Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Hanif, Hira; Ali, Mukarram Jamat; Susheela, Ammu; Khan, Iman Waheed; Luna-Cuadros, María Alejandra; Khan, Muzammil; Lau, Daryl T.Y.

doi:10.3748/wjg.v28.i2.216

Cited by 77 publications

(67 citation statements)

References 92 publications

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“…The outcomes were unsatisfactory, though several diagnostic biomarkers of HBV‐related HCC have been discovered 33 . AFP is still the only certain biomarker of HCC, however, both specificity and sensitivity are insufficient 12 . Thus, it is imperative to discover new diagnosis and prognosis markers for HBV‐related HCC.…”

Section: Discussionmentioning

confidence: 99%

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus‐related hepatocellular carcinoma

Gong

et al. 2022

Intl Journal of Cancer

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Hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. This study aimed to identify the effective diagnostic and prognostic biomarkers for HBV‐related HCC. With HBV‐related HCC RNA‐sequencing data of The Cancer Genome Atlas (TCGA) database, 159 differentially expressed long noncoding RNAs (lncRNAs) between HBV‐related HCC and para‐carcinoma normal samples were identified, and 12 lncRNAs were eventually assessed for deeper research. Classification analysis developed a three‐lncRNA signature of AC005332.5, ELF3‐AS1 and LINC00665, which was demonstrated to be the most discriminatory with an AUC (Area under the curve) value of 0.913 (95% CI: 0.8610‐0.9665) and verified in validation patients. The expression levels of AC005332.5, ELF3‐AS1 and LINC00665 were significantly changed with different tumor stages or grades. Survival analysis revealed that AC005332.5, ELF3‐AS1 and LINC00665 were highly associated with the prognosis of overall survival. Additionally, the lncRNA signature yielded statistical significance to predict clinical outcomes independently from other clinical variables in validation patients, as suggested in the multivariate Cox hazards analysis. Conclusively, a three‐lncRNA signature of AC005332.5, ELF3‐AS1 and LINC00665 may serve as an excellent diagnostic biomarker for HBV‐related HCC and potential prognostic significance for HBV‐related HCC sufferers.

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Section: Discussionmentioning

confidence: 99%

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus‐related hepatocellular carcinoma

Gong

et al. 2022

Intl Journal of Cancer

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“…Although normal-AFP HCC is considered to have a better outcome [ 5 ], increased AFP levels at diagnosis (exceeding laboratory limits) allow the clinician to assess prognosis, as well as treatment responsiveness more easily. Thus, a complete response to the treatment should be expected if previous levels of AFP were lower than normal values on follow-ups, while a novel elevation of AFP after treatment may suggest tumour recurrence or metastatic disease [ 20 ]. AFP assessment is important as detection of small tumours or metastases can at times be difficult on routine imagistic evaluation.…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers have suggested the simultaneous assessment of other tumoral markers, in order to increase the sensitivity in HCC diagnosis and monitoring. One of these markers is AFP-L3, which is secreted in the early stages of HCC development and can therefore be used as an early HCC diagnostic tool [ 20 , 24 ]. It was revealed that in patients with AFP under 200 ng/ml, an AFP-L3 value higher than 35% of the total AFP is associated with specificity for HCC diagnosis that comes close to 100% [ 20 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…One of these markers is AFP-L3, which is secreted in the early stages of HCC development and can therefore be used as an early HCC diagnostic tool [ 20 , 24 ]. It was revealed that in patients with AFP under 200 ng/ml, an AFP-L3 value higher than 35% of the total AFP is associated with specificity for HCC diagnosis that comes close to 100% [ 20 , 24 ]. The development of new technologies, including molecular biology, represents a new promising area concerning the research of new biomarkers associated with HCC.…”

Section: Discussionmentioning

confidence: 99%

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Correlation Between Serum Alpha-Fetoprotein and Tumour Size in Patients With Hepatocellular Carcinoma Treated With Direct-Acting Antivirals

Rusie¹,

Stanciu²,

Toma³

et al. 2022

Cureus

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Objectives: Since its first description, alpha-fetoprotein has become the most widely used marker for diagnosing and monitoring patients with hepatocellular carcinoma (HCC). This study aims to assess the correlation between serum levels of alpha-fetoprotein and tumour dimensions in patients diagnosed with HCC, that were previously treated with direct-acting antivirals for hepatitis C viral infection. Materials and methods: We conducted a retrospective cohort study on 47 patients with a personal history of hepatitis C virus infection, who were diagnosed with different forms of HCC more than one year after achieving sustained virologic response after 12 weeks post-treatment. Patients were monitored by liver function tests, tumoral markers, blood cell count and coagulation profile and underwent imagistic explorations such as abdominal ultrasonography and, in selected cases, computerised tomography/magnetic resonance imaging. Tumour burden was assessed by both tumour burden score and seven-eleven criteria. Results: The study mostly included cirrhotic patients, multinodular HCC being the predominant pattern. All patients had alpha-fetoprotein levels over 100 ng/ml, with values largely varying, in accordance with the tumour dimensions. Most patients had medium-range Tumour Burden Score, a variable that also correlated with nodule size. Conclusions: The study found a significant correlation between serum alpha-fetoprotein and tumour size in patients with HCC. Alpha-fetoprotein also correlated well with Tumour Burden Score and remains a very important diagnostic and prognostic tool for patients with HCC.

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“…Recommended surveillance guidelines for patients at high risk for HCC include abdominal imaging, using ultrasonography coupled with serum alpha-fetoprotein (AFP) measurement, followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) (2)(3)(4)(5). However, some patients with advanced HCC do not secrete AFP, moreover AFP can be elevated in conditions other than HCC, such as chronic hepatitis (6). Because of this, various biomarkers such as des-gammacarboxy prothrombin (DCP) and AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed and reported to be clinically useful (7,8), however a prognostic marker with the ability to predict HCC patient survival has not been discovered.…”

Section: Introductionmentioning

confidence: 99%

The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage

et al. 2022

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BackgroundFragmented cytokeratin 18 (fCK18) is released from damaged hepatocytes undergoing apoptosis and is recognized as a liver condition biomarker. We have developed a highly sensitive serum fCK18 CLEIA and reported that serum levels of this caspase-derived protein were significantly associated with hepatocyte ballooning, thus assisting in the accurate diagnosis of nonalcoholic steatohepatitis (NASH). We aim to investigate serum fCK18 levels in a variety of chronic liver diseases and to explore its potential as a prognostic marker of survival in hepatocellular carcinoma (HCC) patients.MethodsSerum fCK18 levels were measured using a highly sensitive CLEIA in 497 chronic liver disease patients (297 outpatients and 200 hospitalized with HCC).ResultsIn 497 chronic liver disease patients, serum fCK18 levels were significantly correlated with overall liver condition, including ALT, FIB-4 index and albumin-bilirubin (ALBI) score and were significantly increased in patients with HCC. In 200 HCC patients, serum fCK18 levels were significantly correlated with alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), and were significantly associated with HCC stage, whereas FIB-4 index and ALBI score were not changed based on HCC stage. The Survival group had significantly lower levels of serum fCK18, AFP, DCP, FIB-4 index and ALBI score. A ROC analysis yield area under the curve (AUC) value of 0.728 for serum fCK18 is a significantly high value when compared to AUC measurements for other factors. Notably, AUROC values for serum fCK18 levels were constant in the short- and long-term by time-dependent ROC analysis for the prediction of HCC patient survival. HCC patients with serum fCK18 measured at < 1.15 ng/mL, AFP < 7.7 ng/mL, DCP < 133 mAU/mL, ALBI score < -2.97 or FIB-4 index < 6.4 had significantly longer rates of survival when compared to patients with values exceeding these thresholds. Serum fCK18 (HR, 3.5; P < 0.0001), DCP (HR, 3.2; P < 0.0001) and Barcelona Clinic Liver Cancer (BCLC) (HR, 2.4; P = 0.001) values were independent predictors of patient survival. [Conclusion] Serum fCK18 levels reflect overall liver function, the level of liver fibrosis and the progression of HCC, and are a potential predictor of survival in HCC patients.

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Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Cited by 77 publications

References 92 publications

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus‐related hepatocellular carcinoma

Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus‐related hepatocellular carcinoma

Correlation Between Serum Alpha-Fetoprotein and Tumour Size in Patients With Hepatocellular Carcinoma Treated With Direct-Acting Antivirals

The prognostic potential of fragmented CK18 serum levels in HCC patients reflecting disease progression and overall hepatocyte damage

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