Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. [Clinical study on effect of matrine injection to protect the liver function for patients with primary hepatic carcinoma after trans-artery chemo-embolization (TAE)]. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses. A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. Effects of Concomitant Administration of a Dipeptidyl Peptidase-4 Inhibitor in Japanese Patients with Type 2 Diabetes Showing Relatively Good Glycemic Control Under Treatment with a Sodium Glucose Co-Transporter 2 Inhibitor. Effects of silybum marianum on patients with chronic hepatitis C Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group. The Pharmacokinetics of Silymarin Is Altered in Patients with Hepatitis C Virus and Nonalcoholic Fatty Liver Disease and Correlates with Plasma Caspase-3/7 Activity Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial) Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease.
BACKGROUND No pharmacologic agents have been approved for the treatment of non-alcoholic steatohepatitis ( NASH ) that is common in our region . The present study was design ed to evaluate the efficacy of silymarin , a known herbal drug , in the treatment of NASH . METHODS This clinical -trial study was conducted on 64 patients with NASH who were r and omly divided as case group ( 33 ) and control group ( 31 ) . Abdominal sonography and persistent elevation in levels of aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) more than 1.2 times of the upper normal limit within the last six months were selected as inclusion criteria . They were advised to take low-fat , low carbohydrate diet , do regular sport activity to lose weight up to 4 Kg . Patients in the case group received 210 mg/day silymarin orally for 8 weeks and those in the control group received placebo . After 8 weeks , the patients were reevaluated and their AST and ALT levels were measured . This study was registered in the Iranian Registry of Clinical Trial ( www.i rct .ir ) with registration number ID : I RCT 201202159018N1 . RESULTS The mean age of patients in case and control groups was 43.6±8.3 and 39.4±10.5 years , respectively . Their BMI were 27.4±1.7 and 27.5±1.9 , respectively . Their weights were also 79±9.2 and 76.9±9.5 kg , respectively . Serum concentrations of ALT were 91.3±21.3 and 38.4±11.8 in case group before and after the study respectively , whiles the figures were 84.6±23.3 and 52.3±29 in the control group ( P=0.026 ) . The same trend was seen for AST ( P=0.038 ) . CONCLUSION The patients who had taken silymarin experienced more notable fall in hepatic enzymes PURPOSE Milk thistle or its purified extract , silymarin ( Silybum marianum ) , is widely used in treating acute or chronic hepatitis . Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures , its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive . In this study , our purpose was to determine whether silymarin improves symptoms , signs and laboratory test results in patients with acute clinical hepatitis , regardless of etiology . METHODS This is a r and omized , placebo-controlled trial in which participants , treating physicians and data management staff were blinded to treatment group . The study was conducted at two fever hospitals in Tanta and Banha , Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase ( ALT ) levels > 2.5 times the upper limit of normal were enrolled . The intervention consisted of three times daily ingestion of either a st and ard recommended dose of 140 mg of silymarin ( Legalon , MADAUS GmbH , Cologne , Germany ) , or a vitamin placebo for four weeks with an additional four-week follow-up . The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2 , 4 and 7 and weeks 2 , 4 , and 8 . Side-effects and adverse events were ascertained by self-report . RESULTS From July 2003 through October 2005 , 105 eligible patients were enrolled after providing informed consent . No adverse events were noted and both silymarin and placebo were well tolerated . Patients r and omized to the silymarin group had quicker resolution of symptoms related to biliary retention : dark urine ( p=0.013 ) , jaundice ( p=0.02 ) and scleral icterus ( p=0.043 ) . There was a reduction in indirect bilirubin among those assigned to silymarin ( p=0.012 ) , but other variables including direct bilirubin , ALT and aspartate aminotransferase ( AST ) were not significantly reduced . CONCLUSIONS Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion . Despite a modest sample size and multiple etiologies for acute clinical hepatitis , our results suggest that st and ard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process 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 : Non-alcoholic steatohepatitis ( NASH ) is a clinicopathological entity that is being recognized more frequently in recent years . This study aim ed to evaluate the effects of Metformin , with and without a probiotic supplement on liver aminotransferases in patients with NASH . Methods : Sixty four patients 18 - 75 years with NASH confirmed by biopsy and histological assessment were enrolled to study . Patients were r and omized to one of the following treatments for 6 months : Group I , probiotic ( Protexin two tablets per day ) plus Metformin 500 mg two tablets per day ( Met/Pro ) , or group II , Metformin 500 mg two tablets per day plus two placebo tablet ( Met/P ) . After 6 month alanine aminotransferase ( ALT ) , aspartate aminotransferase , and ultrasound grading of NASH were assessed . Results : In group I , serum alanine aminotransferase ( ALT : 133.7 ± 70 vs. 45.2 ± 32.5 ; P < 0.00 ) , and aspartate aminotransferase activity ( AST : 123.1 ± 72 vs. 44.2 ± 33.9 ; P < 0.001 ) , and ultrasound grading of NASH ( P < 0.001 ) all decreased significantly by the end of the treatment period . In group II , while serum alanine aminotransferase ( ALT ) was not significantly reduced ( 118.4 ± 67.9 vs. 112.5 ± 68.7 ; P < 0.064 ) , aspartate aminotransferase activity ( AST : 125.3 ± 71 vs. 113.4 ± 71 ; P < 0.001 ) , and ultrasound grading of NASH did fall significantly ( P < 0.01 ) . Body mass index ( BMI ) , fasting blood sugar ( FBS ) , cholesterol , and triglyceride fell significantly in both groups . Conclusions : Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH 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 AIM To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease ( NAFLD ) and hyperferritinemia , a frequent feature associated with more severe liver damage , despite at least 6 mo of lifestyle changes . METHODS Eligible subjects had to be 18 - 75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia , ferritin levels ≥ 250 ng/mL , and NAFLD activity score > 1 . Iron depletion had to be achieved by removing 350 cc of blood every 10 - 15 d according to baseline hemoglobin values and venesection tolerance , until ferritin < 30 ng/mL and /or transferrin saturation ( TS ) < 25 % . Thirty-eight patients were r and omized 1:1 to phlebotomy  ( n = 21 ) or lifestyle changes alone ( n = 17 ) . The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years , secondary outcomes were improvements in liver enzymes [ alanine aminotransferases ( ALT ) , aspartate aminotransferase ( AST ) , and gamma-glutamyl-transferases ( GGT ) ] . RESULTS Phlebotomy was associated with normalization of iron parameters without adverse events . In the 21 patients compliant to the study protocol , the rate of histological improvement was higher in iron depleted vs control subjects ( 8/12 , 67 % vs 2/9 , 22 % , P = 0.039 ) . There was a better improvement in steatosis grade in iron depleted vs control patients ( P = 0.02 ) . In patients followed-up at two years ( n = 35 ) , ALT , AST , and GGT levels were lower in iron-depleted than in control patients ( P < 0.05 ) . The prevalence of subjects with improvement in histological damage or , in the absence of liver biopsy , ALT decrease ≥ 20 % ( associated with histological improvement in biopsied patients ) was higher in the phlebotomy than in the control arm ( P = 0.022 ) . The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease ≥ 20 % was independent of baseline AST/ALT ratio and insulin resistance ( P = 0.0001 ) . CONCLUSION Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia , and with amelioration of liver enzymes OBJECTIVE To study effect of Matrine injection to prevent the liver function of patients with primary hepatic carcinoma ( PHC ) after trans-artery chemo-embolization . METHODS 122 patients with PHC admitted to our hospital between October 1999 and June 2004 were r and omly divided into therapy group ( 62 cases ) and control group ( 60 cases ) . In therapy group , the patients after trans-artery chemo-embolization ( TAE ) were infused 150 mg Matrine injection once a day for two weeks , while we used other same hepatinica on patients in control group . The levels of alamine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , serum total bilirubin ( STB ) , Albumin ( ALB ) were tested before and after one week and two weeks of TAE . RESULTS In therapy group , the levels of ALT and AST at one week after TAE were much higher than that before TAE ( P < 0.01 ) until two weeks later ( P > 0.05 ) . In control group , the levels of ALT , AST , STB were all elevated at one week ( P < 0.01 ) , and that of the ALT and AST did not come down to the levels at two weeks before TAE . CONCLUSIONS Matrine injection may be used to protect the liver function for patients with PHC after TAE , to relieve the liver cells damage , and to improve the tolerance of TAE , so as to perform the next TAE in time BACKGROUND & AIMS Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and , by measuring organ damage and tumor stage , can influence treatment . Moreover , elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma . We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , and bilirubin ; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment . METHODS Patients ( n=602 ) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase ( not significantly elevated , mildly elevated , or moderately elevated ) , alpha-fetoprotein ( normal or elevated ) , and bilirubin ( normal or elevated ) . Bilirubin was measured at baseline and on day 1 of each cycle . RESULTS Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin had shorter overall survival ( OS ) than those with normal baseline concentrations , irrespective of treatment group . No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin . Median changes from baseline in bilirubin concentration at the last cycle of treatment were + 0.17 and + 0.19 mg/dl in the sorafenib and placebo groups , respectively . CONCLUSIONS These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma , irrespective of baseline alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease , 30 patients with body mass indices higher than 25 , serum levels of alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) or gamma-glutamyltransferase ( gamma-GT ) at least more than 1.5 times the upper limit of normality , and hepatic steatosis demonstrated by ultrasonography were r and omized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months . Abdominal computed tomography was performed to quantify hepatic fat content , which was significantly correlated with histological grading of steatosis ( r s = -0.83 , P < 0.01 ) . Patient body mass index remained stable for both groups throughout the study , but a significant reduction in mean ( + /- SEM ) serum levels of ALT , AST and gamma-GT was observed only in the treated group ( ALT = 81.2 + /- 9.7 , 44.8 + /- 7.7 , 48.1 + /- 7.7 and 52.2 + /- 6.3 IU/l at the beginning and after the first , second and third months , respectively , N = 14 , P < 0.05 ) . For the placebo group ALT values were 66.4 + /- 9.8 , 54.5 + /- 7 , 60 + /- 7.6 and 43.7 5 IU/l , respectively . No alterations in hepatic lipid content were observed in these patients by computed tomography examination ( 50.2 + /- 4.2 Hounsfield units ( HU ) at the beginning versus 51.1 + /- 4.1 HU at the third month ) . These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease , but this effect is not related to modifications in liver fat content We conducted this study to determine whether additional administration of a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor might provide further improvement of the glycemic control in Japanese type 2 diabetes patients showing relatively good glycemic control under treatment with a sodium glucose co-transporter 2 ( SGLT2 ) inhibitor . Five SGLT2 inhibitor ( luseogliflozin , dapagliflozin , tofogliflozin , empagliflozin and canagliflozin ) preparations and five DPP-4 inhibitor ( sitagliptin , vildagliptin , alogliptin , anagliptin and linagliptin ) preparations were used . The results showed that monotherapy with SGLT2 inhibitor produced significant decreases of the body weight and BMI , hemoglobin A1c ( HbA1c ) also decreased , but not to a significant extent . However , decreases of the serum aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , γ-glutamyltransferase ( γ-GTP ) and uric acid were observed in this group . On the other h and , in type 2 diabetes patients treated concomitantly with a DPP-4 inhibitor and SGLT2 inhibitor , significant decrease of the HbA1c was observed , indicating the favorable effect of the concomitant therapy . The body weight and BMI decreased . As for the serum lipid profile , elevation of the serum HDL-cholesterol ( HDL-C ) was observed . Furthermore , AST , ALT , γ-GTP and uric acid decreased in the combined treatment group . Then , the therapeutic responses to concurrent administration with SGLT2 inhibitor of each of the 5 individual DPP-4 inhibitors used in this study were analyzed . The results showed that concomitant administration of sitagliptin , a DPP-4 inhibitor , with the SGLT2 inhibitor yielded the best results in terms of the lowering of the HbA1c and improvement of the serum lipid profile BACKGROUND : Silymarin derived from silybum marianum ( milk thistle ) , a flowering member of the daisy family , may benefit liver function in people infected with the hepatitis C virus . The aims of this pilot study were to assess the efficacy and safety of silymarin on serum hepatitis C virus ( HCV ) RNA , serum aminotransferases ( ALT , AST ) levels , liver fibrosis and well-being in patients with chronic hepatitis C ( CHC ) . METHODS : This prospect i ve self-controlled trial study was conducted from March to September 2006 at Department of Gastroenterology , Isfahan University of Medical Sciences , Isfahan , Iran . 55 patients with HCV ( 10 female and 45 male ) with a mean age of 31.8 ± 6.4 years ( 10 - 67 years ) were participated in the study . Patients received 24 weeks of silymarin ( 630 mg/day ) . Baseline virological biochemical , liver fibrosis ( by a serum fibrosis markers , including YKL–40 and Hyaluronic acid ) , and SF-36 question naire were performed with biochemical tests repeated at the end of the treatment period . RESULTS : There was statistically difference in mean of ALT ( 108.7 ± 86.6 vs 70.3 ± 57.7 ) before and after the treatment ( p < 0.001 ) . The means of AST were 99.4 ± 139.7 and 59.7 ± 64.32 before and after the treatment with statistically differences ( p = 0.004 ) . After the treatment , nine patients were found with negative HCV-RNA ( p = 0.004 ) and statistically significant improvement in results of liver fibrosis markers were found only in fibrosis group ( p = 0.015 ) . Quality of life was improved significantly ( p < 0.001 ) . CONCLUSIONS : This study indicated that in patients with CHC  performing silymarin ( 650 mg/day ) for 6 months , improved serum HCV-RNA titer , serum aminotransferases ( ALT , AST ) , hepatic fibrosis and patient 's quality of life . More future studies are warranted Abstract Objective To examine the relation between the normal range of serum aminotransferase concentration and mortality from liver disease . Design Prospect i ve cohort study . Setting Korea Medical Insurance Corporation study with eight years ' follow up . Participants 94 533 men and 47 522 women aged 35 - 59 years . Main outcome measure Mortality from liver diseases according to death certificate . Results There was a positive association between the aminotransferase concentration , even within normal range ( 35 - 40 IU/l ) , and mortality from liver disease . Compared with the concentration < 20 IU/l , the adjusted relative risks for an aspartate aminotransferase concentration of 20 - 29 IU/l and 30 - 39 IU/l were 2.5 ( 95 % confidence interval 2.0 to 3.0 ) and 8.0 ( 6.6 to 9.8 ) in men and 3.3 ( 1.7 to 6.4 ) and 18.2 ( 8.1 to 40.4 ) in women , respectively , The corresponding risks for alanine aminotransferase were 2.9 ( 2.4 to 3.5 ) and 9.5 ( 7.9 to 11.5 ) in men and 3.8 ( 1.9 to 7.7 ) and 6.6 ( 1.5 to 25.6 ) in women , respectively . According to receiver operating characteristic curves the best cut-off values for the prediction of liver disease in men were 31 IU/l for aspartate aminotransferase and 30 IU/l for alanine aminotransferase . Conclusion People with slightly increased aminotransferase activity , but still within the normal range , should be closely observed and further investigated for liver diseases Aims /hypothesisIn addition to beneficial effects on glycaemia and cardiovascular death , empagliflozin improves adiposity indices . We investigated the effect of empagliflozin on aminotransferases ( correlates of liver fat ) in individuals with type 2 diabetes . Methods Changes from baseline alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) were assessed in the EMPA-REG OUTCOME ® trial ( n = 7020 ) , pooled data from four 24-week placebo-controlled trials ( n = 2477 ) and a trial of empagliflozin vs glimepiride over 104 weeks ( n = 1545 ) . Analyses were performed using data from all participants and by tertiles of baseline aminotransferases . Results In the EMPA-REG OUTCOME ® trial , mean ± SE changes from baseline ALT at week 28 were −2.96 ± 0.18 and −0.73 ± 0.25 U/l with empagliflozin and placebo , respectively ( adjusted mean difference : −2.22 [ 95 % CI −2.83 , −1.62 ] ; p < 0.0001 ) . Reductions in ALT were greatest in the highest ALT tertile ( placebo-adjusted mean difference at week 28 : −4.36 U/l [ 95 % CI −5.51 , −3.21 ] ; p < 0.0001 ) . The adjusted mean difference in change in ALT was −3.15 U/l ( 95 % CI −4.11 , −2.18 ) with empagliflozin vs placebo at week 24 in pooled 24-week data , and −4.88 U/l ( 95 % CI −6.68 , −3.09 ) with empagliflozin vs glimepiride at week 28 . ALT reductions were largely independent of changes in weight or HbA1c . AST changes showed similar patterns to ALT , but the reductions were considerably lower . Conclusions /interpretationThese highly consistent results suggest that empagliflozin reduces aminotransferases in individuals with type 2 diabetes , in a pattern ( reductions in ALT > AST ) that is potentially consistent with a reduction in liver fat , especially when ALT levels are high BACKGROUND We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A , non-B hepatitis . METHODS Consecutive patients who met the inclusion criteria were enrolled in the study . The diagnosis of chronic non-A , non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value ( greater than 1.5 times the normal value ) for at least one year . All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then r and omly assigned to the same treatment for an additional 12 months ( group 1 ) , a regimen of 1 million units three times a week for 12 months ( group 2 ) , or no further treatment ( group 3 ) . Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again . Follow-up continued for two years after the discontinuation of treatment . Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity ( 0 , no activity ; 1 , mild ; 2 , moderate ; or 3 , severe ) between the first liver biopsy and a biopsy performed at 18 months . RESULTS Of the 329 patients initially treated , 303 were r and omized : 103 to group 1 , 101 to group 2 , and 99 to group 3 . Of the 286 patients tested , 252 ( 88.1 percent ) had antibodies to hepatitis C virus . In an intention-to-treat analysis , 46 of the patients in group 1 ( 44.7 percent ) had normal serum alanine aminotransferase values at 18 months , as compared with 27 of the patients in group 2 ( 26.7 percent , P = 0.008 ) and 30 of those in group 3 ( 30.3 percent , P = 0.04 ) . Between 19 and 42 months , 23 of the patients in group 1 ( 22.3 percent ) continued to have normal serum alanine aminotransferase values ( measured every six months ) , as compared with 10 of the patients in group 2 ( 9.9 percent , P = 0.02 ) and 8 of those in group 3 ( 8.1 percent , P = 0.005 ) . Among the 176 patients with repeated liver biopsies at 18 months , more patients in group 1 had improved histologic-activity scores ( 69.6 percent ) than in group 2 ( 47.6 percent , P = 0.02 ) or group 3 ( 38.6 percent , P < 0.001 ) . CONCLUSIONS Among patients with chronic non-A , non-B hepatitis , a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment 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 OBJECTIVE Sodium – glucose cotransporter 2 ( SGLT-2 ) inhibitors have been shown to reduce liver fat in rodent models . Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce . This study examined the effect of empagliflozin ( an SGLT-2 inhibitor ) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease ( NAFLD ) by using MRI-derived proton density fat fraction ( MRI-PDFF ) . RESEARCH DESIGN AND METHODS Fifty patients with type 2 diabetes and NAFLD were r and omly assigned to either the empagliflozin group ( st and ard treatment for type 2 diabetes plus empagliflozin 10 mg daily ) or the control group ( st and ard treatment without empagliflozin ) for 20 weeks . Change in liver fat was measured by MRI-PDFF . Secondary outcome measures were change in alanine transaminase ( ALT ) , aspartate transaminase ( AST ) , and γ-glutamyl transferase ( GGT ) levels . RESULTS When included in the st and ard treatment for type 2 diabetes , empagliflozin was significantly better at reducing liver fat ( mean MRI-PDFF difference between the empagliflozin and control groups −4.0 % ; P < 0.0001 ) . Compared with baseline , significant reduction was found in the end-of-treatment MRI-PDFF for the empagliflozin group ( 16.2 % to 11.3 % ; P < 0.0001 ) and a nonsignificant change was found in the control group ( 16.4 % to 15.5 % ; P = 0.057 ) . The two groups showed a significant difference for change in serum ALT level ( P = 0.005 ) and nonsignificant differences for AST ( P = 0.212 ) and GGT ( P = 0.057 ) levels . CONCLUSIONS When included in the st and ard treatment for type 2 diabetes , empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD AIMS Soluble dipeptidyl peptidase-4 ( sDPP-4 ) is secreted by hepatocytes and induces adipose tissue inflammation and insulin resistance . Sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors can improve hepatic steatosis by inhibiting hepatic de novo lipogenesis . We investigated the effects of dapagliflozin ( an SGLT2 inhibitor ) on serum levels of sDPP-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease ( NAFLD ) . METHODS Fifty-seven patients with type 2 diabetes and NAFLD were r and omized to a  dapagliflozin group ( 5 mg/d for 24 weeks ) ( n = 33 ) or the control group ( n = 24 ) . Serum levels of sDPP-4 were measured with a commercial ELISA kit . Visceral adipose tissue ( VAT ) and subcutaneous adipose tissue ( SAT ) areas were measured by dual bioelectrical impedance analysis . RESULTS In a total of 57 patients  , baseline serum sDPP-4 was positively correlated with aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , γ-glutamyl transferase ( GGT ) and HOMA-IR Both VAT and SAT areas decreased significantly in the dapagliflozin group alone . Liver enzymes were decreased at 24 weeks in the dapagliflozin group , but were unchanged in the control group . Although both groups showed significant reduction of serum sDPP-4 after 24 weeks of treatment , the magnitude of decrease was significantly larger in the dapagliflozin group . Changes in liver enzymes during treatment with dapagliflozin were positively correlated with the change in serum sDPP-4 , but not with changes in VAT volume or HbA1c . CONCLUSIONS Improvement of liver dysfunction after treatment with dapagliflozin was associated with a decrease in serum sDPP-4 , suggesting that reduction of serum sDPP-4 by SGLT2 inhibitors may be a therapeutic strategy for NAFLD/NASH in patients with type 2 diabetes that is independent of glucose lowering or weight loss
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 .
AIM To evaluate the effect of silymarin on the serum levels of alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) and gamma glutamyl transpeptidase ( γGT ) in patients with liver diseases .