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.

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.

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.

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.

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.

A school-based intervention of screening a movie to increase hepatitis B vaccination levels among students in Uttar Pradesh, India: impact on knowledge, awareness, attitudes and vaccination levels.

BACKGROUND: India is home to one in 14 of all chronic hepatitis B virus (HBV) cases, meaning that it is important to develop HBV interventions that are applicable in the Indian context. Vaccination is the foremost tool for interrupting the HBV infection cycle. HBV vaccination was not included in India's government-sponsored expanded immunisation program until 2011, and many children born earlier remain unvaccinated. This study sought to observe the impact of the HOPE Initiative's school-based intervention to increase vaccination coverage by increasing HBV awareness among students in Lucknow, Uttar Pradesh. METHODS: At 430 schools in the administrative areas within and surrounding Lucknow, students viewed an educational documentary film on HBV and completed two questionnaires, one immediately before the screening and the other six weeks later. Both questionnaires asked the same 14 questions, which were organized into five domains: knowledge of the magnitude of the problem of HBV; knowledge of modes of HBV transmission; knowledge of consequences of HBV infection; awareness of HBV; and attitudes regarding HBV. The baseline questionnaire also asked students whether they had been vaccinated against HBV. At two-year follow-up, researchers measured vaccination levels at a subset of 30 intervention schools and six non-intervention schools to further assess the impact of the intervention. RESULTS: Baseline questionnaires were completed by 11,250 students, and post-intervention questionnaires, by 9698 students. Scores for knowledge about the magnitude of the HBV problem improved from 41% at baseline to 74% at follow-up, and scores for knowledge about modes of transmission, from 38% to 75% (p < 0.05 for both). The baseline HBV vaccination level among students receiving the intervention was 21%. Two years after the intervention, 45% of students (N = 4284) reported being vaccinated at intervention schools compared to 22% (N = 1264) at non-intervention schools. CONCLUSIONS: The observed increases in HBV awareness, knowledge and vaccination levels in this study indicate that school-based interventions can be used to achieve higher vaccination coverage among Indian children. The documentary film was found to be an affordable tool for reaching large audiences. More studies are needed to validate the impact of this intervention and to explore its applicability to other social causes.

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.

Polymorphism of Alcohol Metabolizing Gene ADH3 Predisposes to Development of Alcoholic Pancreatitis in North Indian Population.

BACKGROUND AND AIM: Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (ACP). Studies revealed that alcohol could be metabolized by both ways, oxidative and non-oxidative. The main oxidative pathway includes alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P450 enzyme. We investigated the association of polymorphisms in these enzymes with the alcoholic pancreatitis in the north Indian population. METHOD: Patients with alcoholic pancreatitis (ACP; n = 72), tropical calcific pancreatitis (TCP; n = 75), alcoholic controls (AC; n = 40), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH3, ALDH2, and CYP2E1 was done by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). The products were analyzed by gel electrophoresis. RESULT: The frequency distribution of ADH3(*)1/(*)1 genotype was significantly higher in ACP group (59.7%) compared with TCP (38.7%), HC (42%), and AC (37.5%) and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3(*)1/(*)1, ADH3(*)1/(*)2, and ADH3(*)2/(*)2 genotypes between TCP and HC or healthy alcoholics. ALDH2 gene was monomorphic in our population, and the frequencies for CYP2E1 intron 6 Dra I polymorphism were comparable in all the four groups. CONCLUSION: This study shows that carriers of ADH3(*)1/(*)1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3(*)1/(*)2 and ADH3(*)2/(*)2.

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.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part I: Status Report of HCV Infection in India.

Globally, around 150 million people are infected with hepatitis C virus (HCV). India contributes a large proportion of this HCV burden. The prevalence of HCV infection in India is estimated at between 0.5% and 1.5%. It is higher in the northeastern part, tribal populations and Punjab, areas which may represent HCV hotspots, and is lower in western and eastern parts of the country. The predominant modes of HCV transmission in India are blood transfusion and unsafe therapeutic injections. There is a need for large field studies to better understand HCV epidemiology and identify high-prevalence areas, and to identify and spread awareness about the modes of transmission of this infection in an attempt to prevent disease transmission.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part II: INASL Recommendations for Management of HCV in India.

The estimated prevalence of hepatitis C virus (HCV) infection in India is between 0.5 and 1.5% with hotspots showing much higher prevalence in some areas of northeast India, in some tribal populations and in certain parts of Punjab. Genotype 3 is the most prevalent type of infection. Recent years have seen development of a large number of new molecules that are revolutionizing the treatment of hepatitis C. Some of the new directly acting agents (DAAs) like sofosbuvir have been called game-changers because they offer the prospect of interferon-free regimens for the treatment of HCV infection. These new drugs have not yet been approved in India and their cost and availability is uncertain at present. Till these drugs become available at an affordable cost, the treatment that was standard of care for the whole world before these newer drugs were approved should continue to be recommended. For India, cheaper options, which are as effective as the standard-of-care (SOC) in carefully selected patients, are also explored to bring treatment within reach of poorer patients. It may be prudent to withhold treatment at present for selected patients with genotype 1 or 4 infection and low levels of fibrosis (F1 or F2), and for patients who are non-responders to initial therapy, interferon intolerant, those with decompensated liver disease, and patients in special populations such as stable patients after liver and kidney transplantation, HIV co-infected patients and those with cirrhosis of liver.

Procalcitonin as a marker of sepsis in alcoholic hepatitis.

BACKGROUND: Early diagnosis of sepsis in alcoholic hepatitis is important for selecting the appropriate therapy. The role of procalcitonin (PCT) to diagnose sepsis in patients with alcoholic hepatitis and systemic inflammatory response syndrome (SIRS) is not yet clear. METHODS: All patients admitted with alcoholic hepatitis and SIRS underwent measurement of serum PCT and C reactive protein (CRP) levels within 24 h of admission. Patients were classified into two groups: group 1, alcoholic hepatitis with SIRS alone; group 2, alcoholic hepatitis with SIRS and sepsis. The ability of PCT to predict sepsis was evaluated using receiver-operating characteristic (ROC) analyses to compare the two groups. RESULTS: The study included 11 patients in group 1 and 29 in group 2. All were male (median age 42 years; range, 24-65 years). Age, dose and duration of alcohol intake, biochemical parameters and median MELD score were not significantly different between the two groups. PCT and CRP were significantly higher among group 2 than group 1 patients (p < 0.05). ROC analysis showed an AUC of 0.81 (95 % CI 0.66-0.96) and 0.83 (95 % CI 0.68-0.93) for PCT and CRP, respectively, in distinguishing sepsis from SIRS without sepsis. A cutoff level of 0.57 mcg/l for PCT (sensitivity 79 %, specificity 82 %) for diagnosing sepsis in patients with alcoholic hepatitis and SIRS was comparable to a serum CRP cutoff level of 2.3 mg/dl (sensitivity 82.0 %, specificity 75 %). CONCLUSION: Serum PCT can be a useful marker for diagnosing sepsis in patients with alcoholic hepatitis and SIRS and compares favorably with serum CRP levels.

Comparison of Manning, Rome I, II, and III, and Asian diagnostic criteria: report of the Multicentric Indian Irritable Bowel Syndrome (MIIBS) study.

BACKGROUND: Attempts to diagnose and subtype irritable bowel syndrome (IBS) by symptom-based criteria have limitations, as these are developed in the West and might not be applicable in other populations. OBJECTIVES: This study aimed to compare different criteria for diagnosing and subtyping of IBS in India. METHOD: Manning's and the Rome I, II, and III criteria as well as the Asian criteria were applied to 1,618 patients (from 17 centers in India) with chronic lower gastrointestinal (GI) symptoms with no alarm features and negative investigations. RESULTS: Of 1,618 patients (aged 37.5 [SD 12.6] years; 71.2% male), 1,476 (91.2%), 1,098 (67.9%), 649 (40.1%), 849 (52.5%), and 1,206 (74.5%) fulfilled Manning's, Rome I, II, and III, and the Asian criteria, respectively. The most common reason for not fulfilling the criteria was absence of the following symptoms: "more frequent stools with onset of pain," "loose stool with onset of pain," "relief of pain with passage of stool," "other abdominal discomfort/bloating," and, in a minority, not meeting the duration criterion of 3 months/12 weeks. By stool frequency, constipation-predominant IBS (<3 stools/week) was diagnosed in 319 (19.7%), diarrhea-predominant IBS (>3 stools/day) in 43 (2.7%), and unclassified in 1,256 (77.6%). By Bristol stool form, constipation, diarrhea, and unclassified were diagnosed in 655 (40.5%), 709 (43.8%), and 254 (15.7%) patients, respectively. By their own perception, 462 (28.6%), 541 (33.4%), and 452 (27.9%) patients reported constipation-predominant, diarrhea-predominant, and alternating types, respectively. CONCLUSION: By Manning's and the Asian criteria, a diagnosis of IBS was made frequently among Indian patients with chronic functional lower GI symptoms with no alarm features; the Rome II criteria gave the lowest yield. By the stool frequency criteria, a majority of patients had unclassified pattern, unlike by the stool form and patients' perception of their symptoms.

Variants in CPA1 are strongly associated with early onset chronic pancreatitis.

Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets. Functionally impaired variants were present in 29/944 (3.1%) German cases and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 × 10(-16)). The association was strongest in subjects aged ≤ 10 years (9.7%; OR = 84.0, P = 4.1 × 10(-24)). In the replication sets, defective CPA1 variants were present in 8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230 (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and 0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity, as is seen with other genetic risk factors for this disease.

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.