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.

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.

Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture.

BACKGROUND: Though pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal aspirate culture (conventional criteria: ≥ 105 colony forming unit (CFU)/mL and newer cutoff ≥ 103 CFU/mL) and glucose hydrogen breath test. METHODS: Thirty-eight patients with NASH (age 37.5 years, range 20-54, 9, 24% female), diagnosed by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant irritable bowel syndrome as historical controls (age 39.5-y, 26-44; 3, 25% female) without fatty liver were studied. RESULTS: Jejunal aspirates, obtained in 35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%) (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds ratio 4.5, 95% CI 1.0-19.5; p = 0.04); colony counts were higher in NASH than controls (median 380 CFU/mL, 0-200,000 vs. 0 CFU/mL, 0-1000; p = 0.02). Gram negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p = 0.07). Seven out of 35 (20%) patients with NASH (≥ 105 CFU/mL in 5 and 2 other on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO (≥103 CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p = 0.04). There was no correlation between bacterial colony count and bacterial type and anthropometric and biochemical parameters. CONCLUSION: Low-grade bacterial overgrowth, particularly with Gram negative bacteria, was commoner in NASH than controls.

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.

Genetic predisposition and its impact on natural history of idiopathic acute and acute recurrent pancreatitis in children.

BACKGROUND: Genetic predisposition in paediatric idiopathic acute, acute recurrent pancreatitis and its consequences are unknown. We studied frequency of genetic markers in acute, acute recurrent, chronic pancreatitis and their impact on natural history. METHODS: Over a period of 2 years 68 consecutive children with pancreatitis (35.3% acute, 32.3% acute recurrent, 32.3% chronic) and 25 controls were recruited in a single centre. Common mutations for serine-protease-inhibitor (SPINK1 N34S), protease-inhibitor (PRSS1 R122H) and cystic fibrosis transmembrane conductance regulator (CFTR DeltaF508, 5T) were analysed. RESULTS: Mean age was 13.4±2.5 years. Overall, 30 cases (SPINK1 N34S n=26, CFTR 5T n=4) and 1 control (SPINK1 N34S) had mutations (p=0.0001). The prevalence of SPINK1 N34S mutation was similar in chronic and acute recurrent pancreatitis (45%). Six children with severe acute pancreatitis had SPINK1 N34S mutations (25%, p<0.05), and 4 were homozygous. On follow-up 5 acute pancreatitis patients with mutations and 1 without mutations developed chronic pancreatitis (p=0.004); 8 cases of acute recurrent pancreatitis progressed to chronic pancreatitis (38%); of these 66.7% had mutations vs. 16.7% who did not (p=0.03). CONCLUSIONS: Almost 50% of idiopathic chronic, acute recurrent and 33% of acute pancreatitis in children are genetically predisposed. Presence of genetic mutations in acute and recurrent acute pancreatitis increases the risk of developing chronic pancreatitis.

Indian Society of Gastroenterology consensus statements on Crohn's disease in India.

In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

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.

Spectrum and distribution of CFTR gene mutations in asthma and chronic pancreatitis cases of North Indian population.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) gene accounts for an autosomal recessive condition called cystic fibrosis (CF). In the Indian subcontinent, CF and its related diseases are under-diagnosed by the medical community due to poor knowledge of the disease and its confounding diagnosis, and also due to poor medical facilities available for these patients, thus causing an increased infant mortality rate with a low life expectancy in general. The aim of the study was to document the spectrum and distribution of CFTR mutations in controls, asthma and chronic pancreatitis cases of North India. METHODS: A total of 800 subjects including 400 controls, 250 asthma cases and150 chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D, R117H, W1282X, and S549N) and IVS8 Tn polymorphism. RESULTS: Out of 800 subjects, 18% [asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)] were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases while F508del mutation in chronic pancreatitis cases. The carrier frequency of F508del, G542X, G551D, R117H, S549N and T5 was 0.015, 0.025, 0.02, 0.005, 0.005, and 0.022 respectively. The cumulative carrier frequency was 0.093. CONCLUSION: CFTR mutations were underestimated in Indian population. The present study will serve in establishment of genetic screening and prenatal setup for Indian population.

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.

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.

Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease.

AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m(2)). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m(2) to 25.0 ± 3.3 kg/m(2), WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r(s) = 0.90) and liver histology (P = 0.03, r(s) = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.

Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population.

AIM: To find out the association of common HFE mutations (viz., C282Y and H63D) with primary iron overload (PIL) in liver cirrhosis (CLD) patients of Indian origin. METHODS: Polymerase chain reaction-restriction fragment length polymorphism method was used for screening C282Y and H63D mutation in 496 CLD patients (hepatitis B virus associated cirrhosis (HBVc) = 74, hepatitis C virus associated cirrhosis (HCV) = 50, alcoholic cirrhosis with hepatitis (ALcW) = 38, alcoholic cirrhosis without hepatitis (ALc) = 92, cryptogenic cirrhosis (CC) = 242) and 502 healthy controls. Transferrin saturation of >45 or serum ferritin of >300 ng/mL (males)/>200 ng/mL (females) with normal total exogenous iron intake was suggestive of PIL. Histological liver iron grading was done by Perl's Prussian blue stain. RESULTS: Of 496 patients, 13 (2.6; 9 CC, 2 ALc, 1 HBVc, 1 AlcW) had PIL. However, only two (15.3) of 13 patients (1 CC and 1 HBVc) were positive for H63D heterozygous mutation. All the subjects were found to be C282Y wild type, except a single case of double heterozygous (C282Y/H63D) who however, did not have PIL. Overall frequency of H63D allele in patients and controls was not significantly different (5.95 and 4.58 respectively, p = 0.17). A highly significant H63D allele frequency (p < 0.005) was observed in HBVc (10.82) and ALcW (11.84) groups but they were not associated with PIL. CONCLUSION: The frequency of PIL, and the HFE gene mutaion (C282Y) are both rare in Indian patients and explain why hemochromatosis is a rare cause of liver cirrhosis in India. A highly significant H63D allele frequency in HBV and alcohol-related cirrhosis suggest a possible predisposing role for liver fibrosis of this allele.

Chronic diarrhea and malabsorption due to hypogammaglobulinemia: a report on twelve patients.

Hypogammaglobulinemic sprue (HGS), which may predispose to infection, is uncommon. Twelve patients (all men; median age 29 years, 15-50) with HGS (4%) of 296 with chronic small bowel diarrhea and malabsorption syndrome (MAS) during a 10-year period were analyzed. Treatment of HGS was delayed due to misdiagnosis as intestinal tuberculosis (n = 7) and diarrhea-predominant irritable bowel syndrome (n = 1). All had diarrhea and weight loss (median loss 12 Kg). Associated conditions were clubbing, bronchiectasis, and seizure (2 patients each), and hypothyroidism (n = 1). Laboratory parameters were urinary D-xylose median 0.46 g/5 g/5 h (range 0.2-1.6; normal ≥ 1), fecal fat 11.9 g/day (3.8-16.7; normal ≤ 7 g), serum IgA, IgG, and IgM: 23.5 mg/dL (17-114; normal 90-450), 584 mg/dL (145-1051; normal 800-1800), and 23 (0-40.3; normal 60-280). IgA, IgG, and IgM were low in 10, 10, and 11, respectively. Duodenal biopsy was normal in 6 patients and showed partial villous atrophy in 6 and nodular lymphoid hyperplasia in two. Associated infections were giardiasis (n = 1), disseminated strongyloidiasis (1), small intestinal bacterial overgrowth (3), septicemia (2), and septic arthritis (1). Two patients died of sepsis, five are well on immunoglobulin and specific anti-infective treatment, and five are lost to follow up. Approximately 4% patients with MAS have hypogammaglobulinemia, which is often associated with infection and is diagnosed late.

Epidemiology and symptom profile of gastroesophageal reflux in the Indian population: report of the Indian Society of Gastroenterology Task Force.

BACKGROUND: Gastroesophageal reflux disease (GERD) and its complications are thought to be infrequent in India; there are no data from India on the prevalence of and risk factors for GERD. The Indian Society of Gastroenterology formed a task force aiming to study: (a) the frequency and profile of GERD in India, (b) factors including diet associated with GERD. METHODS: In this prospective, multi-center (12 centers) study, data were obtained using a questionnaire from 3224 subjects regarding the frequency, severity and duration of heartburn, regurgitation and other symptoms of GERD. Data were also obtained regarding their dietary habits, addictions, and lifestyle, and whether any of these were related or had been altered because of symptoms. Data were analyzed using univariate and multivariate methods. RESULTS: Two hundred and forty-five (7.6%) of 3224 subjects had heartburn and/or regurgitation at least once a week. On univariate analysis, older age (OR 1.012; 95% CI 1.003-1.021), consumption of non-vegetarian and fried foods, aerated drinks, tea/coffee were associated with GERD. Frequency of smoking was similar among subjects with or without GERD. Body mass index (BMI) was similar in subjects with and without GERD. On multivariate analysis, consumption of non-vegetarian food was independently associated with GERD symptoms. Overlap with symptoms of irritable bowel syndrome was not uncommon; 21% reported difficulty in passage of stool and 9% had mucus in stools. About 25% of patients had consulted a doctor previously for their gastrointestinal symptoms. CONCLUSION: 7.6% of Indian subjects have significant GERD symptoms. Consumption of non-vegetarian foods was an independent predictor of GERD. BMI was comparable among subjects with or without GERD.

Restoration of hepatocytes function following decompression therapy in extrahepatic biliary obstructed patients: metabolite profiling of bile by NMR.

Prolonged biliary obstruction and infection cause retention of biliary constituents in liver followed by hepatocyte dysfunction. Decompression therapy is important for both management and prognostic reasons and restores hepatocyte function. Quantitative metabolite profiling of bile using NMR spectroscopy at the time of obstruction and serially following decompression therapy using percutaneous transhepatic biliary drainage (PTBD) from nineteen patients with extrahepatic malignant biliary obstruction are presented. Based on detailed history, clinical condition, total leucocyte counts (TLC) and microbiological cultures of bile, patients were classified in two groups depending upon absence or presence of cholangitis. Statistical analysis was performed for comparison within each group using Wilcoxan sign square rank test. TLC and liver function tests indicated a trend towards recovery following decompression by one week. While on day 0 biliary constituents were undetectable in both the groups of patients, they increased significantly following one week of drainage with better recovery in patients with cholangitis compared to without. Free amino acids' signals were detected in all specimens starting from day 1 after decompression. This indicates disruption of blood-bile barrier during cholestasis and slow restoration of tight junction of hepatocytes following decompression leading to the appearance of biliary constituents in bile. Decompression therapy tends to restore biliary constituents with a prompt recovery in patients with cholangitis further supports such therapy for clinical management and outcome. To our knowledge this is the first report on the detection of amino acids in bile taken from common bile duct though they have been reported in hepatic bile.

High prevalence of low bone mineral density in patients with tropical calcific pancreatitis.

OBJECTIVES: Patients with tropical calcific pancreatitis (TCP) have multiple risk factors for developing low bone mineral density (BMD). We studied BMD and serum 25-hydroxyvitamin D (25[OH]D) in north Indian TCP patients. METHODS: In a cross-sectional study, 72 TCP patients (mean age, 31 ± 10 years) and 100 controls were studied. Serum 25(OH)D was measured in all subjects; BMD was measured by dual-energy x-ray absorptiometry in 56 adult patients and 4 children and compared with a reference Indian population. RESULTS: Mean BMD and BMD Z-scores at the lumbar spine and total hip were significantly lower in all age groups. The BMD Z-scores at the lumbar spine and total hip were -1.0 ± 1.0 and -1.2 ± 1.2, respectively. Low bone density (Z-score ≤ -2 at ≥ 1 sites) was present in 22 (39%) adult patients and 3 of the 4 children studied. On multivariate analysis, BMD Z-scores were positively associated with body mass index and inversely with pancreatitis. Vitamin D deficiency (25[OH]D < 50 nmol/L) was equally prevalent in patients (86%) and controls (85%). CONCLUSIONS: Despite their young age, patients with TCP have significantly low BMD. Measures to improve nutrition should be instituted in all TCP patients from an early age.

Clinical characteristics of 327 Asian patients with autoimmune pancreatitis based on Asian diagnostic criteria.

OBJECTIVES: To clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) in Asia. METHODS: A retrospective, actual situation survey of AIP diagnosed by Asian criteria was conducted in 10 centers of Japan, Korea, Taiwan, China, and India. RESULTS: A total of 327 AIP cases (258 male and 69 female subjects; average age, 60.0 years) were enrolled. Obstructive jaundice was the most frequent initial symptom (46%-74%), followed by weight loss (4%-51%) and abdominal pain (19%-44%). Diffuse swelling of the pancreas was frequent in Japan (64%) and Korea (81%), but segmental swelling of the pancreas was more frequent in Taiwan (70%) and China (72%) (P < 0.01). Serum immunoglobulin G4 levels were elevated in 58%-100% of cases in Japan, Korea, and Taiwan. Pathologically, almost all AIPs in Asia were lymphoplasmacytic sclerosing pancreatitis. Sclerosing cholangitis was the most frequent extrapancreatic lesion (60%-81%). Steroid therapy was a major and effective therapeutic strategy in Japan, Korea, and Taiwan. However, the rate of resection or bypass operation was higher in Taiwan (40%) and China (72%) (P < 0.01). CONCLUSIONS: Features of AIP are fundamentally similar in Japan, Korea, Taiwan, and China. Knowledge of emerging AIP should be more widespread in Asia to avoid unnecessary operation.

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.

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.