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.

Etiological Patterns, Liver Fibrosis Stages and Prescribing Patterns of Hepato-Protective Agents in Indian Patients with Chronic Liver Disease.

OBJECTIVE: Considering the paucity of relevant data for chronic liver disease (CLD) from India, this PAN-India study was conducted to assess the current etiologic spectrum of CLD, stage of liver fibrosis at presentation and the prescribing patterns of hepato-protective agents by gastroenterologists in Indian real-world setting. This data would aid in early detection and formulation of effective management strategies for CLD in India. MATERIALS AND METHODS: In this cross-sectional, multicentric, epidemiological study, consecutive patients (18 ≥ 65 years) diagnosed with CLD, assessed for liver fibrosis by Vibration Controlled Transient Elastography (VCTE), were evaluated for etiology by standard clinical and laboratory criteria and grouped in to alcoholic liver disease (ALD)/non-alcoholic fatty liver disease (NAFLD)/viral liver disease/ drug induced liver injury (DILI)/others. The doctors' prescription was studied in each case to note the pattern of hepatotropic medications prescribed, in addition to other specific agents. RESULTS: Out of 504 enrolled patients with CLD (mean age: 47.9±11.81 years; men: 67.9%), 39.7% had NAFLD, 25.6% had ALD, 17.5% had hepatitis B (HBV), 7.9% had hepatitis C (HCV), 1.6% had autoimmune hepatitis, 0.4% had DILI and 7.3% had other causes of liver disease. Diabetes (15.9%), hypertension (12.9%), hypothyroidism (3.0%), dyslipidemia (1.2%) and obesity (0.4%) were the commonly reported comorbidities. Liver stiffness corresponding to the diagnosis of F4 liver fibrosis stage was reported in 77.5% HCV, 62.0% ALD, 46.0% NAFLD and 37.5% HBV patients. About 12.5% HCV, 8.0% NAFLD, 5.4% ALD, and 1.1% HBV patients reported F3 liver fibrosis stage. About 38.3% patients were on hepatoprotective drugs; commonly prescribed drugs were ademetionine (23.8%), ursodeoxycholic acid (17.9%) and drugs of herbal origin (11.3%). CONCLUSION: NAFLD is emerging as a predominant etiology of CLD in India, followed by ALD, HBV, and HCV. However, significant regional differences regarding predominant etiology was noted within the country. It was further noted that significant number of patients had advanced fibrosis based on VCTE assessment. This study emphasizes the need for appropriate risk evaluation and early assessment of severity of liver disease, for adequate disease management.

Biodegradable Stents for Caustic Esophageal Strictures: Do They Work?

Biodegradable (BD) stents have been used for the management of various esophageal strictures (ES) but the experience of its use in caustic strictures is limited. The present study, aimed at evaluating efficacy of BD stents for the treatment of refractory caustic-induced ES, was a retrospective multi-center study conducted at three tertiary care centers in India wherein adult patients with refractory caustic induced strictures underwent placement of a BD stent. Patients were followed up for immediate complications and long term outcome. All 13 patients (39.3 ± 15.1 years) underwent successful BD stent placement. Retrosternal chest pain occurred in 2 patients and stent migration in 1 (7.6%) patient. At 3 months, restenosis with recurrence of dysphagia was seen in nine (69.2%) patients, at 6 months, 10 (77%) patients had dysphagia of whom three underwent surgery and the remaining seven patients required dilatations. At 1 year, one patient remained asymptomatic while nine had dysphagia. The requirement for dilatation was once in 3 months in seven patients & once in a month in two patients. At 2 years, the requirement of dilatations was further reduced to once in 4-6 months in all patients. Over a 3 year follow up three (23%) patients had undergone surgery, one was free of symptoms while nine patients continued to be on periodic dilatation although the requirement had reduced to once in 4-6 months. Efficacy of BD stents in patients with caustic-induced ES is limited and the short term radial force applied by the currently available BD stents is inadequate to provide long term relief in such patients.

Frequency of CFTR, SPINK1, and cathepsin B gene mutation in North Indian population: connections between genetics and clinical data.

OBJECTIVES: Genetic mutations and polymorphisms have been correlated with chronic pancreatitis (CP). This study aims to investigate the association of genetic variants of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) genes and Cathepsin B gene polymorphisms with CP and to associate genetic backgrounds with clinical phenotypes. METHODS: 150 CP patients and 150 normal controls were enrolled consecutively. We analyzed SPINK-1 N34S and IVS3+2T>C gene mutations by PCR-restriction-fragment length polymorphism (RFLP). The identification of DF508, G551D, G542X, R117H, and W1282X mutations was carried out by ARMS-PCR. S549N mutation, IVS8 polyTn polymorphism, and Cathepsin B Lec26Val were analysed by PCR-RFLP, nested PCR, and PCR-RFLP plus sequencing, respectively. RESULTS: We found a significant association of SPINK1 (N34S) gene polymorphism. IVS1-37T>C polymorphism shows linkage with 101A>G. 300 chromosomes belonging to the CFTR subgroup exhibited minor allele frequency of 0.04, 0.03, 0.03, 0.013, 0.006, and 0.02 for DF508, G452X, G551D, S549N, R117H, and IVS8 T5, respectively. Except for R117H and IVS8 T5 polymorphisms, all other mutations showed significant variation. CONCLUSION: Analysis of potential susceptibility variants is needed to support nature of the genes and environment in pancreatitis. This data may help establish genetic screening and prenatal setup for Indian population.

Basiliximab does not increase efficacy of corticosteroids in patients with steroid-refractory ulcerative colitis.

BACKGROUND & AIMS: Basiliximab is a chimeric monoclonal antibody that binds CD25 and thereby inhibits interleukin (IL)-2-mediated proliferation of lymphocytes. IL-2 might contribute to the resistance of T cells to corticosteroids. We investigated the efficacy and safety of basiliximab as a corticosteroid-sensitizing agent in patients with corticosteroid-refractory ulcerative colitis (UC). METHODS: We studied 149 patients with moderate to severe UC (Mayo score ≥6 and endoscopic subscore ≥2) despite treatment for at least 14 days with oral prednisone (40-50 mg/day). Subjects were randomly assigned to groups that were given 20 mg (n = 46) or 40 mg (n = 52) basiliximab or placebo (n = 51) at weeks 0, 2, and 4. All subjects received 30 mg/day prednisone through week 2; the dose was reduced by 5 mg each week to 20 mg/day, which was maintained until week 8. At week 8, we compared the rates of clinical remission (Mayo score ≤2, no subscore >1) for patients given basiliximab with the rate for patients given placebo. RESULTS: Twenty-eight percent of patients given placebo, 29% of those given the 40-mg dose of basiliximab, and 26% of those given the 20-mg dose of basiliximab achieved clinical remission (P = 1.00 vs placebo for each dose). Basiliximab was generally well tolerated. Six subjects who received basiliximab had serious adverse events (6.1%) compared with 2 who received placebo (3.9%; P = .72). In subjects given basiliximab, incomplete saturation of CD25 (<50%) on peripheral T cells was associated with the presence of anti-basiliximab antibodies (odds ratio, 21; 95% confidence interval, 2.4-184). CONCLUSIONS: Basiliximab does not increase the effect of corticosteroids in the induction of remission in outpatients with corticosteroid-resistant moderate to severe UC.

Pathogenesis of tropical sprue: a pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake.

BACKGROUND & OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). METHODS: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). RESULTS: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m [2] ) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. INTERPRETATION & CONCLUSIONS: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS.

Primary Gastric Lymphoma Presenting as Acute Pancreatitis: A Case Report.

CONTEXT: Diffuse large B-cell lymphoma is the commonest form of non-Hodgkin lymphoma. Gastro-intestinal tract and bone marrow are common extra-nodal sites of lymphomatous involvement. CASE REPORT: A 54-year-old woman presented with acute onset epigastric pain. On evaluation, raised serum amylase and radiological features of acute pancreatitis were detected. Gastroscopy revealed thickened folds in distal stomach, which on histopathology revealed large B-cell lymphoma. Subsequently, the patient developed extra-hepatic biliary obstruction due to peripancreatic lymph nodal mass that was relieved with plastic biliary stenting. Subsequent chemotherapy regime directed against lymphoma led to resolution of lymphoma. CONCLUSION: In this patient , pancreatitis was the initial presentation of primary gastric lymphoma, which has not been commonly reported and therefore should be considered in the etiological workup.

Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease.

BACKGROUND: Insulin resistance has been recognized as a major factor in the development of non-alcoholic fatty liver disease (NAFLD). The association between insulin resistance and NAFLD, as a risk factor independent of obesity has been less well established. This study aims to determine presence of insulin resistance and components of metabolic syndrome in non-obese patients with NAFLD. METHODS: 150 patients (mean age 42.25 _ 10.50 y; 115 (76%) male, 35 (24%) female) diagnosed with NAFLD participated in the study. We measured body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), fasting lipid profile, fasting glucose, fasting insulin, and liver function. Insulin resistance was calculated using the homeostasis model of assessment (HOMA) formula. Insulin resistance was arbitrarily considered altered when it was >1.64. RESULTS: 120 (80%) of the 150 patients were pbese (BMI >23) according to the Asia Pacific criteria. 40 (30%) had metabolic syndrome. 97.5% (117/120) had insulin resistance with mean HOMA-insulin resistance (IR) of 10.9+/-5.3. Thirty (20%) were non-obese; of these, 7 had central obesity (WC > 90 cm for men, > 80 cm for women). Twenty-three (15.3%) patients were lean NAFLD with BMI 21.6+/-1.5, WC 82.9+/-4.7 (BMI< 23, WC <90 cm in men and < 80 cm in women) 80% of these 23 (18/23) had insulin resistance with mean HOMA-IR of 3.4+/-1.9. Only 4 (17%) did not have any component of metabolic syndrome. CONCLUSION: Insulin resistance often associated with metabolic syndrome is common and plays a key role amongst lean Indian patients with non-alcoholic fatty liver disease.

Non-alcoholic Steatohepatitis in Asians: Current Perspectives and Future Directions.

Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD), which, apart from excess fat in the liver, may be characterised by some level of inflammatory infiltration and fibrogenesis, occasionally progressing to liver cirrhosis or hepatocellular carcinoma (HCC). The objective of the current review is to elucidate the rising prevalence, the role of microbiome and genetics in pathogenesis, diagnostic challenges, and novel treatment alternatives for NASH. Newer diagnostic techniques are being developed since using liver biopsy in a larger population is not a reasonable option and is primarily restricted to clinical research, at least in developing countries. Besides these technical challenges, another important factor leading to deviation from guideline practice is the lack of health insurance coverage in countries like India. It leads to reluctance on the part of physicians and patients to delay required tests to curb out-of-pocket expenditure. There is no cure for NASH, with liver transplantation remaining the last option for those who progress to end-stage liver disease (ESLD) or are detected with early-stage HCC. Thus, lifestyle modification remains the only viable option for many, but compliance and long-term adherence remain major challenges. In obese individuals, bariatric surgery and weight reduction have shown favourable results. In patients with less severe obesity, endoscopic bariatric metabolic therapies (EBMT) are rapidly emerging as less invasive therapies. However, access and acceptability remain poor for these weight reduction methods. Therefore, intense research is being conducted for potential newer drug classes with several agents currently in phase II or III of clinical development. Some of these have demonstrated promising results, such as a reduction in hepatic fat content, and attenuation of fibrosis with an acceptable tolerability profile in phase II studies. The developments in the management of NASH have been fairly encouraging. Further well-designed long-term prospective studies should be undertaken to generate evidence with definitive results.

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.

Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption.

BACKGROUND & OBJECTIVES: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. METHODS: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. RESULTS: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm 3 , P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. INTERPRETATION & CONCLUSIONS: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD.

Capsule endoscopy for obscure gastrointestinal bleeding in the tropics: report from India.

BACKGROUND: Capsule endoscopy (CE) is useful in patients with obscure gastrointestinal bleeding (OGIB). Experience in CE in OGIB in the tropics is limited. METHODS: Eighty-six patients with OGIB were evaluated clinically and using CE (Given Imaging, Yoqneam, Israel) 89 times (twice in three patients) during a 64-month period. Images were downloaded and examined by a single investigator using software (Rapid Reader; Given Imaging, Yoqneam, Israel). Patients received specific treatment and were followed up. Intraoperative findings, response to specific treatment and outcome on follow up (10.3±14.1 months) were considered to confirm CE findings. RESULTS: Of 86 patients (aged 54.5±16.3 years, 63 males), 64 and 22 had OGIB-overt and OGIB-occult, respectively. Lesions were equally detected in OGIB-overt and OGIB-occult patients (48/64, 75% vs 18/22, 81.8%, P= ns). Lesions were detected in 64 of 86 (74.4%) patients [vascular malformations with or without fresh bleeding in 24 (37.5%), tumors in 12 (18.8%), strictures in 15 (23.4%), ulcers in five (7.8%), hookworm in five (7.8%), and more than one lesion in three patients (4.7%)]. Endoscopic insertion of the capsule was required in four patients, and in six it was retained, although none developed intestinal obstruction (surgical removal in two). The sensitivity, specificity, positive and negative predictive values of CE to detect the lesion(s) were 92.9%, 68.2%, 84.8%, and 83.3%, respectively. CONCLUSION: CE is safe and is equally effective in detecting lesion(s) in occult and overt OGIB. Worm infestation and small bowel tuberculosis are unique and important causes of OGIB in the tropics.

Role of ABCG8 D19H (rs11887534) variant in gallstone susceptibility in northern India.

BACKGROUND AND AIM: The excretion of cholesterol from the liver is regulated by the ATP-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 might be related to the genetic predisposition of gallstone disease, which is causatively related to supersaturation of cholesterol in bile. We aimed to examine the role of the ABCG8 D19H (rs11887534) polymorphism in susceptibility to gallstone disease in the northern Indian population. METHODS: The study included 220 confirmed gallstone patients and 230 controls. Genotyping for the ABCG8 D19H polymorphism was carried out using the PCR-RFLP method. RESULTS: We observed that the ABCG8 DH genotype frequency was significantly higher in gallstone patients (P = 0.038; odds ratio [OR] = 2.20; 95% confidence interval [CI] = 1.1-4.6). At allele level also, the ABCG8 variant allele conferred an increased risk for gallstone susceptibility (P = 0.043; OR = 2.12; 95% CI = 1.2-4.3). The risk as a result of ABCG8 D19H variation was more pronounced in female gallstone patients at genotype (P = 0.026; OR = 3.01, 95% CI = 1.1-7.9) as well as allele level (P = 0.030; OR = 2.85; 95% CI = 1.1-7.3). However, the molecular modeling results of the rs11887534 polymorphism showed that the overall configuration of both wild-type and polymorphic ABCG8 protein were similar, with negligible deviation at the site of polymorphism. CONCLUSION: Carriers of the DH genotype and H allele of the ABCG8 D19H polymorphism harbor a higher risk for gallstone susceptibility in the northern Indian population.

Alterations of p53 gene in gallbladder cancer patients of North India.

BACKGROUND: Mutations in p53 gene are found in a majority of human malignancies and usually occur in the exons 5, 6, 7 and 8. Mutated p53 protein is more stable and gets accumulated in the cells that induce the host to develop anti-p53 antibodies in sera of cancer patients. AIM: This study is aimed to observe the frequency and nature of mutations in exons 5-8 of p53 gene and to evaluate its correlation with prevalence of serum p53 antibodies in Indian patients with gallbladder cancer (GBC). METHODS: Mutation studies were done in cancer tissues obtained from 62 patients with proven GBC (40 cytologically proven cases and 22 resected gallbladder cancer tissues) by polymerase chain reaction (PCR), restriction fragment length analysis (RFLP) and single strand conformation polymorphism (SSCP). Presence of serum p53 antibodies was determined using highly specific enzyme linked immunosorbent assay (ELISA) kit in 50 patients with GBC and 30 patients of cholelithiasis. Clinicopathologic characteristics of these patients were given attention. RESULTS: Antibodies to p53 protein was present in the serum in 34% (17/50) of GBC patients and in 3.3% (1/30) patients with cholelithiasis (p < 0.018). RFLP failed to detect common mutations in the exons 5- 8 of the p53 gene in 62 samples. Using SSCP analysis we could detect frameshift mutation in p53 gene in 2 of 22 (9.1%) GBC cases. Mutated samples were sequenced and found to have insertion of adenine at codon 271 (GAG) in exon 8 region. CONCLUSION: Our results show that 1//3rd of the north Indian patients with GBC have antibodies to p53 protein. The commonest identifiable alteration in the p53 gene was a frameshift mutation at codon 271.

Long-term efficacy and safety of N-butylcyanoacrylate in endoscopic treatment of gastric varices.

INTRODUCTION: Endoscopic glue (N-butyl-2-cyanoacrylate) injection has emerged as promising therapy for bleeding gastric varices (GV). We evaluated safety and long term efficacy of this technique in patients with portal hypertension and large bleeding GV. PATIENT AND METHODS: 170 patients (mean age 40.9 +/- 14y; 132 male; 142 had cirrhosis, 40 Child A, 62 Child B, 40 Child C) underwent glue injection into GV (F3 140, F2 30; fundal 114) as emergency procedure for active bleeding in 62 and electively for prevention of rebleeding in 108. Glue was injected intra-variceally under endoscopic vision, 0.5-4 ml/aliquot, repeated at 3 weeks till varices were eradicated/solidified. The efficacy was assessed by hemostasis at 48 h, primary, secondary, definitive success and treatment failure. RESULTS: The overall hemostasis rate at 48h was 82.3% (51/62). Follow up was available in 158 patients for mean of 30.7 + 17.2 months. Repeat injections were performed in 76. The mean number of injections were 1.9 +/- 1.0 (1-4); total volume was 2.5 +/- 1.7 ml/patient. The status of GVs at last follow up was: disappeared in 32 (22.6%); F1 solidified in 46 (32.3%); F2 solidified in 64 (45.0%). Bleeding recurred in 14.5% (23/158); 60% within 2 weeks of injection. The primary, secondary and definitive success rates were 85.4% (135/158), 4.4% (7/158) and 89.9% (142/158) respectively and treatment failure rate was 10% (16/158). No significant complications were noticed except for injection site ulceration in 32. Twenty patients died on follow up (9 died of uncontrolled bleeding, 11 died of liver failure). CONCLUSION: Endoscopic glue injection into bleeding GVs was effective in achieving hemostasis in 82% with a definitive success rate of 90% and had a good safety profile on long-term follow up.

Single nucleotide polymorphism in the ABCG8 transporter gene is associated with gallbladder cancer susceptibility.

BACKGROUND: Gallbladder cancer (GBC) usually arises against the background of gallstone disease, which may be causatively related to supersaturation of cholesterol in bile. An imbalance in cholesterol homeostasis because of oversecretion of cholesterol in the gallbladder promotes gallstone formation. The excretion of cholesterol from the liver is regulated by adenosine triphosphate-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 associated with gallstone disease may be causatively related to the genetic predisposition of GBC. AIM: We aimed to examine the role of ABCG8 D19H (rs11887534) polymorphism in susceptibility to GBC. METHODOLOGY: This study included 171 confirmed GBC patients and 221 controls. Genotyping for the ABCG8 D19H polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We observed that in our population the ABCG8 DH genotype frequency was significantly higher in GBC patients [P=0.011; odds ratio (OR)=1.79; 95% confidence interval (CI)=1.1-2.8]. Also, at the allele level, ABCG8H conferred an increased risk for GBC (P=0.023; OR=1.60; 95% CI=1.0-2.4). The risk was more pronounced in GBC patients with gallstones (P=0.027; OR=1.85; 95% CI=1.0-3.1), and in patients with an early onset of the disease (P=0.013; OR=2.55, 95% CI=1.2-5.3). However, there was no modulation of GBC risk because of the ABCG8 polymorphism in a gender-specific manner. CONCLUSION: The results suggest that the DH genotype and the H allele of the ABCG8 D19H polymorphism are associated with GBC susceptibility. The GBC patients with gallstone disease harbouring the ABCG8 variant allele are at a higher risk, while the effect of this polymorphism on GBC patients without gallstones appears to be small.

Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis.

The association of polymorphism in cytochrome P450 2E1 (CYP2E1), the major microsomal ethanol metabolizing enzyme and its interaction with genes, involved in detoxification of reactive oxygen species, such as glutathione-S-transferases M1 (GSTM1) and alcohol intake, gamma-aminobutyric acid receptor gamma2 (GABRG2) was studied with the risk to alcoholic cirrhosis in a case-control study. A total of 160 alcoholic cirrhotic and 125 non-alcoholic cirrhotic cases, visiting the OPD facility of Gastroenterology Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India and 250 non-alcoholic and 100 alcoholic controls having no evidence of liver disease were included in the study. PCR-based RFLP methodology was followed for genotyping studies. Our data revealed that the variant genotypes of CYP2E1 5B exhibited significant association with the alcoholic liver cirrhosis when compared to non-alcoholic controls (OR: 4.3; 95%CI: 1.5-12.4; p: 0.003) or non-alcoholic cirrhosis patients (OR: 5.4; 95%CI: 1.2-24.5; p: 0.01) or alcoholic controls (OR: 4.3; 95%CI: 0.95-19.62; p: 0.04). Haplotype approach revealed that haplotype T-A-T was found to be associated with more than 5-fold increase in risk for alcoholic cirrhosis. Likewise, combination of variant genotype of CYP2E1 5B with null genotype of GSTM1, a phase II detoxification enzyme, resulted in several fold increase in risk in alcoholic cirrhotic patients when compared with non-alcoholic controls or non-alcoholic cirrhotic patients. Further, the combination of variant genotype of CYP2E1 5B with GABRG2, significantly increased the risk upto 6.5-fold in alcoholic cirrhotic patients when compared with non-alcoholic controls thereby suggesting the role of gene-gene interaction in alcoholic cirrhosis.

Pancreatic diabetes.

Pancreatic endocrine insufficiency secondary to destruction of acinar cells is a well known complication of chronic pancreatitis (CP). Of all patients with diabetes mellitus, 0.5-1% is secondary to CP. The frequency of occurrence of diabetes in CP is about 40-60%. This figure varies according to the aetiology, extent of calcification, and duration of the disease. Pancreatic diabetes is more commonly associated with alcoholic and tropical calcific pancreatitis of long duration. The pathophysiology of pancreatic diabetes is related to beta cell failure and reduced insulin secretory capacity. The development of pancreatic diabetes calls for careful evaluation and management to prevent long term complications. Pancreatic cancer is a known complication of chronic pancreatitis and sometimes manifests with new onset diabetes. As destruction of pancreatic tissue in CP leads to depletion of both insulin and glucagon-producing cells of the islets of Langherhans, pancreatic diabetics are usually not prone to ketoacidosis. A trial of oral hypoglycemic agents followed by insulin therapy when the need arises has been the line of management thus far in these patients. This review focuses on the prevalence, unique pathophysiological aspects, clinical features and special issues in the management of diabetes secondary to chronic pancreatitis.

Potential Implications of Detecting HBsAg in Asymptomatic People in an Endemic Community Through Medical Camps.

BACKGROUND: In a developing country like India with intermediate level of prevalence of hepatitis B, most of the patients remain undiagnosed as they are asymptomatic. The purpose of the study was to diagnose asymptomatic HBsAg positive patients from the general population and evaluate further the potential clinical implications of IDAHS. METHODS: Asymptomatic subjects with unknown HBV status were screened free of cost for hepatitis-B surface antigen. Those who tested positive for HBsAg were further tested to identify those who were potential candidates for anti-viral therapy. To explore the relevance of our screening we assessed potential implications of HBsAg detection. RESULTS: A total of 30,836 patients were screened in medical camps over the period of 7 years. Out of these 704 (2.3%) subjects were found to be positive for HBsAg. Distress of being diagnosed with HBV was expressed by 649 (92%) of the positive subjects. High cost of further testing and antiviral therapy, leading to inability to pursue further management was elicited in 510 (72%) of the positive subjects. HBV DNA was detected in 349 (59%) out of 592 subjects, out of which 236 (67%) had high viral load. CONCLUSION: Incidental detection of asymptomatic HBsAg positive subjects was seen in 2.3% of subjects. One third of these patients had an actively replicating virus and required antiviral therapy. Financial support was required in 72% of the subjects for further HBV management. Detecting HBsAg in asymptomatic person in an endemic community has considerable health and psycho-economic impact on the individual.

Effectiveness and safety of adalimumab biosimilar in inflammatory bowel disease: A multicenter study.

BACKGROUND: Adalimumab has emerged as a useful drug for treating patients with Crohn's disease (CD) and ulcerative colitis (UC), not responding to conventional therapy. There is limited data on effectiveness and safety of adalimumab biosimilar in patients with inflammatory bowel disease (IBD). METHODS: Patients with IBD who received at least one dose of adalimumab biosimilar from October 2015 to February 2018 were retrospectively included in this multicenter data analysis. Its effectiveness in inducing and maintaining clinical remission at 8, 26, and 52 weeks for CD and UC and safety profile of the drug was studied. RESULTS: Seventy patients (49 CD; 21 UC) with a median age of 39 (range 13-73) years, male predominance (64.3%), and median (IQR) disease duration of 72 (33-104) months were included. Adalimumab biosimilar was effective in inducing remission (at 8 weeks) in 46.9% and 52.4% patients with CD and UC, respectively, of whom  32.7% and 33.3% (three fourths of remitters) maintained remission over 1 year, respectively. Twenty (28.6%) patients experienced adverse events; seven (10%) were serious of whom  three had developed tuberculosis. CONCLUSIONS: Adalimumab biosimilar in usual clinical practice is safe and effective in inducing and maintaining remission in Indian patients with IBD. Steroid-free clinical remission was observed in one third of patients with UC and CD at 1 year of therapy. Graphical Abstract.