Primary liver cancer (PLC), most commonly known as hepatocellular carcinoma (HCC), is a common malignancy worldwide. According to recent statistics, there were 626,000 new cases worldwide in 2002, of which up to 55% were patients in China.PLC is also on the rise in Europe and the United States, and is currently the leading cause of death in patients with cirrhosis. Recent years have seen remarkable progress in the study of primary liver cancer, especially HCC. This article mainly outlines the progress in the diagnosis and medical treatment of hepatocellular carcinoma (mainly HCC). I. Diagnosis of hepatocellular carcinoma The clinical diagnosis of hepatocellular carcinoma includes serum tumor markers and imaging examinations. The serum markers currently applied in clinical practice are mainly alpha-fetoprotein (AFP), alpha-fetoprotein variant (AFP-L3) and abnormal prothrombin (DCP). aFP is still the most commonly used serological index. In patients with hepatitis cirrhosis and other specific groups, AFP and ultrasound monitoring every 6 months are recommended for early detection of HCC has been obtained. The only randomized controlled study reported to date in China has shown that early surveillance of HBV-infected patients, regardless of the presence or absence of cirrhosis, improves the rate and efficacy of radical treatment. In developed countries, 30-60% of HCC cases are now diagnosed early and eradication therapy is available. The accuracy of serological markers for early diagnosis of HCC is not high. The markers that are still being investigated are enzymes and isozymes (glutamyl transpeptidase II-GGTII, rockulosidase-AFU, etc.), phosphatidylinositol proteoglycan 3 (GPC3), and Golgi protein 73 (GP73). In addition, tissue markers may provide a more comprehensive and standardized diagnosis for these tumors. Genome-wide DNA microarray or quantitative real-time RT-PCR studies have attempted to identify markers of early HCC, such as heat shock protein 70 (HSP70), GPC3, telomerase invertase (TERT), serine/threonine kinase 15 (STK6), and phospholipase A2 (PLAG12B). Indicators containing a combination of 13 genes have also been proposed, including TERT, TOP2A, and PDGFRA. 120 genetic markers generated by gene chips have recently been reported to identify atypical hyperplastic nodules and HCC in HBV patients. proteomic studies in tissues have so far not identified informative markers for HCC. Recently, a combination of three genes (GPC3, LYVE1 and survivin) has been proposed as a diagnostic for early HCC, with an accuracy of 85% to 95% in more than 70 specimens tested. Therefore, a more accurate method for diagnosing early small HCC is now available, while the validity of the novel markers detected by gene chip analysis still needs to be verified. In recent years, there have been significant advances in medical imaging methods, which provide a reliable basis for the clinical diagnosis of PLC and the development of treatment plans. Ultrasonography is a non-invasive examination, which is simple, intuitive, accurate, inexpensive, convenient and non-invasive, and widely popular for the screening and post-treatment follow-up of liver cancer. Especially with the development of real-time ultrasonography in recent years, its accuracy has become similar to that of CT and MRI, which is of great clinical value for the differential diagnosis of small hepatocellular carcinoma, and is often used for early detection and diagnosis of hepatocellular carcinoma, and is a reference value for the differential diagnosis of hepatocellular carcinoma, liver cyst and hepatic hemangioma. It can detect small intrahepatic lesions that are not detected by CT and ultrasound. Multi-layer spiral CT has high resolution, clear and stable images, and CT-enhanced scan can clearly show the size, number, shape, location, boundary, richness of blood supply and relationship with intrahepatic ducts of liver cancer. Therefore, CT has become an important routine tool for hepatocellular carcinoma diagnosis. Especially, dynamic enhancement scan can significantly improve the detection rate of small hepatocellular carcinoma; CT scan after 3~4 weeks of iodine oil embolization of hepatic artery can also effectively detect small hepatocellular carcinoma lesions. Magnetic resonance imaging (MRI) is another efficient and non-invasive diagnostic method for liver cancer examination because of its high tissue resolution and multi-parameter and multi-directional imaging, as well as the absence of radiation effects. The application of hepatic MRI contrast agent can improve the detection rate of small hepatocellular carcinoma and help to differentiate hepatocellular carcinoma from focal hyperplastic nodules and hepatic adenoma. Positron emission computed tomography-CT (PET-CT) can reflect biochemical metabolic information of liver occupancy by PET functional imaging as well as precise anatomical localization of lesions by CT morphological imaging, and simultaneous scanning can understand the overall condition and assess metastasis to achieve early detection of lesions, as well as to understand the size and metabolic changes before and after tumor treatment. Selective hepatic arteriography is an invasive examination, while performing chemotherapy and iodine oil embolization also has a therapeutic effect, which can clearly show small lesions in the liver and their blood supply, and is suitable for patients whose diagnosis is still not confirmed after other examinations. Foreign data suggest that the diagnosis can be established with one positive imaging test for nodules >2 cm in diameter and two positive imaging tests for nodules 1 to 2 cm in diameter. However, it is difficult to identify microscopic nodules <1 cm in diameter by radiological or pathological examination. The differentiation between atypical hyperplastic nodules and early tumors is also an unresolved challenge. One third of the atypical hyperplastic lesions will develop into malignant tumors, so regular imaging follow-up is required. For unresectable HCC, arterial embolization is the most widely used treatment of choice. In HCC with large vessel supply, hepatic artery embolization can induce widespread necrosis. Arterial chemoembolization can achieve partial remission rates of 15% to 55% and can significantly delay disease progression and vascularity. Current emphasis on hepatic artery embolization chemotherapy should be super-selective for cannulation, MRI dynamic enhancement scans to evaluate tumor survival, and appropriate prolonged treatment intervals. A meta-analysis showed that embolization/chemoembolization prolongs the period of HCC patients. Patients with compensated liver function, asymptomatic multinodular tumors, and no vascular or extrahepatic spread are the best candidates, while patients with hepatic impairment or hepatic decompensation (ChildCPughB~C) should be excluded because ischemic injury can lead to serious adverse events. A clinical phase II trial of extended-release granules containing adriamycin achieved an objective remission rate of 70%. Internal irradiation with 131-I-labeled iodinated oil or Y-90 has emerged as a treatment option for cases of intermediate to advanced HCC, but further phase III trials are needed to understand the efficacy of this treatment alone or in contrast to standard treatment with sorafenib. Local ablative therapy Local ablative therapy includes intratumoral anhydrous ethanol injection (PEI), radiofrequency ablation (RFA), microwave curing (MWCT), high-intensity focused ultrasound (HIFU), and argon-helium cryopreservation. More than 80% of tumors less than 3 cm in diameter achieve complete remission after percutaneous ablation, however, only 50% of tumors 3 to 5 cm in diameter achieve complete remission. In series of HCC patients treated with PEI or RFA, the best outcome is a 5-year rate of 40% to 70%. childCPughA, non-surgically treated patients with small tumors (expected to achieve complete remission) are ideal candidates for PEI and RFA. National randomized controlled studies have shown that RFA has similar rates to local hepatectomy for small HCC. Individualized treatment of patients with larger tumors (3-5 cm), multiple tumors (3 nodes <3 cm), and progressive liver impairment (ChildCPughB) is reasonable. Despite the better results obtained with these treatments, they still do not achieve the same remission rates and regression as surgical treatment, even when used as first choice. Four studies compared RFA with PEI or percutaneous ethanol injection (PAI), and local recurrence rates were significantly lower in the RFA group than in the PEI or PAI groups, either as a primary or secondary endpoint. The radical efficacy of this treatment was diminished by ethanol diffusion being blocked by the intra-tumor fibrous septum and/or tumor envelope, especially in tumors >2 cm. The efficacy (tumor control and long-term) of the combination of RFA + PEI is superior to that of RFA alone. Targeted therapy Studies have shown that epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), Ras/Raf/MEK/ERK and PI3K/AKT/mTOR are highly expressed in hepatocellular carcinoma tissues and play an important role in the development of hepatocellular carcinoma. It is a potential target for hepatocellular carcinoma treatment. Sorafenib is an oral multi-kinase agent that blocks tumor cell proliferation by targeting Raf kinases in the Raf/MEK/ERK signaling pathway on the one hand and VEGFR-2/-3 and platelet-derived growth factor receptor βPDGFR-β tyrosine kinases on the other hand to exert anti-angiogenic effects. Large-scale multicenter, prospective, randomized, double-blind, placebo-controlled clinical phase III studies of advanced HCC were conducted in Europe, the United States, and the Asia-Pacific region, with different conditions in the two groups, but with essentially consistent clinical outcomes, with sorafenib prolonging the median stage of patients with advanced HCC by 44% and 47% in Europe, the United States, and the Asia-Pacific region, respectively (treatment risk ratios of 0.68 and 0.69, respectively), to time to disease progression by 74% and 73% (risk ratios of 0.57 and 0.58, respectively), with similar incidence of serious adverse events and mostly safe tolerability, resulting in a well-documented evidence-based efficacy of sorafenib in patients with HCC of different ethnicities, geographic regions, liver disease backgrounds, disease stages, and degrees of vascular infiltration and distant metastases. The combination of sorafenib with other antitumor therapies is being further explored, including the combination with other targeted drugs for advanced hepatocellular carcinoma, combination with hepatic artery chemoembolization for mid-stage hepatocellular carcinoma and adjuvant therapy to prevent recurrence after radical treatment (hepatectomy or local ablation). Clinical studies of other targeted drugs for HCC, such as erlotinib (Erlotinib, EGFR tyrosine kinase), sunitinib (Sunitinib, dual target of both VEGFR and PDGFR to block tumor angiogenesis and hepatocellular carcinoma proliferation), everolimus (Everolimus, mTOR activity, blocking Akt/mTOR signaling through ), and bevacizumab (Bevacizumab, anti-VEGF monoclonal antibody) have achieved preliminary efficacy in clinical phase II studies. Targeted therapy is expected to bring new hope for liver cancer patients. Evaluation of clinical efficacy of hepatocellular carcinoma With the progress of tumor treatment, evidence-based medicine in clinical research has been increasingly emphasized, and the concept of evaluation of clinical efficacy of hepatocellular carcinoma has been updated and changed. The treatment of primary liver cancer not only needs to focus on the tumor itself, but also the accompanying liver disease seriously affects the prognosis of patients and interferes with the evaluation of clinical efficacy. Mechanistic studies of targeted therapeutic agents and clinical trials for the evaluation of hepatocellular carcinoma efficacy have raised the issue of selecting primary and secondary endpoints in phase II and phase III controlled studies. Phase III is the primary endpoint for the evaluation of phase III clinical studies, while it is the secondary endpoint in phase II clinical studies. The primary endpoint for adjuvant therapy studies is time to relapse (TTR). In most cases, the primary action of these drugs is essentially cell growth. Therefore, the primary endpoint selected for phase II trials must demonstrate a clinically meaningful time period for the effect of stabilizing disease. Time to disease progression (TTP) is included as a primary endpoint in phase II trials and as a secondary endpoint in phase III trials. Objective efficiency is a lesser proxy for efficacy in phase II and III trials and clinical evaluations in hepatocellular carcinoma.