Abstract
Background and AimsSerum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.Methods843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.ResultsBy multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB).ConclusionsIn patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.
Highlights
The prognosis of patients with chronic liver diseases (CLD), independently of the underlying etiology, is decided by the amount of liver fibrosis that will accumulate over the years as a consequence of several mechanisms of tissue injury, with the ultimate development of cirrhosis and its complicances [1,2]
These considerations arise from contrasting evidences about the association between liver fibrosis and insulin resistance (IR) observed in some studies on patients with chronic hepatitis C (CHC) [4,9] or chronic hepatitis B (CHB) [10], and from the evidences that insulin-sensitizer therapies obtain an improvement in histological outcomes in a proportion of nonalcoholic fatty liver disease (NAFLD) patients only [11,12]
Due to the evidence of a higher prevalence of IR in CHC and CHB patients with abnormal c-glutamyl transpeptidase (c-GT) values compared to their counterpart, in both CHC and CHB groups we tested if this association was maintained at multivariate analysis
Summary
The prognosis of patients with chronic liver diseases (CLD), independently of the underlying etiology, is decided by the amount of liver fibrosis that will accumulate over the years as a consequence of several mechanisms of tissue injury, with the ultimate development of cirrhosis and its complicances [1,2]. IR is the key determinant of nonalcoholic fatty liver disease (NAFLD) and its severity [3], is common in western patients with chronic hepatitis C (CHC) [4], due to both viral and host factors [5], and associated with the severity of fibrosis and its progression independently of steatosis and visceral obesity [6,7], and seems associated with the severity of liver fibrosis in patients with chronic hepatitis B (CHB) [8] These data, it is probably that the impact of IR on the severity of liver fibrosis is different according to the clinical setting. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and c-GT serum levels, and we evaluated if normal or high c-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis
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