Prevelence of Fatty Liver Disease in Ageing Population and Effects of Nigella Sativa Tablets on Fatty Liver

Abstract

Non-alcoholic fatty liver disease (NAFLD) prevalence has not been well established. The aim of this study was to define prospectively non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease prevalence in hospitalized and ambulatory patients 20-65 years old during June 2013 to June 2014 were selected from Combined Military Hospital Peshawar Cantonment area. A base line questionnaire and right upper quadrant ultrasound was completed by all patients. On identifications of fatty liver among the selected cases further lab test data and liver biopsy reports were obtained. Mean BMI of female was 29.9 ± 5.65 while prevalence of hypertension and diabetes were 49.8% and 16.6% respectively. Among all patients 62% were Punjabis, 23% were Pathans while 12% were Sindhies. Overall NAFLD prevalence was 47% while NASH was confirmed in 20 patients (12.3% of total and 30%of ultrasound positive patients). Pathans had the highest prevalence of NAFLD (58.5%) as compared to Punjabi’s (44.5%) and Sindhies (35.3%). Pathans also had a higher prevalence of NASH compared with Punjabies (19.5% VS 10%: p-value= .03). In general NAFLD patients were more prevalent among male (59%), Diabetic (p-value <0.00005), hypertensive (p-value< 0.00005) and older (p-value< 0.005). They consumed more fast food (p-value = 0.049) had a higher BMI (p-value<0.0005) and had little or no exercise as compared to their normal or non NAFLD counter parts (p-value= 0.02). NAFLD was found in 75% and NASH in 22.5% among the 26 diabetic patients. ALT, AST, BMI, insulin, quantitative insulin sensitivity checks index and cytokeratin – 18 correlated with NASH. It was concluded that NAFLD and NASH prevalence is higher than estimated previously, Pathans and Patients with diabetes are at high risk.In this part of the study, the effects of tablets Nigella Sativa on fatty liver disease in rats were determined. Fatty liver disease are increasing worldwide due to physical inactivity and increased fructose intake in processed foods. The seeds and oil of the plant Nigella Sativa have been widely used in various countries of the world to promote health and cure disease. The study was conducted on 52 aged (16-18 months) male albino rats to investigate the effect of Nigella sativa tablets dietary supplementation on fatty liver disease. Rats were randomly divided in; Group-I (Control rats C) (n = 20) fed standard rat diet; Group-II (Fatty liver Group-F) (n=14) fed high fructose diet (diet having 60% fructose w/w) and Group-III (Fatty liver/ Nigella sativaGroup-F/NS) (n = 18) fed Group-F diet but mixed with crushed tablets (1.6 g/kg) in order to achieve Nigella sativa daily intake of 170mg/kg b.w. During this study rats were monitored for daily food intake and weekly body weight. The parameters including body weight final, BMI, liver weight, serum glucose,insulin, HOMA-R, TC, HDL-c, LDL-c, vLDL-c, Adiponectin, TNF-α, AST, ALT and bilirubin were monitored after six weeks in the selected group of rats. The rats livers, brains and kidneys histopathological examination were also carried out.The Real-Time PCR(RT- PCR) of superoxide dismutase (Sod1, Sod2) and DNA glycosylase (Ogg1, MutY) were used for the detection ofenzymatic antioxidant defense system. The western blot anlysis of OGG1 expression was used for the detection of DNA repaire. Our results show that that there was a significant increase in visceral fat weight in Group-F compared to Group-C and a significant decrease in Group-F/NS compared to Group-F. Both Group-F and Group-F/NS had significant increase in glucose fasting, insulin, HOMA R, TC, LDL-c, vLDL-c, TNF-α, AST, ALT and bilirubin. While a significant decrease in serum adiponectin compared to Group-C. However, Group-F/NS showed significant decrease in serum glucose fasting, insulin, HOMA-R, TC, LDL-c, TNF-α, AST, ALT and bilirubin as well adiponectin increased significantly compared to Group-F. Histopathological examination in Group-F showed vascular congestion in the liver, kidneys, necrosis of renal tubular cells as well as focal cerebral hemorrhage while Group-F/NS showed almost normal histology. Gene expression of antioxidant defense mechanism: Sod1, Sod2, Ogg1 and MutY decreased significantly in the Group-F but reversed by the Nigella Sativa tablets co-administeration in Group-F/NS. Nigella sativa crushed tablets co-feeding with higher fructose diet showed significant decrease in serum level of glucose fasting, insulin, total cholesterol(TC), LDL-c, HOMA-R, TNF-α, AST, ALT and bilirubin and a significant increase in serum adiponectin in fatty liver disease in aged rats. TheNigella Sativa tablets role in attenuation of hepatic oxidative DNA damage in Group-F/NS may be mediated by up regulation of the antioxidant defense mechanism and oxidative DNA repair activity. The clinical benefits of the Nigella Sativa treatment in the shape of diminution of oxidative damage may explain its role in patients with fatty liver disease. In this part of our study the ad-on effects of tablets Nigella Sativa on different clinical and biochemical parameters in human were determined. Metabolic syndrome and its associated complications have been reported to be extensively increased worldwide. The seeds and oil of the plant Nigella Sativa have been widely used globally to cure various disease and promote health since ancient times especially in the Southeast Asia and in the mejority of the Middle East countries. A lot of work has been done already on this plant. This prospective clinical study was designed to evaluate the ad-on effect of tablets Nigella Sativa on different parameters in fatty liver disease. This clinical study was conducted in medicine departement of a tertiary health care facility the Combined Military Hospital (CMH) Peshawar cantonment from June 2013 to May 2014. After considering inclusion and exclusion criteria and final diagnoses, 60 patients in this prospective study were enrolled. Upon approval from hospital ethical committee all the patients were properly consented in writing and were informed about study scope, Patients were equally distributed in two groups containing 30 each. In Group-1 (Control group) Patients were given Tab Metformine 500mg PO BD and Tab Rosuvastatine 10mg PO at night for a period of six weeks while in Group-II (Nigella Sativa treated group) in additions to standard treatment tablets Nigella sativa 600mg PO BD for a duration of six weeks were given. The parameters including waist circumference, body weight, body mass index, lipid profile, Blood sugar fasting and post parandial, Liver functions test (LFT’s) and Ultrasound right upper quadrant were recorded before and upon treatment completion.The above mentioned methodology was followed and the study findings were : Fasting blood sugar, low density Lipoprotein cholesterol (LDL-c)and total cholesterol (TC) percentage improvements in Group-II were statistically significant (p-value<0.05). In both the groups serum Alanintransaminase (ALT) declined significantly, in the Nigella sativa tablets treated Group-II the reduction was almost 2 fold (48% vs. 26.4%). On ultrsonography a statistically significant reversal of fatty liver was found only in the Nigella sativa tablets treated Group-II (p-value<0.05). As an ad-on therapy tablets Nigella sativa was found effective in fatty liver disease. Nigella sativa tablets has shown significant results especially in diabetic and dyslipidemic patients.