Primary liver cancer (PLC, hereinafter referred to as liver cancer) is a common malignant tumor. Because of insidious onset, no or no obvious symptoms in early stage, and rapid progress, most patients have reached locally advanced stage or distant metastasis when diagnosed, which makes treatment difficult and prognosis very poor. Primary hepatocellular carcinoma mainly includes different pathological types such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma, which have obvious differences in their pathogenesis, biological behavior, histological morphology, clinical manifestations, treatment methods and prognosis; since HCC accounts for more than 90% of them, what this article refers to “(i) Monitoring and screening of high-risk groups The etiological factors of hepatocellular carcinoma in China mainly include hepatitis virus infection, food aflatoxin contamination, long-term alcohol abuse and blue-green algae toxin contamination of rural drinking water, other liver metabolic diseases, autoimmune diseases and cryptogenic liver disease or cryptogenic cirrhosis. Hepatocellular carcinoma can be diagnosed at an early stage. Since early diagnosis of liver cancer is crucial for effective treatment and long-term survival, early screening and early surveillance of liver cancer are highly emphasized. Routine surveillance and screening indicators include serum alpha-fetoprotein (AFP) and liver ultrasonography (US). Screening is generally performed at 6-month intervals for men ≥40 years of age or women ≥50 years of age with HBV and/or HCV infection, alcoholism, comorbid diabetes mellitus, and a family history of liver cancer in high-risk groups. It is generally believed that AFP is a relatively specific tumor marker for HCC, and persistent elevation of AFP is a risk factor for the development of HCC. Recently, some European and American scholars believe that the sensitivity and specificity of AFP is not high, and the 2010 edition of the American Association for the Study of Liver Diseases (AASLD) guidelines no longer use AFP as a screening indicator, but most of HCC in China is associated with HBV infection, which is different from the causative factors of HCC in western countries (mostly HCV, alcohol and metabolic factors), and combined with the results of domestic randomized studies (RCT) and the actual (b) Clinical manifestations 1. Pre-subclinical stage of hepatocellular carcinoma refers to the period from the beginning of the lesion to the diagnosis of subclinical hepatocellular carcinoma, when patients have no clinical symptoms and signs and are difficult to be detected clinically, usually about 10 months. In the subclinical stage (early stage) of hepatocellular carcinoma, the tumor is about 3-5 cm, most patients still have no typical symptoms, so the diagnosis is still difficult, and it is mostly detected by serum AFP census for about 8 months on average, during which a few patients can have symptoms related to chronic underlying liver disease such as epigastric distention, abdominal pain, weakness and loss of appetite. Therefore, for those with high-risk factors, the possibility of hepatocellular carcinoma should be alerted to the occurrence of the above-mentioned conditions. Once the typical symptoms appear, the disease has often reached the middle or advanced stage of liver cancer, at this time, the disease develops rapidly, about 3-6 months in total, and its main manifestations are: (1) pain in the liver area. Pain in the right upper abdomen is the most common and is an important symptom of the disease. It is often intermittent or persistent vague, dull or distending pain, which increases with the development of the disease. If the tumor invades the diaphragm, the pain may spread to the right shoulder or the right back; the tumor growing backward to the right may cause pain in the right lumbar region. The cause of pain is mainly due to the tumor growth which makes the liver envelope tense. Sudden onset of severe abdominal pain and peritoneal irritation may be due to peritoneal irritation caused by rupture and bleeding of subhepatic peritoneal cancer nodules. (2) Loss of appetite. Symptoms such as epigastric fullness after meals, indigestion, nausea, vomiting and diarrhea are easy to be ignored because of the lack of specificity. (3) Wasting and weakness. The whole body is weak, and a few advanced patients may present a cachectic condition. (4) Fever. It is more common, mostly persistent low fever, around 37.5-38℃, or irregular or intermittent, persistent or chilling fever, similar to liver abscess, but no chills before fever, and antibiotic treatment is ineffective. The fever is mostly cancer fever, which is related to the absorption of tumor necrotic material; sometimes it can be caused by cholangitis due to the compression or invasion of bile duct by cancer, or fever due to other infections combined with weakened resistance. (5) Symptoms of extrahepatic metastases. For example, lung metastasis can cause cough and hemoptysis; pleural metastasis can cause chest pain and bloody pleural effusion; bone metastasis can cause bone pain or pathological fracture, etc. (6) Jaundice, bleeding tendency (gingival, nasal bleeding and subcutaneous bruises), upper gastrointestinal bleeding, hepatic encephalopathy and hepatic and renal failure are often seen in advanced stage patients. (7) Paraneoplastic syndrome, which is a syndrome of endocrine or metabolic disorders caused by the abnormal metabolism of liver cancer tissue itself or the multiple effects of cancer tissue on the body. The clinical manifestations are diverse and lack of specificity, including spontaneous hypoglycemia, erythrocytosis, hyperlipidemia, hypercalcemia, precocious puberty, gonadotropin secretion syndrome, cutaneous porphyria, abnormal fibrinogenemia and carcinoid syndrome, but they are relatively rare. 2. Physical signs. In the early stage of hepatocellular carcinoma, most patients do not have obvious positive signs, and only a few patients can find mild hepatomegaly, jaundice and skin pruritus on physical examination, which should be non-specific manifestations of the underlying liver disease. In intermediate to advanced hepatocellular carcinoma, jaundice, liver enlargement (hard texture, uneven surface, with or without nodules, vascular murmur) and peritoneal effusion are common. If there is a background of hepatitis and cirrhosis, liver palms, spider nevus, red nevus, abdominal wall varices and splenomegaly can be found. (1) Liver enlargement: It is often progressively enlarged, with hard texture, uneven surface, nodules of different sizes or even giant lumps, with clear margins and often painful to touch and pressure of varying degrees. If the hepatocellular carcinoma protrudes to the right subcostal arch or subxiphoid process, the corresponding area can be seen to be locally full and elevated; if the carcinoma is located on the diaphragmatic surface of the liver, it mainly shows limited elevation of the diaphragm without enlargement of the lower edge of the liver; the carcinoma nodules located on the surface of the liver near the lower edge are most easily palpable. (2) Vascular murmur: Due to the rich and tortuous blood vessels of hepatocellular carcinoma and the sudden thinning of arteries or the compression of hepatic artery and abdominal aorta by cancer mass, about half of the patients can hear wind-like vascular murmur in the corresponding area; this sign has important diagnostic value, but it is not significant for early diagnosis. (3) Jaundice: yellow staining of the skin and sclera, often appearing in the late stage, mostly due to obstruction of the bile duct caused by the cancer or enlarged lymph nodes, or due to hepatocellular damage. (4) Portal hypertension: Patients with hepatocellular carcinoma mostly have a background of cirrhosis, so they often have portal hypertension and splenomegaly. Bloody effusion is mostly caused by cancer breaking into the peritoneal cavity, and can also be caused by peritoneal metastasis; portal vein and hepatic vein cancer embolism can accelerate the growth of peritoneal effusion. 3.Infiltration and metastasis. (1) Intrahepatic metastasis: initially, most hepatocellular carcinoma is intrahepatic metastasis, which easily invades portal vein and its branches and forms tumor embolus, and causes multiple metastases in the liver after shedding. If the stem branch of portal vein is obstructed, it will often cause or aggravate the existing portal hypertension. (2) Extrahepatic metastasis: ①Lung metastasis is the most common, but it can also be metastasized to pleura, adrenal gland, kidney and bone. (2) Lymphatic metastasis, the most common metastasis is from the hilar lymph nodes, but also to the pancreas, spleen and para-aortic lymph nodes, and occasionally to the supraclavicular lymph nodes. Occasionally, the metastasis can be planted in the peritoneum, diaphragm and thorax, causing bloody abdominal and thoracic effusion; in women, ovarian metastasis can occur and form larger masses. 4.Common complications. (1) Upper gastrointestinal bleeding: Hepatocellular carcinoma often has hepatitis and cirrhosis background with portal hypertension, and portal vein and hepatic vein cancer thrombus can further aggravate portal hypertension, so it often causes bleeding from varices of middle and lower esophagus or gastric fundus. If cancer cells invade the bile duct, it may cause biliary bleeding, vomiting blood and black stool. Some patients may bleed extensively due to gastrointestinal mucosa erosion, ulceration and coagulation dysfunction, and heavy bleeding may lead to shock and hepatic coma. (2) Hepatorenal nephropathy and hepatic encephalopathy (hepatic coma): In advanced stage of hepatocellular carcinoma, especially diffuse hepatocellular carcinoma, hepatic insufficiency or even failure can occur, causing hepatorenal syndrome (HRS), i.e. functional acute renal failure (FARF), which mainly manifests as Significant oliguria and decreased blood pressure with hyponatremia, hypokalemia and azotemia, often progressive. Hepatic encephalopathy (HE), i.e. hepatic coma, is often a manifestation of end-stage hepatocellular carcinoma and is often induced by gastrointestinal bleeding, massive diuretics, electrolyte disorders and secondary infections. (3) Rupture and bleeding of hepatocellular carcinoma nodes: It is the most urgent and serious complication of hepatocellular carcinoma. Therefore, gentle palpation is recommended during clinical examination and no forceful pressure should be applied. The rupture of cancer nodules can be confined to the subhepatic peritoneum, causing acute pain and rapid enlargement of the liver, and soft masses can be palpated locally. A small amount of bleeding can be manifested as bloody peritoneal fluid, while a large amount of bleeding can lead to shock or even rapid death. (4) Secondary infection: Patients with hepatocellular carcinoma have weakened resistance due to long-term consumption and bed-rest, especially after chemotherapy or radiotherapy when their white blood cells are reduced, which can easily lead to various infections, such as pneumonia, intestinal infection, fungal infection and sepsis, etc. (C) Auxiliary examination 1. Blood biochemical examination. Hepatocellular carcinoma may show elevation of portal aminotransferase (AST or GOT) and glutamate aminotransferase (ALT or GPT), serum alkaline phosphatase (AKP), lactate dehydrogenase (LDH) or bilirubin, and abnormal liver function such as lower albumin, as well as changes of immune indexes such as lymphocyte subpopulation. Positive hepatitis B surface antigen (HBsAg) or five quantitative tests (including HBsAg, HBeAg, HBeAb and anti-HBc) and/or positive hepatitis C antibodies (anti-HCVIgG, anti-HCVst, anti-HCVns and anti-HCVIgM) are all important signs of hepatitis virus infection. HBV DNA and HCV mRNA can reflect hepatitis viral load. Serum AFP and its heteroplasm are important indicators and the most specific tumor markers for the diagnosis of hepatocellular carcinoma, and are commonly used for screening, early diagnosis, postoperative monitoring and follow-up of hepatocellular carcinoma in China. For AFP ≥ 400 μg/L for more than 1 month or ≥ 200 μg/L for 2 months, excluding pregnancy, germinal gland embryonal carcinoma and active liver disease, liver cancer should be highly suspected; the key is whether imaging examination (CT/MRI) with characteristic occupancy of liver cancer is performed at the same time. There are still 30%-40% of liver cancer patients with negative AFP test, including ICC, highly differentiated and hypofractionated HCC, or HCC with necrotic liquefaction, AFP may not be increased. Therefore, AFP alone cannot diagnose all hepatocellular carcinoma. The positive rate of AFP for hepatocellular carcinoma diagnosis is generally 60%-70%, and sometimes it varies greatly, emphasizing the need for regular testing and dynamic observation, and the need for imaging or even ultrasound-guided puncture biopsy to clarify the diagnosis. Other markers that can be used to aid in the diagnosis of HCC are various serum enzymes, including r-glutamyl transpeptidase (GGT) and its isoenzymes, alpha-L-arginase (AFU), abnormal prothrombin (DCP), Golgi protein 73 (GP73), 5-nucleotide phosphodiesterase (5’NPD) isoenzyme, aldolase isoenzyme A (ALD-A) and placental glutathione S -transferase (GST), etc., and abnormal prothrombin (DCP), ferritin (FT) and acid ferritin (AIF). Some patients with HCC may have abnormal increase of carcinoembryonic antigen (CEA) and glycoantigen CA19-9, etc. 3.Imaging examination (1) abdominal ultrasound (US) examination: US examination has become the most common and important method for liver examination because of its easy operation, intuition, non-invasiveness and low cost. This method can determine whether there are occupying lesions in the liver, suggest their nature, identify whether they are fluid or substantial occupations, clarify the specific location of cancer foci in the liver and their relationship with important blood vessels in the liver, so as to guide the selection of treatment methods and surgery; it helps to understand the spread and infiltration of liver cancer in the liver and adjacent tissues and organs. It is of great reference value for the differential diagnosis of hepatocellular carcinoma and liver cysts, hepatic hemangioma and other diseases, but its sensitivity and qualitative accuracy of detection are somewhat affected by the limitations of instrumentation, anatomical site, operator’s technique and experience, etc. Real-time US imaging (ultrasonography CEUS) can dynamically observe the hemodynamic situation of the lesion and help improve the qualitative diagnosis, but it can be false positive for ICC patients and should be noted; while intraoperative US probes directly from the surface of the liver after opening, which can avoid ultrasound attenuation and interference from the abdominal wall and ribs, and can detect small intrahepatic lesions that are not detected by preoperative imaging. (2) Computed tomography (CT): it is the most important imaging method for diagnosis and differential diagnosis of hepatocellular carcinoma, which is used to observe the morphology and blood supply of hepatocellular carcinoma, to detect, characterize and stage hepatocellular carcinoma, and to review hepatocellular carcinoma after treatment; CT has high resolution, especially multi-row spiral CT, which is extremely fast and can scan the whole liver within a few seconds, avoiding breathing motion artifacts; it can perform multi-phase dynamic The minimum layer thickness is 0.5mm, which significantly improves the detection rate and qualitative accuracy of small lesions of liver cancer. Usually, under plain scan, most hepatocellular carcinomas are low-density occupants with different manifestations of clear or blurred edges, some of them have halo signs, and large hepatocellular carcinomas often have central necrosis and liquefaction; it can indicate the nature of lesions and understand whether there are cancer foci in the surrounding tissues and organs of the liver, which can help the localization of radiotherapy; in addition to clearly showing the number, size, morphology and intensification characteristics of lesions, enhanced scan can also clarify the relationship between lesions and important blood vessels, and the relationship between the hilum and the abdomen. In addition to clearly showing the number, size, morphology and enhancement characteristics of the lesion, it can also clarify the relationship between the lesion and important blood vessels, the relationship between the liver gate and the abdominal cavity, the presence of lymph node enlargement and the invasion of adjacent organs, which provides a reliable basis for accurate clinical staging and helps identify hepatic hemangioma. The typical imaging presentation of HCC is significant enhancement in the arterial phase, which is less than that of the surrounding liver tissue in the venous phase, while the contrast continues to fade in the delayed phase, and is therefore highly specific. (3) Magnetic resonance imaging (MRI or MR): no radioactive radiation, high tissue resolution, multi-directional and multi-sequence imaging, superior to CT and US in terms of display and resolution of tissue structural changes inside the hepatocellular carcinoma lesion, such as hemorrhagic necrosis, steatosis and envelope; may be superior to CT in the differentiation of benign and malignant intrahepatic occupancies, especially with hemangioma; meanwhile, it can show the branches of portal vein and hepatic vein without enhancement. MRI is superior to CT for small hepatocellular carcinomas, for which there is more evidence. In particular, the increasing popularity and development of high field strength MR equipment has greatly accelerated the speed of MR scanning, which can be completed with thin layer and multi-phase dynamic enhancement scanning like CT, fully displaying the enhancement characteristics of the lesion and improving the detection rate and qualitative accuracy of the lesion. In addition, MR functional imaging techniques (such as diffusion-weighted imaging, perfusion-weighted imaging, and spectral analysis) and the use of hepatocyte-specific contrast agents can provide valuable additional information for lesion detection and characterization, which can further improve the sensitivity and accuracy of hepatocellular carcinoma detection and characterization, as well as the comprehensive and accurate assessment of the efficacy of various local treatments. The above three important imaging techniques have their own characteristics and complementary advantages, and should be emphasized for comprehensive examination and overall assessment. (4) Selective hepatic arteriography (DSA): Currently, digital subtraction angiography is mostly used to clearly show small lesions in the liver and their blood supply, while chemotherapy and iodine oil embolization can be performed. The main manifestations of hepatocellular carcinoma in DSA are: ① tumor vessels, which appear in the early arterial phase; ② tumor staining, which appears in the parenchymal phase; ③ larger tumors can be seen as displacement, straightening and twisting of intrahepatic arteries; ④ intrahepatic arteries invaded by hepatoma can appear as jagged, beaded or stiff; ⑤ arteriovenous fistula; “pool-like” or (5) arteriovenous fistula; “pool” or “lake” contrast-filled area, etc. The significance of DSA examination not only lies in the diagnosis and differential diagnosis, but also can be used to estimate the extent of the lesion before surgery or treatment, especially to understand the situation of disseminated sub-nodules in the liver; it can also provide correct and objective information on the anatomical variation of vessels and the anatomical relationship of important vessels as well as portal vein infiltration, which is of great value in judging the possibility and completeness of surgical resection and deciding the reasonable treatment plan. DSA is an invasive and invasive test and can be used for patients whose diagnosis cannot be confirmed after other tests. In addition, for resectable hepatocellular carcinoma, even if the imaging shows limited resectable hepatocellular carcinoma, some scholars advocate preoperative DSA, which has the potential to detect lesions that cannot be detected by other imaging means and clarify the presence of vascular invasion. (5) Positron emission computed tomography (PET-CT): PET-CT is a functional molecular imaging system integrating PET and CT, which can reflect the biochemical and metabolic information of liver occupancy by PET functional imaging, and precisely locate the lesion by CT morphological imaging, and the whole-body scan can understand the overall condition and evaluate the metastasis to achieve early detection of the lesion. The purpose of early detection of lesions can be achieved, and the size and metabolic changes before and after tumor treatment can be understood. However, the sensitivity and specificity of PET-CT for clinical diagnosis of liver cancer need to be further improved, and it has not yet been popularly used in most hospitals in China, so it is not recommended as a routine examination for liver cancer diagnosis, but can be used as a supplement to other means. (6) Emission single photon computed tomography (ECT): ECT whole-body bone imaging is helpful for the diagnosis of bone metastasis of liver cancer, and can detect bone metastasis 3-6 months earlier than X-ray and CT examination. 4.Liver aspiration biopsy . Core biopsy or fine needle aspiration (FNA) can be performed under ultrasound guidance for histological or cytological examination to obtain pathological diagnosis of hepatocellular carcinoma and molecular markers, which are very important for definite diagnosis, pathological type, judgment of disease, guidance of treatment and prognosis assessment. It is very important for definite diagnosis, pathological type, judgment, treatment and prognosis, and has been increasingly used in recent years, but it also has certain limitations and risks. When performing liver puncture biopsy, care should be taken to prevent liver bleeding and needle tract cancer cell implantation; contraindications are patients with obvious bleeding tendency, severe cardiopulmonary, cerebral and renal disorders and systemic failure. (D) Diagnostic criteria of hepatocellular carcinoma 1. Pathological diagnostic criteria: biopsy or surgical excision of tissue specimens from occupied liver lesions or extrahepatic metastases, diagnosed as HCC by pathological histological and/or cytological examination, which is the gold standard. 2. Clinical diagnostic criteria: Among all solid tumors, only HCC can be diagnosed using clinical diagnostic criteria, which are recognized both domestically and externally as non-invasive, simple, convenient and operable, and are generally considered to depend on three major factors, namely, the background of chronic liver disease, imaging findings and serum AFP level; however, the understanding and specific requirements of academia vary and often change, and there are errors in practical application. Therefore, taking into account China’s national situation, previous domestic standards and clinical practice, the expert group proposed that a strict control and joint analysis is advisable, requiring that the clinical diagnosis of HCC can be established when both (1)+(2)a or (1)+(2)b+(3) of the following conditions are met: (1) evidence of cirrhosis and HBV and/or HCV infection (HBV and/or HCV antigen-positive) (2) typical imaging features of HCC: simultaneous multi-row CT scan and/or dynamic contrast-enhanced MRI showing rapid heterogeneous vascularity in the arterial phase and rapid washout in the venous or delayed phase. (1) If the diameter of liver occupancy is ≥ 2 cm, one of the two imaging examinations of CT and MRI shows that the liver occupancy has the characteristics of hepatocellular carcinoma mentioned above, HCC can be diagnosed; (2) If the diameter of liver occupancy is 1-2 cm, both imaging examinations of CT and MRI need to show that the liver occupancy has the characteristics of hepatocellular carcinoma mentioned above before HCC can be diagnosed to enhance the specificity of diagnosis. (3) Serum AFP ≥ 400 μg/L for 1 month or ≥ 200 μg/L for 2 months, and other causes of elevated AFP can be excluded, including pregnancy, germline embryonic-derived tumors, active liver disease and secondary liver cancer. 3. Precautions and instructions. (1) Several foreign guidelines (including AASLD, EASL and NCCN’s CPGs) emphasize that multi-row CT scans and/or dynamic contrast-enhanced MRI examinations should be performed for hepatic occlusions and should be performed at experienced imaging centers; also, it is believed that the exact HCC imaging diagnosis requires a four-phase scan with a plain phase, an arterial phase, a venous phase and a delayed phase, and the lesion Local thin scan of 5 mm should be performed, and the important role of arterial phase enhancement in imaging is highly valued. HCC is characterized by early arterial lesions that can be significantly enhanced with higher density than normal liver tissue, and rapid disappearance of enhancement in the venous phase with lower density than surrounding normal liver tissue. If the imaging features of liver occupancy are atypical, or the two CT and MRI examinations are inconsistent, liver puncture biopsy should be performed, but even if the negative result does not completely exclude, follow-up observation is still required. (2) In recent years, clinical observations and research results at home and abroad have suggested that serum AFP can also be elevated in some patients with ICC and liver metastases from gastrointestinal cancer, and ICC is also mostly accompanied by cirrhosis. Although the incidence of ICC is much lower than that of HCC, both are commonly seen in patients with cirrhosis; therefore, liver-occupying lesions with elevated AFP do not necessarily mean HCC and need to be carefully differentiated. In China and most countries in the Asia-Pacific region, patients with significantly elevated AFP are more likely to have HCC, which still has a differential value compared with ICC, and is therefore used here as a diagnostic index for HCC. (3) For those with serum AFP ≥ 400 μg/L and no liver occupancy detected by ultrasound, attention should be paid to exclude pregnancy, germline embryonic-derived tumors, active liver disease and gastrointestinal liver-like adenocarcinoma; if it can be excluded, multi-row CT and/or dynamic contrast-enhanced MRI scan must be performed promptly. The diagnosis of HCC is made if typical HCC imaging features are presented (rich vascularity in the arterial phase with regression in the portal or delayed phase.) If the findings or vascularity are not typical, contrast-enhanced examination with other imaging modalities or liver biopsy of the lesion should be performed. Arterial phase enhancement alone without venous phase regression is not sufficient evidence for the diagnosis of HCC. If AFP is elevated but not at diagnostic levels, in addition to the above-mentioned conditions that may cause increased AFP should be ruled out, it is important to closely observe and follow the changes in AFP by reducing the interval between ultrasound examinations to 1-2 months and performing CT and/or MRI dynamic observation when needed. If hepatocellular carcinoma is highly suspected, further selective hepatic arteriography (DSA) is recommended, and liver aspiration biopsy may be performed if necessary and appropriate. (4) For those who have hepatic occupying lesions, but no elevated serum AFP and no imaging features of hepatocellular carcinoma on imaging, if the diameter is <1 cm, they can be closely observed. If no vascular enhancement is seen in dynamic imaging of the liver occupancy, malignancy is unlikely. If the occupancy gradually increases or reaches ≥2 cm in diameter, further examination such as ultrasound-guided liver aspiration biopsy should be performed. Even if the liver biopsy result is negative, it should not be easily dismissed and should be followed up; imaging follow-up should be performed at 6-month intervals until the lesion disappears, increases in size, or presents diagnostic features of HCC; if the lesion increases in size but still does not have typical HCC changes, repeat liver biopsy can be considered. (5) It should be noted that 5%-20% of patients with HCC in China do not have a background of cirrhosis, about 10% have no evidence of HBV/HCV infection, and about 30% have serum AFP consistently <200 μg/L; also, most of the imaging HCC has features of rich vascularity, but a few do show lack of vascularity. In addition, in Europe and the United States, patients with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and then HCC (NASH-related HCC), and there have been more reports, but there is a lack of relevant data in China. (E) Differential diagnosis 1. When the serum AFP is positive, HCC should be differentiated from the following diseases: (1) chronic liver disease: such as hepatitis, cirrhosis, the patient's serum AFP level should be dynamically observed. When liver disease is active, AFP is mostly active in the same direction as ALT, and is mostly transient or fluctuates repeatedly, usually not exceeding 400 μg/L for a short period of time. If the curves of AFP and ALT are separated, AFP rises while SGPT falls, i.e., AFP and ALT are heterogeneously active and/or AFP is persistently high, then the possibility of HCC should be alerted. (2) Tumors such as pregnancy, gonadal or embryonic type: Identification is mainly by history, physical examination, abdominopelvic ultrasound and CT examination. (3) Gastrointestinal tumors: Some adenocarcinomas in the gastrointestinal tract and pancreas can also cause elevated serum AFP, called hepatoid adenocarcinoma. In addition to detailed medical history, physical examination and imaging, the determination of serum AFP heterogeneity can help to identify the origin of the tumor. For example, in gastric liver-like adenocarcinoma, AFP is dominated by lentil agglutinin unconjugated type. When serum AFP is negative, HCC should be differentiated from the following diseases: (1) secondary hepatocellular carcinoma: mostly seen in metastases from GI tract tumors, but also common in lung cancer and breast cancer. Patients may not have a background of liver disease, but may have a history of GI tumor manifestations such as blood in stool, fullness, anemia, and weight loss, and normal serum AFP, while GI tumor markers such as CEA, CA199, CA50, CA724, and CA242 may be elevated. (2) The typical image of metastatic tumor can be seen as "bull's-eye sign" (a halo around the mass and hypoechoic or hypointense in the center due to the lack of blood supply); (3) Enhanced CT or DSA imaging can show that the tumor is less vascular and the blood supply is not as rich as that of HCC; (4) Gastrointestinal endoscopy or X-ray imaging may reveal the presence of tumor vessels. (4) Gastrointestinal endoscopy or X-ray imaging may reveal the primary cancerous lesions in the gastrointestinal tract. (2) Intrahepatic cholangiocarcinoma (ICC): it is a rare pathological type of primary hepatocellular carcinoma, with a predilection for age 30-50 years old, non-specific clinical symptoms and no background of liver disease. However, the most meaningful CT scan shows that the blood supply to the liver is not as rich as that of HCC, and the fibrous component is more, and there is delayed enhancement with "fast-in, slow-out" characteristics. Sometimes irregular dilatation of intrahepatic bile ducts can be seen; there can also be localized hepatic lobe atrophy and invagination of liver envelope, and sometimes there are linear high-density shadows in the parenchyma of liver tumor (linear sign). The diagnostic rate of imaging examination is not high, and it mainly relies on pathological examination after surgery to confirm. (3) Hepatic sarcoma: it often has no background of liver disease, and imaging examination shows a homogeneous solid occupancy with rich blood supply, which is not easily distinguished from AFP-negative HCC. (4) benign liver lesions: including: ① hepatic adenoma: often without a background of liver disease, more females, often with a history of oral contraceptive use, not easily distinguished from highly differentiated HCC, the more meaningful test for differentiation is 99mTc nuclear scan, hepatic adenoma can take up nuclear, and the delayed phase shows a strong positive image; ② hepatic hemangioma: often without a background of liver disease, more females, CT-enhanced scans can be seen from the periphery of the occupancy reinforcement filling (2) Hepatic hemangioma: often without a background of liver disease, more females, CT scan shows the filling from the periphery of the occupancy, with "fast in and slow out", which is different from the "fast in and fast out" of HCC, and MRI shows the typical "light bulb sign"; (3) Hepatic abscess: often with a history of dysentery or septic disease without a history of liver disease Ultrasound examination is often confused with hepatocellular carcinoma when the abscess is not liquefied or pus thick, and after liquefaction, it shows liquid dark area, which should be distinguished from central necrosis of hepatocellular carcinoma; DSA imaging does not have tumor vessels and staining. If necessary, fine needle aspiration can be performed at the pressure point. Anti-amoebic test treatment is a better differential diagnosis method. The liver is progressively enlarged, hard and nodular, and most of the liver is destroyed in the advanced stage, and the clinical manifestations can be very similar to liver cancer; however, the disease generally has a long course, often with a history of many years, and progresses slowly. Intradermal test (Casoni test) is a specific test with a positive rate of 90-95%. Ultrasound examination can reveal strong echogenicity of floating cysts in the cystic space, and CT sometimes reveals calcified head nodes in the cyst wall. Puncture biopsy is not recommended because of the serious allergic reaction that can be induced. (vi) Pathological diagnosis Pathological histological and/or cytological examination is the basis for the gold standard diagnosis of hepatocellular carcinoma, but it is still necessary to pay attention to the combination with clinical evidence when making pathological diagnosis, and to fully understand the patient's HBV/HCV infection, the results of serum AFP and other tumor markers, as well as the imaging features of liver occupancy. Currently, new modern molecular biology techniques based on genomics, proteomics and metabolic enzymology are being established and applied, which will have higher specificity and accuracy and may help predict tumor response to treatment, propensity for metastatic recurrence, and prognosis. In pathological diagnosis, the following three main pathological types should be defined as well as other rare types of cancer should be noted: 1. Hepatocellular carcinoma (HCC): It accounts for more than 90% of primary liver cancer and is the most common type of pathology. (1) Gross typing: It can be divided into nodular, massive and diffuse types; also refer to the classification of "five large and six subtypes" developed by the Chinese Hepatocellular Carcinoma Pathology Research Collaborative Group in 1977. The tumor diameter <1 cm is called microscopic cancer, 1-3 cm is called small liver cancer, 3-5 cm is called medium liver cancer, 5-10 cm is called large liver cancer, >10 cm is called massive liver cancer, and small foci scattered throughout the liver (similar to cirrhotic nodules) are called diffuse liver cancer. At present, the criteria for small hepatocellular carcinoma in China are: the maximum diameter of a single cancer nodule is ≤3cm; the number of multiple cancer nodules does not exceed 2, and the total maximum diameter is ≤3cm. small hepatocellular carcinoma is small in size, mainly single nodular and swelling growth, with clear demarcation or envelope formation with surrounding liver tissues, and has the characteristics of slow growth, low malignancy, low possibility of metastasis and better prognosis. (2) Histologic features: the cancer cells are mainly arranged in the form of beams and cords, with polygonal shape, eosinophilic cytoplasm, round nuclei, and blood sinusoids lining between the beams and cords, and there can be many special types of cytology and histology. The degree of differentiation of cancer cells can be classified by the classical Edmondson-Steiner four-grade grading method for hepatocellular carcinoma, or into good, intermediate and poor grades. (3) Representative immunohistochemical markers: hepatocyte antigen (Hep Par1) shows cytoplasmic positivity, polyclonal carcinoembryonic antigen (pCEA) shows positive cell membrane capillaries, CD34 shows diffuse distribution of hepatic sinusoidal microvessels, and phosphatidylinositol protein-3 (GPC-3) is usually expressed in the cytoplasm of HCC cancer cells. Histopathological examination of liver biopsy for small lesions should be performed and evaluated by experienced pathologists; GPC-3, heat shock protein 70 (HSP) and glutamine synthetase (GS) staining can be performed, and if two of the three items are positive, HCC can be diagnosed. 2. Intrahepatic cholangiocarcinoma (ICC): less common, originating from the epithelial cells of the bile ducts far from the secondary branches of the intrahepatic bile ducts, generally accounting for only It generally accounts for only Q5% of primary hepatocellular carcinoma. (1) Gross typing: It can be divided into nodular, periductal infiltrative, nodular infiltrative and intraductal growth type. (2) Histologic features: adenocarcinoma structure is predominant, and cancer cells are arranged into a glandular lumen similar to bile ducts, but the glandular lumen does not contain bile but secretes mucus. The cancer cells are rectangular or low columnar in shape, with lightly stained cytoplasm, transparent cytoplasm and abundant fibrous interstitium, i.e. the cancer cells are surrounded by more fibrous tissue. There are also several cytologic and histologic specific types, and if there is beam-like arrangement, it may resemble hepatocellular carcinoma, which needs to be distinguished. The degree of differentiation of cancer cells can be classified as good, moderate or poor. (3) Representative markers: immunohistochemical examination of cytokeratin 19 (CK19) and mucoglycoprotein-1 (MUC-1), which can show positive cytoplasm. 3. Mixed hepatocellular carcinoma: i.e. HCC-ICC mixed hepatocellular carcinoma, which is relatively rare. Within a liver tumor nodule, both HCC and ICC components are present, and the two are mixed in distribution with unclear boundaries, expressing their respective immunohistochemical markers. 4. Other types. There are some rare types of primary liver cancer, such as clear cell type, giant cell type, sclerosing type and fibrolamellar carcinoma of liver (FLC). Among them, FLC is a special and rare histological subtype of HCC; its characteristics are that it is mostly seen in young patients under 35 years old, usually without hepatitis B virus infection and hepatic sclerosis background, and is less malignant than HCC, and the tumor is often confined, so the disease usually has a chance of surgical resection and a better prognosis. Most of the tumors are located in the left lobe of the liver, often single, with clear boundaries and hard scalloped edges, and fibrous septum across the tumor body. 5.Main contents of pathology report. The pathological report of hepatocellular carcinoma emphasizes standardization and standardization. The contents should include tumor size and number, growth pattern, pathological staging, vascular cancer thrombus, histological type, differentiation degree, envelope invasion, satellite foci, surgical margins, paracancerous liver tissue (pathological grading and staging of chronic hepatitis and type of cirrhosis), immunohistochemistry and molecular pathology indexes. In addition, the results of molecular markers related to drug-targeted therapy, biological behavior and prognosis of hepatocellular carcinoma are also available.