Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development
Open Access
- 1 January 2001
- Vol. 48 (1) , 110-115
- https://doi.org/10.1136/gut.48.1.110
Abstract
BACKGROUND Patients with liver cirrhosis are at significant risk of hepatocellular carcinoma (HCC) that may develop as well defined nodular lesions or as more aggressive infiltrating tumours. AIM To compare prospectively risk factors associated with nodular or infiltrating HCC in cirrhotic patients. PATIENTS AND METHODS We studied 370 patients with cirrhosis, followed prospectively by periodic ultrasound (US) of the liver, for a mean period of 74.6 (SD 32.4) months to define the incidence and patterns of HCC development. Patients who developed HCC were compared according to tumour pattern using univariate and multivariate analysis. RESULTS Sixty one (16.5%) patients developed HCC: HCC was classified as nodular in 49 (80.3%) and infiltrating in 12 (19.7%) according to US and computerised tomography (CT) imaging. The five and 10 year cumulative probabilities were 8.1% (95% confidence interval (CI) 5.2%-11%) and 25.2% (15.0–35.4%) for nodular HCC and 2.1% (0.5–3.7%) and 6.9% (2.1–11.7%) for infiltrating HCC. Patients with infiltrating HCC were younger than those with nodular HCC (59.5 v66.2 years, 95% CI 55.2–63.8 and 64.1–68.3 years; p=0.014). Using multivariate analysis, development of nodular HCC was associated with older age (p=0.0002; relative risk (RR) 3.1; 95% CI 1.6–5.2), longer duration (p=0.09; RR 2.6; 95% CI 1.8–3.4), and more advanced stage (p=0.002; RR 2.5; 95% CI 1.3–4.5) of cirrhosis but not with the aetiology of liver disease. In contrast, development of infiltrating HCC appeared to be unrelated to age or disease duration or stage, while it was associated with hepatitis B virus infection (p=0.07; RR 3.96; 95% CI 1.1–5.2) and with hepatitis B/hepatitis C virus coinfection (p=0.0007; RR 16.9; 95% CI 3.8–36.7). CONCLUSIONS In liver cirrhosis, we identified two patterns of HCC developing with distinct risk factors. Nodular HCC was related to the cirrhotic process per se independent of aetiological factors and may depend on the proliferative activity within regenerative nodules, while the infiltrating form of HCC was linked to hepatitis B virus infection and may reflect more direct virus induced carcinogenesis.Keywords
This publication has 28 references indexed in Scilit:
- Screening for hepatocellular carcinomaHepatology, 1998
- Clonal analysis of precancerous lesion of hepatocellular carcinomaGastroenterology, 1996
- Clinical and pathologic features of hepatocellular carcinoma in young and older italian patientsCancer, 1996
- Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosisJournal of Hepatology, 1994
- Screening for hepatocellular carcinoma in patients with Child's A cirrhosis: an 8-year prospective study by ultrasound and alphafetoproteinJournal of Hepatology, 1994
- RISK FACTORS IN DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CIRRHOSIS: PROSPECTIVE STUDY OF 613 PATIENTSThe Lancet, 1985
- HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUSThe Lancet, 1981
- Integration of Hepatitis B Virus DNA into the Genome of Liver Cells in Chronic Liver Disease and Hepatocellular CarcinomaNew England Journal of Medicine, 1981
- Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinomaNature, 1980
- Transection of the oesophagus for bleeding oesophageal varicesBritish Journal of Surgery, 1973