Time-dependent analysis of predisposing factors for the recurrence of hepatocellular carcinoma

There are many reports dealing with the risk factors for hepatocellular carcinoma (HCC) recurrence. However, in most of these reported studies, factors were analysed only at the initial treatment stage, and the predisposing factors for the recurrence during follow-up have not been well studied. The aim of this study is to evaluate the predisposing factors after treatments.

Two hundred and seventy-one consecutive HCC patients curatively treated between January 1994 and March 2004 were followed up and analysed. The recurrence rate was estimated by the Kaplan- Meier method and the predisposing factors were evaluated by time-fixed Cox regression analysis and by time-dependent covariate analysis using multiple parameters.

The mean follow-up period was 4.86 years and recurrence was observed in 169 patients (62.4%). The recurrence rates were 27.9, 65.1 and 84.3% at 1, 3 and 5 years respectively. Among the variables determined before treatment, predisposing factors for recurrence were low serum albumin [< or =3.5 g/dl, hazard ratio (HR)=1.47, 95% confidence interval (CI)=1.07-2.01] and multiple tumour number (HR=2.04, 95% CI=1.46-2.84) by time-fixed multivariate analysis. In the time-dependent analysis, six variables with 12 013 plots were examined. The multivariate analysis revealed that high des- gamma-carboxy prothrombin (DCP > or =40 mAU/ml, HR=2.33, 95% CI=1.61-3.39), high alpha-fetoprotein (AFP > or =100 ng/ml, HR=2.01, 95% CI=1.3-3.35) and high alanine aminotransferase (ALT > or = 40 IU/L, HR= 1.52, 95% CI=1.1-2.1) were significant predisposing factors for recurrence.

Predisposing factors for the recurrence of HCC after treatment are different from those before treatments and special cautions are required when AFP, DCP or ALT is high during follow-up.