慢性C型肝炎患者抗核抗體(ANA)陽性率對臨床表徵及對干擾素合併ribavirin治療療效之影響

Abstract

Background: Positive serum antinuclear antibody (ANA) emerges in some proportion of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in chronic hepatitis C (CHC) patients and to elucidate its clinical implication in the virologic and histologic characteristics. This prospective study also evaluated the impact of ANA on the response to combined antiviral treatment in CHC patients. Methods: Total 614 CHC patients were enrolled in this prospective, hospital-based study. Amongst those enrolled patients, 243 consecutive patients received either peginterferon (PEG-IFN) α-2b or PEG-IFNα-2a plus ribavirin for 24 weeks and were monitored for a further 24 weeks after the treatment ended. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ANA, HCV genotypes, HCV RNA levels and histologic activity index (HAI) scores for liver histopathology were determined. Results: The prevalence of positive ANA (titer > 1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2% vs. 31.0%, p = 0.012). Patients with positive ANA were significantly older (mean 53.7 ± 10.5 vs. 49.7 ± 11.3 yrs, p < 0.001) and had higher mean ALT levels (186.9 ± 178.8 vs. 155.50 ± 113.5 IU/L, p < 0.001) and lower mean HCV RNA levels (5.2 ± 0.9 vs. 5.4 ± 1.0 log IU/mL, p = 0.048) than those without. Amongst 447 patients receiving liver biopsy, those with positive ANA significantly had a higher mean fibrosis score (2.0 ± 1.3 vs. 1.5 ± 1.1, p < 0.001) and a higher frequency of F3-4 (69/187, 36.9% vs. 50/260, 19.2%, p < 0.001) than those without. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels, and age were significant factors related to positive ANA. Amongst those 243 patients who received antiviral therapy, 187 (77.0%) patients showed a sustained virological response (SVR) to treatment. In the 105 patients with HCV-non 1 infection, those who were negative for ANA had significantly higher SVR rate (95.8% vs. 67.7%, p = 0.013) compared to those positive for ANA. On the contrast, in the 138 patients with HCV-1 infection, there was no significant difference in SVR rate between patients with negative or positive ANA. ANA seropositivity, age and HCV RNA levels were independent factors related to SVR in patients with HCV-non 1 infection. HCV RNA levels and severity of fibrosis were independent factors related to SVR in patients with HCV-1 infection. Conclusion: ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA levels in CHC patients. PEG-IFN/ribavirin combination therapy is effective and safe in ANA-positive patients with CHC. High titer of ANA is predictive of nonresponse in patients with HCV-non 1 infection.