Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma

Background & Goals: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. Methods: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (6<HVPG≤10), HS-3 (10<HVPG≤12), HS-4 (12<HVPG≤20), and HS-5 (20<HVPG). CS was classified as follows: CS-0 (no cirrhosis), CS-1 (cirrhosis without varix), CS-2 (cirrhosis with varix), CS-3 (varix bleeding without other complications), CS-4 (first nonbleeding decompensating event), and CS-5 (any second decompensating event). The HCC development and risk factors for HCC were evaluated in all patients and patients with cirrhosis, respectively. Results: HCC developed in 53 patients (6.6%). The incidence densities of HCC according to HS-1 to HS-5 and CS-0 to CS-5 were 4, 16, 36, 45, and 49/1000 person years and 0, 15, 25, 33, 36, and 53/1000 person years of observation, respectively. Ascites aggravation [ P =0.008, odd ratio (OR)=2.33], HVPG>12 mm Hg ( P =0.033, OR=2.17), CS>2 ( P =0.039, OR=2.36), and alpha-fetoprotein (AFP; P =0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. Conclusions: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.