The surgical treatment of hepatocellular carcinoma mainly includes hepatectomy and liver transplantation. (a) Hepatectomy. The basic principles of hepatectomy are: (1) Completeness, to maximize the complete removal of tumor, so that there is no residual tumor at the cutting edge; (2) Safety, to maximize the preservation of normal liver tissues and reduce the surgical mortality and complications. Preoperative selection and evaluation, improvement of surgical details and postoperative prevention and treatment of recurrence and metastasis are the key points of surgical treatment for middle and advanced hepatocellular carcinoma. A comprehensive evaluation of liver function reserve should be performed before surgery, usually using a comprehensive evaluation of liver parenchymal function such as Child-Pugh classification and ICG clearance test, and CT and/or MRI to calculate the volume of the remaining liver. Most of the intermediate and advanced HCC are single tumors >10 cm in diameter, multiple tumors, with portal vein or hepatic vein carcinoma thrombosis or with bile duct carcinoma thrombosis. Because hepatic resection is only considered when the patient is in good general condition and has satisfactory liver reserve function, only a small proportion of intermediate to advanced HCC is suitable for surgery, regardless of the staging used. The hepatic function (Child-Pugh) score and indocyanine green 15-minute retention rate (ICG15) are commonly used to assess hepatic reserve function, and the BCLC group also advocates the use of hepatic venous pressure gradient (HVPG) to assess the degree of portal hypertension. For mid- to late-stage HCC, a Child-Pugh grade A, HVPG <12 mmHg and ICG15 <20% represent good hepatic reserve function and acceptable portal hypertension. On this basis, the expected residual liver volume after resection was then estimated using imaging techniques, and the residual liver volume must account for more than 40% of the standard liver volume to ensure safe surgery. The long-term survival rate after surgery is significantly higher in patients with surgically resectable intermediate to advanced HCC than in those with non-surgical or palliative treatment. 2. Classification of hepatectomy methods. Hepatectomy includes radical resection and palliative resection. It is generally believed that the criteria for radical resection of hepatocellular carcinoma can be classified into 3 levels according to the degree of surgical perfection. Grade I: complete resection of the tumor seen by the naked eye and no residual cancer at the cut edge. Grade Ⅱ criteria: 4 conditions are added to the grade Ⅰ criteria: (1) the number of tumors is ≤ 2; (2) there is no portal trunk and primary branches, common hepatic duct and primary branches, hepatic vein trunk and inferior vena cava thrombus; (3) there is no portal lymph node metastasis; (4) there is no extrahepatic metastasis. Grade III criteria: On the basis of grade II criteria, the condition of negative postoperative follow-up results should be added, that is, if the serum AFP is increased before surgery, the AFP should be reduced to normal and no tumor remains in the imaging examination within 2 months after surgery. 3. Indications for hepatectomy. (1) Basic conditions of patients: mainly the general condition can tolerate the operation; the liver lesion can be removed; the reserved liver function can be fully compensated. Specific conditions include: good general condition, no obvious organic lesions of important organs such as heart, lungs and kidneys; normal liver function, or only mild impairment (Child-Pugh grade A), or liver function grading is grade B, which is restored to grade A after short-term liver protection treatment; liver reserve function (such as ICGR15) is basically within the normal range; no unresectable extrahepatic metastatic tumor. It is generally considered that ICG15 <14% can be used as the threshold for safely performing major hepatectomy with low chance of liver failure. (2) Local lesions for radical hepatectomy must meet the following conditions: ① single hepatocellular carcinoma with smooth surface, clear surrounding boundaries or pseudo-envelope formation, and <30% of liver tissue destroyed by tumor; or >30% of liver tissue destroyed by tumor, but the tumor-free side of the liver has obvious compensatory enlargement, reaching more than 50% of the standard liver volume; ② multiple tumors with <3 nodes and confined to one segment or one lobe of the liver. one segment or within one lobe. For multiple hepatocellular carcinoma, studies have shown that patients with multiple hepatocellular carcinoma with <3 tumors can benefit significantly from surgery if the conditions for surgery are met; if the number of tumors is >3, the outcome is not better than non-surgical treatment such as hepatic artery interventional embolization, even if surgical resection has been performed. (3) Laparoscopic hepatectomy: At present, laparoscopic hepatectomy for hepatocellular carcinoma is increasingly performed, and its main indications are isolated cancer foci, <5cm, located in 2-6 liver segments; it has the advantages of small trauma, low blood loss and operative mortality. Therefore, some scholars believe that laparoscopic hepatectomy performs better for well-positioned hepatocellular carcinoma, especially for early-stage hepatocellular carcinoma; however, prospective comparative studies with traditional open surgery are still needed. (4) Local lesions for palliative hepatectomy must meet the following conditions: ① 3-5 multiple tumors beyond half of the liver with multiple limited resections; ② tumors confined to 2-3 adjacent liver segments or half of the liver with significant compensatory enlargement of tumor-free liver tissue to more than 50% of the standard liver volume; ③ hepatocellular carcinoma in the central region of the liver (middle lobe or segments IV, V, VIII) with significant compensatory enlargement of tumor-free liver tissue (3) Hepatocellular carcinoma in the central region of the liver (middle lobe or segments IV and V and VIII) with significant compensatory enlargement of tumor-free liver tissue, reaching more than 50% of the standard liver volume (5) Palliative hepatectomy also involves the following cases: hepatocellular carcinoma combined with portal vein thrombosis (PVTT) and/or vena cava thrombosis, hepatocellular carcinoma combined with bile duct thrombosis, hepatocellular carcinoma combined with cirrhotic portal hypertension, and resection of difficult-to-cut hepatocellular carcinoma. Each of these conditions has its corresponding indications for surgical treatment (see Table 3). Hepatocellular carcinoma with portal vein carcinoma thrombosis is a common presentation of intermediate to advanced HCC. In this group of patients, if the tumor is limited to half of the liver and the embolus is expected to be removed intraoperatively, surgical resection of the tumor and removal of the embolus via the portal vein can be considered, followed by interventional embolization and portal vein chemotherapy. It is also common for hepatocellular carcinoma to invade the bile ducts and form bile duct emboli, resulting in obvious jaundice. For obstructive jaundice formed by cancer embolus, if the tumor can be surgically resected and the embolus can be removed, jaundice can be relieved quickly, so jaundice is not an obvious contraindication to surgery. In addition, for hepatocellular carcinoma that is not suitable for palliative resection, palliative non-resective surgical treatment should be considered, such as intraoperative hepatic artery ligation and/or hepatic artery and portal vein cannulation chemotherapy. Treatment of microscopic intrahepatic lesions deserves attention. Some microscopic lesions are not detected by imaging or intraoperative exploration, resulting in a higher recurrence rate after hepatic resection. If incomplete resection is suspected, then postoperative TACE is the ideal choice, which has the significance of checking residual cancer foci in addition to the significance of treatment. If there are residual cancer foci, timely remedial measures should be taken. In addition, postoperative cases should be examined for hepatitis viral load (HBV DNA and/or HCV RNA); if indicated, antiviral treatment should be actively carried out to reduce the possibility of recurrence of liver cancer. 4. Improve surgical techniques. In principle, hepatectomy should be considered for single tumor with sufficient liver reserve function, no extrahepatic metastasis, large vessel invasion and portal vein thrombosis; hepatectomy should also be considered for multiple tumors that are technically feasible and meet the above conditions. However, the surgical complexity and radical resection rate of intermediate and advanced hepatocellular carcinoma, especially giant or multiple tumors, are still relatively low. The means to improve the resectability of liver tumors include: preoperative chemoembolization via hepatic artery can shrink the tumor in some patients and then resect it; embolization of the liver lobe where the main tumor is located via portal vein can compensate for the enlargement of the remaining liver and then resect it, which is clinically reported to have few toxic side effects and is safer and more effective. For large tumors, an anterior approach to hepatectomy without freeing the periportal ligament can be used to directly separate the liver parenchyma and intrahepatic ducts, and then free the ligament and remove the tumor. For multiple tumors, surgical resection combined with intraoperative ablation (e.g., intraoperative radiofrequency) can be used to treat the tumors at the margins of the liver and radiofrequency to treat the deeper tumors. For portal vein or hepatic vein embolism, portal vein embolization should be performed by blocking the portal vein flow on the healthy side to prevent the spread of the embolism. For hepatic vein embolism, whole liver blood flow can be blocked and the embolism can be removed as much as possible. For hepatocellular carcinoma with bile duct embolism, if the tumor has partially invaded the bile duct wall while removing the embolism, the affected bile duct should be removed and the bile duct should be reconstructed at the same time to reduce the local recurrence rate. 5.Preventing postoperative metastasis recurrence. The high rate of recurrence and metastasis after surgical resection of middle and late stage hepatocellular carcinoma is related to the existence of microscopic disseminated foci or multicenter occurrence before surgery. Once recurrence occurs, it is often difficult to have another chance of resection. Local non-surgical treatment and systemic treatment can be adopted to control tumor development and prolong patients' survival. For high-risk recurrences, clinical studies have confirmed the effectiveness of postoperative prophylactic interventional embolization to detect and control postoperative microscopic intrahepatic residual cancer. Although there are randomized clinical studies suggesting that alpha interferon can prevent recurrence, its effect on the long-term recurrence rate and different types of hepatitis patients is still controversial, and it is not a recognized standard treatment for recurrence prevention. 6. Contraindications to surgery: (1) poor cardiopulmonary function or combined with serious diseases of other important organ systems that cannot tolerate surgery; (2) severe cirrhosis and poor liver function Child-Pugh grade C; (3) extrahepatic metastases already exist. Table 3 Indications for palliative hepatectomy for primary hepatocellular carcinoma Hepatocellular carcinoma combined with portal vein thrombosis (PVTT) and/or vena cava thrombosis Portal vein trunk dissection for thrombosis with palliative hepatectomy The tumor is resectable according to the criteria for indication for hepatectomy for primary hepatocellular carcinoma The thrombus fills the main branch or/and trunk of the portal vein, and further development will soon endanger the patient's life If the tumor is located in a small portal vein branch above the liver segment, the tumor can be removed together with the portal vein branch at the same time. If the tumor is found to be unresectable intraoperatively, the tumor can be removed by incision in the portal vein trunk to remove the tumor. If the tumor is found to be unresectable, the tumor can be resected together with the portal vein trunk dissection to remove the cancer embolus, followed by intraoperative selective hepatic artery cannulation embolization chemotherapy or portal vein cannulation chemotherapy, cryotherapy or radiofrequency therapy. The cancer thrombus is located in the left or right hepatic duct, common hepatic duct, or common bile duct The cancer thrombus has not invaded the bile duct branches above the second level of the healthy side The formation of the cancer thrombus is estimated to be short, and no mechanization has occurred yet If the cancer thrombus is located in a small branch of the hepatic duct above the hepatic segment, the liver tumor can be removed together with the branch of the hepatic duct If the tumor is found to be unresectable, intraoperative selective hepatic artery cannulation and embolization, cryotherapy or radiofrequency therapy can be performed after resection of the common bile duct to remove the thrombus. In cases of severe gastric mucosal lesions, splenorenal shunt or other types of selective portal shunt can be considered. In cases of unresectable hepatocellular carcinoma with obvious splenomegaly and hypersplenism without obvious esophageal fundic varices, splenectomy can be performed along with intraoperative selective hepatic artery embolization chemotherapy, cryotherapy or radiofrequency therapy. If there is obvious esophagogastric fundic varices, especially if there has been hemorrhage of esophagogastric fundic vein rupture, without serious gastric mucosal lesions, splenectomy or splenic artery ligation with coronary vein suture can be performed; whether to perform dissection is decided according to what the patient sees intraoperatively. Hepatocellular carcinoma can be treated by radiofrequency or cryotherapy intraoperatively, but not by hepatic artery cannulation and embolization chemotherapy (b) Liver transplantation. 1. Selection criteria of liver transplantation. At present, liver transplantation for hepatocellular carcinoma in China is mostly used as a supplementary treatment for patients who cannot be surgically resected, cannot be treated with microwave ablation or TACE, and whose liver function cannot be tolerated. The selection of appropriate indications is the key to improve the efficacy of liver transplantation for hepatocellular carcinoma and to ensure the fair and effective utilization of the extremely valuable liver donor resources. Regarding the indications for liver transplantation, the Milan criteria are mainly used internationally, as well as the UCSF criteria and the Pittsburgh modified TNM criteria. (1) Milan criteria: proposed by Mazzaferro and others in Italy in 1996. In 1998, the United States Organ Allocation Network (UNOS) began to adopt the Milan criteria (plus MELD/PELD score, also known as UNOS criteria) as the main basis for screening liver transplant recipients for liver cancer. The Milan criteria have gradually become the most widely used liver transplantation screening criteria for liver cancer in the world. The advantages of the Milan criteria are that the efficacy is certain, the 5-year survival rate is ≥75%, the recurrence rate is <10%, and only the size and number of tumors need to be considered, which is convenient for clinical operation. However, the Milan criteria are too stringent, and many patients with liver cancer who could potentially be treated well with liver transplantation are denied access. Due to the shortage of donors, patients with liver cancer who originally met the Milan criteria were easily eliminated while waiting for a donor liver due to tumor growth beyond the criteria. Secondly, there is no significant difference in the overall survival rate between liver transplantation and liver resection for small hepatocellular carcinoma meeting the Milan criteria, except that the tumor-free survival rate of the former is significantly higher than that of the latter. Considering the lack of donors and the high cost, it is controversial, especially in some developing countries, whether liver transplantation should be performed directly for hepatocellular carcinoma that meets the criteria and is resistant to liver resection. In addition, the Milan criteria are difficult to apply to living donor liver transplantation and to the screening of liver transplant recipients after down-staging of intermediate to advanced liver cancer. (2) University of California, San Francisco (UCSF) criteria: In 2001, Yao et al. proposed the Milan criteria and expanded the indications for liver transplantation to a certain extent, including: the diameter of a single tumor does not exceed 6 or 5 cm; the number of multiple tumors ≤ 3, the maximum diameter ≤ 4 or 5 cm, and the total tumor diameter ≤ 8 cm; and there is no vascular or lymph node invasion. The UCSF criteria also expand the scope of indications of the Milan criteria without significantly reducing postoperative survival; therefore, in recent years, there has been an increase in the literature supporting the application of the UCSF criteria to screen liver transplant recipients for hepatocellular carcinoma, but there are also controversies; for example, the lymph node metastasis and tumor vascular invasion (especially microvascular invasion) proposed by the criteria are difficult to be diagnosed preoperatively. After thorough discussion by the panel, this guideline tends to recommend the UCSF criteria. (3) Pittsburgh modified TNM: In 2000, Marsh et al. proposed that only the presence of any one of the three criteria: large vessel invasion, lymph node involvement or distant metastasis as a contraindication to liver transplantation, but not the size, number and distribution of tumors as criteria for exclusion, thus significantly expanding the scope of liver transplantation for liver cancer, and may have nearly 50% of patients In recent years, there have been more and more studies supporting the UCSF criteria. However, this criterion also has significant drawbacks. For example, it is difficult to make an accurate preoperative assessment of microvascular or branch vessel invasion in liver segments, and many patients with hepatocellular carcinoma with a background of hepatitis may have inflammatory lymph node enlargement in the hilum and other areas, requiring intraoperative frozen sections for a definitive diagnosis. Second, due to the deepening conflict between liver supply and demand, although the expanded liver transplantation indications for liver cancer may allow some individual patients with intermediate to advanced liver cancer to potentially benefit from this, their overall survival rate is significantly reduced, and this reduces the availability of donor livers for patients with benign liver disease who may be able to achieve long-term survival. (4) Domestic standards: Nowadays, there is no unified standard in China, and several units and scholars have successively proposed different standards, including Hangzhou standard, Shanghai Fudan standard, Huaxi standard and Sanya consensus. The requirements for the absence of large vessel invasion, lymph node metastasis and extrahepatic metastasis are relatively consistent, but the requirements for the size and number of tumors are not the same. The above-mentioned domestic standards have expanded the scope of indications for liver transplantation for hepatocellular carcinoma, which can benefit more patients with hepatocellular carcinoma by liver transplantation, and have not significantly reduced the cumulative survival rate and tumor-free survival rate after surgery, which may be more in line with the national situation and the actual situation of patients in China. However, a standardized multicenter collaborative study is needed to support and prove this, so as to obtain high-level evidence-based medical evidence to achieve recognition and uniformity. 2. Prevention of recurrence after liver transplantation. The common feature of the above-mentioned domestic and foreign liver cancer liver transplantation recipient selection criteria is that the tumor size is the main judgment indicator, which is more objective and easy to grasp, but the biological characteristics of liver cancer are not considered enough. It is generally believed that the biological behavior of the tumor is the most important factor in determining the patient's prognosis. Therefore, with the continuous development of molecular biology, some molecular markers that can better reflect the biological behavior of liver cancer and predict the prognosis of patients will be discovered, which may help to improve the current liver transplantation criteria for liver cancer and improve the overall survival rate. At present, it is believed that appropriate drug therapy (including antiviral therapy as well as chemotherapy, etc.) can be administered after liver transplantation, which may reduce and delay the recurrence of liver cancer and improve survival, but further studies are needed to obtain sufficient evidence-based medical evidence. 3. The choice of liver transplantation and hepatectomy. There is no unified standard on how surgical treatment should be selected, mainly hepatic resection and liver transplantation. It is generally believed that for limited hepatocellular carcinoma, hepatic resection should be preferred if the patient is not accompanied by cirrhosis; if combined with cirrhosis, liver function is decompensated (Child-Pugh grade C) and eligible for transplantation, liver transplantation should be preferred. However, it is more controversial whether to perform liver transplantation for resectable limited hepatocellular carcinoma with good liver function compensation (Child-Pugh grade A). For example, experts in Europe support the preference for liver transplantation on the grounds of the high recurrence rate of hepatic resection and the significantly better long-term survival and tumor-free survival of patients who meet the Milan criteria for liver transplantation than those who undergo hepatic resection. This guideline temporarily excludes from the indications for liver transplantation patients who have good liver function and can tolerate hepatic resection. In the case of a particular patient, emphasis is placed on a comprehensive evaluation and analysis of the surgical plan on a case-by-case basis.