Prospective study of α-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma

Abstract

The usefulness of measurements of serum alpha-fetoprotein elevation for diagnosis of the development of hepatocellular carcinoma was evaluated by a prospective study of 260 patients with cirrhosis. Hepatocellular carcinoma was found in 55 patients during the 5-yr follow-up, excluding 7 found to have hepatocellular carcinoma in the first 6 mo. The cumulative incidence of hepatocellular carcinoma was 26% in the 185 patients who had alpha-fetoprotein levels below 20 ng/ml at the time of entry and 46% in the 68 patients who had alpha-fetoprotein levels of 20 ng/ml or more but below 200 ng/ml. In 169 of the patients, serum levels of alpha-fetoprotein were assayed regularly for at least 2 yr. The incidence of hepatocellular carcinoma development in the 36 patients who had repeated transient increases in alpha-fetoprotein to above 100 ng/ml was 36%. This was significantly higher than the incidence in the 99 patients who had alpha-fetoprotein levels consistently below 20 ng/ml. Thus patients who had alpha-fetoprotein levels of 20 ng/ml or more, who had transient increases in alpha-fetoprotein or who had both should be treated as being in a super-high-risk group for hepatocellular carcinoma. Frequent and careful examination by ultrasonography of such patients is recommended.

Immunohistologic Attempt to Find Carcinogenesis from Hepatic Progenitor Cell in Hepatocellular Carcinoma

“…However, some HCCs (except hepatoblastoma and mixed hepatocellular cancer and ICC) [8,9,10, 22, 23] express both cholangiocellular and hepatocellular epithelial markers, and many HCCs produce α-fetoprotein [15, 18, 24], as do hepatoblasts [25]. These findings indicate the possibility of HCC carcinogenesis from hepatic stem cells and progenitor cells, or metaplasia to cholangiocellular epithelium.…”

“…Some patients with HCC demonstrate high serum levels of CK19 fragments (CYFRA 21-1) [16], yet the morphologic features of these HCCs are not cholangiocellular but rather hepatocellular. Additionally, some HCCs produce α-fetoprotein [15, 17, 18] which is also produced by hepatoblasts and hepatoblastomas [19]. These data suggest that some HCCs originate from hepatic progenitor cells with both hepatocellular and cholangiocellular characteristics as well as hepatic stem cells (hepatoblasts), and that HCCs acquire bile duct characteristics by metaplasia.…”

Early Decrease in α-Fetoprotein, but Not Des-γ-Carboxy Prothrombin, Predicts Sorafenib Efficacy in Patients with Advanced Hepatocellular Carcinoma

“…α-Fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are well-known and widely used serological tumor markers in the screening and diagnosis of HCC [7,8,9,10,11]. These tumor markers are also useful as indicators of the therapeutic effect by evaluating serial changes in these values before and after tumor resection and local ablation therapy.…”

Validation of a New Prognostic Staging System for Hepatocellular Carcinoma: A Comparison of the Biomarker-Combined Japan Integrated Staging Score, the Conventional Japan Integrated Staging Score and the BALAD Score

“…These three tumor markers are commonly used in daily practice in Japan. AFP is the tumor marker that is routinely and most widely used for the surveillance of HCC, the evaluation of treatment efficacy, and malignant grade [1,2,3]. AFP-L3, which has a 1–6 fucose residue attached at the reducing terminus of N-acetylglucosamine, has been reported to be a more specific marker for HCC [4].…”