Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis.

BACKGROUND & AIMS: SPD476 (MMX mesalamine), a novel, once-daily mesalamine formulation, uses MMX Multi Matrix System (MMX) technology to delay and extend delivery of active drug throughout the colon. We performed a randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III study in patients with mild to moderately active ulcerative colitis. METHODS: Two hundred eighty patients with mild to moderately active ulcerative colitis received MMX mesalamine 2.4 g/day given twice daily (n = 93), 4.8 g/day given once daily (n = 94), or placebo (n = 93) for 8 weeks. The primary end point was the percentage of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index score of < or =1, with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at week 8. Patients with mucosal friability were not considered to have achieved this end point. RESULTS: Clinical and endoscopic remission at week 8 was achieved by 34.1% and 29.2% of patients receiving MMX mesalamine 2.4 g/day given twice daily and MMX mesalamine 4.8 g/day given once daily, respectively, versus 12.9% receiving placebo (P < .01). MMX mesalamine was generally well-tolerated. CONCLUSIONS: MMX mesalamine given once or twice daily is well-tolerated and, compared with placebo, demonstrated efficacy for the induction of clinical and endoscopic remission in mild to moderately active ulcerative colitis.

DNA methylation in esophageal diseases including cancer: special reference to hMLH1 gene promoter status.

AIMS AND BACKGROUND: Chronic inflammation leading to malignancy in the esophagus may be due to errors in mismatch repair (MMR) genes such as hMLH1. Promoter hypermethylation has been suggested as the main cause of hMLH1 silencing. In this study we assessed hMLH1 promoter hypermethylation in a range of esophageal diseases. Further, we evaluated the role of factors affecting the methylation cycle: (1) methylenetetrahydrofolate reductase (MTHFR) C677T mutation and (2) serum homocysteine levels. METHODS: We endoscopically and histologically categorized 124 paired tissue and blood samples from patients into cancer, precancer, reflux esophagitis, other inflammatory esophagitis and controls (endoscopically normal). Restriction enzyme-based methylation analysis was carried out to assess hMLH1 promoter hypermethylation. RESULTS AND CONCLUSIONS: hMLH1 promoter hypermethylation in tissue was seen in 63.5% of patients with cancer and 53.8% of those with precancer, which was significantly increased when compared with controls (P < 0.001). There appears to be an increasing degree of hMLH1 hypermethylation with disease progression. Patients with gastroesophageal reflux disease (GERD) showed a high degree of hMLH1 hypermethylation (88.8%), indicating that local environment due to reflux may be promoting hypermethylation. We suggest that GERD is a progressive condition with an increased risk for developing into cancer. Only 14.5% of cases exhibited hypermethylation both in tissue and blood. Hence, we conclude that hMLH1 promoter hypermethylation is a tissue-specific change in the esophagus and blood testing cannot be used as a noninvasive tool to assess it. DNA methylation is dependent on the methylation cycle; MTHFR is a major enzyme in this pathway. MTHFR mutations did not correlate with hypermethylation or clinical pathology (P > 0.5). Elevated homocysteine levels, independent of MTHFR mutation, correlated significantly with hMLH1 hypermethylation in tissue (P < 0.005). Our study shows that hMLH1 hypermethylation in tissue may be the primary event caused by endogenous/exogenous factors in esophageal diseases, aiding disease progression.