***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 Hepatitis C virus ( HCV ) infection , especially genotypes 1 and 4 , is associated with wide metabolic disarrangements . AIM To assess whether host metabolic factors influence sustained virological response ( SVR ) in patients with chronic hepatitis C genotype 4 ( HCV-4 ) treated with peginterferon / ribavirin  and to evaluate the impact of antiviral therapy on insulin resistance ( IR ) and serum levels of adipocytokines . METHODS Changes in levels of adiponectin , leptin , TNF-α and the homeostasis model assessment for insulin resistance ( HOMA-IR ) on antiviral combination in patients with HCV-4 were analyzed and effect on response was studied . RESULTS 107 patients were included ( M/F 86/21 ; mean age 41.4±5.6 years ) . Neither serum adipocytokines nor HOMA-IR was correlated with viral load . SVR was achieved by 57 % of patients and was associated with fibrosis score ( odds ratio : 6.5 ; P = 0.001 ) and adiponectin level ( odds ratio : 1.3 ; P = 0.01 ) . At the end of follow-up , HOMA-IR , adiponectin , leptin and TNF-α were reduced , all these changes unrelated to predicting the outcome of treatment . At follow-up , HOMA-IR and adiponectin continued to decrease in patients with SVR , but remained unchanged significantly in patients who did not response or relapse . CONCLUSIONS Serum adiponectin at baseline appears to be an independent predictor for the achievement of SVR and can be utilized as an additional predictive marker . Changes of IR and adipocytokines occur under treatment which is more evident with the resolution of HCV infection , suggesting that HCV could have a direct role in these metabolic changes ABSTRACT Background : The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus ( HCV ) patients during viral clearance is unclear and warrants investigation . Methods : A prospect i ve study including 747 consecutive chronic hepatitis C ( CHC ) patients , of whom 546 had completed a course of anti-HCV therapy and underwent pre- , peri- and post-therapy surveys for anthropomorphic , viral , metabolic and hepatic profiles and adiponectin levels , was conducted in a tertiary care center . Results : Multivariate analyses indicated associations of sex , triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 ( IFNL3 ) genotype with homeostasis model assessment -estimated insulin resistance ( HOMA-IR ) levels before anti-HCV therapy . In patients with a sustained virological response ( SVR ; n = 455 ) , at 24 weeks post-therapy , sex , BMI , aspartate aminotransferase to platelet ratio index ( APRI ) , HOMA-IR and steatosis were associated with adiponectin levels , and IFNL3 genotype was associated with HOMA-IR levels . GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels . Compared with pre-therapy levels , adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients , regardless of baseline insulin resistance ( IR ) . However , HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR . Compared with controls , immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis . Conclusions : During HCV infection , adiponectin may affect insulin sensitivity through triglycerides . After viral clearance , adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis ; with a link to the IFNL3 genotype , insulin sensitivity improved only in patients with baseline IR Many studies showed insulin resistance amelioration in HCV- patients achieving Sustained Virologic Response ( SVR ) but results on glycemic control in diabetic patients are unclear . This study aim ed to assess fasting glucose ( FG ) and glycated hemoglobin ( HbA1c ) values before and after therapy with direct-acting antivirals ( DAAs ) in HCV- patients with type 2 diabetes mellitus ( T2DM ) . Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM , 110 patients were treated with DAAs  and 12 remained  untreated .  Clinical , biochemical , virological , and metabolic features were collected both at baseline and at 12 weeks after the end of therapy ( EOT ) or after a comparable period of time in untreated patients . A total of 101 patients obtained a SVR ( Group 1 ) , while nine were relapsers . Group 2 ( 21 patients ) was composed by the nine relapsers and the 12 untreated patients . A significant reduction of mean FG ( 134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL , P = 0.002 ) and HbA1c values ( 46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL , P < 0.001 ) was found in Group 1 but not in Group 2 ( 140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL , P = 0.707 , and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL , P = 0.780 ) . In Group 1 , 20.7 % of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 ( P = 0.03 ) , despite the significant weight increase observed in Group 1 . SVR induced a significant amelioration of glycemic control in diabetic HCV- patients , despite a significant weight increase ; larger prospect i ve studies are needed to verify whether these results are maintained over the long-term Objectives Genotype-specific associations between hepatitis C virus ( HCV ) and insulin resistance ( IR ) have been described , but a causal relationship remains unclear . This study investigated the association between a sustained virological response ( SVR ) and IR after chronic HCV therapy . Methods 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks , respectively . IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR . Results Paired HOMA-IR measurements were available in 1038 non-diabetic patients ( 497 with genotype 1 ; 541 with genotype 2/3 ) . At baseline the prevalence of HOMA-IR > 3 was greater in patients with genotype 1 than 2/3 ( 33 % vs 27 % ; p=0.048 ) . There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR ( δ 10 % ; p<0.001 ) , but not in genotype 1 non-responders or those with genotype 2/3 . Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 ( p=0.004 ) , but not in those with genotype 2/3 , which was independent of body mass index , alanine transaminase , γ-glutamyl transpeptidase and lipid level changes . Conclusions SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3 . Genotype 1 may have a direct effect on the development of IR , independent of host metabolic factors , and may be partially reversed by viral eradication BACKGROUND & AIMS Our study was design ed to test the association between insulin resistance ( IR ) and hepatitis C virus ( HCV ) genotypes , serum HCV RNA level and liver fibrosis stage in a large prospect i ve cohort of chronic hepatitis C ( CHC ) patients . METHODS Six hundred consecutive patients ( CHC , n = 500 ; chronic hepatitis B ( CHB ) , n = 100 ) were evaluated on the day of liver biopsy .  IR ( Homeostasis Model for Assessment of Insulin Resistance )  and all components of the metabolic syndrome were assessed . By logistic regression , independent factors associated with IR and those associated with significant fibrosis were assessed in nondiabetic and noncirrhotic CHC , respectively . Parameters of IR were compared between hepatitis B and 240 CHC matched by epidemiologic , metabolic , and histologic features . RESULTS IR was present in 32.4 % of the 462 nondiabetic CHC and associated with the metabolic syndrome , genotypes 1 and 4 , significant fibrosis , and severe steatosis . IR was diagnosed in 15 % of 145 CHC without metabolic syndrome or significant fibrosis , and associated with genotypes 1 and 4 , high serum HCV RNA level , and moderate-severe necroinflammation . Significant fibrosis was present in 51.1 % of the 454 noncirrhotic CHC patients and associated with male sex , age > 40 years , IR , moderate-severe necroinflammation , and severe steatosis . IR was less frequent in CHB than in matched CHC ( 5 % vs 35 % , respectively , P < .001 ) . CONCLUSIONS IR is a specific feature of CHC , associated with genotypes 1 and 4 and high serum HCV RNA level . Significant fibrosis is associated with IR independent from steatosis UNLABELLED Treatment response remains suboptimal for many patients with chronic hepatitis C , particularly those with genotype 1 and high levels of viremia . The efficacy of high-dose regimens of peginterferon alfa-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses . Eligible treatment-naïve adults with genotype 1 infection , hepatitis C virus ( HCV ) RNA > 800,000 IU/mL and body weight > 85 kg were r and omized to double-blind treatment with  peginterferon alfa-2a at 180 or 270 microg/week plus ribavirin at 1200 or 1600 mg/day for 48 weeks ( four regimens were evaluated ) . The primary endpoint was viral kinetics during the first 24 weeks of therapy . Among patients receiving peginterferon alfa-2a ( 270 microg/week ) the magnitude of HCV RNA reduction was significantly greater than for patients r and omized to the conventional dose of peginterferon alfa-2a ( 180 microg/week ) for the pairwise comparison for ribavirin at 1600 mg/day ( P = 0.036 ) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day ( P = 0.060 ) . Patients r and omized to the highest doses of peginterferon alfa-2a ( 270 microg/week ) and ribavirin ( 1600 mg/day ) experienced the numerically highest rates of sustained virologic response ( HCV RNA < 50 IU/mL ) and the lowest relapse rate ( 47 % and 19 % , respectively ) . The arm with the higher doses of both drugs was less well-tolerated than the other regimens . CONCLUSION Higher fixed doses of peginterferon alfa-2a ( 270 microg/week ) and ribavirin ( 1600 mg/day ) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult-to-treat characteristics BACKGROUND Insulin resistance ( IR ) is a key factor in the development of hepatic steatosis and fibrosis in chronic hepatitis C virus infection . Little is known about the impact of viral clearance on IR . AIM The aim of this study was to determine the impact of viral clearance on IR . METHODS Eighty-six patients treated according to st and ard clinical practice at an Australian teaching hospital between 2003 and 2007 were prospect ively studied . Demographic , biochemical and histological data were collected . RESULTS The mean pretreatment homeostatic model assessment -IR ( HOMA-IR ) was similar in the sustained virological response ( SVR ) and non-SVR groups ( 2.7 ± 0.5 and 2.8 ± 0.4 , respectively ) , and both values were consistent with significant IR . There was a significant improvement in HOMA-IR ( from 3.0 ± 1.0 to 2.2 ± 0.5 , P = 0.04 ) at the end of treatment in the SVR group only . This trended towards significance at 6 months post-treatment . Multiple regression analysis found improvement in both gamma-glutamyl transpeptidase and alanine aminotransferase predicted improvement in HOMA-IR when controlled for other potential factors ( P = 0.01 ) . CONCLUSIONS Hepatitis C virus clearance is associated with improvement in IR . Although baseline hepatic 
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In conclusion , HCV patients who achieved SVR after IFN-based therapy  exhibited improvement in HOMA-IR and HOMA-β .
The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients