Beneficial effect of a weight-stable, low-fat/low-saturated fat/low-glycaemic index diet to reduce liver fat in older subjects. Effect of a 6-month intervention with cooking oils containing a high concentration of monounsaturated fatty acids (olive and canola oils) compared with control oil in male Asian Indians with nonalcoholic fatty liver disease. Effect of two different hypocaloric diets in transaminases and insulin resistance in nonalcoholic fatty liver disease and obese patients. A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): study protocol Liver Fat Is Reduced by an Isoenergetic MUFA Diet in a Controlled Randomized Study in Type 2 Diabetic Patients Effect of a high monounsaturated vs high polyunsaturated fat hypocaloric diets in nonalcoholic fatty liver disease. Effect of 6-month nutritional intervention on non-alcoholic fatty liver disease. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis [An analysis of the efficacy of low-calorie and isocaloric diets in obese patients with nonalcoholic steatohepatitis]. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease is associated with insulin resistance and dyslipidaemia and can progress to steatohepatitis and cirrhosis . We sought to determine whether dietary fat and saturated fat content alter liver fat in the absence of weight change in an older population . Liver fat was quantified by magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low-fat/low-saturated fat/low-glycaemic index ( LGI ) ( LSAT : 23 % fat/7 % saturated fat/GI < 55 ) or a high-fat/high-saturated fat/high-GI ( HSAT : 43 % fat/24 % saturated fat/GI>70 ) diet in older subjects . In the present study , twenty subjects ( seven males/thirteen females ; age 69.3 ( SEM 1.6 ) years , BMI 26.9 ( SEM 0.8 ) kg/m2 ) were r and omised to the LSAT diet and fifteen subjects ( six males/nine females ; age 68.6 ( SEM 1.8 ) years , BMI 28.1 ( SEM 0.9 ) kg/m2 ) to the HSAT diet .  Weight remained stable . Liver fat decreased significantly on the LSAT diet ( median 2.2 ( interquartile range ( IQR ) 3.1 ) to 1.7 ( IQR 1.8 ) % , P= 0.002 ) but did not change on the HSAT diet ( median 1.2 ( IQR 4.1 ) to 1.6 ( IQR 3.9 ) % ) . The LSAT diet  lowered fasting glucose and total cholesterol , HDL-cholesterol and LDL-cholesterol and raised TAG ( P < 0.05 ) , while the HSAT diet had no effect on glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol ( P < 0.05 ) . Fasting insulin and homeostasis model of insulin resistance did not change significantly on either diet , but the Matsuda index of insulin sensitivity improved on the LSAT diet ( P < 0.05 ) . Assignment to the LSAT v. HSAT diet was a predictor of changes in lipid parameters but not liver fat . We conclude that diet composition may be an important factor in the accumulation of liver fat , with a low-fat/low-saturated fat/LGI diet being beneficial OBJECTIVE We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease ( NAFLD ) . SUBJECTS AND METHODS This was a 6-month intervention study including 93 males with NAFLD , matched for age and body mass index ( BMI ) . Subjects were r and omized into three groups to receive olive oil ( n=30 ) , canola oil ( n=33 ) , and commonly used soyabean/safflower oil ( control ; n=30 ) as cooking medium ( not exceeding 20 g/day ) along with counseling for therapeutic lifestyle changes . The BMI , fasting blood glucose ( FBG ) and insulin levels , lipids , homeostasis model of assessment for insulin resistance ( HOMA-IR ) , HOMA denoting β-cell function ( HOMA-βCF ) , and disposition index ( DI ) were measured at pre- and post-intervention . Data were analyzed with one-way analysis of variance ( ANOVA ) and Tukey 's Honestly Significant Difference multiple comparison test procedures . RESULTS Olive oil intervention led to a significant decrease in weight and BMI ( ANOVA , P=0.01 ) compared with the control oil group . In a comparison of olive and canola oil , a significant decrease in fasting insulin level , HOMA-IR , HOMA-βCF , and DI ( P<0.001 ) was observed in the olive oil group . Pre- and post-intervention analysis revealed a significant increase in high-density lipoprotein level ( P=0.004 ) in the olive oil group and a significant decrease in FBG ( P=0.03 ) and triglyceride ( P=0.02 ) levels in the canola oil group . The pre- and post-intervention difference in liver span was significant only in the olive ( 1.14 ± 2 cm ; P<0.05 ) and canola ( 0.66 ± 0.33 cm ; P<0.05 ) oil groups . In the olive and canola oil  groups , post-intervention grading of fatty liver was reduced significantly ( grade I , from 73.3 % to 23.3 % and from 60.5 % to 20 % , respectively [ P<0.01 ] ; grade II , from 20 % to 10 % and from 33.4 % to 3.3 % , respectively [ P<0.01 ] ; and grade III , from 6.7 % to none and from 6.1 % to none , respectively ) . In contrast , in the control oil group no significant change was observed . CONCLUSIONS Results suggest significant improvements in grading of fatty liver , liver span , measures of insulin resistance , and lipids with use of canola and olive oil compared with control oils in Asian Indians with NAFLD OBJECTIVE The aim of our study was to examine the changes in hypertransaminasemia after weight reduction in obese patients with and without NAFLD and the relation with insulin resistance . RESEARCH METHODS A population of 162 obese patients was r and omly allocated to two groups : a ) diet I ( low fat ) and b ) diet II ( low carbohydrate ) , dieting along 3 months .  Patients were classified as group I ( n=112 ) when serum ALT activity was normal or group II ( NAFLD , n=30 ) when serum ALT activity was ( > or=43 UI/L ) . RESULTS In control group with diet I , BMI , weight , fat mass , waist to hip ratio , waist circumference , systolic pressure , total cholesterol , LDL cholesterol , HOMA and insulin levels decreased . In NAFLD group with diet I improved the same parameters and glucose , triglycerides , ALT , AST , gamaglutamine transferase levels , too . In control group with diet II , BMI , weight , fat mass , waist to hip ratio , waist circumference , systolic pressure , total cholesterol , LDL cholesterol , HOMA and insulin levels decreased . In NAFLD group with diet II improved the same parameters and glucose , triglycerides , ALT and gamaglutamine transferase levels , without statistical changes in AST . CONCLUSION We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hipertransaminasemia and insulin resistance in NAFLD patients Background Non-alcoholic fatty liver disease , the most prevalent liver disease in developed countries , remains difficult to manage with no proven safe and effective pharmacotherapy available . While weight reduction is the most commonly practice d treatment strategy , this is difficult to both achieve and /or maintain in the majority . Furthermore evidence -based dietary recommendations to guide the nutritional management of these patients are lacking . Using a r and omised controlled trial design , this study compares the effectiveness of the Mediterranean diet to a st and ard low fat diet in terms of differences in insulin sensitivity , hepatic steatosis and metabolic outcomes in participants with non-alcoholic fatty liver disease . Methods Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant , will be r and omised into either a Mediterranean or low fat diet group for a 3 month intervention period . Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy . Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian . The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The st and ard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines . Study recruitment will take place at four major metropolitan hospitals in Melbourne , Australia . Data collection will occur at all face to face review s including baseline , 6 , and 12 weeks . A follow up assessment to measure sustainability will take place at 6 and 12 months . The primary end point is improved insulin sensitivity scores at the 12 week time point . Discussion This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight loss can result in significant benefits in liver fat and insulin sensitivity and that these changes are sustained at 12 months . These metabolic changes would potentially lead to reductions in the risk of chronic liver disease , heart disease , type 2 diabetes and liver cancer . Trial registration Australia and New Zeal and Clinical Trials Register ACTRN : ACTRN12615001010583 OBJECTIVE To evaluate the effects of qualitative dietary changes and the interaction with aerobic exercise training on liver fat content independent of weight loss in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS With use of a factorial 2 × 2 r and omized parallel-group design , 37 men and 8 women , aged 35–70 years , with type 2 diabetes in satisfactory blood glucose control on diet or diet plus metformin treatment  were assigned to one of the following groups for an 8-week period : 1 ) high-carbohydrate/high-fiber/low – glycemic index diet ( CHO/fiber group ) , 2 ) high-MUFA diet ( MUFA group ) , 3 ) high-carbohydrate/high-fiber/low – glycemic index diet plus physical activity program ( CHO/fiber+Ex group ) , and 4 ) high-MUFA diet plus physical activity program ( MUFA+Ex group ) . Before and after intervention , hepatic fat content was measured by 1H NMR . RESULTS Dietary compliance was optimal and body weight remained stable in all groups . Liver fat content decreased more in MUFA ( −29 % ) and MUFA+Ex ( −25 % ) groups than in CHO/fiber ( −4 % ) and CHO/fiber+Ex groups ( −6 % ) . Two-way repeated- measures ANOVA , including baseline values as covariate , showed a significant effect on liver fat content for diet ( P = 0.006 ) , with no effects for exercise training ( P = 0.789 ) or diet-exercise interaction ( P = 0.712 ) . CONCLUSIONS An isocaloric diet enriched in MUFA compared with a diet higher in carbohydrate and fiber was associated with a clinical ly relevant reduction of hepatic fat content in type 2 diabetic patients independent of an aerobic training program and should be considered for the nutritional management of hepatic steatosis in people with type 2 diabetes OBJECTIVE Hyperaminotransferasemia is an important problem in obese patients . We decide to examine the changes in hyperaminotransferasemia after weight reduction in obese patients with and without NAFLD secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets . PATIENTS AND METHODS A population of 306 obese patients was r and omly allocated to two groups : Diet M ( high monounsaturated fat hypocaloric diet ) and Diet P ( high polyunsaturated fat hypocaloric diet ) . Patients were classified as group I ( obese subjects ; n=262 ) when serum ALT activity was normal or group II ( NAFLD patients ; n=44 ) when serum ALT activity was ( ≥ 43 UI/L ) . RESULTS In NAFLD group with diet M , BMI , weight , fat mass , waist circumference , systolic blood pressure , total cholesterol , LDL cholesterol ) , insulin and HOMA-R decreased . In NAFLD group with diet P , BMI , weight , fat mass , waist circumference , systolic blood pressure , total cholesterol , LDL cholesterol ) , insulin and HOMA-R decreased , too . In NAFLD group , alanine aminotransferase [ ( diet M ) -20.3±19.2 UI/L vs. ( diet P ) -14.2±20.1 UI/L ] , aspartate aminotransferase [ ( diet M ) -11.3±12.2 UI/L vs. ( diet P ) -11.1±10.1 UI/L ] , and gammaglutamyl transferase [ ( diet M ) -18.1±12.2 UI/L vs. ( diet P ) -10.9±20.1 UI/L ] improved with both diets . CONCLUSIONS We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hypertransaminasemia and insulin resistance in NAFLD patients OBJECTIVE We evaluated the effect of diet therapy as exclusive treatment on insulin resistance , biochemical parameters of metabolic syndrome , and degree of hepatic steatosis in patients with non-alcoholic fatty liver disease . METHODS Thirty-one patients with non-alcoholic fatty liver disease received a diet with a reduction of 500 to 1000 cal/d , containing 15 % protein , 55 % carbohydrates , and 30 % fat , for 6 mo . At entry and 6 mo after dietary instructions , degrees of hepatic steatosis and visceral obesity were assessed by computed tomography ; serum aspartate aminotransferase , alanine aminotransferase , γ-glutamyl transferase , glucose , triacylglycerols , and high-density lipoprotein cholesterol were measured by automated methods . Body mass index , waist circumference , waist-to-hip ratio , and food intake ( 7-d diary ) were also evaluated . At the end of follow-up , the patients were classified as adherent or non-adherent to treatment according to a weight loss of more or less than 5 % of initial body weight , respectively . RESULTS Seventeen patients were classified as adherent ( group 1 ) and 14 as non-adherent ( group 2 ) . Group 2 only presented a significant reduction in body mass index and waist circumference . In contrast , in group 1 , in addition to significant improvement of all anthropometric parameters , a significant reduction was observed in alanine aminotransferase and γ-glutamyl transferase levels , homeostasis model assessment for insulin resistance , visceral fat and tomographic liver density , together with an increase in serum high-density lipoprotein cholesterol levels . These patients presented a significant decrease in total energy intake and in total and saturated fats . CONCLUSION Nutritional intervention as exclusive treatment , with a loss of at least 5 % of initial weight , is effective in the treatment of non-alcoholic fatty liver disease UNLABELLED Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease . Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids . We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard . A total of 170 overweight and obese , otherwise healthy subjects were r and omized to either reduced carbohydrate ( n = 84 ) or reduced fat ( n = 86 ) , total energy restricted diet ( -30 % of energy intake before diet ) for 6 months . Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography . Subjects were also su bmi tted to fat spectroscopy of liver and oral glucose tolerance testing . In all , 102 subjects completed the diet intervention with measurements of intrahepatic lipid content . Both hypocaloric diets decreased body weight , total body fat , visceral fat , and intrahepatic lipid content . Subjects with high baseline intrahepatic lipids ( > 5.56 % ) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values ( < 5.56 % ) irrespective of diet composition . In contrast , changes in visceral fat mass and insulin sensitivity were similar between subgroups , with low and high baseline intrahepatic lipids . CONCLUSION A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet . The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet BACKGROUND Nonalcoholic steatohepatitis ( NASH ) is commonly associated with overweight and insulin resistance . Aerobic exercise is known to reduce insulin resistance . We studied the effect of regular aerobic exercise on serum aminotransferase levels in patients with NASH . METHODS Sixty-five ( mean age 38.7+/-9.5 years ; 46 [ 78 % ] males ) out of 94 patients diagnosed with NASH participated in the study . Each patient was advised regular aerobic exercise for 30 min duration per day , and trained to achieve a heart rate of 60 - 70 % of his/her maximal heart rate for at least 5 days a week . In addition , those with a high body mass index ( BMI ) were advised a moderately energy-restricted diet . Patients were followed up monthly for at least 3 months by BMI , waist-hip ratio ( WHR ) , waist circumference ( WC ) , aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) . RESULTS Forty-three ( 72.8 % ) patients had a high BMI .  Central obesity ( WHR > or=0.90 cm in men and > or=0.85 cm in women ) was present in 58 ( 98.3 % ) patients and metabolic syndrome in 12 ( 20.3 % ) patients . In the 44 patients who complied regularly with the exercise program , serum ALT normalized in 20 ( 45 % ; P<0.05 ) , and mean AST and ALT values declined from 70.5 and 104.0 - 41.5 ( P<0.001 ) and 63.2 ( P<0.001 ) , respectively . Overweight patients lost a mean 3.1 kg ( range 0 - 13 kg ) weight and showed a decline in BMI ( 28.7 vs 27.5 ; P<0.001 ) and WC ( 99.4 cm vs 96.1 cm ; P=0.001 ) . Serum ALT did not normalize in any of the 15 patients who failed to comply with the exercise program ; their pre- and post-AST ( 82.8 and 81.2 , respectively ) and ALT ( 98.0 and 96.1 , respectively ) levels , BMI ( 27.5 and 27.6 , respectively ) and WHR ( 0.99 cm and 0.99 cm , respectively ) did not show any significant change at 3 months , and also for an extended mean follow-up period of 5.3 months . CONCLUSION Moderate intensity aerobic exercise helps in normalizing ALT levels in patients with NASH Unexplained abnormalities on liver function tests are common and often perplexing . Fatty liver , or hepatic steatosis , is a common clinical and histologic finding . When hepatic steatosis does not coexist with alcoholic hepatitis or steatohepatitis , it is a benign condition ( 1 , 2 ) . Fatty liver is usually attributed to alcohol abuse . Although the hepatotoxicity of ethanol has been well established , only 8 % to 20 % of persons with chronic alcoholism develop cirrhosis ( 3 ) . In the Dionysos Study , a survey of the prevalence of chronic liver disease in the general population that included 6917 participants ( 3 , 4 ) , the risk threshold for ethanol-induced liver disease was the ingestion of more than 30 g of alcohol per day . However , only 74 of 1349 participants at risk ( 5.5 % ) showed persistent signs of alcoholic liver damage ( 4 ) . Steatosis can also occur in association with other conditions , such as obesity , hypernutritional support , drug- or toxin-induced hepatitis , type 2 diabetes mellitus , and cachexia , and it can occur after jejunoileal bypass surgery for refractory obesity ( 1 , 5 - 12 ) . The role of obesity compared with that of alcohol in inducing fatty liver or abnormal results on liver function tests is still controversial . Although the presence of excess weight for at least 10 years has been cl aim ed to be a potential additional risk factor for acute alcoholic hepatitis and cirrhosis ( 13 ) , most data have been collected from selected series or retrospectively . To explore the relative roles of obesity and alcohol abuse , alone and in combination , in inducing steatosis , we performed an intracohort study in the general population of two towns of northeastern Italy ( Campogalliano , in the province of Modena , and Cormons , in the province of Gorizia ) that participated in the Dionysos Study ( 3 ) . Data indicate that obesity plays a greater role than excessive alcohol intake in inducing fatty liver . Methods Patients The details of the overall design of the Dionysos Study have been described elsewhere ( 3 , 4 ) . Briefly , 6917 of the 10 150 inhabitants ( age range , 12 to 65 years ) of two northern Italian communities were screened . For each participant , an extensive medical history was obtained that included history of chronic liver disease in first-degree relatives ; a detailed history of acute hepatitis , gallstone disease , surgical operations , blood transfusions , drug abuse , dental procedures , dog or other domestic animal bites , homosexual sex , or tattooing ; previous diagnosis of chronic hepatitis , cirrhosis , hemochromatosis , Wilson disease , primary biliary cirrhosis , other congenital liver diseases , diabetes , hyperlipoproteinemia , pericarditis , or heart diseases ; careful question ing for any current symptoms of liver or biliary diseases , including biliary colic , anorexia , pruritus , jaundice , dark urine , and ascites ; and personal habits , including tobacco and coffee consumption and type and duration of past and present professions and duties . Each participant also underwent a detailed physical examination aim ed at detecting liver diseases or physical signs related to chronic liver disease , including jaundice , excoriation of skin , ascites , pretibial edema , flapping tremor , spider nevi , palmar erythema , liver enlargement , and palpable spleen ; measurement of height , weight , body mass index ( calculated as weight in kg/height in square meters ) , and left wrist circumference ; and assay for serum levels of alanine aminotransferase , aspartate aminotransferase , -glutamyltransferase , glucose , mean corpuscular volume of erythrocytes , platelet count , and presence of hepatitis B surface antigen and antibody to hepatitis C virus . The current study involves 257 persons 19 to 70 years of age from the Dionysos cohort who tested negative for infection with hepatitis B virus or hepatitis C virus and had no evidence of chronic liver disease . Design The intracohort study began in March 1997 . The study was approved by the ethical committee of Fondo Studio Malattie del Fegato , Trieste , Italy . Of 6917 participants in the initial Dionysos Study cohort ( 3 ) , 3618 were excluded : Three hundred twelve tested positive for hepatitis B surface antigen ( n=86 ) or antibody to hepatitis C virus ( n=226 ) , 2 had histologically proven hemochromatosis or primary biliary cirrhosis , 19 had histologically proven cryptogenetic cirrhosis , and 3285 of them were overweight but not obese ( body mass , 25 kg/m2 to 30 kg/m2 ) or were obese but drank less than 60 g of alcohol per day . The remaining 3299 participants were divided into four groups according to body mass index and daily ( g/d ) and lifetime ( kg ) alcohol intake . The control group consisted of 2753 persons of normal weight ( body mass index<25 kg/m2 ) who drank less than 100 kg of alcohol over a lifetime and did not drink more than 30 g of alcohol per day . The obese group included 283 obese persons ( body mass index>30 kg/m2 ) who drank less than 100 kg of alcohol over a lifetime and did not drink more than 30 g of alcohol per day . The heavy drinker group comprised 168 persons of normal weight who drank more than 100 kg of alcohol over a lifetime and drank more than 60 g of alcohol per day . Finally , the obese and heavy drinker group consisted of 95 obese persons who drank more than 100 kg of alcohol over a lifetime and drank more than 60 g of alcohol per day . The definition of heavy drinker as consumption of 30 g of alcohol per day or 100 kg of alcohol over a lifetime was based on previous data indicating these amounts of alcohol as the risk threshold for alcoholic liver disease in both sexes ( 4 ) . Alcohol intake was calculated by using data from a semi-quantitative , color food question naire ( 14 , 15 ) that included detailed questions on the use of alcoholic beverages ( 16 , 17 ) . Each participant was asked , in multiple-choice form , whether he or she drank beer , red wine , white wine , alcoholic aperitifs , or hard liquors daily , weekly , monthly , or hardly ever or never . For each type of alcoholic beverage , a color picture of a glass containing a st and ard unit of the beverage ( 200 mL for beer , 100 mL for wine , 70 mL for aperitif , and 40 mL for hard liquor ) was printed in the question naire . Each participant was asked if he or she usually drank a glass like the one reported in the picture , a smaller one , or a larger one . If the participant answered that he or she usually drank a glass that was smaller or larger than the one pictured , the amount of the beverage consumed per day was reduced or increased by 25 % . To calculate accurately the amount of alcohol in grams for each unit ( glass ) , the br and of beverage was also recorded . Daily alcohol intake was computed by multiplying the frequency of consumption of each unit of beverage by the alcohol content of the specified portions , according to st and ard procedures ( 14 - 17 ) . Total lifetime intake of alcohol was computed by multiplying the daily alcohol intake by years of alcohol intake . As described in detail elsewhere ( 4 ) , alcohol consumption was vali date d by monitoring wine intake ( liters per year per person ) from purchase records of wine sellers in the two participating towns and by cross-checking the alcohol consumption declared by the participant with family members . Among the participants who fit the inclusion criteria , 300 ( 150  residents of Campogalliano and 150 residents of Cormons , pair-matched for age ) were r and omly selected from the four groups by using the r and om procedure of the SPSS software package ( SPSS , Inc. , Chicago , Illinois ) . Informed consent to participate was obtained from 285 participants . Twenty-eight persons were excluded : Nineteen stated that they had reduced their daily alcohol intake to less than 30 g/d for at least 2 years or that their body mass index was less than 30 kg/m2 from 1993 to 1997 ; 6 who had type 2 diabetes mellitus ( 3 women and 1 man ) or hyperlipoproteinemia type 2b ( 2 men ) took oral antidiabetic drugs or cholestyramine , and 3 regularly took drugs . The remaining 257 participants , who were 19 to 70 years of age and had taken no drugs in the past 6 months , were enrolled in the study . Sixty-seven were assigned to the control group , 66 to the obese group , 69 to the heavy drinker group , and 55 to the obese and heavy drinker group . Two consecutive blood sample s were obtained 15 days apart from all of the enrolled participants , and the following were measured : serum levels of alanine aminotransferase , aspartate aminotransferase , and -glutamyltransferase ; mean corpuscular volume of erythrocytes ; platelet count ; and levels of glucose , cholesterol , and triglycerides All participants also underwent hepatobiliarysplenic ultrasonography , which was performed by two operators ( one in each center ) . The ultrasonograph operators were unaware of the participants ' clinical and biochemical profiles and the aim of the study . Steatosis was defined as the presence of an ultrasonographic pattern consistent with bright liver , with evident ultrasonographic contrast between hepatic and renal parenchyma , vessel blurring , focal sparing , and narrowing of the lumen of the hepatic veins , according to international guidelines ( 18 , 19 ) . Previous studies indicated that ultrasonography can detect and quantitate hepatic fat accumulation with an accuracy similar to that of computed tomography and liver biopsy ( 20 ) . The biochemical and ultrasonographic findings ( presence or absence of steatosis and gallstones ) were reported to the physician of the study participant . Statistical Analysis Statistical analysis was performed by using the SPSS statistical package , version 7.1 ( SPSS , Inc. ) . Data are expressed as the mean SD or the median with 95 % CIs for continuous variables . Statistical comparison was done by using the F-test ( analysis of variance ) ( 21 ) . Bivariate risk ratios ( 22 , 23 ) with 95 % CIs ( StatXact 3 for Windows , CYTEL Software Co. , Cambridge , Massachusetts ) and positive predictive values were calculated . Role of the Funding Source The funding source did not have any role in the analysis or Objective : We aim ed at evaluating whether the addition of low-dose metformin to dietary treatment could be an effective approach in nondiabetic patients with nonalcoholic fatty liver disease ( NAFLD ) . Methods : We carried out a 6-month prospect i ve study in a series of overweight or obese patients with ultrasonographic diagnosis of hepatic steatosis . In total , 50 patients were enrolled and r and omized into two groups : the first group ( n=25 ) was given metformin ( 1 g per day ) plus dietary treatment and the second group ( n=25 ) was given dietary treatment alone . Results : At the end of the study , the proportion of patients with echographic evidence of fatty liver was reduced in both the metformin ( P<0.0001 ) and the diet group ( P=0.029 ) . Moreover , patient body mass index and waist circumference significantly decreased in both groups ( P<0.001 ) . Fasting glucose , insulin resistance ( evaluated as homeostasis model assessment of insulin resistance ( HOMA-IR ) ) and serum adiponectin decreased in both groups , although these changes reached statistical significance only in the metformin group . In this group , HOMA-IR decreased from 3.3±1.6 to 2.4±1.2 ( P=0.003 ) , whereas it decreased from 3.2±1.6 to 2.8±1.1 ( not significant , NS ) in the diet group . Similarly , the proportion of patients with impaired fasting glucose declined from 35 to 5 % ( P=0.04 ) in the metformin and from 32 to 12 % ( NS ) in the diet group . At baseline , ∼40 % of patients in both groups met the diagnostic criteria of metabolic syndrome . This proportion decreased to 20 % in the metformin group ( P=0.008 ) and to 32 % in the diet group ( NS ) . Conclusions : In our 6-month prospect i ve study , both low-dose metformin and dietary treatment alone ameliorated liver steatosis and metabolic derangements in patients with NAFLD . However , metformin was more effective than dietary treatment alone in normalizing several metabolic parameters in these patients BACKGROUND Long-term statin treatment reduces the frequency of cardiovascular events , but safety and efficacy in patients with abnormal liver tests is unclear . We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation ( GREACE ) study population . METHODS GREACE was a prospect i ve , intention-to-treat study that r and omly assigned by a computer-generated r and omisation list 1600 patients with coronary heart disease ( aged < 75 years , with serum concentrations of LDL cholesterol > 2·6 mmol/L and triglycerides < 4·5 mmol/L ) at the Hippokration University Hospital , Thessaloniki , Greece to receive statin or usual care , which could include statins .  The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests ( defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal ) compared with patients with abnormal liver tests who did not receive a statin . This risk reduction was compared with that for patients treated ( or not ) with statin and normal liver tests . FINDINGS Of 437 patients with moderately abnormal liver tests at baseline , which were possibly associated with non-alcoholic fatty liver disease , 227 who were treated with a statin ( mainly atorvastatin 24 mg per day ) had substantial improvement in liver tests ( p<0·0001 ) whereas 210 not treated with a statin had further increases of liver enzyme concentrations . Cardiovascular events occurred in 22 ( 10 % ) of 227 patients with abnormal liver tests who received statin ( 3·2 events per 100 patient-years ) and 63 ( 30 % ) of 210 patients with abnormal liver tests who did not receive statin ( 10·0 events per 100 patient-years ; 68 % relative risk reduction , p<0·0001 ) . This cardiovascular disease benefit was greater ( p=0·0074 ) than it was in patients with normal liver tests ( 90 [ 14 % ] events in 653 patients receiving a statin [ 4·6 per 100 patient-years ] vs 117 [ 23 % ] in 510 patients not receiving a statin [ 7·6 per 100 patient-years ] ; 39 % relative risk reduction , p<0·0001 ) . Seven ( < 1 % ) of 880 participants  who received a statin discontinued statin treatment because of liver-related adverse effects ( transaminase concentrations more than three-times the upper limit of normal ) . INTERPRETATION Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease . FUNDING None Diet modification is widely used for the treatment of non.alcoholic steatohepatitis ( NASH ) . Caloric restriction was shown to be effective in normalizing bldod lipid profile , increasing insulin sensitivity and subsequent normalization of aminotrasferases blood level . The aim of the study was to compare low-calorie diet ( LCD ) with isocaloric diet ( ICD ) in patients w , ith NASH . 174 NASH patients [ 86 females ( 39,43±1,53 years old ) and 88 males ( 41,7±2,0 ) , BMI 36,8±0,8 kg/m2 ] were r and omly assigned ( as 1:2 ) for LCD ( 1600 - 1700 kcal/day ) or ICD ( 2500 - 2700 kcal/day ) calculated according to patients ' sex , age , resting energy expenditures and daily physical activity . Caloric restriction was achieved by decreasing consumption of carbohydrates and fat in LCD , whereas for ICD the caloric consumption was established according to the recommended daily values for proteins , fat and carbohydrates for ideal BMI for every patient . Blood chemistry and body composition were assessed at baseline and after 1 mo of prescribed diets . Compliance for the diet was also evaluated using previously vali date d question naire . After 1 mo of dietetic interventions total body mass and lean mass significantly decreased in both groups , but in LCD group it was significantly more prominent decrease in compare to ICD group ( 9,3±1,8 vs 6,2±1,7 kg and 6,6±0,4 vs 1,4±0,6 kg , p<0,05 ) , whereas fat mass decreased better in ICD group ( 4,8±0,7 vs 2 , 7±0,8 kg , p<0,05 ) . Mean ALT level was decreased in ICD group ( 77,5±41,7 vs 98,8±45,7 , p<0,01 ) , but not in LCD group ( 81,2±50,6 vs 77,2±31,8 , p = NS ) whereas blood cholesterol , triglycerides , high density lipoprotein woere significantly decreased in both groups . Moreover during the diet intervention in 72 % of patients from LCD group ALT increased . Compliance index was much higher in ICD group , than in LCD group ( 85 % vs 54 % ) . Thus , one month of lCD leads to decrease in ALT activity in majority of NASH patients , higher loss of fat mass , lower loss of lean mass and associated with better compliance in compare to LCD UNLABELLED Nonalcoholic steatohepatitis ( NASH ) is a chronic progressive liver disease that is strongly associated with obesity . Currently , there is no approved therapy for NASH . Weight reduction is typically recommended , but efficacy data are lacking . We performed a r and omized controlled trial to examine the effects of lifestyle intervention using a combination of diet , exercise , and behavior modification , with a goal of 7 % to 10 % weight reduction , on clinical parameters of NASH . The primary outcome measure was the change in NASH histological activity score ( NAS ) after 48 weeks of intervention . Thirty-one overweight or obese individuals ( body mass index [ BMI ] , 25 - 40 kg/m(2 ) ) with biopsy-proven NASH were r and omized in a 2:1 ratio to receive intensive lifestyle intervention ( LS ) or structured education ( control ) . After 48 weeks of intervention , participants assigned to LS  lost an average of 9.3 % of their weight versus 0.2 % in the control group ( P = 0.003 ) . A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group ( 72 % versus 30 % , P = 0.03 ) . NAS improved significantly in the LS group ( from 4.4 to 2.0 ) in comparison with the control group ( from 4.9 to 3.5 ) ( P = 0.05 ) . Percent weight reduction correlated significantly with improvement in NAS ( r = 0.497 , P = 0.007 ) . Participants who achieved the study weight loss goal ( > or=7 % ) , compared with those who lost less than 7 % , had significant improvements in steatosis ( -1.36 versus -0.41 , P < 0.001 ) , lobular inflammation ( -0.82 versus -0.24 , P = 0.03 ) , ballooning injury ( -1.27 versus -0.53 , P = 0.03 ) and NAS ( -3.45 versus -1.18 , P < 0.001 ) . CONCLUSION Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH BACKGROUND & AIMS Non-alcoholic fatty liver disease ( NAFLD ) affects up to 30 % of the population and signifies increased risk of liver fibrosis and cirrhosis , type 2 diabetes , and cardiovascular disease . Therapies are limited . Weight loss is of benefit but is difficult to maintain . We aim ed at examining the effect of the Mediterranean diet ( MD ) , a diet high in monounsaturated fatty acids , on steatosis and insulin sensitivity , using gold st and ard techniques . METHODS Twelve non-diabetic subjects ( 6 Females/6 Males ) with biopsy-proven NAFLD were recruited for a r and omised , cross-over 6-week dietary intervention study . All subjects undertook both the MD and a control diet , a low fat-high carbohydrate diet ( LF/HCD ) , in r and om order with a 6-week wash-out period in- between . Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ( (1)H-MRS ) . RESULTS At baseline , subjects were abdominally obese with elevated fasting concentrations of glucose , insulin , triglycerides , ALT , and GGT . Insulin sensitivity at baseline was low ( M=2.7 ± 1.0 mg/kg/min(-1 ) ) . Mean weight loss was not different between the two diets ( p=0.22 ) . There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD : 39 ± 4 % versus 7 ± 3 % , as measured by (1)H-MRS ( p=0.012 ) . Insulin sensitivity improved with the MD , whereas after the LF/HCD there was no change ( p=0.03 between diets ) . CONCLUSIONS Even without weight loss , MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD , compared to current dietary advice . This diet should be further investigated in subjects with NAFLD
Nonalcoholic fatty liver disease ( NAFLD ) results from excessive fat accumulation in the liver in the absence of excessive alcohol consumption .
Insulin resistance ( IR ) is proposed to be an underlying pathogenic factor in the development and progression of disease .
There are currently no proven pharmacotherapies and weight loss is the only prescribed treatment despite a lack of evidence to support a specific diet or lifestyle therapy .
The aim of this review is to evaluate the efficacy of dietary lifestyle interventions on IR measured by Homeostasis model assessment in patients with NAFLD .