| Biomarker | CEA | Full name | Carcinoembryonic antigen | Molecular Type | Protein |
| Molecular Formula | Complex glycoprotein | Molecular Weight | ~180-200 kDa | Core Functional Dimensions | Aid in diagnosis and monitoring |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | iCCA, eCCA | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (immunoassay, ELISA) | ||
| Pathobiological Mechanisms | Abnormal expression of tumor cells, involved in tumor invasion and metastasis; A variety of benign diseases and other tumors may also increase | ||||
| Clinical Availability Status | Commonly used in clinic (auxiliary diagnosis); Low sensitivity and specificity | ||||
| Notes and Dynamics | Combined detection with CA19-9 can improve the diagnostic efficiency and can be used to dynamically monitor disease progression | ||||
| Biomarker | CA19-9 | Full name | Carbohydrate antigen 19-9 | Molecular Type | Protein |
| Molecular Formula | Carbohydrate antigen 19-9 | Molecular Weight | ~1000 Da | Core Functional Dimensions | Diagnosis, Prognosis |
| Disease(or Constitution) | Cholangiocarcinoma (CCA) | Disease Subtypes | Intrahepatic cholangiocarcinoma (iCCA), Extrahepatic cholangiocarcinoma (eCCA) | ||
| Organ | Bile duct/Liver | Test Sample / Technology Platform | Serum (immunoassay, ELISA) | ||
| Pathobiological Mechanisms | It is abnormally elevated in malignant tumors such as cholangiocarcinoma, and may also be elevated in benign biliary diseases such as obstruction and cholangitis. Those with negative Lewis antigen (about 5-10% of the population) do not secrete it | ||||
| Clinical Availability Status | Commonly used in clinic (auxiliary diagnosis); The specificity is limited, so it should be combined with other indicator | ||||
| Notes and Dynamics | It is often used in combination with CEA to monitor treatment response. The false positive rate is more than 50% in biliary obstruction, which limits its diagnostic value | ||||
| Biomarker | Liver enzymes (ALT/AST) | Full name | Alanine Aminotransferase / Aspartate Aminotransferase | Molecular Type | Proteins (enzymes) |
| Molecular Formula | Human ALT: C₁₁₀₇H₁₇₅₃N₂₉₃O₃₃₁S₆; Human AST: C₁₁₁₃H₁₇₆₁N₂₉₅O₃₃₅S₆ | Molecular Weight | ALT: ~120 kDa; AST: ~121 kDa | Core Functional Dimensions | Liver injury monitoring and disease assessment |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), other viral hepatitis | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (biochemical analysis, colorimetry) | ||
| Pathobiological Mechanisms | When liver cells are damaged, intracellular ALT/AST are released into the blood, and the degree of increase in enzyme activity is positively correlated with the extent and severity of liver cell injury. | ||||
| Clinical Availability Status | Clinical routine use: general liver injury monitoring index, non-specific. | ||||
| Notes and Dynamics | Sensitive indicators reflecting liver cell injury can quickly indicate liver inflammation or injury, but lack etiological specificity. It is necessary to combine with virological markers to determine whether it is caused by viral hepatitis. | ||||
| Biomarker | HBsAg (hepatitis B surface antigen) | Full name | Hepatitis B surface antigen | Molecular Type | Protein (viral antigen) |
| Molecular Formula | Human HBsAg: C₂₂₆H₃₄₈N₅₄O₆₂S₂ | Molecular Weight | ~24 kDa | Core Functional Dimensions | Diagnosis, infection status determination |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV) | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (ELISA, chemiluminescence) | ||
| Pathobiological Mechanisms | The surface protein of hepatitis B virus (HBV) expressed in liver cells after infection is a marker of viral infection. Persistent positivity indicates chronic infection. | ||||
| Clinical Availability Status | Clinical routine use: core screening and diagnostic markers, widely used. | ||||
| Notes and Dynamics | The first choice for screening hepatitis B virus infection is simple to operate and the cost is controllable, but its negative result cannot completely exclude infection (such as occult hepatitis B), so it needs to be combined with other indicators for comprehensive judgment. | ||||
| Biomarker | HBV-DNA/HCV-RNA | Full name | Hepatitis B Virus DNA / Hepatitis C Virus RNA | Molecular Type | Nucleic acid (viral nucleic acid) |
| Molecular Formula | HBV-DNA (genotype C): ~3.2 kb double-stranded DNA; HCV-RNA (genotype 1a): ~9.6 kb single-stranded RNA | Molecular Weight | HBV-DNA: ~1.06 MDa (per 3.2 kb); HCV-RNA: ~3.1 MDa (per 9.6 kb) | Core Functional Dimensions | Diagnosis, efficacy monitoring and prognosis |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV) | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (qPCR, digital PCR) | ||
| Pathobiological Mechanisms | HBV/HCV replicates in hepatocytes after infection. Viral nucleic acid is the direct evidence of the presence and replication activity of the virus, and its load reflects the severity of infection and the effect of treatment. | ||||
| Clinical Availability Status | Routine clinical use: core diagnostic and monitoring markers, included in the diagnosis and treatment guidelines. | ||||
| Notes and Dynamics | Viral nucleic acid detection is the "gold standard" for the etiological diagnosis and treatment response evaluation of viral hepatitis, with high specificity and sensitivity, and the core basis for guiding clinical medication adjustment. | ||||
| Biomarker | Short-chain fatty acids (SCFA, such as acetic acid, propionic acid, butyrate) | Full name | propionic acid, butyrate) Short-chain fatty acids (acetic acid, propionic acid, butyrate) | Molecular Type | Metabolites |
| Molecular Formula | Acetic acid: C₂H₄O₂; Propionic acid: C₃H₆O₂; Butyrate: C₄H₈O₂ | Molecular Weight | Acetic acid: 60.05 Da; Propionic acid: 74.08 Da; Butyrate: 88.11 Da | Core Functional Dimensions | Intestinal barrier maintenance, liver inflammation regulation |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related gut-liver axis dysfunction | ||
| Organ | Liver/Gut | Test Sample / Technology Platform | Stool and serum | ||
| Pathobiological Mechanisms | Gut microbiota metabolize the main products of dietary fiber and inhibit liver inflammation through GPR41/GPR43 receptors. Butyrate can promote the tight junction of intestinal epithelial cells and reduce the inflow of LPS into the blood. The decrease of SCFA level indicates the dysfunction of gut-liver axis | ||||
| Clinical Availability Status | Clinical research phase | ||||
| Notes and Dynamics | "Functional markers" of gut microbiota metabolism, levels of which are inversely correlated with MASLD and severity of cirrhosis, can be used to evaluate the efficacy of microbiota-modulating therapies such as prebiotics. Standardized methods are needed | ||||
| Biomarker | Platelet Count (PLT) | Full name | Platelet Count | Molecular Type | Cell types |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Diagnosis of liver cirrhosis and evaluation of portal hypertension | ||
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related cirrhosis | ||
| Organ | Liver | Test Sample / Technology Platform | Whole blood | ||
| Pathobiological Mechanisms | Thrombocytopenia due to hypersplenism in liver cirrhosis; PLT < 100×10⁹/L indicates the risk of portal hypertension; Combination of AST/ALT ratio (e.g., APRI index) can improve the accuracy of liver fibrosis assessment | ||||
| Clinical Availability Status | Routine clinical use | ||||
| Notes and Dynamics | Simple and easily available auxiliary markers of liver cirrhosis, although with low specificity (other diseases can also lead to PLT reduction), combined with other indicators (such as APRI and FIB-4) can significantly improve the clinical value and is an important screening tool in the primary care setting | ||||
| Biomarker | Enhanced Liver Fibrosis Testing (ELF™) | Full name | Enhanced Liver Fibrosis Testing | Molecular Type | Composite indicators (hyaluronic acid, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinase-1) |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Staging and prognosis of liver fibrosis | ||
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related cirrhosis | ||
| Organ | Liver | Test Sample / Technology Platform | Serum | ||
| Pathobiological Mechanisms | Based on the molecular markers related to liver fibrosis, it directly reflects the degree of liver fibrosis activity. It can predict the risk of complications of liver cirrhosis (such as variceal bleeding) and liver cancer | ||||
| Clinical Availability Status | Clinical research phase (used in clinical practice in some areas) | ||||
| Notes and Dynamics | Compared with FIB-4, it reflects fibrosis activity more accurately and is suitable for fibrosis staging of chronic liver diseases (such as MASLD and chronic hepatitis B). However, its high detection cost limits its large-scale popularization | ||||
| Biomarker | Fibrosis-4 index (FIB-4) | Full name | Fibrosis-4 index | Molecular Type | Composite index (AST, ALT, platelet, age) |
| Molecular Formula | Staging of liver fibrosis and risk assessment of cirrhosis | Molecular Weight | Core Functional Dimensions | ||
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related fibrosis | ||
| Organ | Liver | Test Sample / Technology Platform | Serum (all the required indicators for calculation are routine tests) | ||
| Pathobiological Mechanisms | Based on AST, ALT, platelet count and age, the degree of liver fibrosis was reflected by comprehensive indicators. FIB-4 < 1.45 indicates no advanced fibrosis, and FIB-4 > 3.25 indicates high risk | ||||
| Clinical Availability Status | Routine clinical use (as one of the preferred tools for non-invasive fibrosis assessment) | ||||
| Notes and Dynamics | These simple, inexpensive non-invasive markers are suitable for large-scale screening in the primary care setting. However, ELF™ and FibroScan should be combined for further evaluation in patients with intermediate values (1.45-3.25) | ||||
| Biomarker | Alpha-fetoprotein (AFP) | Full name | Alpha-fetoprotein | Molecular Type | Proteins |
| Molecular Formula | Human AFP: C₅₈₀H₉₁₃N₁₅₇O₁₇₄S₄ | Molecular Weight | ~69 kDa | Core Functional Dimensions | Liver cancer screening and therapeutic efficacy monitoring |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Viral hepatitis-related liver cancer (HCC) | ||
| Organ | Liver | Test Sample / Technology Platform | Serum | ||
| Pathobiological Mechanisms | Abnormal glycoprotein secreted by hepatocellular carcinoma cells is related to the proliferation activity of hepatocellular carcinoma; It is used for HCC screening (AFP > 400 ng/mL indicates high risk) and postoperative recurrence monitoring. However, the sensitivity is insufficient in early stage liver cancer (about 60%). | ||||
| Clinical Availability Status | Routine clinical use (as an adjunct to liver cancer screening) | ||||
| Notes and Dynamics | Although the traditional liver cancer markers have limited sensitivity, their combination with ultrasound and PIVKA-II can improve the early diagnosis rate. They are still the basic indicators for clinical management of liver cancer, and need to be optimized in combination with new markers (such as circulating tumor DNA) | ||||
| Biomarker | Gamma-glutamyltransferase (GGT) | Full name | Gamma-glutamyltransferase | Molecular Type | Enzymes |
| Molecular Formula | Human GGT: C₁₁₇₆H₁₈₄₈N₃₀₈O₃₄₈S₁₂ | Molecular Weight | ~130 kDa | Core Functional Dimensions | Evaluation of cholestasis, diagnosis of alcoholic liver disease, and monitoring of metabolic abnormalities |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), alcoholic viral hepatitis overlap | ||
| Organ | Liver | Test Sample / Technology Platform | Serum | ||
| Pathobiological Mechanisms | It is mainly present in hepatobiliary cells and increases in cholestasis and alcohol intake. It is positively correlated with the severity of alcohol-related liver disease (ALD). And can be used as an auxiliary marker of metabolic syndrome such as MASLD | ||||
| Clinical Availability Status | Routine clinical use | ||||
| Notes and Dynamics | It has high sensitivity but low specificity, and should be judged comprehensively in combination with clinical background (such as drinking history and other enzyme indicators). It is an important auxiliary diagnostic indicator for alcoholic liver disease and cholestatic diseases | ||||
| Biomarker | Alkaline phosphatase (ALP) | Full name | Alkaline phosphatase | Molecular Type | Enzymes |
| Molecular Formula | Human ALP (isoform liver/bone/kidney): C₁₀₈₀H₁₇₀₄N₂₈₈O₃₂₄P₆Zn₂ | Molecular Weight | ~240 kDa | Core Functional Dimensions | Diagnosis of cholestasis and identification of types of liver injury |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related cholestasis | ||
| Organ | Liver | Test Sample / Technology Platform | Serum | ||
| Pathobiological Mechanisms | They were mainly expressed in hepatobiliary epithelial cells and increased significantly in cholestasis. Combined with GGT, hepatocyte injury (ALT/AST mainly increased) and cholestatic injury (ALP/GGT mainly increased) could be distinguished. It is used for monitoring the efficacy of primary biliary cholangitis (PBC) | ||||
| Clinical Availability Status | Routine clinical use | ||||
| Notes and Dynamics | The core index for the diagnosis of cholestatic liver disease combined with GGT can improve the diagnostic specificity, and is an important tool for the classification and treatment monitoring of hepatobiliary diseases | ||||
| Biomarker | Hepatitis B surface antigen (HBsAg) and its subtypes: LHB, MHB, SHB | Full name | Hepatitis B surface antigen and its subtypes: Large Hepatitis B Surface Antigen, Middle Hepatitis B Surface Antigen, Small Hepatitis B Surface Antigen | Molecular Type | Proteins |
| Molecular Formula | Human HBsAg (SHB): C₂₂₆H₃₄₈N₅₄O₆₂S₂; LHB: C₄₃₋₄⁷ kDa subtype; MHB: C₃₋₄₂ kDa subtype | Molecular Weight | ~24 kDa (SHB), ~36 kDa (MHB), ~42 kDa (LHB) | Core Functional Dimensions | Diagnosis of viral infection, assessment of immune status, determination of treatment endpoint |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV) | ||
| Organ | Liver | Test Sample / Technology Platform | Serum | ||
| Pathobiological Mechanisms | Viral envelope proteins, whose subtypes are involved in the process of viral adsorption to hepatocytes and immune escape; Changes in the proportion of subtypes can indicate the stage of infection and treatment response, which is the core evaluation index for functional cure | ||||
| Clinical Availability Status | Markers are routinely used in clinical practice | ||||
| Notes and Dynamics | As the gold standard for the diagnosis of HBV infection, subtype analysis can improve the accuracy of disease staging and prognosis, and is a key target for vaccine development and new antiviral drugs, which needs to be optimized in combination with high-sensitivity detection techniques | ||||
| Biomarker | Gut microbiota (specific flora: Bifidobacterium, Lactobacilli, Enterobacteriaceae, etc.) | Full name | Gut microbiota (specific flora: Bifidobacterium, Lactobacilli, Enterobacteriaceae, etc.) | Molecular Type | Microbial communities |
| Molecular Formula | Molecular Weight | Core Functional Dimensions | Metabolic regulation, immune regulation, gut-liver axis regulation | ||
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related fibrosis | ||
| Organ | Liver/Gut | Test Sample / Technology Platform | Stool, Serum | ||
| Pathobiological Mechanisms | Through metabolites (short-chain fatty acids, LPS) to affect liver immune and inflammatory response; The imbalance of microbiota (the increase of harmful bacteria and the decrease of beneficial bacteria) destroys the intestinal barrier and promotes the occurrence of liver fibrosis and liver cancer | ||||
| Clinical Availability Status | Clinical research phase | ||||
| Notes and Dynamics | As a non-invasive marker, it can reflect the function of gut-liver axis, and its modulation therapy (probiotics and prebiotics) has shown potential in adjuvant treatment. However, the composition of the microbiota is highly heterogeneous, and standardized detection and analysis methods are needed | ||||
| Biomarker | Fibrinogen-like protein 2 (FGL2) | Full name | Fibrinogen-like protein 2 | Molecular Type | Proteins |
| Molecular Formula | Human FGL2: C₅₈₈H₉₂₇N₁₅₉O₁₈₀S₆ | Molecular Weight | ~132 kDa | Core Functional Dimensions | Coagulation regulation, immunosuppression, disease progression |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related fibrosis/cancer | ||
| Organ | Liver | Test Sample / Technology Platform | Serum and tissue samples | ||
| Pathobiological Mechanisms | The membrane type (mFGL2) has prothrombin activity and promotes thrombosis. Soluble (sFGL2) inhibits immune cell function and aggravates liver fibrosis and tumor progression | ||||
| Clinical Availability Status | Clinical research phase | ||||
| Notes and Dynamics | It is involved in the pathological process of a variety of liver diseases, and is a potential therapeutic target and marker for viral hepatitis, liver cancer and other diseases. However, its versatility increases the complexity of clinical application, and targeted intervention strategies need to be developed | ||||
| Biomarker | Fibrin-like protein 1 (FGL1) | Full name | Fibrin-like protein 1 | Molecular Type | Proteins |
| Molecular Formula | Human FGL1: C₆₉₉H₁₁₀₇N₁₈₉O₂₁₀S₆ | Molecular Weight | ~156 kDa | Core Functional Dimensions | Liver injury repair, metabolic regulation, tumor immunity |
| Disease(or Constitution) | Viral Hepatitis | Disease Subtypes | Hepatitis B (HBV), Hepatitis C (HCV), viral hepatitis-related liver cancer | ||
| Organ | Liver | Test Sample / Technology Platform | Serum, tumor tissue | ||
| Pathobiological Mechanisms | Promote hepatocyte proliferation and liver regeneration, participate in lipid metabolism; As LAG-3 ligand, it inhibits T cell activity and promotes tumor immune escape, which is related to the progression of liver cancer | ||||
| Clinical Availability Status | Clinical research phase | ||||
| Notes and Dynamics | It has a protective effect in the repair of liver injury, but has a carcinogenic effect in liver cancer, and its function is dual. As an immunotherapy target and disease marker, it has potential clinical transformation value, and the mechanism of action needs to be further clarified | ||||