title: Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.
abstract: BACKGROUND
  Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion.
  
  
  OBJECTIVE
  To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities.
  
  
  METHODS
  This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis.
  
  
  RESULTS
  Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia.
  
  
  CONCLUSIONS
  This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.
authors.affiliation: Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cimino
authors.forename: G
authors.initials: G
authors.lastname: Oriani
authors.forename: A
authors.initials: A
authors.lastname: D'Arienzo
authors.forename: F
authors.initials: F
authors.lastname: Manguso
authors.forename: C
authors.initials: C
authors.lastname: Loguercio
authors.forename: A
authors.initials: A
authors.lastname: Ascione
authors.forename: N
authors.initials: N
authors.lastname: Caporaso
authors.forename: C
authors.initials: C
authors.lastname: Del Vecchio Blanco
authors.forename: G
authors.initials: G
authors.lastname: Budillon
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology*; D002769:Cholelithiasis / Q000175:diagnosis / Q000453:epidemiology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006306:Health Surveys; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000453:epidemiology; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis / Q000453:epidemiology*; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution