients with complex IBD.

Clinical profile of hepatitis C virus infection in a developing country: India.

BACKGROUND AND AIM: The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South-East Asia (India). METHODS: This observational study assessed patient demographics, viral characteristics, risk factors for virus acquisition, and disease characteristics in HCV patients diagnosed between January 2004 and December 2015. RESULTS: Of 8035 patients who were diagnosed with HCV infection, a majority were men (68.3%), middle aged (52.2%), and from low (34%) to middle (46%) socioeconomic status and rural population (69.8%). Eighty-two percent had identifiable risk factors, the most common being history of dental treatment (52%) and therapeutic injections with reusable syringes/needles (45%). Household contacts of index patients had high prevalence of HCV (15.3%). Common genotypes were genotype 3 (70.4%) and genotype 1 (19.3%). Although a majority of patients were either asymptomatic (54.8%) or had non-specific symptoms (6.7%) at presentation, a significant proportion (9.3%) had advanced liver disease. Presentation with cirrhosis (38.8%) was associated with male gender, higher age at time of virus detection, rural residence, alcohol or opium intake, and coinfections with hepatitis B virus or human immunodeficiency virus. CONCLUSIONS: Hepatitis C virus infection in northern India is seen more commonly in men, the middle aged and people from rural background and low to middle socioeconomic status. The common possible risk factors are dental treatment and exposure to reused syringes and needles. Although the most common presentation is incidental detection, a large number of patients present with advanced liver disease.

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

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

Prevalence and clinical significance of IgA anti-tissue transglutaminase antibodies in patients with chronic liver disease.

BACKGROUND AND AIM: Celiac disease is a multi-systemic disease, which can affect any organ system including liver. However, the prevalence of celiac disease and the sensitivity and specificity of anti-tissue transglutaminase (anti-tTG) in diagnosing celiac disease in patients with cirrhosis of liver is not well established. METHODS: We screened a cohort of patients with chronic liver disease for an associated diagnosis of celiac disease. Anti-tTG was carried out in all patients, and those with a high value were subjected to duodenal biopsy for histological confirmation. In patients where biopsy was contraindicated or refused, anti-endomysial antibody (anti-EMA) was tested. RESULTS: Of a total of 595 patients with chronic liver disease, high levels of anti-tTG were noted in 150 (25.2%) patients, and celiac disease was diagnosed in 14 patients (2.4%). Celiac autoimmunity (high levels of both anti-tTG and anti-EMA) was noted in seven patients (1.2%). CONCLUSIONS: Although a large number of cirrhotic patients have high levels of anti-tTG, duodenal histology and/or anti-EMA is normal in majority of these patients. This suggests high false positivity of anti-tTG in patients with cirrhosis and highlights the need of duodenal biopsy for histological confirmation of the diagnosis of celiac disease.

Results of sofosbuvir-based combination therapy for chronic hepatitis C cohort of Indian patients in real-life clinical practice.

BACKGROUND AND AIM: The introduction of sofosbuvir has revolutionized the treatment of chronic hepatitis C. This study was planned to observe whether the efficacy and tolerability of sofosbuvir-based regimens demonstrated in phase 3 clinical trial results translate into real-life clinical practice. METHODS: This prospective, non-randomized observational study conducted in Dayanand Medical College and Hospital, Punjab, included all consecutive treatment-naïve patients with chronic hepatitis C (genotypes 1-5) who were treated with sofosbuvir-based regimens. Response to therapy was assessed at week 4 (rapid virological response), week 12 or 24 (end of treatment response), and 12 weeks after cessation of therapy (sustained virological response [SVR]). RESULTS: Of 947 patients diagnosed with chronic hepatitis C virus and considered for treatment with direct-acting antivirals, 736 patients (77.1%) opted for treatment (age 45.1 ± 10.1 years, 64% men, genotype 3 [80%], genotype 1 [14.7%], and genotype 4 [4.9%]). Viral load was high (>600 000 IU/mL) in 361/736 (49%); 330 patients (44.8%) had cirrhosis (80 [14.3%] were decompensated). Patients with genotypes 1, 4, and 5 (n = 135) were treated with triple drug regime (pegylated interferon, ribavirin, and sofosbuvir) for 12 weeks. Patients with genotype 3 (n = 589) were treated either with dual therapy (sofosbuvir and ribavirin) for 24 weeks (n = 405) or triple therapy for 12 weeks (n = 184). SVR was achieved in 453/473 (95.8%). SVR rates did not differ among different genotypes but were higher in non-cirrhotics. CONCLUSION: Sofosbuvir-based treatment regimens achieve high SVR rates in real-life cohort of Indian patients with chronic hepatitis C infection (including those with cirrhosis).