Etiology of elevated alanine aminotransferase in a south Indian population: A community based study

INTRODUCTION: Liver diseases are among the top ten killer diseases in India. Besides this, liver diseases are associated with lot of morbidity leading to recurrent hospitalizations and prolonged medical attention, leaving the patients physically, mentally, emotionally and financially devastated. The common risk factors for chronic liver disease include non alcoholic fatty liver disease (NAFLD), chronic viral hepatitis and alcohol(8). Other etiologies include autoimmune hepatitis, Wilson’s disease, hemochromatosis and vascular diseases of the liver. Knowledge of the cause of liver disease helps predict complications and direct treatment decisions. It also helps to prevent similar diseases in the family by early screening (viral hepatitis B and C) or genetic testing (in Wilson’s disease and hemochromatosis). AIM / OBJECTIVES: To estimate the burden of liver disease in a southern Indian community by determining the prevalence and etiology of elevated alanine aminotransferase in this population. MATERIAL AND METHODS: A total of 9000 individuals from the city of Vellore and its neighbouring rural areas were screened for a seroprevalence study of celiac disease conducted by the Christian Medical College, Vellore as part of a three centre study in northern, north-eastern and southern India. Of these, 199 healthy individuals (145 males) had elevated ALT (>44U/l). Ninety one participants (77 males) had persistently elevated ALT, of which 56 patients (52 males) underwent further evaluation. These individuals were invited to answer a questionnaire and undergo anthropometry, blood investigations and ultrasonography to assess various etiologies of liver disease. Standard descriptive statistics were used. RESULTS: The estimated prevalence of persistently elevated ALT suggestive of possible liver damage in this south Indian population was 1.73% (1.01% to 1.93%). The most common etiologies of elevated ALT were alcohol intake (46.4%), NAFLD (42.9%) and hepatitis B (10.7%). No participant had hepatitis C infection. A majority (71.4%) of individuals had metabolic syndrome, 92% of whom had NAFLD. CONCLUSIONS: From a public health perspective, early clinical intervention and primary prevention are important and strategies to reduce both alcohol consumption and obesity may lead to reduction in liver disease

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis

Background/Aims Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal

Impact of “Sambhav” Program (Financial Assistance and Counselor Services) on Hepatitis C Pegylated Interferon Alpha Treatment Initiation in India

Abstract Background: Financial constraints, social taboos and beliefs in alternative medicine are common reasons for delaying or not considering treatment for hepatitis C in India. The present study was planned to analyze the impact of non-banking interest free loan facility in patients affected with hepatitis C virus (HCV) in North India. Methods: This one year observational, retrospective study was conducted in Department of Gastroenterology (January 2012-December 2013), Dayanand Medical College and Hospital Ludhiana, to evaluate the impact of program titled “Sambhav” (which provided non-banking financial assistance and counselor services) on treatment initiation and therapeutic compliance in HCV patients. Data of fully evaluated patients with chronic hepatitis, and/or cirrhosis due to HCV infection who were treated with Peginterferon alfa and ribavirin (RBV) combination during this duration (2012- 2013) was collected from patient medical records and analyzed. In the year 2012, eligible patients who were offered antiviral treatment paid for treatment themselves, while in 2013, ‘Sambhav’ program was launched and this provided interest free financing by non-banking financial company (NBFC) for the treatment of HCV in addition to free counselor services for disease management. The treatment initiation and compliance rates were compared between the patients (n = 585) enrolled in 2013 who were offered ‘Sambhav’ assistance and those enrolled in 2012 (n = 628) when ‘Sambhav’ was not available. Results: Introduction of Sambhav program improved the rates of treatment initiation (59% in 2013 vs. 51% in 2012, P=.004). Of the 585 eligible patients offered ‘Sambhav’ assistance in 2013, 233 patients (39.8%) applied but 106/233 (45.4%) received assistance. Antiviral therapy was started in 93/106 (87.7%) of these patients, while only 52 (42.5%) of 127 patients whose applications were rejected underwent treatment. Compliance to antiviral therapy also improved with the introduction of ‘Sambhav’ program (87.7% vs. 74.1%, P=.001). Conclusion: ‘Sambhav’ program had significant impact on the initiation of antiviral therapy by overcoming the financial hurdles. The free counselor services helped to mitigate social taboos and imparted adequate awareness about the disease to the patients. Initiatives like ‘Sambhav’ can be utilized for improving healthcare services in developing countries, especially for chronic diseases

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed

Use of thiopurines in inflammatory bowel disease : an update

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.Peer reviewe

Association of endoscopic and histological remission with clinical course in patients of ulcerative colitis

Background/AimsThe therapeutic goal for treating ulcerative colitis (UC) patients has shifted to achieving mucosal healing over the past few years. However, at present, limited data is available on the correlation between endoscopic findings and histological remission in patients with endoscopic mucosal healing.MethodsThis was a prospective observational study conducted over a period of 18 months (January 2014 to June 2015) at Dayanand Medical College and Hospital, Ludhiana, Punjab, India. Patients diagnosed with UC who had been in clinical remission (n=76) for at least 6 months were evaluated for endoscopic remission. Those in endoscopic remission (Mayo score ≤1; 46/76, 60.5%) were subjected to multiple biopsies from the rectosigmoid region and histological remission, which was then defined as grade 0/1 as per the Geboes criteria.ResultsOf the 46 patients in endoscopic remission (age, 18–73 years; male:female=1.5:1.0), majority had E1 (proctitis) disease (21/46, 45.6%) followed by E2 (left sided colitis) (18/46, 39.1%) and E3 disease (pancolitis) (7/46, 15.2%) at baseline. Histological remission was noted in 67.3% (31/46) of the patients, while 32.7% (15/46) still retained the histologically active disease in the form of infiltration of the lamina propria by eosinophils and neutrophils (13/15, 86.6%), cryptitis (14/15, 93.3%), and crypt abscesses (8/15, 53.3%). On follow-up, after 1 year, 87.1% (27/31) of the patients who had been in histological remission remained clinically asymptomatic, while 12.9% (4/31) had relapsed. Among the 15 histologically active patients, 46.6% (7/15) remained in clinical remission, while 53.3% (8/15) had relapsed.ConclusionsHistological remission, rather than endoscopic remission, predicts a sustained clinical remission and allows monitoring of therapy for the subsequent disease course in patients with UC

Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis

Background/AimsData on the efficacy and safety of the adalimumab biosimilar Exemptia are limited.MethodsPatients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score.ResultsA total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis.ConclusionsThe adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India

Enrichment of Lactic Acid-Producing Bacteria in the Fecal Microbiota of Patients with Ulcerative Colitis in North India

Previous studies have established the relationship between the gut microbiota and ulcerative colitis (UC); however, there is a scarcity of data on the fecal microbiome profile of patients with UC in the Indian population. This study aimed to examine the fecal microbiome profile of north Indian patients with UC (n=105), including with active disease (n=64) and in remission (n=41), compared to healthy controls (n=36), using 16S rRNA gene sequencing. Both relative abundance analysis and linear discriminant analysis effect size (LEfSe) revealed a significant enrichment of lactic acid-producing facultative anaerobic pathobionts, namely, Bifidobacterium, Lactobacillus, and Streptococcus, in patients with UC (both with active disease and those in remission). Additionally, a significant decrease was observed in anaerobic genera responsible for the synthesis of short-chain fatty acids (SCFAs), especially butyrate, such as Blautia, Roseburia, Lachnospiraceae, and Ruminococcaceae. Differential metabolic pathway analysis using PICRUSt2 confirmed a loss of SCFAs production and increased lactose and nitrate metabolism in UC patients. Biochemical analysis of fecal samples confirmed the increased colonization of nitrate-reducing microbes in UC patients, suggesting inflammation-driven dysbiosis. LEfSe and PICRUSt2 analyses revealed an enrichment of Prevotella and Blautia microbes and the upregulation of two specific metabolic pathways, sulfolactate degradation and reductive acetyl coenzyme A pathway-I, which can distinguish UC patients in remission from those with active disease. Our findings caution against the use of lactic acid-producing bacteria (LABs) and recommend the exploration of butyrate-producing microbes as probiotics to restore SCFAs levels in UC patients

A simple phenotypic classification for celiac disease

Background/AimsCeliac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease.MethodsVarious variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields.ResultsAfter empirical verification, age at diagnosis was considered appropriate in between A1 (<18) and A2 (≥18). The disease presentation has been classified into 3 types–P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived.ConclusionsAPC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis