Special reports and reviewsSteatosis and hepatitis C virus: Mechanisms and significance for hepatic and extrahepatic disease☆
Section snippets
Epidemiology
Is the concurrence of HCV infection and steatosis a chance or causal association? The precise prevalence of NAFLD in the general population is unknown. Epidemiologic studies using ultrasonography both from Japan19, 20 and Italy21, 22 have reported that the prevalence of “fatty liver syndromes” (fatty liver and steatohepatitis of alcoholic and nonalcoholic etiology) in the general population is around 20% (reviewed in Loria et al.23). An ad hoc analysis of the NHANES III database suggests that
Insulin resistance
It has recently been shown that the presence of steatosis in some patients with chronic HCV infection is associated with risk factors for NASH rather than with alcohol consumption.31 This finding implies that steatosis in the context of HCV chronic infection may represent a host-related reaction and enables us to anticipate that conditions associated with NAFLD, principally insulin resistance and its clinical correlates, including obesity, diabetes, and arterial hypertension, will also be
Steatosis and progression of chronic hepatitis C
Given that steatosis is common in chronic HCV, what is the evidence that it plays a role in disease progression? Similar to studies in NAFLD,58, 59 indirect evidence supporting a role for steatosis in progression of chronic HCV has come from several studies showing that the severity of steatosis on index biopsy or its worsening are independent predictors of both the severity and the progression of fibrosis in HCV-positive patients with and without genotype 3.40, 43, 60, 61, 62, 63 Further
Mechanisms of fibrosis associated with steatosis in HCV
If, as seems likely, steatosis is involved in the fibrotic progression of HCV, what are the potential mechanisms of this effect? A recent study has reported that steatohepatitis-type lesions, sinusoidal fibrosis, and ballooning degeneration are present in 16% and 19% of patients with chronic HCV, respectively, and, along with age and the presence of T2DM, correlate with the severity of fibrosis.42 A second study has confirmed that the pattern of fibrosis in HCV (subsinusoidal and central vein)
Type 2 diabetes mellitus and NAFLD
Previous studies have reported that between 21% and 55% of patients with NAFLD have either overt T2DM or hyperglycemia.87 More recent studies have reported that insulin resistance is present in almost all patients with NAFLD irrespective of the coexistence of impaired glucose tolerance or obesity,35, 81, 88, 89 leading to the suggestion that NAFLD/NASH is the liver manifestation of the insulin resistance or metabolic syndrome.88 Contrary to previous reports, these studies showed that the
Steatosis, HCV, and atherosclerosis
The observation that arterial hypertension is highly prevalent in subjects with ultrasonographic evidence of steatosis114, 115 further supports the notion that NAFLD is part of the metabolic syndrome. More unexpectedly, hypertension has been shown to be an independent predictor of advanced fibrosis in obesity-associated NAFLD, attributed by the authors of the study to a potential fibrogenic effect of angiotensin II.68 Hypertension, along with other features of the metabolic syndrome,
Current therapy for NAFLD
If it is accepted that the steatosis occurring in association with chronic HCV infection is important in disease progression and possibly some of the extrahepatic manifestations, can this be used to inform treatment strategies for this growing number of patients? Optimal therapy for NAFLD has not been established but traditionally includes dietary intervention and correction of comorbid risk factors.6, 7, 13, 117, 118 Weight loss achieved by a moderately restricted diet, with or without
Summary
Steatosis is common in patients with chronic HCV infection because of a combination of the usual risk factors for NAFLD and to a direct steatogenic effect of some genotypes of the virus. The capacity of HCV to induce steatosis directly through interference with lipid metabolism may teleologically represent a mechanism favoring the entry of HCV into hepatocytes with a subsequent increase in viral replication. A growing body of evidence supports the view that steatosis plays a role in the
Future research needs
Although a considerable body of work has been performed on the mechanisms and significance of steatosis occurring in patients with chronic HCV infection, a number of outstanding questions remain unanswered that clearly warrant further study. First, with respect to mechanisms of steatosis, more direct evidence of a role for insulin resistance in the pathogenesis of HCV-related steatosis should be sought by correlating steatosis severity with measures of hepatic, muscle, and adipose tissue
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Supported in part by a grant from the Ministero dell’Istuzione, Università e Ricerca Scientifica (MIUR) Anno 2002 - prot. 2002062883_001 and _002.