The potential impact on nearly quality of life, survival, and cirrhosis-related morbidity, particularly variceal bleeding, justifies the performance of such a trial. Acknowledgments This study was supported by Novartis Pharma AG. Appendix A Table A1 Table A1
Hepatocellular carcinoma (HCC), one of the most common primary malignant tumours worldwide, is a leading cause of death (Pisani et al, 1999). Since chronic infection with hepatitis B or C virus (HBV or HCV) is closely related to development of HCC (Ikeda et al, 1993; Nishiguchi et al, 1995; Takano et al, 1995), close follow-up of patients with HBV or HCV infection has been recommended to improve early HCC detection and maximise opportunity for successful treatment (Liaw et al, 1986; Curley et al, 1995; Trevisani et al, 2002).

While various imaging modalities can be applied to diagnosis of primary liver cancer, the main diagnostic test remains measurement of ��-fetoprotein (AFP), the best accepted serum tumour marker for HCC, in addition to imaging (Oka et al, 1994; Curley et al, 1995; Trevisani et al, 2002). Recent studies reported an increased risk of developing intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis, as is true for HCC (Sorensen et al, 1998; Kobayashi et al, 2000). In Japan and east Asia, chronic HCV infection has been linked to a high incidence of ICC, including combined hepato-cholangiocellular carcinoma (c-HCC-CC) (Tomimatsu et al, 1993; Shin et al, 1996; Su et al, 1996; Taguchi et al, 1996; Yamamoto et al, 1998). Follow-up of patients with HCV infection therefore can detect many cases of ICC as well as HCC.

Although serum concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured to detect and monitor of ICC, insufficient sensitivity and specificity has been a problem with using these established markers in this form of cancer (Kawarada and Mizumoto, 1984, 1990; Wang et al, 1994; Yamanaka et al, 1995; Nakamura et al, 1996; Chu et al, 1997; Kim et al, 1999). A more accurate marker for ICC is needed. In malignant epithelial cells, activated protease increases degradation of cytokeratin; this results in release of large amounts of cytokeratin fragments into the blood (Dohmoto et al, 2001; Wu et al, 2002). The CYFRA 21-1 assay was developed to measure a soluble fragment of cytokeratin 19 in serum. In non-small-cell lung cancer, CYFRA 21-1 was found to be significantly more sensitive than established markers, Dacomitinib and this test may be a useful adjunct in clinical monitoring during and following treatment (Pujol et al, 1993; Stieber et al, 1993; Sugama et al, 1994; van der Gaast et al, 1994; Takada et al, 1995; Lai et al, 1996; Brechot et al, 1997; Nisman et al, 1998).