Digestive Diseases and Sciences, Vol. 48, No. 2 (February 2003), pp. 349–353 ( C  2003) High Prevalence of Non-Organ-Specific Autoantibodies in Hepatitis C Virus-Infected Cirrhotic Patients from Southern Italy GIOVANNI SQUADRITO, MD,* MARCELLO PREVITI, MD,* MARCO LENZI, MD,† ENRICO PAGANO LE ROSE, MD,* GAIA CACCAMO, MD,* TEA RESTUCCIA, MD,* ENRICO DI CESARE, MD,* TERESA POLLICINO, MD,* and GIOVANNI RAIMONDO, MD* Non-organ-specific autoantibodies (NOSAs) are frequently found in patients with hepatitis C virus (HCV) chronic infection. Genetics is likely involved in the development of autoimmune reactivities, and differences in the prevalence of HCV-related autoantibodies among populations of various geographic areas should be expected. We evaluated the prevalence and the clinical impact of NOSAs in a series of HCV-infected patients from southern Italy. We studied 283 consecutive anti-HCV positive patients (162 men, 121 women, mean age 54.5 ± 13.5 years), 94 of whom were cirrhotics and 189 noncirrhotics. Serum from each patient and from 41 hepatitis B surface antigen (HBsAg)- positive/anti-HCV negative control subjects were tested (dilution 1:40) for autoantibodies by indirect immunofluorescence. Qualitative/quantitative HCV-RNA determinations were also performed. The prevalence of NOSAs was significantly higher in anti-HCV-positive subjects than in HBsAg-positive patients ( P < 0.006). Autoantibodies were significantly associated with both cirrhosis ( P < 0.0001) and older age ( P < 0.05). No significant association between NOSAs and either female gender or virological parameters (HCV-RNA positivity, viral load, and genotype) was found. In conclusion, the autoantibody positivity in HCV-infected patients from southern Italy is significantly related to cirrhosis and older age, although its general prevalence is similar to that reported in populations from the north of the country. KEY WORDS: hepatitis C virus; anti-nuclear antibodies; anti-mitochondrial antibodies; anti-smooth muscle antibodies; anti-liver-kidney-microsomes type-1 antibodies; indirect immunofluorescence. Hepatitis C virus (HCV) is a small-enveloped RNA virus of approximately 9.5 kb classified in the Flaviviridae fam- ily (1–3). HCV is one of the most prevalent hepatotropic viruses worldwide, and it is estimated that about 200 mil- lion persons are chronically infected with this virus (4). HCV infection does not cause acute hepatitis in most cases, but up to 60–80% of infected patients develop a Manuscript received May 8, 2002; accepted October 29, 2002. From the *Dipartimento di Medicina Interna, Universit` a di Messina, and †Dipartimento di Medicina Interna, Cardiologia ed Epatologia, Uni- versit` a di Bologna, Italy. Address for reprint requests: Prof. Giovanni Raimondo, Diparti- mento di Medicina Interna, Policlinico Universitario di Messina 98124 Messina, Italy. chronic infection that may lead to a large spectrum of clinical forms ranging from the asymptomatic carrier state to cirrhosis and hepatocellular carcinoma (5–9). Despite the recent therapeutic progress achieved by the use of inteferon-α (IFN-α) in combination with ribavirin, around 50% of patients with chronic C hepatitis still do not re- spond to treatment (10–14). The mechanisms responsible for the failure of therapy in so many cases as well as for the wide range of clinical outcomes are mostly unknown. An intriguing aspect of chronic HCV infection concerns its frequent association with immunological disorders (15, 16). Although these disorders may have a relevant clinical impact (ie, mixed cryoglobulinemia, membranoprolifera- tive glomerulonephritis, autoimmune thyroiditis) (16–22), Digestive Diseases and Sciences, Vol. 48, No. 2 (February 2003) 349 0163-2116/03/0200-0349/0 C  2003 Plenum Publishing Corporation