Impact of Hepatocellular Carcinoma on the risk of liver decompensation: a comparative analysis of patients with and without HCC

Background & Aims: Hepatocellular Carcinoma (HCC) is a leading cause of death and the large majority of HCC occurs in the setting of cirrhosis.Nevertheless, its impact on the development of decompensation in these patients has not been investigated, yet.Our aim was to investigate the role of HCC in the development of decompensating events in patients with cirrhosis.Methods: Clinical data of outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were collected and followed prospectively from January 2000 to December 2021, until the end of the study, death or liver transplantation.Demographic, clinical, and laboratory data were collected.The primary outcome was the development of decompensating events after the diagnosis of HCC.HCC and effective etiological treatment were considered as a time-varying covariate for the statistical analysis.Results: Overall, 1,176 cirrhotics of any etiology were enrolled (Padua 876, Milan 300), and 358 (30.4%) developed HCC.In the study cohort (Padua cohort), patients who developed HCC on compensated cirrhosis had a higher risk of developing the first decompensation event (hazard ratio[HR] = 4.05; p < 0.001), primarily occurring as ascites (HR = 4.79; p < 0.001), hepatic encephalopathy (HR = 3.68; p <0.001), and gastro-intestinal bleeding (HR = 2.98; p = 0.004).All these findings were confirmed in the extended cohort (Milan cohort).HCC remained an independent predictor of first decompensation even considering the study period in two eras (2000-2013 and 2014-2021) (HR 3.64, 95% CI 2.10-6.31,2000-2013; HR 4.95, 95% CI 1.62-15.1,2014-2021). Conclusions:The occurrence of HCC is associated with a high risk of first decompensation.Further prospective studies are needed to confirm these results.