human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a prospect i ve , r and omized , double-blind therapeutic trial , 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d . orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate ( Ietepar ) ( 96 patients ) or with undistinguishable placebo capsules ( 95 patients ) . The verum treatment effectively reduced by 25 % hepatic steatosis ( p < 0.01 ) and by 6 % hepatomegaly ( p < 0.05 ) , while placebo did not significantly reduce the disorders . Verum was also more effective than placebo on discomfort in abdominal upper right quadrant . The global efficacy of treatment was rated by the doctor " very good " or " good " in 48 % of verum treated patients and only in 17 % after placcbo ( P of difference = 9 x 10(-6 ) ) . 52 % of patients self-rated efficacy as " very good " or " good " after verum and only 34 % after placebo ( P of difference = 0.017 ) . The verum treatment provoked a significant reduction of the increased liver transaminases ( ALT , AST and gamma-GT ) while placebo was ineffective . Adverse events were recorded in 10 % of verum-treated patients and in 7 % under placebo ( no significant difference ) . In both groups the adverse events were mild and transient , did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders . In conclusion , the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis , a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective Nonalcoholic steatohepatitis ( NASH ) is increasing in prevalence and is related to underlying insulin resistance . The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH . This was a 12-month prospect i ve , r and omized , placebo-controlled trial comparing diet and exercise alone to diet , exercise and metformin in nondiabetic patients with insulin resistance and NASH . Patients were r and omized to either group A or B. Group A received placebo , dietary counseling , recommendations for weight loss and exercise four times per week . Group B received long-acting metformin 500 mg daily ( titrated to 1000 mg daily ) plus dietary counseling , recommendations for weight loss and exercise four times per week . Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data . Twenty-three subjects were screened and 19 were r and omized to either group A ( n = 10 ) or group B ( n = 9 ) . Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study . Body mass index improved in both groups decreasing by 1.7 kg/m2 in group A and 0.9 kg/m 2 in group B ( not significant , control versus treatment ) . Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B ( not significant , control versus treatment ) . No significant difference in histopathology was seen between groups on follow-up liver biopsy . Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH . Decrease in BMI through diet and exercise significantly improved HOMA-IR scores , serum aminotransferases and liver histology Background Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common reasons of enzyme increase in liver . In About 10 percent of patients with NAFLD , the disease progresses toward Non Alcoholic Steatohepatitis ( NASH ) and about one third of them may progress toward cirrhosis , liver dysfunction , and even hepatocellular carcinoma . Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease , the aim of this study was to assess the effects of metformin , pioglitazone , and silymarin on treatment of NAFLD . Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital , Qazvin , Iran , were assigned r and omly into three groups ( n = 22 ) . First group was treated by pioglitazone 15 mg/d , second group by metformin 500 mg/d , and third group by silymarin 140 mg/d . All patients underwent clinical and biochemical evaluations including weight , fasting blood sugar ( FBS ) , lipid profiles , body mass index ( BMI ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and serum insulin levels in pre- and post-intervention after eight-week follow up . Results Before the treatment there was no significant difference between three groups with respect to average age , BMI and gender , FBS , lipid profile , AST , ALT , serum insulin level , and Homeostasis Model Assessment ( HOMA ) index for insulin resistance . After the intervention , a significant reduction was observed in average amount of FBS , lipid profile , ALT , AST , serum insulin level and HOMA index in three groups ( P < 0.01 ) . The most reduction in average FBS , TG , serum insulin level , and HOMA index was observed in pioglitazone group , the most reduction in average amount of cholesterol was seen in metformin group , and the most decrease in average amount of AST and ALT occurred in silymarin group . Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD . Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis ( NASH ) . Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota . Aims To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides ( Fos ) in the treatment of NASH . Methods A total of 66 patients were r and omly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification ( i.e. , diet and exercise ) versus lifestyle modification alone . The following variables were assessed at −4 ( beginning of the dietary lead-in period ) , 0 ( r and omization ) , 6 , 12 , 18 , and 24 weeks : aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , bilirubin , albumin , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides , fasting plasma glucose , insulin , C-peptide , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and serum endotoxins . Liver biopsies were performed at entry and repeated after 24 weeks of treatment . Results At the end of study period , we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL ( P < 0.05 ) , LDL cholesterol −0.84 versus −0.18 mmol/L ( P < 0.001 ) , CRP −2.9 versus −0.7 mg/L ( P < 0.05 ) , TNF-α −0.45 versus −0.12 ng/mL ( P < 0.001 ) , HOMA-IR −1.1 versus −0.6 ( P < 0.001 ) , serum endotoxin −45.2 versus −30.6 pg/mL ( P < 0.001 ) , steatosis ( P < 0.05 ) , and the NASH activity index ( P < 0.05 ) . Conclusions Bifidobacterium longum with Fos and lifestyle modification , when compared to lifestyle modification alone , significantly reduces TNF-α , CRP , serum AST levels , HOMA-IR , serum endotoxin , steatosis , and the NASH activity index UNLABELLED In uncontrolled clinical studies , ursodeoxycholic acid ( UDCA ) had a beneficial effect on  nonalcoholic steatohepatitis ( NASH ) .  However , a large controlled trial using UDCA ( 13 - 15 mg/kg/day ) was unable to confirm these results . Accordingly , a r and omized , placebo-controlled study was initiated with a high dose of UDCA ( 23 - 28 mg/kg/day ) . The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score ( NAS ) . With the modified Brunt score , 185 patients with histologically proven NASH were r and omized [ intention to treat ( ITT ) ] , and 147 were treated per protocol ( PP ) . With the NAS , 137 patients were confirmed to have NASH , 48 had borderline NASH , and 1 did not have NASH . The treatment time was 18 months . At entry , the treatment groups were comparable . A second biopsy sample was obtained from 139 of 185 patients ( NAS : 107/137 ) . The primary criterion for evaluation was a change in the liver histology ; the secondary criteria were single histological variables and liver biochemistry . Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score ( P = 0.881 ) or NAS ( P = 0.355 ) . Only lobular inflammation improved significantly ( P for the modified Brunt score = 0.011 , P for NAS = 0.005 ) . In subgroup analyses , significant improvements in lobular inflammation were also observed in males , younger patients up to 50 years of age , slightly overweight patients , and patients with hypertension and an increased histology score . The fibrosis score did not change ( P for ITT = 0.133 , P for PP = 0.140 ) . With the exception of gamma-glutamyl transferase , UDCA did not improve laboratory data . CONCLUSION High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo BACKGROUND / AIMS Non-Alcoholic Steatohepatitis ( NASH ) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus ( T2DM ) . Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH , but also leads to weight gain . To underst and the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat ( WBF ) and total body water ( TBW ) .  METHODS Twenty-one patients received pioglitazone and 14 placebo in a double-blind , r and omized fashion for a period of 6 months . WBF and TBW were measured before and after treatment using DXA , a water dilution technique and bioimpedance . RESULTS Pioglitazone increased body weight ( from 93.6+/-4.2 to 96.1+/-4.5 kg , p<0.003 ) and WBF measured with DXA ( from 32.9+/-2.1 to 35.4+/-2.5 kg , p<0.002 ) while no changes were seen with placebo .  Total body water was not altered significantly either after pioglitazone ( from 45.4+/-2.3 to 45.6+/-2.7 l , p = NS ) or placebo . Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments . CONCLUSIONS Six months of pioglitazone  treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention BACKGROUND / AIMS Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis , antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis . Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease . METHODS This was an open-labeled , prospect i ve , r and omized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase , despite a three-month reducing diet . Patients consuming alcohol ( more than 20 g/day ) were excluded . The patients were r and omly prescribed either oral vitamin E ( 600 IU/day ) plus vitamin C ( 500 mg/day ) or ursodeoxycholic acid ( 10 mg/kg/day ) . Patients were r and omized as two groups to receive vitamin E plus vitamin C combination ( 28 patients ,  
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In a prospect i ve , r and omized , double-blind therapeutic trial , 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d . orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate ( Ietepar ) ( 96 patients ) or with undistinguishable placebo capsules ( 95 patients ) . The verum treatment effectively reduced by 25 % hepatic steatosis ( p < 0.01 ) and by 6 % hepatomegaly ( p < 0.05 ) , while placebo did not significantly reduce the disorders . Verum was also more effective than placebo on discomfort in abdominal upper right quadrant . The global efficacy of treatment was rated by the doctor " very good " or " good " in 48 % of verum treated patients and only in 17 % after placcbo ( P of difference = 9 x 10(-6 ) ) . 52 % of patients self-rated efficacy as " very good " or " good " after verum and only 34 % after placebo ( P of difference = 0.017 ) . The verum treatment provoked a significant reduction of the increased liver transaminases ( ALT , AST and gamma-GT ) while placebo was ineffective . Adverse events were recorded in 10 % of verum-treated patients and in 7 % under placebo ( no significant difference ) . In both groups the adverse events were mild and transient , did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders . In conclusion , the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis , a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective Nonalcoholic steatohepatitis ( NASH ) is increasing in prevalence and is related to underlying insulin resistance . The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH . This was a 12-month prospect i ve , r and omized , placebo-controlled trial comparing diet and exercise alone to diet , exercise and metformin in nondiabetic patients with insulin resistance and NASH . Patients were r and omized to either group A or B. Group A received placebo , dietary counseling , recommendations for weight loss and exercise four times per week . Group B received long-acting metformin 500 mg daily ( titrated to 1000 mg daily ) plus dietary counseling , recommendations for weight loss and exercise four times per week . Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data . Twenty-three subjects were screened and 19 were r and omized to either group A ( n = 10 ) or group B ( n = 9 ) . Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study . Body mass index improved in both groups decreasing by 1.7 kg/m2 in group A and 0.9 kg/m 2 in group B ( not significant , control versus treatment ) . Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B ( not significant , control versus treatment ) . No significant difference in histopathology was seen between groups on follow-up liver biopsy . Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH . Decrease in BMI through diet and exercise significantly improved HOMA-IR scores , serum aminotransferases and liver histology Background Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common reasons of enzyme increase in liver . In About 10 percent of patients with NAFLD , the disease progresses toward Non Alcoholic Steatohepatitis ( NASH ) and about one third of them may progress toward cirrhosis , liver dysfunction , and even hepatocellular carcinoma . Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease , the aim of this study was to assess the effects of metformin , pioglitazone , and silymarin on treatment of NAFLD . Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital , Qazvin , Iran , were assigned r and omly into three groups ( n = 22 ) . First group was treated by pioglitazone 15 mg/d , second group by metformin 500 mg/d , and third group by silymarin 140 mg/d . All patients underwent clinical and biochemical evaluations including weight , fasting blood sugar ( FBS ) , lipid profiles , body mass index ( BMI ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and serum insulin levels in pre- and post-intervention after eight-week follow up . Results Before the treatment there was no significant difference between three groups with respect to average age , BMI and gender , FBS , lipid profile , AST , ALT , serum insulin level , and Homeostasis Model Assessment ( HOMA ) index for insulin resistance . After the intervention , a significant reduction was observed in average amount of FBS , lipid profile , ALT , AST , serum insulin level and HOMA index in three groups ( P < 0.01 ) . The most reduction in average FBS , TG , serum insulin level , and HOMA index was observed in pioglitazone group , the most reduction in average amount of cholesterol was seen in metformin group , and the most decrease in average amount of AST and ALT occurred in silymarin group . Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD . Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis ( NASH ) . Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota . Aims To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides ( Fos ) in the treatment of NASH . Methods A total of 66 patients were r and omly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification ( i.e. , diet and exercise ) versus lifestyle modification alone . The following variables were assessed at −4 ( beginning of the dietary lead-in period ) , 0 ( r and omization ) , 6 , 12 , 18 , and 24 weeks : aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , bilirubin , albumin , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides , fasting plasma glucose , insulin , C-peptide , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and serum endotoxins . Liver biopsies were performed at entry and repeated after 24 weeks of treatment . Results At the end of study period , we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL ( P < 0.05 ) , LDL cholesterol −0.84 versus −0.18 mmol/L ( P < 0.001 ) , CRP −2.9 versus −0.7 mg/L ( P < 0.05 ) , TNF-α −0.45 versus −0.12 ng/mL ( P < 0.001 ) , HOMA-IR −1.1 versus −0.6 ( P < 0.001 ) , serum endotoxin −45.2 versus −30.6 pg/mL ( P < 0.001 ) , steatosis ( P < 0.05 ) , and the NASH activity index ( P < 0.05 ) . Conclusions Bifidobacterium longum with Fos and lifestyle modification , when compared to lifestyle modification alone , significantly reduces TNF-α , CRP , serum AST levels , HOMA-IR , serum endotoxin , steatosis , and the NASH activity index UNLABELLED In uncontrolled clinical studies , ursodeoxycholic acid ( UDCA ) had a beneficial effect on  nonalcoholic steatohepatitis ( NASH ) .  However , a large controlled trial using UDCA ( 13 - 15 mg/kg/day ) was unable to confirm these results . Accordingly , a r and omized , placebo-controlled study was initiated with a high dose of UDCA ( 23 - 28 mg/kg/day ) . The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score ( NAS ) . With the modified Brunt score , 185 patients with histologically proven NASH were r and omized [ intention to treat ( ITT ) ] , and 147 were treated per protocol ( PP ) . With the NAS , 137 patients were confirmed to have NASH , 48 had borderline NASH , and 1 did not have NASH . The treatment time was 18 months . At entry , the treatment groups were comparable . A second biopsy sample was obtained from 139 of 185 patients ( NAS : 107/137 ) . The primary criterion for evaluation was a change in the liver histology ; the secondary criteria were single histological variables and liver biochemistry . Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score ( P = 0.881 ) or NAS ( P = 0.355 ) . Only lobular inflammation improved significantly ( P for the modified Brunt score = 0.011 , P for NAS = 0.005 ) . In subgroup analyses , significant improvements in lobular inflammation were also observed in males , younger patients up to 50 years of age , slightly overweight patients , and patients with hypertension and an increased histology score . The fibrosis score did not change ( P for ITT = 0.133 , P for PP = 0.140 ) . With the exception of gamma-glutamyl transferase , UDCA did not improve laboratory data . CONCLUSION High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo BACKGROUND / AIMS Non-Alcoholic Steatohepatitis ( NASH ) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus ( T2DM ) . Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH , but also leads to weight gain . To underst and the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat ( WBF ) and total body water ( TBW ) .  METHODS Twenty-one patients received pioglitazone and 14 placebo in a double-blind , r and omized fashion for a period of 6 months . WBF and TBW were measured before and after treatment using DXA , a water dilution technique and bioimpedance . RESULTS Pioglitazone increased body weight ( from 93.6+/-4.2 to 96.1+/-4.5 kg , p<0.003 ) and WBF measured with DXA ( from 32.9+/-2.1 to 35.4+/-2.5 kg , p<0.002 ) while no changes were seen with placebo .  Total body water was not altered significantly either after pioglitazone ( from 45.4+/-2.3 to 45.6+/-2.7 l , p = NS ) or placebo . Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments . CONCLUSIONS Six months of pioglitazone  treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention BACKGROUND / AIMS Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis , antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis . Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease . METHODS This was an open-labeled , prospect i ve , r and omized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase , despite a three-month reducing diet . Patients consuming alcohol ( more than 20 g/day ) were excluded . The patients were r and omly prescribed either oral vitamin E ( 600 IU/day ) plus vitamin C ( 500 mg/day ) or ursodeoxycholic acid ( 10 mg/kg/day ) . Patients were r and omized as two groups to receive vitamin E plus vitamin C combination ( 28 patients ,  
    Output:
    