Clinical and Pathological Factors Associated with the Development of Hepatocellular Carcinoma in Patients with Hepatitis Virus-related Cirrhosis: A Long-term Follow-up Study

Abstract 

Aims

Hepatocellular carcinoma (HCC) represents >90% of primary liver neoplasms and develops mainly in patients with liver cirrhosis. Risk factor identification for the development of HCC in patients with cirrhosis possesses great clinical relevance due to its high incidence and poor prognosis when detected at advanced stages. The aim of this study was to identify HCC development-associated risk factors in a cohort of patients with hepatitis virus-related chronic liver disease and cirrhosis.

Materials and methods

Patients with a diagnosis of hepatitis virus-related cirrhosis between January 1980 and January 2000 were included. Patients were followed with an abdominal ultrasound and the determination of alpha-fetoprotein levels, a physical examination, and routine biochemical tests every 3–6 months. The end point of the study was defined as the development of HCC. Liver histology was evaluated according to the French METAVIR Cooperative Study Group (METAVIR) score.

Results

Two hundred and eighty-two patients met the inclusion criteria; most of these (86%) had a serologic diagnosis of hepatitis C virus, and only 14% had hepatitis B virus at the time of the diagnosis of cirrhosis, whereas 56 and 37% were classified as Child A and B, respectively, and only 7% as Child C. Histological activity was mild in 59% of patients, and moderate and severe in 41%. The mean annual incidence was 1.87%, and 22 and 35% of patients developed HCC at 10 and 15 years of follow-up, respectively. The diagnosis of HCC was made by histopathology in 37% and by tumoural lesion-associated alpha-fetoprotein elevation confirmed by imaging studies in 63%. In multivariate analysis, we found three variables associated with HCC: moderate to severe histological activity; a platelet count <105×10³/mm³, and alpha-fetoprotein >5ng/ml. The patients were divided into two groups according to regression coefficient: low and high risk; patients assigned to the low-risk group showed 5-, 10- and 15-year HCC incidences of 3.4, 6.4 and 6.4%, respectively, in contrast to patients from the high-risk group, who showed incidences of 17.8, 33.5 and 56.8%, respectively.

Conclusions

We found three HCC-associated variables: histological activity, platelet count and alpha-fetoprotein levels. Patients considered as high risk for developing HCC must be considered candidates for closer follow-up.

Key words: Alpha-fetoprotein, hepatitis C virus, hepatocellular carcinoma, histological activity, liver cirrhosis, risk factors