Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Table 1 Non-invasive biomarkers for early diagnosis of hepatocellular carcinoma

Type of biomarker	Examples
Proteins	AFP; DCP; GALAD score; HES algorithm; ASAP model
Metabolites	A panel based on phenylalanyl-tryptophan and glycocholate
Circulating cell-free DNAs	Somatic mutations; DNA methylation; 5-hydroxymethylcytosine
Circulating non-coding RNAs	Micro-RNAs (mirR-125b, miR-122, and miR-21); Circular RNAs; Long non-coding RNAs; Exosomal non-coding RNAs

AFP: Alpha-fetoprotein; DCP: Des-gamma-carboxy prothrombin; HCC: Hepatocellular carcinoma; RNA: Ribonucleic acid.

Table 2 Introduction of alpha-fetoprotein-based diagnostic models for hepatocellular carcinoma

Model	Parameters	Ref.	Notes
GALAD score	Gender, Age, AFP-L3, AFP, and DCP	[4,7,8]	Validated in different cohorts from Germany, Japan, Hong Kong, the United Kingdom; Surpassing the ability of ultrasound to predict HCC; Excelling in diagnosing early-stage HCC in the setting of cirrhosis or CHB or NASH
HES algorithm	Current level of AFP, rate of AFP change, level of alanine aminotransferase, platelet count, and age	[5,9,10]	Validated in the detection of HCC in patients with cirrhosis of any etiology; Superior to the AFP measuring alone in detecting early-stage HCC
ASAP model	Age, gender, AFP, and DCP	[6]	Validated in the presence of HCC in patients with CHB; Exhibiting 73.8% sensitivity and 90.0% specificity for detecting BCLC stage 0-A HCC

AFP: Alpha-fetoprotein; AFP-L3: Lens culinaris agglutinin-reactive fraction of AFP; BCLC: Barcelona clinic liver cancer; CHB: Chronic hepatitis B; DCP: Des-gamma-carboxy prothrombin; HCC: Hepatocellular carcinoma; NASH: Nonalcoholic steatohepatitis.