***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 
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    Input: GOAL We evaluated the effect of venesections and restricted diet on iron and metabolic indices and liver function tests in patients with insulin-resistance hepatic iron overload ( IR-HIO ) . MATERIAL S AND METHODS Patients were divided in three groups : ( a ) patients without any therapy who were followed-up for 36 + 28 months ; ( b ) patients venesected ; and ( c ) patients on dietary treatment .  In each group baseline and end-point levels of serum iron and metabolic indices , and liver function tests were compared by Student 's paired t-test and the relationship between serum ferritin and the other variables during treatment was evaluated by linear regression analysis . FINDINGS AND CONCLUSIONS In the follow-up group , iron and metabolic indices did not change over time . Serum alanine aminotransferase , gamma-glutamyl transferase , cholesterol and triglycerides significantly decreased after iron depletion . Serum glucose , cholesterol , triglyceride , ferritin and liver function tests significantly decreased after dietary treatment . Transferrin saturation decreased below 20 % during phlebotomy treatment in 52 % of the patients . In conclusion , our results show that IR-HIO patients had relatively low amount of iron overload that seems not to increase even after a long follow-up period . Both venesections and diet improved iron , metabolic and hepatic indices . Data suggest a relationship between hepatic iron overload and insulin resistance , and a role for both iron overload and insulin resistance in hepatocellular damage . The behaviour of iron indices during venesections suggests an impaired iron release from hepatic cells Patients with chronic hepatitis C and low serum and hepatic iron stores may have an improved response to interferon ( IFN ) . We tested whether iron reduction before and during IFN therapy would lead to an improved sustained biochemical and virological response compared with IFN alone . Eighty-two previously untreated patients with chronic hepatitis C were r and omized to either : group A IFN-alpha2b 3 MU 3 times per week for 6 months , or group B iron reduction before and during IFN-alpha2b 3 MU 3 times per week for 6 months . Group B patients had lower mean serum alanine transaminase ( ALT ) levels than group A patients during treatment and follow-up . Group B patients had significantly lower mean hepatitis C virus (HCV)-RNA levels at treatment weeks 4 and 12 ( P < .05 ) . Serum HCV RNA was undetectable at the end of treatment in 15 group B patients compared with 7 group A patients ( P = .03 ) ; 7 group B patients and 3 group A patients had persistently undetectable serum HCV RNA 24 weeks after the end of therapy ( P = .20 ) . Paired pre- and posttreatment liver biopsies in 18 group B patients demonstrated significant improvements in 2 of the 3 inflammation scores of the Knodell histological activity index ( P < . 05 ) . No changes occurred in the paired biopsies from 15 group A patients . We conclude that iron reduction via therapeutic phlebotomy improves the end-of-treatment virological and histological response to short-term IFN therapy . Additional studies are needed to determine if iron reduction in combination with higher doses or longer duration of IFN may be of benefit OBJECTIVE : There is considerable evidence that iron is a risk factor for liver injury in chronic hepatitis C. Known as iron reduction therapy , phlebotomy reduces serum ALT activity . This effect might continue with maintenance phlebotomy and result in slower progression of liver fibrosis . METHODS : We examined the biochemical parameters and liver histology of patients with chronic hepatitis C treated by maintenance phlebotomy .  For biochemical evaluation , 25 patients were treated by initial phlebotomy  to reduce serum ferritin levels to 10 ng/ml or less and then observed for 5 yr with maintenance phlebotomy to maintain the iron-deficient state . For histological evaluation , liver biopsies were performed before and after the study period in 13 of the patients . Thirteen patients who were virological nonresponders to interferon alone and had undergone second liver biopsies after more than 3 yr served as histological controls . RESULTS : Serum aminotransferase levels were decreased significantly by initial phlebotomy and remained at the same levels during the study period ( p < 0.05 ) . The grading scores were improved significantly in the study group ( p < 0.05 ) and unchanged in the controls . The staging scores remained unchanged in the study group but were increased in the controls ( p < 0.005 ) . Disease progression was significantly different between the two groups ( p < 0.05 ) . CONCLUSIONS : These results suggest that phlebotomy with maintenance lowers serum aminotransferase levels , improves liver inflammation , and suppresses the progression of liver fibrosis in chronic hepatitis Iron is implicated in the pathogenesis of liver injury and insulin resistance ( IR ) and thus phlebotomy has been proposed as a treatment for nonalcoholic fatty liver disease ( NAFLD ) . We performed a prospect i ve 6‐month r and omized , controlled trial examining the impact of phlebotomy on the background of lifestyle advice in patients with NAFLD . Primary endpoints were hepatic steatosis ( HS ; quantified by magnetic resonance imaging ) and liver injury ( determined by alanine aminotransaminase [ ALT ] and cytokeratin‐18 [ CK‐18 ] ) . Secondary endpoints included insulin resistance measured by the insulin sensitivity index ( ISI ) and homeostasis model of assessment ( HOMA ) , and systemic lipid peroxidation determined by plasma F2‐isoprostane levels . A total of 74 subjects were r and omized ( 33 phlebotomy and 41 control ) . The phlebotomy group underwent a median ( range ) of 7 ( 1‐19 ) venesection sessions and had a significantly greater reduction in ferritin levels over 6 months , compared to controls ( −148 ± 114 vs. −38 ± 89 ng/mL ; P < 0.001 ) . At 6 months , there was no difference between phlebotomy and control groups in HS ( 17.7 % vs. 15.5 % ; P = 0.4 ) , serum ALT ( 36 vs. 46 IU/L ; P = 0.4 ) , or CK‐18 levels ( 175 vs. 196 U/L ; P = 0.9 ) . Similarly , there was no difference in end‐of‐ study ISI ( 2.5 vs. 2.7 ; P = 0.9 ) , HOMA ( 3.2 vs. 3.2 ; P = 0.6 ) , or F2‐isoprostane levels ( 1,332 vs. 1,190 pmmol/L ; P = 0.6 ) between phlebotomy and control groups . No differences in any endpoint were noted in patients with hyperferritinemia at baseline . Among patients undergoing phlebotomy , there was no correlation between number of phlebotomy sessions and change in HS , liver injury , or IR from baseline to end of study . Conclusion : Reduction in ferritin by phlebotomy does not improve liver enzymes , hepatic fat , or IR in subjects with NAFLD . ( Hepatology 2015;61:1555–1564 Elevated iron indices are described in non‐alcoholic fatty liver disease and iron reduction has been suggested as a potential therapy 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 In a recent study , iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease . We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration . RESEARCH DESIGN AND METHODS A total of 28 type 2 diabetic male patients with serum ferritin levels > 200 ng/ml ( approximately 18 % of consecutive type 2 diabetic men attending our outpatient clinic ) were r and omized to iron depletion  ( three extraction s of 500 ml blood at 2-week intervals ; group 1A ) or to observation ( group 1B ) . C282Y mutation was absent in all patients . Vascular reactivity ( high-resolution external ultrasound ) was evaluated at baseline and at 4 and 12 months thereafter . The two groups of patients were matched for age , BMI , pharmacological treatment , and chronic diabetic complications . RESULTS Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients . In contrast , the vasodilation induced by glyceryl trinitrate ( GTN )  improved significantly after iron depletion ( P = 0.006 ) . These changes occurred in parallel to decreases in transferrin saturation index and HbA(1c ) levels ( -0.6 % , P < 0.05 ) only in group 1A patients . The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA(1c ) levels . Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin ( r = -0.45 , P = 0.04 ) . At 12 months , transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects . CONCLUSIONS Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations . The mechanisms by which these changes occur should be further investigated BACKGROUND / AIM To test the short-term clinical usefulness of venesection associated with lifestyle counselling as against counselling alone on insulin resistance and liver enzymes in subjects with non-alcoholic fatty liver disease ( NAFLD ) , using a propensity score approach . METHODS We carried out a 6- to 8-month observational analysis of 198 NAFLD patients in three Italian referral centres ( 79 venesection and 119 counselling alone ) .  Insulin resistance was measured by the homeostasis model assessment ( HOMA ) method . Logistic regression was used to identify factors associated with normal HOMA and normal alanine aminotransferase ( ALT ) at the end of observation . The results were adjusted for the propensity score to be enrolled in the venesection programme , based on clinical and laboratory data , including common HFE polymorphisms and liver biopsy ( available in 161 cases ) . RESULTS After adjustment for propensity and changes in BMI , venesection was significantly associated with normal HOMA [ all cases : odds ratio ( OR ) 3.00 ; 95 % confidence interval ( CI ) 1.51 - 5.97 ; cases with histology : OR 2.29 ; 95 % CI 1.08 - 4.87 ] and ALT within normal limits ( all cases : OR 2.56 ; 95 % CI 1.29 - 5.10 ; cases with histology : OR 2.81 ; 95 % CI 1.20 - 5 
    Output:
    
Even in the subgroup of patients with NAFLD and hyperferritinemia , phlebotomy did not improve the HOMA index , insulin level , ALT , or AST .
Phlebotomy does not bring about significant improvement in indices of insulin resistance , liver enzymes , or liver histology in patients with DIOS and /or NAFLD compared to lifestyle changes alone .
Current evidence does not support the use of phlebotomy in patients with DIOS or NAFLD