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: OBJECTIVES The effect of long-term oral zinc supplementation , in addition to st and ard therapy ( protein-restricted diet and lactulose ) on recurrent hepatic encephalopathy , was assessed in a double-blind study . METHODS Ninety cirrhotic patients with stable recurrent hepatic encephalopathy , after following a one month period of st and ard therapy , were r and omized to receive oral zinc acetate supplementation ( 600 mg/day ) in addition to st and ard therapy or to continue only st and ard therapy ( a diet containing 0.8 g/kg/day of protein and 90 g/day of lactulose ) for six months . Psychometric tests , NCT ( number correction test ) and PSE ( portal-systemic encephalopathy ) Index , were used to evaluate the degree of hepatic encephalopathy , both at the beginning and the end of each treatment period . RESULTS Oral zinc supplementation in addition to st and ard therapy was able to normalize serum zinc levels .  The patients who never showed clinical signs of hepatic encephalopathy during the trial were 88.6 % in zinc-group and 86 % in only st and ard therapy group . Psychometric tests , NCT and PSE Index , were statistically better than basal values either in zinc-group or in only st and ard therapy group . CONCLUSIONS Final values of psychometric tests were better in zinc-group than only st and ard therapy group but the differences were not statistically significant We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase ( AST ) and alanine aminotaransferase ( ALT ) levels decreased , and platelet counts increased , significantly in the group with increased serum zinc concentrations . We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma ( HCC ) . We administered polaprezinc to 32 patients , r and omly selected for zinc therapy ( treatment group ) , while another 30 formed the control group . We measured the serum zinc and albumin concentrations and conducted a prospect i ve study to determine long-term outcomes . The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and + 0.302 ± 0.30 % in the treatment group and 56.7 ± 12.4 µg/dl and + 0.033 ± 0.21 % in the control group and had increased significantly ( p = 0.0002 , p = 0.0036 ) . Progression of liver disease seemed to vary , depending on serum albumin concentrations . In the group with baseline serum albumin concentrations of 4.0 g/dl or more , the change and rate of change of serum zinc concentrations increased significantly , and the cumulative incidence of HCC tended to decrease , in the treated group . According to multivariate analysis , the factors that contribute to a reduction in the incidence of HCC are  zinc therapy ( risk ratio : 0.113 , 95 % CI : 0.015–0.870 , p = 0.0362 ) , and platelet counts ( 0.766 , 0.594–0.989 , 0.0409 ) . Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC OBJECTIVE To our knowledge , no r and omized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis ; therefore , we performed a double-blind , placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy . METHODS Patients with liver cirrhosis and hyperammonemia ( at or above the institutional reference value ) and hypozincemia ( ≤65 μg/dL ) were enrolled in the outpatient units of the participating institutions and were r and omly divided to receive placebo ( P group ) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d ( Z group ) by the envelope method . Of the 18 enrolled patients , 6 dropped out ; thus , the analyses included 12 patients ( 5 in the P group and 7 in the Z group ) . Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared . RESULTS Blood zinc levels significantly increased in the Z group ( P = 0.0037 ; Friedman test ) but not the P group . Blood ammonia levels significantly decreased in the Z group ( P = 0.0114 ; Friedman test ) but not the P group . The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group ( P = 0.0188 : Mann-Whitney test ) . No serious adverse events attributable to the zinc preparation were noted . CONCLUSION Although this study is preliminary and includes a small sample , it is , to our knowledge , the first r and omized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis . Studies with a larger sample size are needed to confirm our findings BACKGROUND The present study aim ed to evaluate the effects of low dose zinc ( Zn ) supplementation on biochemical markers and underlying disease status in non-alcoholic cirrhotic patients . METHODS We enrolled 60 cirrhotic patients in a double-blind ,  placebo-controlled  , r and omized clinical trial . All patients in the interventional group ( n = 30 ) received long-term , low dose Zn supplementation ( 50 mg elemental Zn sulfate daily ) . The control group ( n = 30 ) received placebo ( starch ) .  Child-Pugh scores and biochemical markers were assessed for both interventional and control groups at the first day and the end of the 90th day of the interventional period . A per- protocol analysis was performed after excluding all participants who did not receive or complete the r and omized intervention . The mean differences of quantitative variables between and within groups were evaluated by independent sample s t-test and paired- sample s t-test , respectively . SPSS version 13.00 was used for statistical analysis . RESULTS In the initial evaluation , 16 ( 53.30 % ) patients from the interventional group had a Child-Pugh score of 5 - 8 and 14 ( 46 . 70 % ) had a score of 9 - 12 . In the control group 18 ( 60.00 % ) had a Child-Pugh score of 5 - 8 and 12 ( 40.00 % ) scored 9 - 12 . After three months the mean Child-Pugh score in the interventional group showed a significant improvement ( from 6.56 ± 0.21 to 5.72 ± 0.22 , P = 0.001 ) whereas in the control group despite no significant decline , the mean Child-Pugh score increased slightly ( from 6.25 ± 0.27 to 6.67 ± 0.31 , P = 0.14 ) . Zn supplementation significantly decreased copper ( Cu ; P = 0.01 ) and creatinine ( Cr ; P < 0.0001 ) levels . CONCLUSION In this study , we determined that low dose Zn supplementation could prevent deterioration of clinical status of cirrhosis and prevent excess Cu accumulation in non-alcoholic cirrhotic patients . Zn supplementation produces metabolic effects and trends towards improvements in liver function , hepatic encephalopathy , and nutritional status . Registration ID in I RCT : I RCT 201106122017N4 We have evaluated the efficacy of  interferon-α ( IFN-α ) plus zinc therapy  in hepatitis C patients with genotype 1b , poor responders for IFN alone . Ten patients were injected with 10 MU of IFN-α every day for 4 wk , followed by three times a week for 20 wk ( control group ) . Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy ( zinc sulfate group ) , and 15 patients took IFN-α and 150 mg of polaprezinc ( polaprezinc group).On the d 8 of IFN therapy , circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the zinc sulfate group or control group . Serum ALT levels normalized in 73.3 % of the polaprezinc group , 55.6 % of the zinc sulfate group , and 40.0 % of the control group at 6 mo after the end of IFN therapy . Sustained eradication for the hepatitis C virus RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group ( 53.3 % vs 11.1 % , p<0.05 ) or the control group ( 20.0 % ) . No clinical side effects of zinc were observed at the dose used . The data suggest that polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b We evaluated the synergistic effect of zinc supplementation on the response to interferon ( IFN ) therapy  in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc . No clinical differences were observed between patients treated with IFN alone ( n=40 ) and IFN with polaprezinc ( IFN + Zn , n=35 ) . All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum .  Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks . In the IFN + Zn group , patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course . No additional side-effects of polaprezinc  were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects . Complete response ( CR ) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy . Incomplete response ( IR ) was normal liver enzyme and positive serum HCV RNA . Both of them were evaluated at the 6 months after the completion of the treatment . Patients with higher levels of serum HCV ( more than 5 x 105 copies/mL ) had little response in both treatment groups . Patients with moderate amount of HCV ( 105 to 4.99 x 105/mL ) showed high response rates in combination group ( CR : 11/27 , 40.7 % ; CR + IR 15/27 , 64.3 % ) , better than IFN alone ( CR : 2/15 , 18.2 % ; CR + IR : 2/15 , 18.2 % ) . Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group . Our results indicate that zinc supplementation enhances the response to interferon therapy  in patients with intractable chronic hepatitis Background : Minimal hepatic encephalopathy ( MHE ) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy . There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy . The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose . Methods : Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests , including  number connection test part A ( NCT-A ) , digit symbol test ( DST ) and block design tests ( BDTs ) . Patients were r and omized to receive 175 mg zinc gluconate , 50,000 IU vitamin A , 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose , dose 30–60 ml/day for 3 months [ group A ( n = 31 ) ] or initiated and maintained on lactulose dose 30–60 ml/day for 3 months [ group B ( n = 27 ) ] . Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy . Results : Compared with the baseline neuropsychometric tests , a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy ( group A ) versus patients with lactulose therapy ( group B ) ( NCT-A , p < 0.001 ; DST , p = 0.006 ; BDT , p < 0.001 ) . Antioxidant and zinc supplementation significantly decreased arterial ammonia level , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) ( p < 0.001 ) and improved Child – Pugh score in MHE after 3 months of therapy ( p= 0.024 ) . Conclusion : Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis OBJECTIVES To evaluate the effects of zinc supplementation on serum zinc and copper levels , and the severity of adverse reactions and v 
    Output:
    
agent
Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting .
There are possible benefits of zinc supplementation on hepatic encephalopathy , however , this is based on limited evidence .
***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: OBJECTIVES The effect of long-term oral zinc supplementation , in addition to st and ard therapy ( protein-restricted diet and lactulose ) on recurrent hepatic encephalopathy , was assessed in a double-blind study . METHODS Ninety cirrhotic patients with stable recurrent hepatic encephalopathy , after following a one month period of st and ard therapy , were r and omized to receive oral zinc acetate supplementation ( 600 mg/day ) in addition to st and ard therapy or to continue only st and ard therapy ( a diet containing 0.8 g/kg/day of protein and 90 g/day of lactulose ) for six months . Psychometric tests , NCT ( number correction test ) and PSE ( portal-systemic encephalopathy ) Index , were used to evaluate the degree of hepatic encephalopathy , both at the beginning and the end of each treatment period . RESULTS Oral zinc supplementation in addition to st and ard therapy was able to normalize serum zinc levels .  The patients who never showed clinical signs of hepatic encephalopathy during the trial were 88.6 % in zinc-group and 86 % in only st and ard therapy group . Psychometric tests , NCT and PSE Index , were statistically better than basal values either in zinc-group or in only st and ard therapy group . CONCLUSIONS Final values of psychometric tests were better in zinc-group than only st and ard therapy group but the differences were not statistically significant We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase ( AST ) and alanine aminotaransferase ( ALT ) levels decreased , and platelet counts increased , significantly in the group with increased serum zinc concentrations . We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma ( HCC ) . We administered polaprezinc to 32 patients , r and omly selected for zinc therapy ( treatment group ) , while another 30 formed the control group . We measured the serum zinc and albumin concentrations and conducted a prospect i ve study to determine long-term outcomes . The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and + 0.302 ± 0.30 % in the treatment group and 56.7 ± 12.4 µg/dl and + 0.033 ± 0.21 % in the control group and had increased significantly ( p = 0.0002 , p = 0.0036 ) . Progression of liver disease seemed to vary , depending on serum albumin concentrations . In the group with baseline serum albumin concentrations of 4.0 g/dl or more , the change and rate of change of serum zinc concentrations increased significantly , and the cumulative incidence of HCC tended to decrease , in the treated group . According to multivariate analysis , the factors that contribute to a reduction in the incidence of HCC are  zinc therapy ( risk ratio : 0.113 , 95 % CI : 0.015–0.870 , p = 0.0362 ) , and platelet counts ( 0.766 , 0.594–0.989 , 0.0409 ) . Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC OBJECTIVE To our knowledge , no r and omized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis ; therefore , we performed a double-blind , placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy . METHODS Patients with liver cirrhosis and hyperammonemia ( at or above the institutional reference value ) and hypozincemia ( ≤65 μg/dL ) were enrolled in the outpatient units of the participating institutions and were r and omly divided to receive placebo ( P group ) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d ( Z group ) by the envelope method . Of the 18 enrolled patients , 6 dropped out ; thus , the analyses included 12 patients ( 5 in the P group and 7 in the Z group ) . Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared . RESULTS Blood zinc levels significantly increased in the Z group ( P = 0.0037 ; Friedman test ) but not the P group . Blood ammonia levels significantly decreased in the Z group ( P = 0.0114 ; Friedman test ) but not the P group . The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group ( P = 0.0188 : Mann-Whitney test ) . No serious adverse events attributable to the zinc preparation were noted . CONCLUSION Although this study is preliminary and includes a small sample , it is , to our knowledge , the first r and omized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis . Studies with a larger sample size are needed to confirm our findings BACKGROUND The present study aim ed to evaluate the effects of low dose zinc ( Zn ) supplementation on biochemical markers and underlying disease status in non-alcoholic cirrhotic patients . METHODS We enrolled 60 cirrhotic patients in a double-blind ,  placebo-controlled  , r and omized clinical trial . All patients in the interventional group ( n = 30 ) received long-term , low dose Zn supplementation ( 50 mg elemental Zn sulfate daily ) . The control group ( n = 30 ) received placebo ( starch ) .  Child-Pugh scores and biochemical markers were assessed for both interventional and control groups at the first day and the end of the 90th day of the interventional period . A per- protocol analysis was performed after excluding all participants who did not receive or complete the r and omized intervention . The mean differences of quantitative variables between and within groups were evaluated by independent sample s t-test and paired- sample s t-test , respectively . SPSS version 13.00 was used for statistical analysis . RESULTS In the initial evaluation , 16 ( 53.30 % ) patients from the interventional group had a Child-Pugh score of 5 - 8 and 14 ( 46 . 70 % ) had a score of 9 - 12 . In the control group 18 ( 60.00 % ) had a Child-Pugh score of 5 - 8 and 12 ( 40.00 % ) scored 9 - 12 . After three months the mean Child-Pugh score in the interventional group showed a significant improvement ( from 6.56 ± 0.21 to 5.72 ± 0.22 , P = 0.001 ) whereas in the control group despite no significant decline , the mean Child-Pugh score increased slightly ( from 6.25 ± 0.27 to 6.67 ± 0.31 , P = 0.14 ) . Zn supplementation significantly decreased copper ( Cu ; P = 0.01 ) and creatinine ( Cr ; P < 0.0001 ) levels . CONCLUSION In this study , we determined that low dose Zn supplementation could prevent deterioration of clinical status of cirrhosis and prevent excess Cu accumulation in non-alcoholic cirrhotic patients . Zn supplementation produces metabolic effects and trends towards improvements in liver function , hepatic encephalopathy , and nutritional status . Registration ID in I RCT : I RCT 201106122017N4 We have evaluated the efficacy of  interferon-α ( IFN-α ) plus zinc therapy  in hepatitis C patients with genotype 1b , poor responders for IFN alone . Ten patients were injected with 10 MU of IFN-α every day for 4 wk , followed by three times a week for 20 wk ( control group ) . Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy ( zinc sulfate group ) , and 15 patients took IFN-α and 150 mg of polaprezinc ( polaprezinc group).On the d 8 of IFN therapy , circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the zinc sulfate group or control group . Serum ALT levels normalized in 73.3 % of the polaprezinc group , 55.6 % of the zinc sulfate group , and 40.0 % of the control group at 6 mo after the end of IFN therapy . Sustained eradication for the hepatitis C virus RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group ( 53.3 % vs 11.1 % , p<0.05 ) or the control group ( 20.0 % ) . No clinical side effects of zinc were observed at the dose used . The data suggest that polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b We evaluated the synergistic effect of zinc supplementation on the response to interferon ( IFN ) therapy  in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc . No clinical differences were observed between patients treated with IFN alone ( n=40 ) and IFN with polaprezinc ( IFN + Zn , n=35 ) . All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum .  Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks . In the IFN + Zn group , patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course . No additional side-effects of polaprezinc  were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects . Complete response ( CR ) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy . Incomplete response ( IR ) was normal liver enzyme and positive serum HCV RNA . Both of them were evaluated at the 6 months after the completion of the treatment . Patients with higher levels of serum HCV ( more than 5 x 105 copies/mL ) had little response in both treatment groups . Patients with moderate amount of HCV ( 105 to 4.99 x 105/mL ) showed high response rates in combination group ( CR : 11/27 , 40.7 % ; CR + IR 15/27 , 64.3 % ) , better than IFN alone ( CR : 2/15 , 18.2 % ; CR + IR : 2/15 , 18.2 % ) . Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group . Our results indicate that zinc supplementation enhances the response to interferon therapy  in patients with intractable chronic hepatitis Background : Minimal hepatic encephalopathy ( MHE ) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy . There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy . The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose . Methods : Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests , including  number connection test part A ( NCT-A ) , digit symbol test ( DST ) and block design tests ( BDTs ) . Patients were r and omized to receive 175 mg zinc gluconate , 50,000 IU vitamin A , 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose , dose 30–60 ml/day for 3 months [ group A ( n = 31 ) ] or initiated and maintained on lactulose dose 30–60 ml/day for 3 months [ group B ( n = 27 ) ] . Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy . Results : Compared with the baseline neuropsychometric tests , a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy ( group A ) versus patients with lactulose therapy ( group B ) ( NCT-A , p < 0.001 ; DST , p = 0.006 ; BDT , p < 0.001 ) . Antioxidant and zinc supplementation significantly decreased arterial ammonia level , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) ( p < 0.001 ) and improved Child – Pugh score in MHE after 3 months of therapy ( p= 0.024 ) . Conclusion : Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis OBJECTIVES To evaluate the effects of zinc supplementation on serum zinc and copper levels , and the severity of adverse reactions and v 
    Output:
    