Persistently Rising Alpha-fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Review

Abstract

Hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide, is known for its grim prognosis, with untreated life expectancy being only a matter of months after the diagnosis. The difficulty in making a diagnosis early is one of the main contributing factors to the poor prognosis. Alpha-fetoprotein (AFP) had long been used as a surveillance tool, but suboptimal specificity and sensitivity has prompted liver societies to abandon the recommendation for its universal use, even in combination with ultrasonography. Most studies have shown no obvious correlation between serum AFP level and HCC tumor size, stage, or survival post-diagnosis. However, some studies concluded that a gradual rise or persistent elevation in AFP were positive predictors for tumor development. Other studies reported a fall in AFP followed by a rise in patients with HCC as well as persistently rising AFP levels without development of HCC on follow up. Our calculation of the sensitivity and specificity of persistently rising AFP for HCC were both low, at 60% and 35.8%, respectively, indicating that the presence of persistently rising AFP per se did not offer diagnostic benefit. In addition, our calculated mean slopes of persistently rising AFP levels in HCC and non-HCC patients were numerically very different, but the difference was not statistically significant. We conclude that the published data do not support a role for rising AFP levels per se in the diagnosis of HCC.

Combined Liver Stiffness and Α-fetoprotein Further beyond the Sustained Virologic Response Visit as Predictors of Long-Term Liver-Related Events in Patients with Chronic Hepatitis C

“…AFP, an oncofetal glycoprotein discovered decades ago, has also been used as a serum and gene expression marker to evaluate hepatocyte regeneration activity closely related to concurrent hepatic necroinflammation or damage predisposing the liver to progression to advanced fibrosis, cirrhosis, or HCC [ 34 ]. Growing evidence has revealed that mildly elevated AFP levels (<150 ng/mL) might reflect the status of liver regeneration and damage [ 35 , 36 ]. AFP may be used as an additional predictor of post-SVR LREs to enhance the performance of predictive models for liver-related pathogenesis, which may not be explained by liver fibrosis or its surrogate markers alone [ 3 ].…”

Hepatocellular Carcinoma Detection in Hepatitis C Virus-Related Cirrhosis by Glypican-3

“…The core of this criticism is that Serum AFP levels are normal in 30-40% of patients with HCC, with good specificity AFP lacks sensitivity as it is also released by the normal liver in the set of the inflammatory process and hepatocyte damage and most of HCCs develop in cases of long-standing liver disease, to distinguish HCC from background liver pathology as hepatitis requires a high diagnostic cut-off level of AFP about 400-500 ng/mL range. Thus, many HCCs did not achieve these diagnostic levels until the late stages which magnitude the burden of HCC (7) .…”

Diagnostic and Prognostic Value of Protein Post-Translational Modifications in Hepatocellular Carcinoma

“…The clinical utility of AFP has been recently reviewed. [25][26][27][28] Glypican-3 (GPC3), as a member of the proteoglycan family, is a promising therapeutic target and biomarker for the diagnosis and prognosis of HCC. Further discussion of the clinical value of GPC3 in HCC can be found in several reviews.…”