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: 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 This prospect i ve study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet .  Fourty-one morbidly obese , non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg . Fatty change improved ( p less than 0.001 ) , but 24 % of the patients developed slight portal inflammation ( p = 0.039 ) or slight portal fibrosis ( p = 0.063 ) . Patients developing portal fibrosis had a higher degree of fatty change at entry ( p = 0.029 ) , a more pronounced reduction of fatty change ( p = 0.014 ) and a faster weight loss ( p = 0.026 ) . Liver biochemistry , which was of no individual diagnostic value , improved . It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions OBJECTIVE Non-alcoholic fatty liver disease ( NAFLD ) is an increasingly recognized health problem . Various treatment strategies such as thiazolidinediones , metformin , lipid-lowering agents and antioxidants have been evaluated . So far , no single intervention has convincingly improved liver histology . Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature . The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD . PATIENTS AND METHODS A sample of 36 patients was enrolled . The diagnosis of NAFLD was confirmed by percutaneous liver biopsy . All patients were r and omized to one of the following intervention groups : group I : treated with 2 tablets per day of silymarin plus vitamin E ( Eurosil 85 ® , MEDAS SL ) and a lifestyle modification program consisting of hypocaloric diet ( 1520 kcal , 52 % of carbohydrates , 25 % of lipids and 23 % of proteins ) and exercise for 3 months and group II ( only with the hypocaloric diet )  . Anthropometric variables as waist circumference , weight , body mass index ( BMI ) were measured . Biochemical parameters : Glucose , triglycerides , AST , ALT , GGt levels and insulin resistance ( HOMA-IR ) were determined under fasting conditions . Non-invasive NAFLD-index were applied before and after the treatments : Fatty liver index ( FLI ) , liver accumulation product ( LAP ) and NAFLD-Fibrosis score ( FS ) . RESULTS The mean age was 47.4 ± 11.2 years old ( range 18 - 67 ) ; 22 men and 14 women . In group I , 11 patients ( 61 % ) have a NAS-score > 5 and 10 ( 55.5 % ) in the group II ( NS ) . Anthropometric parameters decreased after treatment in both groups . Patients in both groups showed a decrease in GGt levels after treatment ( group I : 68 IU/L vs. 46.2 ± 27 IU/L ; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L ; p < 0.05 ) . Only in group II we observed a significant decrease in AST and ALT levels . In both groups , we observed a decrease in : FLI index ( group I : 86.2 ± 19 vs. 76.9 + 20 ; p < 0.05 and in group II : 85.2 ± 18 vs. 77.5 ± 23 ; p < 0.05 ) , and NAFLD-FS index ( group I : -1.6 ± 1.8 vs. -2.1 ± 1.5 ; p < 0.05 and in group II -1 ± 1.9 vs. -1.5 ± 2.1 ; p < 0.05 ) . Patients in group I who did not get a 5 % loss of weight also displayed decreased GGt levels , and in the FLI and NAFLD-FS indexes ; whereas patients in group II without decrease of 5 % by weight showed no improvement in any of the analyzed parameters . CONCLUSIONS Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test , and non-invasive NAFLD index . Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs Silymarin , used by 30 to 40 % of liver disease patients , is composed of six major flavonolignans , each of which may contribute to silymarin 's hepatoprotective properties . Previous studies have only described the pharmacokinetics for two flavonolignans , silybin A and silybin B , in healthy volunteers . The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients . Healthy volunteers and three patient cohorts were administered a single , 600-mg p.o . dose of milk thistle extract , and 14 blood sample s were obtained over 24 h. Silybin A and B accounted for 43 % of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38 % in liver disease cohorts as a result of accumulation of silychristin ( 20–36 % ) . Area under the curve ( AUC0–24h ) for the sum of total silymarin flavonolignans was 2.4- , 3.3- , and 4.7-fold higher for hepatitis C virus ( HCV ) noncirrhosis , nonalcoholic fatty liver disease ( p ≤ 0.03 ) , and HCV cirrhosis cohorts ( p ≤ 0.03 ) , respectively , compared with healthy volunteers ( AUC0–24h = 2021 ng · h/ml ) . Caspase-3/7 activity correlated with the AUC0–24h for the sum of all silymarin conjugates among all subjects ( R2 = 0.52 ) and was 5-fold higher in the HCV cirrhosis cohort ( p ≤ 0.005 versus healthy ) . No correlation was observed with other measures of disease activity , including plasma alanine aminotransferase , interleukin 6 , and 8-isoprostane F2α , a measure of oxidative stress . These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease . Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans BACKGROUND AND AIM Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury ( ATLI ) . However , their biological mechanisms have not yet been clearly demonstrated . This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China . METHODS A r and omized controlled trial was performed in Jiangsu , China . Tuberculosis patients were r and omly allocated to the experimental group ( anti-tuberculosis therapy plus S. marianum capsule ) or the control group ( anti-tuberculosis therapy plus vitamin C tablet ) . The primary outcomes were the occurrence of probable and possible ATLI , the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase . RESULTS The final analysis comprised 183 cases in the experiment group and 187 cases in the control group . The risk of developing probable ATLI was not significantly different between the two groups . During the follow-up period , 43.72 % of cases in the experiment group and 35.83 % of cases in the control group were determined to have possible ATLI ( relative risk = 1.23 , 95 % confidence interval : 0.94 - 1.54 ) . When using a more strict definition of possible ATLI , the adjusted relative risk ( 95 % confidence interval ) was 1.76 ( 1.14 - 2.56 ) . The risks of adverse drug reactions , prolonged treatment length , taking second-line tuberculosis drugs , and the clearance of tuberculosis bacteria were similar between the two groups . CONCLUSIONS No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes . Worse , we even found a potential risk of liver damage caused by the hepatoprotectant Liver steatosis can evolve to steatohepatitis ( NASH ) through a series of biochemical steps related to oxidative stress in hepatocytes . Antioxidants , such as silybin , have been proposed as a treatment of patients with nonalcoholic fatty liver disease ( NAFLD ) and NASH . In this study , we evaluated , in patients with histologically documented NASH , the oxidant/antioxidant status and lipid “ fingerprint ” in the serum of NASH patients , both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil ( RA ) . The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease ( NAS scores 4.67 ± 2.5 ) and a second group corresponding to borderline NASH ( NAS scores = 3.8 ± 1.5 ) . The chronic treatment with RA  changed the NAS score in both groups that reached the statistical significance only in group 2 , in which there was also a significant decrease of serum lipid peroxidation . The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol , lysoPC , SM , and PC only in group 2 of patients after treatment with RA . Conclusion . These data suggest that lipidomic and /or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment Background Spirulina platensis , a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities . It had been found to activate macrophages , NK cells , T cells , B cells , and to stimulate the production of Interferon gamma ( IFN-γ ) and other cytokines . Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells . We aim ed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation . Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been r and omized to either Spirulina or Silymarin treated groups for a period of six months treatment . The two groups were followed up and blindly compared for early ( after 3 months ) and end of 6 months treatment virological response . The effects of both treatments on each of alanine aminotransferase ( ALT ) , Chronic Liver Disease Question naire scores ( CLDQ ) , Arizona Sexual Experience Scale scores ( ASEX ) and the 
    Output:
    
agent
There was no significant change in the γGT levels .
Significant differences were not found .
CONCLUSION Silymarin minimally reduced , but without clinical relevance , the serum levels of ALT and AST .
***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: 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 This prospect i ve study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet .  Fourty-one morbidly obese , non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg . Fatty change improved ( p less than 0.001 ) , but 24 % of the patients developed slight portal inflammation ( p = 0.039 ) or slight portal fibrosis ( p = 0.063 ) . Patients developing portal fibrosis had a higher degree of fatty change at entry ( p = 0.029 ) , a more pronounced reduction of fatty change ( p = 0.014 ) and a faster weight loss ( p = 0.026 ) . Liver biochemistry , which was of no individual diagnostic value , improved . It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions OBJECTIVE Non-alcoholic fatty liver disease ( NAFLD ) is an increasingly recognized health problem . Various treatment strategies such as thiazolidinediones , metformin , lipid-lowering agents and antioxidants have been evaluated . So far , no single intervention has convincingly improved liver histology . Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature . The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD . PATIENTS AND METHODS A sample of 36 patients was enrolled . The diagnosis of NAFLD was confirmed by percutaneous liver biopsy . All patients were r and omized to one of the following intervention groups : group I : treated with 2 tablets per day of silymarin plus vitamin E ( Eurosil 85 ® , MEDAS SL ) and a lifestyle modification program consisting of hypocaloric diet ( 1520 kcal , 52 % of carbohydrates , 25 % of lipids and 23 % of proteins ) and exercise for 3 months and group II ( only with the hypocaloric diet )  . Anthropometric variables as waist circumference , weight , body mass index ( BMI ) were measured . Biochemical parameters : Glucose , triglycerides , AST , ALT , GGt levels and insulin resistance ( HOMA-IR ) were determined under fasting conditions . Non-invasive NAFLD-index were applied before and after the treatments : Fatty liver index ( FLI ) , liver accumulation product ( LAP ) and NAFLD-Fibrosis score ( FS ) . RESULTS The mean age was 47.4 ± 11.2 years old ( range 18 - 67 ) ; 22 men and 14 women . In group I , 11 patients ( 61 % ) have a NAS-score > 5 and 10 ( 55.5 % ) in the group II ( NS ) . Anthropometric parameters decreased after treatment in both groups . Patients in both groups showed a decrease in GGt levels after treatment ( group I : 68 IU/L vs. 46.2 ± 27 IU/L ; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L ; p < 0.05 ) . Only in group II we observed a significant decrease in AST and ALT levels . In both groups , we observed a decrease in : FLI index ( group I : 86.2 ± 19 vs. 76.9 + 20 ; p < 0.05 and in group II : 85.2 ± 18 vs. 77.5 ± 23 ; p < 0.05 ) , and NAFLD-FS index ( group I : -1.6 ± 1.8 vs. -2.1 ± 1.5 ; p < 0.05 and in group II -1 ± 1.9 vs. -1.5 ± 2.1 ; p < 0.05 ) . Patients in group I who did not get a 5 % loss of weight also displayed decreased GGt levels , and in the FLI and NAFLD-FS indexes ; whereas patients in group II without decrease of 5 % by weight showed no improvement in any of the analyzed parameters . CONCLUSIONS Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test , and non-invasive NAFLD index . Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs Silymarin , used by 30 to 40 % of liver disease patients , is composed of six major flavonolignans , each of which may contribute to silymarin 's hepatoprotective properties . Previous studies have only described the pharmacokinetics for two flavonolignans , silybin A and silybin B , in healthy volunteers . The aim of this study was to determine the pharmacokinetics of the major silymarin flavonolignans in liver disease patients . Healthy volunteers and three patient cohorts were administered a single , 600-mg p.o . dose of milk thistle extract , and 14 blood sample s were obtained over 24 h. Silybin A and B accounted for 43 % of the exposure to the sum of total silymarin flavonolignans in healthy volunteers and only 31 to 38 % in liver disease cohorts as a result of accumulation of silychristin ( 20–36 % ) . Area under the curve ( AUC0–24h ) for the sum of total silymarin flavonolignans was 2.4- , 3.3- , and 4.7-fold higher for hepatitis C virus ( HCV ) noncirrhosis , nonalcoholic fatty liver disease ( p ≤ 0.03 ) , and HCV cirrhosis cohorts ( p ≤ 0.03 ) , respectively , compared with healthy volunteers ( AUC0–24h = 2021 ng · h/ml ) . Caspase-3/7 activity correlated with the AUC0–24h for the sum of all silymarin conjugates among all subjects ( R2 = 0.52 ) and was 5-fold higher in the HCV cirrhosis cohort ( p ≤ 0.005 versus healthy ) . No correlation was observed with other measures of disease activity , including plasma alanine aminotransferase , interleukin 6 , and 8-isoprostane F2α , a measure of oxidative stress . These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease . Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans BACKGROUND AND AIM Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury ( ATLI ) . However , their biological mechanisms have not yet been clearly demonstrated . This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China . METHODS A r and omized controlled trial was performed in Jiangsu , China . Tuberculosis patients were r and omly allocated to the experimental group ( anti-tuberculosis therapy plus S. marianum capsule ) or the control group ( anti-tuberculosis therapy plus vitamin C tablet ) . The primary outcomes were the occurrence of probable and possible ATLI , the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase . RESULTS The final analysis comprised 183 cases in the experiment group and 187 cases in the control group . The risk of developing probable ATLI was not significantly different between the two groups . During the follow-up period , 43.72 % of cases in the experiment group and 35.83 % of cases in the control group were determined to have possible ATLI ( relative risk = 1.23 , 95 % confidence interval : 0.94 - 1.54 ) . When using a more strict definition of possible ATLI , the adjusted relative risk ( 95 % confidence interval ) was 1.76 ( 1.14 - 2.56 ) . The risks of adverse drug reactions , prolonged treatment length , taking second-line tuberculosis drugs , and the clearance of tuberculosis bacteria were similar between the two groups . CONCLUSIONS No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes . Worse , we even found a potential risk of liver damage caused by the hepatoprotectant Liver steatosis can evolve to steatohepatitis ( NASH ) through a series of biochemical steps related to oxidative stress in hepatocytes . Antioxidants , such as silybin , have been proposed as a treatment of patients with nonalcoholic fatty liver disease ( NAFLD ) and NASH . In this study , we evaluated , in patients with histologically documented NASH , the oxidant/antioxidant status and lipid “ fingerprint ” in the serum of NASH patients , both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil ( RA ) . The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease ( NAS scores 4.67 ± 2.5 ) and a second group corresponding to borderline NASH ( NAS scores = 3.8 ± 1.5 ) . The chronic treatment with RA  changed the NAS score in both groups that reached the statistical significance only in group 2 , in which there was also a significant decrease of serum lipid peroxidation . The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol , lysoPC , SM , and PC only in group 2 of patients after treatment with RA . Conclusion . These data suggest that lipidomic and /or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment Background Spirulina platensis , a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities . It had been found to activate macrophages , NK cells , T cells , B cells , and to stimulate the production of Interferon gamma ( IFN-γ ) and other cytokines . Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells . We aim ed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation . Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been r and omized to either Spirulina or Silymarin treated groups for a period of six months treatment . The two groups were followed up and blindly compared for early ( after 3 months ) and end of 6 months treatment virological response . The effects of both treatments on each of alanine aminotransferase ( ALT ) , Chronic Liver Disease Question naire scores ( CLDQ ) , Arizona Sexual Experience Scale scores ( ASEX ) and the 
    Output:
    