Interval to vascularization development in cirrhotic precursor nodules in patients with hepatitis B and C virus co-infections

With the widespread use of gadoxetic acid-enhanced magnetic resonance imaging, liver nodules appearing as hypovascular in the arterial phase and hypointense in the hepatobiliary phase, defined as hypovascular hypointense nodules, are increasingly detected in patients with cirrhosis and are considered precursor nodules. We sought to evaluate the interval to vascularization development in hepatitis C virus/hepatitis B virus co-infected-associated precursor nodules (BC-HHN group) compared with that in hepatitis C virus mono-infected-associated precursor nodules (C-HHN group) in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging. The interval to vascularization development was estimated by the Kaplan-Meier method and compared using the Cox proportional hazards model. The mean intervals to vascularization development in the BC-HHN and C-HHN groups were 272.9±31.1 and 603.8±47.6 days, respectively (p<0.001). The cumulative vascularization development incidence at 6, 12, and 18 months was 44.9%, 73.5%, and 91.8%, respectively, in the BC-HHN group and 16.9%, 39.0%, and 55.8%, respectively, in the C-HHN group (p<0.001). The multivariate analysis showed that the presence of hepatitis B virus co-infection (hazard ratio: 1.819; 95% confidence interval: 1.222-2.707; p = 0.003) and male sex (hazard ratio: 1.753; 95% confidence interval: 1.029-2.985; p = 0.039) were predictors of vascularization development. More than half of the hypovascular hypointense nodules showed high-signal changes on T2-weighted imaging, and almost half of them showed restricted diffusion on diffusion-weighted images, but these did not predict vascularization development. In a hepatitis C virus- and hepatitis B virus-endemic area, such as Taiwan, precursor nodules in the BC-HHN group tended to have shorter intervals to vascularization development, especially in male patients.