Significance of pre-treatment serum alpha-fetoprotein in hepatocellular carcinoma of non-viral aetiology

Abstract

INTRODUCTION: Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear. METHOD: Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011-2015 were screened. Clinical evaluation, liver biochemistry, pt-AFP and contrast enhanced CT abdomen were performed. HCC was diagnosed using American Association for the Study of Liver Disease guidelines and TNM staged. nvHCC was diagnosed in HCC, negative for HBsAg and anti-HCVAb. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. All values are presented as median (range). Differences between groups were tested using Pearson’s Chi-square, Mann Whitney U and Kruskal-Wallis tests. Cumulative survival and recurrence rates were calculated by the Kaplan-Meier method. Difference between survival was evaluated by the log-rank test. A p<0.05 was considered significant. RESULTS: Three hundred and eighty nine patients with nvHCC [age 64 (12-88) years; 344 (88.4%) males] were screened. Two hundred and thirty three (59.9%) had diabetes; 187 (48.1%) were regular, 79 (20.3%) social, 123 (31.6%) non-consumers of alcohol]. Three hundred and twenty nine (84.6%) had cirrhosis [Child A (57.3%), B (32.4%), C (10.3%); median CTP 6 (1-14), MELD 11(5-28)]. One hundred and seventy seven (45.5%) HCCs were TNM stage 3, with median diameter 6cm (0.9-26.5). Two hundred and thirty three (59.9%) had no vascular or visceral invasion. Median AFP was 25.46ng/ml (1.16-100,000) [AFP<10ng/ml: n=160(41.2%), AFP>400ng/ml: n=89(22.9%)]. Females (p<0.05), vascular invasion (p<0.001), diameter>5cm (p<0.05), late TNM stage (p<0.001) and non-surgical candidates had higher AFP levels. Diffuse (p<0.001), invasive (p<0.001) and late stage tumours (p<0.001) had AFP>400ng/ml. AFP<400ng/ml was associated with longer survival compared to AFP>400ng/ml (16 vs. 7 months, p<0.001). CONCLUSIONS: Although pt-AFP was not helpful for diagnosis of nvHCC, AFP>400ng/ml was associated with aggressive tumour behaviour and poor prognosis.