Biliary tract carcinoma and chronic viral hepatitis in Italy: the GICO (Gruppo Italiano COlangiocarcinoma) experience

Abstract

Background: Chronic hepatitis (hep) is an established etiologic factor of biliary tract carcinoma (BTC) in Eastern countries, mostly in intrahepatic cholangiocarcinoma (IHC), whereas in Western world the lower prevalence of hep has prevented a clear correlation so far. A possible prognostic role is still matter of debate. Methods: A cohort of 830 advanced BTC patients (pts), treated in 12 Italian centers, was retrospectively analyzed by the Gruppo Italiano COlangiocarcinoma (GICO). Hep status was assessed through the collection of anamnestic findings, serology (HBsAg, HBcAb, HCV Ab), and molecular test (HCV RNA, HBV DNA). Results: Hep status was available for 562 pts (67.7%); of these, 50 (8.9%) were labeled hep-positive (hep+). Among the 273 IHC pts with hep status available, 35 were positive (14 hep B, 21 hep C), resulting in a significantly higher hep prevalence in IHC than other BTC sites (12.8 vs 4.9%, p=0.001). Among IHC pts, no significant differences were found between hep+ and hep- in relation to nodal involvement (62 vs 69%), metastatic disease (66 vs 67%) or mean number of metastatic sites (1.5 vs 1.7) at diagnosis. Hep+ pts were older than hep- (median 68.4 vs 64.4 years). At time of start of first-line chemotherapy (CT1), IHC hep+ pts shown significantly higher mean levels of leucocytes (8500 vs 6900 c/mmc, p=0.012), neutrophils (5800 vs 4200 c/mmc, p=0.008), neutrophiles-to-lymphocytes ratio (NLR, 4.1 vs 2.9, p=0.043), plateletsto- lymphocytes ratio (167 vs 123, p=0.014), but were not characterized by a higher prevalence of leucocytosis, neutrophilia, lymphocytosis or thrombocytosis. Median CEA was higher in hep+ pts (3.3 vs 1.5 ng/ml, p<0.0001), but the fraction of abnormally high levels was halved (25 vs 51%, p=0.009); median Ca19.9 was unaffected by hep status. Hep did not affect either progression-free survival to CT1 (median 4.4 months in hep+ vs 3.6 in hep-, HR 0.86, IC95% 0.59-1.27) or overall survival (11.2 months vs 11.3, HR 0.81, IC95% 0.53-1.24). Conclusions: The higher prevalence of hep in IHC pts suggests an epidemiological nexus between these two entities. Albeit in hep+ IHC pts there was an increased pretreatment NLR, hemocromocytometric analysis failed to reflect at systemic level a supposedly more pronounced local inflammatory background. Hep+ IHC doesn't show evidence of an accelerated carcinogenesis, such as worse clinical-radiological presentation or younger age at diagnosis, nor is characterized by worse survival in treated pts.