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 Alcoholic hepatitis ( AH ) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods , which is characterised by jaundice and liver failure . Severe disease is associated with high short-term mortality . Prednisolone and pentoxifylline ( PTX ) are recommended in guidelines for treatment of severe AH , but trials supporting their use have given heterogeneous results and controversy persists about their benefit . OBJECTIVES The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX . DESIGN The trial was a r and omised , double-blind , 2 × 2 factorial , multicentre design . SETTING Sixty-five gastroenterology and hepatology inpatient units across the UK . PARTICIPANTS Patients with a clinical diagnosis of AH who had a Maddrey 's discriminant function value of ≥ 32 were r and omised into four arms : A , placebo/placebo ; B , placebo/prednisolone ; C , PTX/placebo ; and D , PTX/prednisolone . Of the 5234 patients screened for the trial , 1103 were r and omised and after withdrawals , 1053 were available for primary end-point analysis . INTERVENTIONS Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days . OUTCOMES The primary outcome measure was mortality at 28 days . Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year . Rates of recidivism among survivors and the impact of recidivism on mortality were assessed . RESULTS At 28 days , in arm A , 45 of 269 ( 16.7 % ) patients died ; in arm B , 38 of 266 ( 14.3 % ) died ; in arm C , 50 of 258 ( 19.4 % ) died ; and in arm D , 35 of 260 ( 13.5 % ) died . For PTX , the odds ratio for 28-day mortality was 1.07 [ 95 % confidence interval ( CI ) 0.77 to 1.40 ; p = 0.686 ) ] and for prednisolone the odds ratio was 0.72 ( 95 % CI 0.52 to 1.01 ; p = 0.056 ) . In the logistic regression analysis , accounting for indices of disease severity and prognosis , the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 ( 95 % CI 0.41 to 0.91 ; p = 0.015 ) . At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups . Serious infections occurred in 13 % of patients treated with prednisolone compared with 7 % of controls ( p = 0.002 ) . At the 90-day follow-up , 45 % of patients reported being completely abstinent , 9 % reported drinking within safety limits and 33 % had an unknown level of alcohol consumption . At 1 year , 37 % of patients reported being completely abstinent , 10 % reported drinking within safety limits and 39 % had an unknown level of alcohol consumption . Only 22 % of patients had attended alcohol rehabilitation treatment at 90 days and 1 year . CONCLUSIONS We conclude that prednisolone reduces the risk of mortality at 28 days , but this benefit is not sustained beyond 28 days . PTX had no impact on survival . Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection . TRIAL REGISTRATION This trial is registered as EudraCT 2009 - 013897 - 42 and Current Controlled Trials IS RCT N88782125 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 102 . See the NIHR Journals Library website for further project information . The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding Sixty-seven patients entered a double-blind , controlled trial to evaluate the efficacy of propylthiouracil treatment in severe alcoholic hepatitis . Twenty-three percent ( 7 of 31 ) given propylthiouracil and 19 % ( 7 of 36 ) given placebo  died during the 6-wk study . Propylthiouracil treatment did not reduce the frequency and incidence of complications in alcoholic hepatitis , but induced hypothyroidism in 4 patients . Treatment produced no beneficial effect on any of the hepatic biochemical tests . We were unable to show any beneficial effect of propylthiouracil treatment on morbidity and mortality in patients with severe acute alcoholic hepatitis BACKGROUND / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000  I.U.  of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo .  Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis In a r and omized , controlled trial to investigate the possible benefit of insulin and glucagon therapy in severe acute alcoholic hepatitis , 86 patients were r and omized to receive 30 U insulin and 3 mg glucagon in 250 ml 5 % dextrose over 12 hr each day for 3 wk or a similar regime of identical placebo . No significant differences were seen in patients ' clinical characteristics and disease severity in the treated and placebo groups . Of the 43 patients receiving insulin and glucagon , 15 ( 35 % ) died within 4 wk of r and omization , compared with 14 deaths ( 33 % ) in the control patients ( p = not significant ) . When the patients surviving the first 4 wk were examined there were five more deaths in the treatment group , compared with one death in the control group at 6-mo follow-up ( p = not significant ) . No significant differences in the frequency of short-term or long-term complications of alcoholic liver disease or relapse to alcohol were seen when the two groups were compared , although hypoglycemia was seen in six patients during infusion of insulin and glucagon . Similarly , no significant differences were seen in the improvement in clinical or biochemical features at 4 wk and at 6 mo in survivors when the insulin and glucagon-treated patients were compared with patients in the placebo group . This study does not confirm previous reports that insulin and glucagon infusion improves the outcome of severe acute alcoholic hepatitis The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival .  Four hundred and seven patients with alcoholic liver diseases , from seven European liver units , entered a r and omized placebo-controlled , double-blind trial : 140 patients received malotilate 1500 mg/day , 133 patients received 750 mg/day , and 134 patients received placebo . The patients were included in the study over a period of 3 1/2 years , and the study was closed 1 year after the entry of the last patient . Eighty-four patients died ( 35 , 19 , 30 patients in groups 1500 mg/day , 750 mg/day , and placebo , respectively ) . Survival was slightly better in the 750 mg/day group than in the two other treatment groups , when tested by conventional log-rank tests ( p = 0.06 ) . However , a treatment effect was supported by a highly significant ( p = 0.006 ) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo . Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables , as determined at entry into the study . The analysis was stratified for the three treatment regimens . In the analysis including liver histology variables , independent significant prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , immunoglobulin M , white blood cell count , and liver cell steatosis . In the analysis without liver histology variables , prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , and immunoglobulin Although propylthiouracil has previously been shown to reduce the risk of mortality in alcoholic liver disease by 60 % , generalized use of propylthiouracil for this condition has not occurred . Additional data are therefore presented on four aspects to provide a better assessment of its therapeutic effectiveness . First , the characteristics and the prognosis of dropouts were virtually identical in both the drug and placebo groups . Also the methodology and analysis employed , were design ed to control for dropouts , thus providing an accurate interpretation of the outcome . Secondly , since 97 % of the patients continued to drink , abstinence was not a precondition for the beneficial effect of propylthiouracil . However , the beneficial effect was observed most clearly in those patients who continued to drink at lower levels , whereas lower level drinking per se did not afford protection in placebo patients . Thirdly , serious side effects or clinical hypothyroidism occurred extremely rarely in these patients , many of whom have now received propylthiouracil for over 4 years . Fourthly , we discuss why the outcome in long-term clinical trials in alcoholic liver disease can not be compared with effects observed in clinical trials lasting only a few weeks . Journal of Hepatology A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year . Fifty-one patients were studied ; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule .  Patients were examined in a special clinic once a month or more if required . Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine sample s on at least one occasion . Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects ( p < .0001 ) . Nine patients  died during the study , three case patients and six control patients ( p = NS ) . The frequency of hospitalizations was significantly less in the experimental group . This difference was attributed to a reduction in severe infections . Mid-arm circumference , serum albumin concentration , and h and grip strength improved earlier in case patients , although both groups had a significant improvement in these parameters . Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period , without differences between groups . It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease BACKGROUND & AIMS An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline ( PTX ) , an inhibitor of tumor necrosis factor ( TNF ) , in severe acute alcoholic hepatitis . The aim of the present study was to evaluate this treatment in a larger cohort of patients . METHODS One hundred one patients with severe alcoholic hepatitis ( Maddrey discriminant factor > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo  died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.2 
    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: BACKGROUND Alcoholic hepatitis ( AH ) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods , which is characterised by jaundice and liver failure . Severe disease is associated with high short-term mortality . Prednisolone and pentoxifylline ( PTX ) are recommended in guidelines for treatment of severe AH , but trials supporting their use have given heterogeneous results and controversy persists about their benefit . OBJECTIVES The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX . DESIGN The trial was a r and omised , double-blind , 2 × 2 factorial , multicentre design . SETTING Sixty-five gastroenterology and hepatology inpatient units across the UK . PARTICIPANTS Patients with a clinical diagnosis of AH who had a Maddrey 's discriminant function value of ≥ 32 were r and omised into four arms : A , placebo/placebo ; B , placebo/prednisolone ; C , PTX/placebo ; and D , PTX/prednisolone . Of the 5234 patients screened for the trial , 1103 were r and omised and after withdrawals , 1053 were available for primary end-point analysis . INTERVENTIONS Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days . OUTCOMES The primary outcome measure was mortality at 28 days . Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year . Rates of recidivism among survivors and the impact of recidivism on mortality were assessed . RESULTS At 28 days , in arm A , 45 of 269 ( 16.7 % ) patients died ; in arm B , 38 of 266 ( 14.3 % ) died ; in arm C , 50 of 258 ( 19.4 % ) died ; and in arm D , 35 of 260 ( 13.5 % ) died . For PTX , the odds ratio for 28-day mortality was 1.07 [ 95 % confidence interval ( CI ) 0.77 to 1.40 ; p = 0.686 ) ] and for prednisolone the odds ratio was 0.72 ( 95 % CI 0.52 to 1.01 ; p = 0.056 ) . In the logistic regression analysis , accounting for indices of disease severity and prognosis , the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 ( 95 % CI 0.41 to 0.91 ; p = 0.015 ) . At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups . Serious infections occurred in 13 % of patients treated with prednisolone compared with 7 % of controls ( p = 0.002 ) . At the 90-day follow-up , 45 % of patients reported being completely abstinent , 9 % reported drinking within safety limits and 33 % had an unknown level of alcohol consumption . At 1 year , 37 % of patients reported being completely abstinent , 10 % reported drinking within safety limits and 39 % had an unknown level of alcohol consumption . Only 22 % of patients had attended alcohol rehabilitation treatment at 90 days and 1 year . CONCLUSIONS We conclude that prednisolone reduces the risk of mortality at 28 days , but this benefit is not sustained beyond 28 days . PTX had no impact on survival . Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection . TRIAL REGISTRATION This trial is registered as EudraCT 2009 - 013897 - 42 and Current Controlled Trials IS RCT N88782125 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No. 102 . See the NIHR Journals Library website for further project information . The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding Sixty-seven patients entered a double-blind , controlled trial to evaluate the efficacy of propylthiouracil treatment in severe alcoholic hepatitis . Twenty-three percent ( 7 of 31 ) given propylthiouracil and 19 % ( 7 of 36 ) given placebo  died during the 6-wk study . Propylthiouracil treatment did not reduce the frequency and incidence of complications in alcoholic hepatitis , but induced hypothyroidism in 4 patients . Treatment produced no beneficial effect on any of the hepatic biochemical tests . We were unable to show any beneficial effect of propylthiouracil treatment on morbidity and mortality in patients with severe acute alcoholic hepatitis BACKGROUND / AIMS The effect of vitamin E administration on clinical and laboratory parameters of liver function and on markers of fibrogenesis was assessed in patients with mild to moderate alcoholic hepatitis in a double blind placebo controlled r and omized trial . METHODS Twenty-five patients received 1000  I.U.  of vitamin E per day , while 26 patients received placebo for 3 months . The patients were followed for 1 year after entry into the trial . RESULTS Vitamin E did not result in significant greater decreases in serum aminotransferases and serum bilirubin or in greater increases in serum albumin as compared with placebo .  Prothrombin time did not change , while serum creatinine remained in the normal range . Monocyte nuclear nuclear factor-kappa B binding activity decreased in patients who remained abstinent , regardless of whether they received vitamin E. As regards markers of hepatic fibrogenesis , vitamin E treatment decreased serum hyaluronic acid ( P<0.05 ) while serum aminoterminal peptide of type III procollagen did not change in either group . Four patients in the treatment group and five in the placebo group died during the 1-year study . CONCLUSIONS Vitamin E treatment improves serum hyaluronic acid but has no beneficial effects on tests of liver function in patients with mild to moderate alcoholic hepatitis In a r and omized , controlled trial to investigate the possible benefit of insulin and glucagon therapy in severe acute alcoholic hepatitis , 86 patients were r and omized to receive 30 U insulin and 3 mg glucagon in 250 ml 5 % dextrose over 12 hr each day for 3 wk or a similar regime of identical placebo . No significant differences were seen in patients ' clinical characteristics and disease severity in the treated and placebo groups . Of the 43 patients receiving insulin and glucagon , 15 ( 35 % ) died within 4 wk of r and omization , compared with 14 deaths ( 33 % ) in the control patients ( p = not significant ) . When the patients surviving the first 4 wk were examined there were five more deaths in the treatment group , compared with one death in the control group at 6-mo follow-up ( p = not significant ) . No significant differences in the frequency of short-term or long-term complications of alcoholic liver disease or relapse to alcohol were seen when the two groups were compared , although hypoglycemia was seen in six patients during infusion of insulin and glucagon . Similarly , no significant differences were seen in the improvement in clinical or biochemical features at 4 wk and at 6 mo in survivors when the insulin and glucagon-treated patients were compared with patients in the placebo group . This study does not confirm previous reports that insulin and glucagon infusion improves the outcome of severe acute alcoholic hepatitis The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival .  Four hundred and seven patients with alcoholic liver diseases , from seven European liver units , entered a r and omized placebo-controlled , double-blind trial : 140 patients received malotilate 1500 mg/day , 133 patients received 750 mg/day , and 134 patients received placebo . The patients were included in the study over a period of 3 1/2 years , and the study was closed 1 year after the entry of the last patient . Eighty-four patients died ( 35 , 19 , 30 patients in groups 1500 mg/day , 750 mg/day , and placebo , respectively ) . Survival was slightly better in the 750 mg/day group than in the two other treatment groups , when tested by conventional log-rank tests ( p = 0.06 ) . However , a treatment effect was supported by a highly significant ( p = 0.006 ) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo . Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables , as determined at entry into the study . The analysis was stratified for the three treatment regimens . In the analysis including liver histology variables , independent significant prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , immunoglobulin M , white blood cell count , and liver cell steatosis . In the analysis without liver histology variables , prognostic variables were : years of high alcohol intake , prothrombin index , alkaline phosphatases , creatinine , and immunoglobulin Although propylthiouracil has previously been shown to reduce the risk of mortality in alcoholic liver disease by 60 % , generalized use of propylthiouracil for this condition has not occurred . Additional data are therefore presented on four aspects to provide a better assessment of its therapeutic effectiveness . First , the characteristics and the prognosis of dropouts were virtually identical in both the drug and placebo groups . Also the methodology and analysis employed , were design ed to control for dropouts , thus providing an accurate interpretation of the outcome . Secondly , since 97 % of the patients continued to drink , abstinence was not a precondition for the beneficial effect of propylthiouracil . However , the beneficial effect was observed most clearly in those patients who continued to drink at lower levels , whereas lower level drinking per se did not afford protection in placebo patients . Thirdly , serious side effects or clinical hypothyroidism occurred extremely rarely in these patients , many of whom have now received propylthiouracil for over 4 years . Fourthly , we discuss why the outcome in long-term clinical trials in alcoholic liver disease can not be compared with effects observed in clinical trials lasting only a few weeks . Journal of Hepatology A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year . Fifty-one patients were studied ; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule .  Patients were examined in a special clinic once a month or more if required . Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine sample s on at least one occasion . Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects ( p < .0001 ) . Nine patients  died during the study , three case patients and six control patients ( p = NS ) . The frequency of hospitalizations was significantly less in the experimental group . This difference was attributed to a reduction in severe infections . Mid-arm circumference , serum albumin concentration , and h and grip strength improved earlier in case patients , although both groups had a significant improvement in these parameters . Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period , without differences between groups . It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease BACKGROUND & AIMS An earlier pilot study from our liver unit suggested benefit from treatment with pentoxifylline ( PTX ) , an inhibitor of tumor necrosis factor ( TNF ) , in severe acute alcoholic hepatitis . The aim of the present study was to evaluate this treatment in a larger cohort of patients . METHODS One hundred one patients with severe alcoholic hepatitis ( Maddrey discriminant factor > or = 32 ) entered a 4-week double-blind r and omized trial of PTX ( 400 mg orally 3 times daily ) vs. placebo . Primary endpoints of the study were the effect of PTX on ( 1 ) short-term survival and ( 2 ) progression to hepatorenal syndrome . On r and omization , there were no differences in demographic and clinical characteristics or laboratory values ( including TNF ) between the 2 groups . RESULTS Twelve ( 24.5 % ) of the 49 patients who received PTX and 24 ( 46.1 % ) of the 52 patients who received placebo  died during the index hospitalization ( P = 0.037 ; relative risk , 0.59 ; 95 % confidence interval , 0.35 - 0.97 ) . Hepatorenal syndrome was the cause of death in 6 ( 50 % ) and 22 ( 91.7 % ) patients ( P = 0.009 ; relative risk , 0.2 
    Output:
    