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: 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 Based on uncontrolled observations , we have proposed ursodeoxycholic acid ( UDCA ) as a novel therapeutic approach in primary biliary cirrhosis ( PBC ) . To confirm and extend our original findings , we have design ed a double-blind multicentre r and omized clinical trial . An interim analysis was planned at 6 months , involving all subjects included in the trial , with a final analysis at 2 years . The  UDCA-PBC trial began in June 1987 and will be completed in March 1990 . Seventy patients were r and omized to receive UDCA and 68 a placebo .  The two groups were well matched with respect to age , sex , duration and prevalence of symptoms and histologic severity ( 50 % of the UDCA group had stage III-IV disease vs. 37 % of the placebo group ) . During the first 6 months of follow-up , six patients withdrew from the trial . At 6 months , the proportion of patients with jaundice was significantly lower ( p less than 0.01 ) in UDCA recipients than in the placebo group . There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups . The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy : serum bilirubin , alkaline phosphatase , alanine aminotransferase ( ALAT ) , aspartate aminotransferase ( ASAT ) , gamma-glutamyltranspeptidase activities ( p less than 0.001 ) , cholesterol ( p less than 0.003 ) and IgM levels ( p less than 0.03 ) . The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study . However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC The administration of ursodeoxycholic acid , a hydrophilic bile acid not hepatotoxic to humans , has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage . Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease . In January 1988 , to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease , we started a multicenter , double-blind , placebo-controlled trial in patients with symptomatic disease , that is , with pruritus or serum bilirubin exceeding 2 mg/dl . Forty-four patients were assigned to ursodeoxycholic acid , 500 mg daily ( corresponding to about 8.7 mg/kg body weight in these patients ) , and 44 to a placebo . As planned at the beginning of the study , a preliminary analysis was performed when all patients had been followed for at least 6 months ( 33 patients up to 12 months ) . Pruritus , self-evaluated by the patients , and cholestyramine consumption , as recorded in a diary , decreased significantly ( p < 0.01 ) in both groups . In patients who initially had abnormal levels , serum bilirubin decreased significantly ( p < 0.05 ) in the ursodeoxycholic acid group compared to placebo . After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group : a composite weighted biochemical index taking into account the changes in serum bilirubin , alkaline phosphatase , gamma-GT and AST ( p < 0.001 ) ; serum prealbumin ( p < 0.05 ) ; IgG ( p < 0.01 ) and IgM ( p < 0.01 ) levels . ( ABSTRACT TRUNCATED AT 250 WORDS Background and purpose Nonalcoholic fatty liver disease ( NAFLD ) is one of the causes of a fatty liver , occurring when fat is deposited ( steatosis ) in the liver not due to excessive alcohol use . It is related to insulin resistance and the metabolic syndrome . The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid ( ALA ) and ursodeoxycholic acid ( UDCA ) on NAFLD . Methods Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day ( ALAUDCA ) was investigated in patients over a period of 12 months using a r and omized , placebo (PLA)-controlled study with four parallel groups . Serum concentration of gamma-glutamyl transpeptidase ( GGT ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , albumin and platelets ( PLT ) were measured at the beginning and at the end of the treatment . Moreover , the AST/ALT ratio and the NAFLD fibrosis score were examined . Results A total of 120 patients were r and omly assigned to the four groups . ALA and UDCA were safe and well tolerated in the oral daily administration only . AST , ALT , GGT ( p < 0.001 ) showed a significant difference between ALAUDCA and other three groups . Besides , NAFLD fibrosis score underlined a significant reduction ( p < 0.04 ) in the ALAUDCA group , while AST/ALT ratio presented a moderate decline ( p > 0.05 ) . Conclusion ALAUDCA therapy reduced AST , ALT , GGT values and improved NAFLD fibrosis score and AST/ALT ratio , especially in patients who were on a hypocaloric diet . These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies OBJECTIVE Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to end-stage liver disease . We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease . RESEARCH METHODS AND PROCEDURES A double-blind , placebo-controlled trial . Twenty-seven women with a body mass index of > 30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups ( ursodeoxycholic acid , n = 14 : placebo n = 13 ) . Both groups received a normal diet ( 1,200 kcal/d ) plus 1200 mg/d of ursodeoxycholic acid or placebo .  Hepatic steatosis , was assessed by abdominal ultrasound . Fasting glucose , cholesterol , triglycerides , and aminotransferases levels were determined before and after treatment . RESULTS Body mass index decreases significantly from 34.2 + /- 4.2 kg/m2 and 33.3 + /- 1.6 kg/m2 to 31.8 + /- 4.5 kg/m2 and 30.6 + /- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups , p < 0.001 . The hepatic steatosis index decreased from 2.3 + /- 0.7 to 1.0 + /- 0.6 and 2.2 + /- 0.7 to 1.1 + /- 0.7 in the ursodeoxycholic acid and placebo groups , p<0.003 . Serum AST decreased significantly from 41.2 + /- 5.6 to 34.5 + /- 3.4 in the ursodeoxycholic acid group , p < 0.001 , and from 43.6 + /- 4.2 to 35.3 + /- 2.9 in the placebo group , p < 0.001 . Serum ALT decreased from 62.9 + /- 6.5 to 44.0 + /- 3.5 in the ursodeoxycholic acid group , p < 0.001 , and from 63.5 + /- 4.5 to 44.0 + /- 3.5 in the placebo group . We did not find any differences in all variables studied between groups . CONCLUSIONS The present study shows beneficial effect of weight reduction , producing improvements in biochemical and imaging markers of liver disease BACKGROUND / AIM The aim of this study was to assess the efficacy of ursodeoxycholic acid ( UDCA ) for primary biliary cirrhosis in a r and omized , double-blind placebo-controlled trial . METHODS Consecutive patients ( n=192 ) were r and omized to receive 14 - 16 mg UDCA/kg/day or placebo .  Patients underwent a complete history , physical examination , liver chemistries , immunological determinations and liver biopsy at entry and at the end of the trial , which lasted for at least 2 years . Patients were seen every 3 months and the median follow-up was 3.4 years ( range 0.3 to 6.1 years ) . RESULTS Patients receiving UDCA ( 99 ) or placebo ( 93 ) were comparable with regard to age , sex , biochemical parameters and liver histology . UDCA treatment was associated with decreases in alkaline phosphatase , gammaglutamyl transferase , alanine aminotransferase , and cholesterol levels , effects which were conspicuous after 3 months of treatment and remained similar during the follow-up . During the study 31 patients ( 10 receiving UDCA and 21 placebo ) discontinued the trial because of noncompliance ( n=11 ) , voluntary withdrawal ( n=19 ) or adverse effects ( n=1 ) .  Treatment failure ( death or liver transplantation ) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo . Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo . Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression . By contrast , histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo . CONCLUSIONS Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications , the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis 44 patients with radiolucent gallstones in gallbladders visible on cholecystography were r and omly alloted to three treatment groups : ursodeoxycholic acid ( 600 mg/day ) , ursodeoxycholic acid ( 150 mg/day ) , a placebo . At the end of six months ' treatment , cholecystograms of all the patients were interpreted by radiologists who were not aware of the treatment . Dissolution of gallstones occurred in 8 ( 26 % ) of the 31 patients treated with ursodeoxycholic acid , but not in the placebo group . Ursodeoxycholic acid had no hepatotoxicity , as assessed by st and ard liver-function tests . These results indicate that ursodeoxycholic acid , the 7beta epimer of chenodeoxycholic acid , is effective in the dissolution of cholesterol gallstones A r and omized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis ( PBC ) on serum lipids during ursodeoxycholic acid ( URSO ) and colchicine treatments .  In addition to serum bilirubin and alkaline phosphatase ( AFOS ) , two variables considered to reflect liver function , serum lipoproteins , cholesterol precursors ( squalene , delta 8-cholestenol , lathosterol and desmosterol ) , markers of ch 
    Output:
    
agent
In the subgroup of patients with primary biliary cirrhosis  , ursodeoxycholic acid  reduced total cholesterol ( WMD : − 29.86 mg/dL , 95 % CI : -47.39 , − 12.33 , p = 0.001 ) and LDL-C ( WMD : -37.27 mg/dL , 95 % CI : -54.16 , − 20.38 , p < 0.001 ) concentrations without affecting TG and HDL-C. Conclusion This meta- analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis
***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: 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 Based on uncontrolled observations , we have proposed ursodeoxycholic acid ( UDCA ) as a novel therapeutic approach in primary biliary cirrhosis ( PBC ) . To confirm and extend our original findings , we have design ed a double-blind multicentre r and omized clinical trial . An interim analysis was planned at 6 months , involving all subjects included in the trial , with a final analysis at 2 years . The  UDCA-PBC trial began in June 1987 and will be completed in March 1990 . Seventy patients were r and omized to receive UDCA and 68 a placebo .  The two groups were well matched with respect to age , sex , duration and prevalence of symptoms and histologic severity ( 50 % of the UDCA group had stage III-IV disease vs. 37 % of the placebo group ) . During the first 6 months of follow-up , six patients withdrew from the trial . At 6 months , the proportion of patients with jaundice was significantly lower ( p less than 0.01 ) in UDCA recipients than in the placebo group . There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups . The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy : serum bilirubin , alkaline phosphatase , alanine aminotransferase ( ALAT ) , aspartate aminotransferase ( ASAT ) , gamma-glutamyltranspeptidase activities ( p less than 0.001 ) , cholesterol ( p less than 0.003 ) and IgM levels ( p less than 0.03 ) . The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study . However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC The administration of ursodeoxycholic acid , a hydrophilic bile acid not hepatotoxic to humans , has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage . Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease . In January 1988 , to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease , we started a multicenter , double-blind , placebo-controlled trial in patients with symptomatic disease , that is , with pruritus or serum bilirubin exceeding 2 mg/dl . Forty-four patients were assigned to ursodeoxycholic acid , 500 mg daily ( corresponding to about 8.7 mg/kg body weight in these patients ) , and 44 to a placebo . As planned at the beginning of the study , a preliminary analysis was performed when all patients had been followed for at least 6 months ( 33 patients up to 12 months ) . Pruritus , self-evaluated by the patients , and cholestyramine consumption , as recorded in a diary , decreased significantly ( p < 0.01 ) in both groups . In patients who initially had abnormal levels , serum bilirubin decreased significantly ( p < 0.05 ) in the ursodeoxycholic acid group compared to placebo . After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group : a composite weighted biochemical index taking into account the changes in serum bilirubin , alkaline phosphatase , gamma-GT and AST ( p < 0.001 ) ; serum prealbumin ( p < 0.05 ) ; IgG ( p < 0.01 ) and IgM ( p < 0.01 ) levels . ( ABSTRACT TRUNCATED AT 250 WORDS Background and purpose Nonalcoholic fatty liver disease ( NAFLD ) is one of the causes of a fatty liver , occurring when fat is deposited ( steatosis ) in the liver not due to excessive alcohol use . It is related to insulin resistance and the metabolic syndrome . The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid ( ALA ) and ursodeoxycholic acid ( UDCA ) on NAFLD . Methods Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day ( ALAUDCA ) was investigated in patients over a period of 12 months using a r and omized , placebo (PLA)-controlled study with four parallel groups . Serum concentration of gamma-glutamyl transpeptidase ( GGT ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , albumin and platelets ( PLT ) were measured at the beginning and at the end of the treatment . Moreover , the AST/ALT ratio and the NAFLD fibrosis score were examined . Results A total of 120 patients were r and omly assigned to the four groups . ALA and UDCA were safe and well tolerated in the oral daily administration only . AST , ALT , GGT ( p < 0.001 ) showed a significant difference between ALAUDCA and other three groups . Besides , NAFLD fibrosis score underlined a significant reduction ( p < 0.04 ) in the ALAUDCA group , while AST/ALT ratio presented a moderate decline ( p > 0.05 ) . Conclusion ALAUDCA therapy reduced AST , ALT , GGT values and improved NAFLD fibrosis score and AST/ALT ratio , especially in patients who were on a hypocaloric diet . These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies OBJECTIVE Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to end-stage liver disease . We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease . RESEARCH METHODS AND PROCEDURES A double-blind , placebo-controlled trial . Twenty-seven women with a body mass index of > 30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups ( ursodeoxycholic acid , n = 14 : placebo n = 13 ) . Both groups received a normal diet ( 1,200 kcal/d ) plus 1200 mg/d of ursodeoxycholic acid or placebo .  Hepatic steatosis , was assessed by abdominal ultrasound . Fasting glucose , cholesterol , triglycerides , and aminotransferases levels were determined before and after treatment . RESULTS Body mass index decreases significantly from 34.2 + /- 4.2 kg/m2 and 33.3 + /- 1.6 kg/m2 to 31.8 + /- 4.5 kg/m2 and 30.6 + /- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups , p < 0.001 . The hepatic steatosis index decreased from 2.3 + /- 0.7 to 1.0 + /- 0.6 and 2.2 + /- 0.7 to 1.1 + /- 0.7 in the ursodeoxycholic acid and placebo groups , p<0.003 . Serum AST decreased significantly from 41.2 + /- 5.6 to 34.5 + /- 3.4 in the ursodeoxycholic acid group , p < 0.001 , and from 43.6 + /- 4.2 to 35.3 + /- 2.9 in the placebo group , p < 0.001 . Serum ALT decreased from 62.9 + /- 6.5 to 44.0 + /- 3.5 in the ursodeoxycholic acid group , p < 0.001 , and from 63.5 + /- 4.5 to 44.0 + /- 3.5 in the placebo group . We did not find any differences in all variables studied between groups . CONCLUSIONS The present study shows beneficial effect of weight reduction , producing improvements in biochemical and imaging markers of liver disease BACKGROUND / AIM The aim of this study was to assess the efficacy of ursodeoxycholic acid ( UDCA ) for primary biliary cirrhosis in a r and omized , double-blind placebo-controlled trial . METHODS Consecutive patients ( n=192 ) were r and omized to receive 14 - 16 mg UDCA/kg/day or placebo .  Patients underwent a complete history , physical examination , liver chemistries , immunological determinations and liver biopsy at entry and at the end of the trial , which lasted for at least 2 years . Patients were seen every 3 months and the median follow-up was 3.4 years ( range 0.3 to 6.1 years ) . RESULTS Patients receiving UDCA ( 99 ) or placebo ( 93 ) were comparable with regard to age , sex , biochemical parameters and liver histology . UDCA treatment was associated with decreases in alkaline phosphatase , gammaglutamyl transferase , alanine aminotransferase , and cholesterol levels , effects which were conspicuous after 3 months of treatment and remained similar during the follow-up . During the study 31 patients ( 10 receiving UDCA and 21 placebo ) discontinued the trial because of noncompliance ( n=11 ) , voluntary withdrawal ( n=19 ) or adverse effects ( n=1 ) .  Treatment failure ( death or liver transplantation ) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo . Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo . Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression . By contrast , histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo . CONCLUSIONS Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications , the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis 44 patients with radiolucent gallstones in gallbladders visible on cholecystography were r and omly alloted to three treatment groups : ursodeoxycholic acid ( 600 mg/day ) , ursodeoxycholic acid ( 150 mg/day ) , a placebo . At the end of six months ' treatment , cholecystograms of all the patients were interpreted by radiologists who were not aware of the treatment . Dissolution of gallstones occurred in 8 ( 26 % ) of the 31 patients treated with ursodeoxycholic acid , but not in the placebo group . Ursodeoxycholic acid had no hepatotoxicity , as assessed by st and ard liver-function tests . These results indicate that ursodeoxycholic acid , the 7beta epimer of chenodeoxycholic acid , is effective in the dissolution of cholesterol gallstones A r and omized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis ( PBC ) on serum lipids during ursodeoxycholic acid ( URSO ) and colchicine treatments .  In addition to serum bilirubin and alkaline phosphatase ( AFOS ) , two variables considered to reflect liver function , serum lipoproteins , cholesterol precursors ( squalene , delta 8-cholestenol , lathosterol and desmosterol ) , markers of ch 
    Output:
    