The Emerging Extrahepatic Manifestations of Hepatitis C Virus Infection in Chronic Hepatitis and Mixed Cryoglobulinemia

Hepatitis c virus (hcy) is known to be responsible for both hepatic and extrahepatic diseases. mixed cryoglobulinemia,sjogren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations ofhcy infection. the most frequent and clinically important extrahepatic endocrine manifestations of chronic hcyinfection are thyroid disorders and type 2 diabetes mellitus. from a meta-analysis of the literature, a significantassociation between hcy infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence ofthyroid cancer have been reported. the pattern of thyroid disorders observed in hcy infected patients is characterizedby the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism.several clinical epidemiologic studies have reported that hcy infection is a risk factor for type 2 diabetes. the type ofdiabetes manifested by subjects with chronic hcy infection is not of the classical type 2 diabetes; in fact, hcy-relateddiabetic patients are leaner than the classical diabetic patients, and have a significantly lower ldl-cholesterol, and bothsystolic and diastolic blood pressure. furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia) andchronic hcy infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabeticpatients with mixed cryoglobulinemia and those with chronic hcy infection. based on the above-mentioned findings, ithas been hypothesized that diabetes in hcy infection may have an immune-mediated pathogenesis. in patients withchronic hcy infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. thesefindings suggested a possible role for chronic hepatitis c in the pathogenesis of carotid artery remodelling. recently,high prevalence rates of anti-hcy antibodies were shown in patients with hypertrophic cardiomyopathy or dilatatedcardiomyopathy; association with myocarditis has also been suggested. many studies have linked the thl immuneresponse with hcy infection, autoimmune thyroid disorders and diabetes. these findings suggest that a possiblecommon immunological thl pattern could be the pathophysiological basis of the association.