Clinical, anthropometric, biochemical, and histological characteristics of nonobese nonalcoholic fatty liver disease patients of Bangladesh.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is considered to be a disease of obese individuals, yet lean patients are increasingly susceptible to have NAFLD. The aim of this study was to evaluate the profile of nonobese patients by comparing with obese NAFLD patients. METHODS: We have included 465 patients of NAFLD after exclusion of other diseases, and 220 with elevated alanine aminotransferase (ALT) were biopsied. Patients were biochemically and clinically evaluated: blood pressure, body mass index (BMI), and waist circumference (WC) were recorded for every patient. A BMI ≥ 25 kg/m(2) was defined as obese, and those with a BMI of <25 kg/m(2) were labeled as nonobese. Histological activity was expressed with NAFLD activity score (NAS). RESULTS: Of 465 cases, 119 (25.6 %) were nonobese. Diabetes was noted in 122 (26.2 %) and hypertension in 122 (26.2 %). Metabolic syndrome was present in 253 (59.7 %), low HDL cholesterol in 228 (64.8 %), hypertriglyceridemia in 297 (73.2 %), and WC above normal in 308 (70.2 %). Males were predominating in the nonobese compared to females in the obese (p = 0.001). Hypertriglyceridemia and low high-density lipoprotein was similar in the obese and nonobese (76.2 % vs. 72.3 %, p = 0.5 and 65.2 % vs. 64.6 %, p = 1.0, respectively). The grades of steatosis, lobular inflammation, ballooning, NAS, and the stage of fibrosis did not also significantly differ between obese and nonobese patients. Nonalcoholic steatohepatitis (NASH) was 53.1 % in nonobese. CONCLUSION: Nonobese was 25.6 % among NAFLD patients of Bangladesh, and 53.1 % of nonobese NAFLD cases were NASH. Though they were nonobese by BMI grade, they were metabolically similar to obese. Males were predominant in the nonobese, whereas females in the obese. NASH and fibrosis were similar in the obese and nonobese.

Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms.

BACKGROUND: Analysis of the literature for nonsteroidal anti-inflammatory drugs (NSAIDs) suggests that a low incidence of developmental anomalies occurs in rats given NSAIDs on specific days during organogenesis. Aspirin (acetylsalicylic acid [ASA]), an irreversible cyclooxygenase 1 and 2 inhibitor, induces developmental anomalies when administered to Wistar rats on gestational day (GD) 9, 10, or 11 (Kimmel CA, Wilson JG, Schumacher HJ. Teratology 4:15-24, 1971). There are no published ASA studies using the multiple dosing paradigm of GDs 6 to 17. Objectives of the current study were to compare results between Sprague-Dawley (SD) and Wistar strains when ASA is administered on GD 9, 10, or 11; to compare the malformation patterns following single and multiple dosings during organogenesis in SD rats; and to test the hypothesis that maternal gastrointestinal toxicity confounds the detection of low incidence malformations with ASA when a multiple dosing paradigm is used. METHODS: ASA was administered as a single dose on GD 9 (0, 250, 500, or 625 mg/kg), 10 (0, 500, 625, or 750 mg/kg), or 11 (0, 500, 750, or 1000 mg/kg) and from GD 6 to GD 17 (0, 50, 125, or 250 mg/kg a day) in the multiple dose study to SD rats. Animals were killed on GD 21, and fetuses were examined viscerally. RESULTS: The literature evaluation suggested that NSAIDs induce ventricular septal defects (VSDs) and midline defects (MDs) in rats and diaphragmatic hernia (DH), MDs, and VSDs in rabbits (Cook JC et al., 2003); hence, the present study focused on these malformations, even though ASA induces several other low-incidence malformations. In single dose studies, DH, MD, and VSD were induced on GDs 9 and 10. VSD also was noted following treatment on GD 11. In contrast, DH and MD were noted in the multiple dose study design only in the high-dose group, and VSD was noted across all dose groups. CONCLUSIONS: High concordance in major developmental anomalies between Wistar and SD rats were noted with the exception of VSD in the SD rats and hydrocephalus in the Wistar rats. Variations and malformations were similar when ASA was administered as a single dose or during the period of organogenesis (GDs 6 to 17). It was also evident that, by titrating the dose to achieve a maximum tolerated dose, malformations that normally occur at low incidence, as reported from previous single dose studies, could also be induced with ASA given at multiple doses.