Primary liver cancer

　　Etiology of primary liver cancer

　　It is not yet clear. According to the epidemiological investigation in high-incidence areas, the following factors may be related to the prevalence of liver cancer.

　　(I) Etiology

　　The etiology and pathogenesis of HCC have not been determined and may be related to the combined effects of various factors. It is found in any region of the world that chronic liver disease caused by any reason may play an important role in the occurrence and development of liver cancer. Epidemiological and experimental studies have shown that there is a specific relationship between viral hepatitis and the occurrence of primary liver cancer. At present, the three types of viral hepatitis that are relatively clear in relation to liver cancer are hepatitis B, C, and D, among which hepatitis B is most closely related to liver cancer. In recent years, the increase in HBsAg-negative liver cancer is related to hepatitis C, while in the former Soviet Union, hepatitis D is more common. About 90% of Chinese liver cancer patients have a hepatitis B virus (HBV) infection background. Other risk factors include alcoholic liver cirrhosis, liver adenoma, long-term intake of aflatoxin B1, other types of chronic active hepatitis, Wilson's disease, phenylketonuria, and glycogen storage disease. In recent years, research has focused on hepatitis B, C, aflatoxin B1, and other chemical carcinogens.

　　1. Liver cirrhosis

　　Any cause of liver cirrhosis can be accompanied by HCC, HCC often occurs on the basis of liver cirrhosis. Worldwide, about 70% of primary liver cancers occur on the basis of liver cirrhosis. The incidence of liver cancer patients with liver cirrhosis reported in the UK is 68% to 74%, in Japan it is about 70%. The detection rate of primary liver cancer in autopsies of patients who died of liver cirrhosis is 12% to over 25%. In China, the incidence of liver cirrhosis in 500 autopsies of liver cancer from 1949 to 1979 was 84.6%. The Second Military Medical University reported that 85.2% of the 1102 cases of liver cancer surgically resected had liver cirrhosis, and all were hepatocellular carcinoma, with no liver cirrhosis in cholangiocellular carcinoma. Not all types of liver cirrhosis patients have the same incidence of liver cancer. Liver cancer mostly occurs in nodular cirrhosis caused by hepatitis B and C, while biliary, schistosomal, alcoholic, and congestive cirrhosis are less likely to be accompanied by liver cancer. Foreign reports indicate that the incidence of liver cancer in autopsies of patients who died of primary biliary cirrhosis is 3%, while the incidence of liver cancer in autopsies of patients who died of chronic active hepatitis B with HBsAg positivity is over 40%. In China, the incidence of liver cancer in 334 cases of nodular cirrhosis was 55.9%. Early reports indicate that liver cancer accompanied by liver cirrhosis is mainly of large nodular type, accounting for 73.6%. However, the study of 1000 liver cancer specimens surgically resected since the 1980s by the Second Military Medical University shows that the incidence of liver cirrhosis is 68%, with small nodular cirrhosis as the main type, accounting for 54.4%, mixed type cirrhosis accounting for 29.3%, and large nodular cirrhosis accounting for only 16.3%. This suggests that with the improvement of the level of diagnosis and treatment of hepatitis, mild hepatitis is more common than severe hepatitis, and the former is mainly characterized by the formation of small nodular cirrhosis.

　　Animal experimental studies on chemical carcinogens show that regeneration nodules are promoting factors for the transformation of liver cells into cancer. Alcoholic liver cirrhosis is mostly small nodular, and after giving up alcohol, small nodules gradually transform into large nodules, and the rate of canceration also increases, supporting the above argument. Liver cirrhosis caused by other reasons, such as primary biliary cirrhosis, alpha-1 antitrypsin deficiency, hepatolenticular degeneration, hemochromatosis, and Budd-Chiari syndrome, autoimmune chronic active hepatitis, can all be complicated by HCC. At present, there are two explanations for the mechanism of liver cirrhosis and canceration: the first explanation is that liver cirrhosis itself is a precancerous disease, and without other factors, it can lead to the formation of cancer from hyperplasia and anaplasia; the second explanation is that the rapid turnover rate of liver cells during liver cirrhosis makes these cells more sensitive to environmental carcinogens, that is, carcinogens can cause liver cell damage, and before the damage is repaired, DNA replication occurs, thus producing permanently altered abnormal cells.

　　Data show that about 32% of liver cancers do not have liver cirrhosis, but even in liver cancer without liver cirrhosis, the positivity rate of HBsAg is as high as 75.3%, indicating that chronic hepatitis can lead to liver cancer without going through the stage of liver cirrhosis. Liver cell damage and regeneration nodule formation caused by HBV or HCV infection are the basis for the occurrence of liver cirrhosis and liver cancer. When HBV infects the host liver cells, the gene integration form exists mainly, which does not cause liver cell necrosis and proliferation, and may lead to liver cancer directly without liver cirrhosis in a relatively short period of time.

　　2. Hepatitis B virus

　　About one-third of patients with primary liver cancer have a history of chronic hepatitis, and epidemiological surveys have found that the positivity rate of HBsAg in the high-incidence area of HCC is lower than that in the low-incidence area, while the positivity rate of HBsAg and other hepatitis B virus markers in HCC patients is as high as 90%, significantly higher than that in the healthy population. There is a positive correlation between the incidence of HCC and the prevalence of HBV carrier status, and there is also a close geographical relationship.

　　(1)The correlation between HBV and HCC can be explained from the following points:

　　①The incidence of HCC is parallel to that of HBsAg carriers: areas with a high incidence of primary liver cancer are also areas with a high rate of HBsAg carriage, while the carriage rate of HBsAg in the natural population in areas with a low incidence of liver cancer is lower. The carriage rate of HBsAg in the Chinese population is about 10％, with 120 million HBV carriers in the country, and about 1 million newborns are infected with HBV each year due to their mothers being carriers. In the low-incidence areas of liver cancer in Europe, America, and Oceania, the carriage rate of HBsAg is only 1％.

　　②The incidence of chronic HBV infection in liver cancer patients is significantly higher than that in the control group: among 1000 cases of liver cancer patients at the Eastern Hepatobiliary Surgery Research Institute of the Second Military Medical University, the positive rate of HBsAg is 68.6％; among 992 inpatients with liver cancer at Zhongshan Hospital in Shanghai, the carriage rate of HBsAg is 69.1％, and the positive rate of antiHBc is 72.1％; both are significantly higher than the 10％ carriage rate of HBsAg in the natural Chinese population. Taiwan reported that the carriage rate of HBsAg is 15％ among liver cancer patients, while it is 80％ in liver cancer patients, and the positive rate of antiHBc can reach 95％. Even in areas with low incidence of primary liver cancer, the incidence of HBV infection in liver cancer patients is significantly higher than that in the natural population, such as in the United States, where the positive rate of antiHBc in liver cancer patients is 24％, six times higher than that in the control group, and in the United Kingdom, the positive rate of HBsAg in liver cancer patients is 25％, significantly higher than 1％ in the natural population. Detection by immunofluorescence and immunoperoxidase techniques shows that about 80％ of liver cancer specimens have HBsAg in the paracancerous tissue or cytoplasm of liver cells, and 20％ have HBcAg in the nucleus; lichen red staining shows that the positive rate of HBsAg in liver cancer specimens is 70.4％ to 90％ and significantly higher than 4.7％ in the control group.

　　Serum from HCC patients often contains one of s antigen, s antibody, c antigen, c antibody, e antigen, and e antibody positive, among which s antigen and c antibody double positivity is more common, and in recent years, positive e antibody has also become more common.

　　③The familial aggregation of HCC is seen in families with HBsAg-positive, chronic hepatitis, and liver cirrhosis, indicating that in addition to possible genetic factors, HBV infection is still the main carcinogenic factor.

　　④In liver cancer with positive s antigen, the cytoplasm of non-cancerous cells can also contain s antigen.

　　⑤Human liver cancer cell lines can secrete HBsAg and AFP.

　　⑥The cancer cells of HCC patients have HBV-DNA integration. Molecular biological research has found that the DNA of liver cancer cells contains the base sequence of HBV-DNA integrated, and some liver cancer cell lines can continuously secrete HBsAg and AFP. After Alexander discovered that the human liver cancer cell line PLC/PRE/5 could constantly secrete HBsAg, it was subsequently found that cell lines such as Hep-3B, Hah-1, Huk-4, and C2HC/8571 also produce HBsAg.

　　⑦ Duck liver cancer and woodchuck liver cancer also have hepatitis viruses similar to human hepatitis B virus: The epidemiology of animal liver cancer provides important clues to the relationship between hepatitis and liver cancer, and serves as a model for etiological research. Abroad, it has been found that the occurrence of woodchuck liver cancer is related to hepatitis, and in China, it has also been found that the liver cancer of Qidong mule duck is also related to infection with a virus similar to human hepatitis B virus. Woodchuck liver cancer is caused directly from acute hepatitis, while Qidong mule duck has the process of chronic hepatitis → liver cirrhosis → liver cancer. In summary, HBV infection is an important factor in the occurrence of liver cancer. Although there are a large number of clues suggesting the close relationship between HBV and liver cancer, the exact mechanism and process by which HBV causes liver cancer are still not fully clear. Recent research in liver cancer molecular biology has provided new evidence for the carcinogenic mechanism of HBV.

　　⑧ In the same population, the incidence of HCC in carriers of s antigen is much higher than that in non-carriers. In a prospective study, among 3,500 HBsAg carriers followed up for 3.5 years, 49 cases of liver cancer were found, and the risk of developing liver cancer was 250 times higher than that in the control group.

　　(2) During the development of HCC, HBV is almost certainly an initiating factor. Animal experiments and human studies both support the direct carcinogenic effect of HBV, mainly including:

　　① HBV integration causes chromosomal deletion and translocation.

　　② The integration of woodchuck hepatitis virus often activates proto-oncogenes (N, C-myc).

　　③ The integration of HBV can alter the genes of human retinoic acid receptors and cyclosporin A proteins, affecting cell differentiation and cell cycle operation.

　　④ Hepadnavirus genes (HBV, WHV, GSH) as transcriptional activator viruses and cell promoting factors.

　　⑤ The X gene protein of HBV has transforming oncogene activity in transgenic mice.

　　(3) HBV-DNA and liver cancer oncogenes: The molecular pathogenic mechanism of HBV-DNA and its interaction with liver cancer oncogenes are related. The HBV genome consists of two circular complementary DNA strands. The HBV-DNA genome includes the S region, X gene, C region, and P gene. The S region encodes HBsAg; the X gene encodes HBxAg, the C region encodes HBcAg and HBeAg. After HBV-DNA integrates into the DNA of liver cells, it may activate oncogenes and/or inactivate tumor suppressor genes through interaction with them (and/or), thereby causing cancer. The product of the HBV X gene integrated into liver cells, X protein, has transactivation function and may activate the transcription of certain cell regulatory genes, leading to liver cancer.

　　3. Hepatitis C Virus (HCV)

　　Since 1989, the relationship between HCV and HCC has begun to receive attention. With the increase in non-HBV-related HCC cases, the carcinogenic effect of chronic non-A and non-B hepatitis (NANB) has been confirmed. It is believed that more than 90% of NANB hepatitis patients are infected with HCV. Many reports have shown that HCV infection is a major risk factor for the occurrence of HCC. In Japan and Italy, the number of HBV-infected individuals is relatively low, while other environmental factors such as aflatoxins do not exist. The incidence of HCC related to HBV has decreased, but the overall incidence of HCC has not changed significantly or even increased, indicating that the role of other factors has increased, including HCV. Ksbayashi's study on the etiology of HCC in Japan found that 77% even up to 80% of HCC patients had detectable HCV in their serum. It was also found that HCV sequences were present in the HCC tissue. A follow-up of 401 patients with liver cirrhosis for an average of 4.4 years showed that the cumulative risk of HCC in the HCV-positive group was significantly higher than that in the HBV group. 15% of liver cirrhosis caused by HCV infection developed into HCC. Ikeda et al. found in a 15-year observation that the risk of HCC in chronic HCV-related liver cirrhosis was about 3 times higher than that in HBV-related liver cirrhosis. Wang Chunjie of China used immunohistochemical methods to study the antigen localization of HCV and HBV in 102 HCC tissues, and found that the positive detection rates of HCV C33 antigen and HBxAg in HCC were 81.4% and 74.5% respectively. In HCC, the highest positive rate of anti-HCV is in southern Europe and Japan, followed by Greece, Australia, Switzerland, Saudi Arabia, and Taiwan. The lowest is in the United States, Africa, India, and other countries in the Far East. From Wang Chunjie's research results, the positive rate of HCV in HCC in China is similar to that in Japan. HCV, due to its high replication rate and very low or lack of correction ability, can escape the host's immune defense and easily become a chronic persistent infection, rarely showing self-limitation. Chronic active liver disease caused by HCV can cause continuous liver cell变性 and necrosis, which is one of the mechanisms of carcinogenesis. This carcinogenesis is not a direct transformation of liver cells by HCV, but may play an indirect role in cell growth and differentiation, such as activating growth factors, activating oncogenes, or the role of DNA-binding proteins. The liver tissue of most HCC patients with anti-HCV positivity can detect HCV sequences, supporting the hypothesis that HCV infection is involved in the mechanism of liver cancer.

　　The Second Military Medical University examined 96 patients with liver cancer, 43 with chronic hepatitis, and 40 with liver cirrhosis, and the positive rates of HCV-Ab in serum were 11.5%, 9.3%, and 10% respectively. The results indicate that the infection rate of HCV in patients with liver cancer in China is still relatively low, and a portion of them are dual infections, suggesting that HCV infection is not the main etiology of liver cancer in China. However, in recent years, there has been an increasing trend of HCV infection related to blood transfusion and the use of biological products, which may lead to the occurrence of certain HBsAg-negative liver cancers. Therefore, the prevention and treatment of HCV should not be ignored.

　　4. Aflatoxin (aflatoxin, AFT)

　　Aflatoxin (AFT) is produced by Aspergillus flavus, a group of toxins that can be divided into aflatoxin B (AFB) and aflatoxin G (AFG) based on their different fluorescence. AFB is further divided into AFBl and AFB2, while AFG is divided into AFG1 and AFG2. Among them, AFB1 has the strongest hepatotoxicity and is most closely related to HCC. It can cause HCC in marmosets, rats, mice, and ducks, but there is no direct evidence of carcinogenicity in humans. There is a relationship between the severity of AFT contamination and the higher incidence of HCC in Africa and Southeast Asia. Qidong, Fusui, and Chongming Island in China are the three major high-incidence areas for HCC. The high content of AFT in moldy corn, peanuts, wheat, cotton seeds, and rice is a carcinogenic factor in these high-incidence areas. It is unclear whether AFT plays a primary or secondary role in the occurrence of HCC. In Greenland, the high prevalence of HBsAg carriers and low AFT content is associated with a low incidence of HCC. Feeding food with high AFT content to ducks infected with the hepatitis B virus can lead to faster growth of HCC compared to those not fed such food. The correlation study conducted by Van Rensburg and others in 9 regions, including Mozambique and Transkei, observed that the HBsAg carrier status is a carcinogenic indicator, and AFT plays a certain role in the later stage or promotion of cancer. A survey in 1982 found a positive correlation between the estimated exposure to AFT from dietary and grain samples and the lowest incidence of HCC in males. The joint effect of AFT and HBsAg on the incidence of HCC was evaluated by multivariate analysis, revealing that AFT is the most influential factor in the geographic variation of HCC in Swaziland. Some scholars in Guangxi, China, have also studied the relationship between AFB1, HBsAg, and HCC, believing that HBsAg may precede AFT exposure, laying a certain pathological basis for AFT-induced HCC. There is an interaction between AFT and HBsAg infection, especially in the late stage and in the formation of HCC. The Philippines compared 90 confirmed HCC patients with 90 controls and investigated their AFT exposure using a recall method. The results showed that the average intake of the HCC group was 44% higher than that of the control group. Both AFT intake and alcohol consumption were present in both the light and heavy exposure groups, indicating a synergistic effect. It is believed that alcohol can enhance the carcinogenic effect of AFT. Van Rensburg has experimentally proven that there is a logarithmic relationship and linear correlation between AFT and the occurrence of HCC. Aflatoxins can be quickly converted into active substances in the liver and can bind to macromolecular substances. The metabolites of AFBl may be a ring oxide that can form a covalent bond with the guanine residue at position N7 of DNA molecules, changing the template nature of DNA and interfering with DNA transcription. The mutation of the codon 249 G to T of the suppressor gene P53 has been detected in a large number of HCC patients, suggesting that this specific substitution in P53 may be a characteristic of gene changes caused by AFT, indirectly supporting the carcinogenic effect of this fungal toxin.

　　5. Parasitic Diseases

　　The relationship between liver parasitic disease and HCC has not been confirmed to date. Clonorchis sinensis infection is considered to be one of the causes of cholangiocellular liver cancer. A report from Thailand showed that 11% of Clonorchis sinensis carriers developed HCC, indicating that liver fluke disease is somewhat related to HCC. Among patients with liver cancer in Fusui County, Guangxi, 43.3% had a history of eating raw fish, and 94.1% of liver cancers were HCC rather than cholangiocellular carcinoma, and 85.2% were complicated with liver cirrhosis, which can suggest that liver fluke disease and liver cancer do not have a direct relationship. The relationship between schistosomiasis and HCC has also not been determined. Most scholars believe that there is no causal relationship between the two, because the geographical distribution of liver cancer and schistosomiasis is not consistent, and most cases of HCC in advanced schistosomiasis are on the basis of mixed nodular and small nodular liver cirrhosis, not the liver fibrosis specific to schistosomiasis. At the same time, 1/4 of them also have HBsAg positivity, so there is a lack of evidence to support schistosomiasis as a direct cause of HCC.

　　6. Oral Contraceptives and Androgens

　　In 1971, the first report of oral contraceptives causing liver adenoma was published. In experimental studies, 15mg of diethylstilbestrol pellets were implanted subcutaneously in Armenian hamsters, and HCC occurred within a few months. If the estrogen antagonist tamoxifen (triphenoxyamine) was administered at the same time, the occurrence of HCC could be completely prevented, indicating that estrogen is involved in the occurrence of HCC. In the United States, the estrogen content of oral contraceptives is 8 times higher than in China, which can cause benign liver adenoma, and some can develop into HCC. Stopping the medication can cause liver cancer to regress, but some believe that oral contraceptives and HCC are only coincidental, and it was also found that liver cancer is an androgen-dependent tumor, with more androgen receptors than estrogen receptors in HCC tissues, and more male than female patients with HCC.

　　7. Ethanol

　　In Western countries, alcohol is the most important factor in the etiology of chronic liver disease, but retrospective pathological anatomical studies and prospective clinical and epidemiological studies have shown that there is no direct relationship between ethanol and HCC, at most it is a co-carcinogen. Ethanol can enhance the role of HBV, nitriles, AFT in诱发 HCC, and the mechanism of its promotion is unclear. Some reports suggest that ethanol can affect the metabolism of vitamin A and affect the activity of cytochrome P450, thereby accelerating the biological transformation of carcinogens.

　　8. Environmental factors

　　The incidence rate of HCC among those drinking pond water in Qidong, Jiangsu, is 60 per 100,000 to 101 per 100,000, while among those drinking well water, it is only 0-10 per 100,000. The relative risk of drinking pond water has increased. In recent years, the incidence rate of HCC in this area has decreased after the improvement of water quality. The intrinsic factors are not yet fully understood. The water sources in the epidemic area have a high content of copper, zinc, and molybdenum, and a low content of iron. The change in the content of copper in HCC patients is consistent with that in water sources. These trace elements provide some insights into the etiology of HCC. In recent years, it has been found that selenium deficiency is related to HCC. Selenium deficiency is a conditional factor in the occurrence and development of HCC. The latest data from Africa shows that excessive iron intake can cause HCC. In addition, after Chinese people migrate to the United States, the incidence rates of HCC in the second generation and later generations are all lower than those of the first generation and those born in the place of migration, which also illustrates the importance of environmental factors.

　　In Qidong, Jiangsu, the incidence rate of liver cancer among those drinking pond water is 60-101 per 100,000, while among those drinking well water, it is only 0-19 per 100,000. The relative risk of drinking pond water is 3.00. The survey found that a blue-green alga in the pond water produces a toxin that may be a clue to the relationship between drinking water pollution and the occurrence of liver cancer.

　　9. Genetic factors

　　In high-incidence areas, HCC sometimes shows a familial aggregation phenomenon, especially among those living together and having blood relations, with a high incidence rate of HCC. Some people believe that this may be related to the vertical transmission of hepatitis virus factors, but it is yet to be confirmed. Other research results suggest that patients with α1-antitrypsin deficiency have an increased risk of HCC. The association between HCC and hemochromatosis exists only in those who have this disease and can survive for a long time, leading to liver cirrhosis.

　　10. Other carcinogens

　　Nitriles can cause solitary nodular liver cancer in baboons and monkeys, and the coexistence of HBV and nitriles can lead to multifocal and multinodular liver cancer. Materials such as奶油黄 (dimethyl azo benzene), hexachlorobenzene, benzopyrene, polychlorinated biphenyls, trichloromethane, 1,2-dibromoethane, and others have been confirmed to be carcinogenic.

　　Aflatoxin, especially in the high-incidence areas of liver cancer, particularly in southern regions where corn is the main staple food, suggests that the prevalence of liver cancer may be related to the contamination of grain by aflatoxin. The concentration of aflatoxin B1 metabolites, aflatoxin M1, in human urine is very high. Aflatoxin B1 is the strongest carcinogen causing liver cancer in animals, but there is no direct evidence of its relationship with human liver cancer to date.

　　In summary, the occurrence of liver cancer is the result of the combined action of multiple factors, and the exact etiology and mechanism are still waiting for further research.

　　The disease progresses rapidly, with a high mortality rate, posing a serious threat to life and health. Since it is difficult to satisfactorily explain the causes and distribution of liver cancer in China and around the world with a single factor at present, the occurrence of liver cancer may be caused by multiple factors through multiple pathways; the carcinogenic and promoting factors in different regions may not be completely the same. What is the main factor, and how do the various factors interact, are still waiting to be studied.

　　Complications may be caused by liver cancer itself or coexisting liver cirrhosis, common in the late stage of the disease, so it is often a fatal cause.

　　(One) Hepatic encephalopathy It is often a complication of the terminal stage, accounting for 34.9% of the causes of death.

　　(Two) Gastrointestinal bleeding Accounting for 15.1% of the causes of death. Patients with liver cirrhosis or portal vein, hepatic vein cancer thrombus may experience esophageal or gastric fundus varices rupture due to portal hypertension. Bleeding may also occur due to erosion of gastrointestinal mucosa and disorders of coagulation mechanism.

　　((Three) Rupture hemorrhage of liver cancer nodules The incidence is about 9-14%. The necrosis and liquefaction of liver cancer tissue can lead to spontaneous rupture or rupture due to external force. If limited under the capsule, there may be acute pain, and the liver rapidly increases in size; if it breaks into the peritoneal cavity, it can cause acute abdominal pain, peritoneal irritation signs, and in severe cases, it can lead to hemorrhagic shock or death. The mild ones may stop bleeding after a few days, and the pain gradually decreases.

　　(Four) Bloody pleural and peritoneal effusion The diaphragmatic liver cancer can directly infiltrate or cause hemoptysis through blood flow or lymphatic metastasis, which is common on the right side.

　　(Five) Secondary infection Due to the long-term consumption of the tumor, the resistance is weakened, especially for those with decreased blood leukocytes after radiotherapy and chemotherapy, it is easy to develop various infections such as pneumonia, intestinal infection, and fungal infection.

　　1. Liver pain

　　More than half of the patients have liver pain as the first symptom, mostly persistent dull pain, piercing pain, or bloating pain. This is mainly due to the rapid growth of the tumor, which increases the tension of the liver capsule. If the tumor in the right lobe of the liver involves the diaphragm, the pain may radiate to the right shoulder and back. When the liver cancer nodules develop necrosis and rupture, it can cause intra-abdominal hemorrhage, resulting in peritoneal irritation signs and other acute abdominal symptoms.

　　2. General and gastrointestinal symptoms

　　Mainly manifested as fatigue, weight loss, decreased appetite, abdominal distension, and so on. Some patients may be accompanied by symptoms such as nausea, vomiting, fever, diarrhea, and so on. In the later stage, anemia, jaundice, ascites, lower limb edema, subcutaneous hemorrhage, and cachexia may occur.

　　3. Liver enlargement

　　Liver enlargement is progressive, hard in texture, irregular in margin, and presents with nodules or large masses on an uneven surface.

　　4. Symptoms of liver cancer metastasis

　　Primary liver cancer, if it metastasizes to the lung, bone, brain, or other places, can produce corresponding symptoms. A small number of patients may have special manifestations such as hypoglycemia, polycythemia, hypercalcemia, and hypercholesterolemia. The main complications of primary liver cancer include hepatic coma, upper gastrointestinal bleeding, tumor rupture hemorrhage, and secondary infection.

　　Loss of taste or hypersensitivity to hearing, feeling the food tasteless.

　　The condition usually reaches its peak within 3 to 4 days and begins to gradually recover after a week. Some patients with primary liver cancer may have ipsilateral external auditory herpes and dizziness, also known as Hunter's syndrome.

　　Active prevention and treatment of toxic hepatitis is of great significance in reducing the incidence of liver cancer. The inactivated hepatitis B virus vaccine not only has the effect of preventing and treating hepatitis but will also play a certain role in the prevention of liver cancer. Preventing grain moldiness and improving water quality are also important measures for preventing liver cancer.

　　In the absence of perfect prevention of liver cancer, the early detection, early diagnosis, and early treatment of liver cancer are known as 'second-level prevention' in oncology. Since the 1970s, when alpha-fetoprotein has been used for liver cancer screening in China, the diagnosis of primary liver cancer has entered the subclinical level, and the proportion of early liver cancer has continuously increased, with a significant improvement in five-year survival rate. Since the 1980s, the detection rate of high-risk populations (history of hepatitis, HBsAg positive, over 40 years old) in general surveys has been about 501 per 100,000, 34.4 times higher than that of the natural population. Among them, one-third is early liver cancer. The combination of high-sensitivity AFP detection methods and ultrasound imaging once or twice a year is the basic method for detecting early liver cancer. The combined detection rate can reach 97.9%, not only to make up for the deficiencies of missed detection in AFP-negative patients, but also to have important value for the timely confirmation of low-concentration AFP liver cancer. There is a contradiction between 'cost and benefit' in liver cancer screening, and some people also believe that the early detection in general survey is essentially 'leading time' (leading time) in diagnosis and treatment.

　　But before the prevention of liver cancer etiology has achieved results, the 'lead time' won by the general survey is of great value for the increasing number of long-term survival cases detected. It must be emphasized that early-stage small liver cancer should be treated as actively as possible by surgical resection to achieve the goal of radical cure. The five-year survival rate after radical resection of small liver cancer is about 70%, while non-surgical treatment mostly results in death within two years. The data from Zhongshan Hospital of Shanghai Medical University show that 212 cases have survived for more than 5 years after radical resection, the vast majority of which were early-stage liver cancer detected by general survey. Therefore, general survey not only improves the level of early diagnosis and early treatment but also promotes the basic medical research on the occurrence and development of early liver cancer. In recent years, there have been significant advances in the treatment of liver cancer. The Liver Cancer Research Institute of Shanghai Medical University reported that the five-year survival rate after radical resection of subclinical liver cancer reached 72.9%, with a diameter

　　1. Detection of liver cancer serum markers

　　(1) Alpha-fetoprotein (AFP) measurement This method has relative specificity for the diagnosis of this disease. The determination of a continuous serum AFP ≥ 400 μg/L by radioimmunoassay, and the exclusion of pregnancy, active liver disease, etc., can consider the diagnosis of liver cancer. Clinically, about 30% of patients with liver cancer have negative AFP. If AFP heterogeneity is detected at the same time, the positive rate can be significantly increased.

　　(2) Hematological enzymes and other tumor markers examination The serum gamma-glutamyl transpeptidase and its isoenzymes, abnormal prothrombin, alkaline phosphatase, and lactate dehydrogenase isoenzymes in patients with liver cancer can be higher than normal. However, they lack specificity.

　　2. Imaging examination

　　(1) Ultrasound examination It can show the size, shape, location of the tumor, and whether there are cancer emboli in the hepatic veins or portal veins, and its diagnostic accuracy can reach 90%, and it is a non-invasive examination method with good diagnostic value.

　　(2) CT examination CT has high resolution, and the diagnostic accuracy for liver cancer can reach over 90%, and it can detect micro-cancers with a diameter of about 1.0cm.

　　(3) Magnetic Resonance Imaging (MRI) The diagnostic value is similar to that of CT, and it is superior to CT in distinguishing between benign and malignant liver space-occupying lesions, especially in differentiating from hemangiomas.

　　(4) Selective mesenteric or hepatic artery angiography examination For richly vascularized tumors, the resolution limit is about 1cm, and

　　(5) Liver puncture needle aspiration cytology examination Under the guidance of B-ultrasound, fine needle puncture helps to improve the positive rate. It is suitable for those who have undergone various examinations but still cannot be diagnosed, but are highly suspected.

　　Principles of diet for primary liver cancer

　　1. Daily meals should be regular, moderate, and eat more frequent, smaller meals to reduce the burden on the gastrointestinal tract.

　　2. Eat more foods rich in vitamin A, C, and E, and eat more green vegetables and fruits.

　　3. Often eat foods containing anti-cancer effects, such as Chinese kale, cabbage, carrots, rapeseed, vegetable oil, and fish.

　　4. Adhere to low-fat, high-protein, easily digestible foods, such as lean meat, eggs, yogurt, fresh fruit juice, and fresh vegetable juice.

　　5. Foods should be fresh, and avoid moldy and deteriorated foods.

　　6. Keep the bowels smooth, and for patients with constipation, eat foods rich in fiber and drink some honey every day.

　　7. The main foods should include: milk, eggs, soy milk, lotus root starch, fruit juice, vegetable juice, minced lean meat, and liver puree, etc.

　　Diet for primary liver cancer - Should not

　　1. Avoid smoking and drinking.

　　2. Avoid overeating, greasy foods, salted, smoked, roasted, and fried foods, especially charred and carbonized foods.

　　3. Avoid spicy and刺激性 foods such as scallions, garlic, Sichuan pepper, chili, and cassia.

　　4. Avoid moldy and pickled foods, such as moldy peanuts, moldy soybeans, salted fish, pickled vegetables, etc.

　　5. Avoid foods with too many bones, rough and hard textures, sticky and hard to digest, and foods rich in rough fibers.

　　6. Avoid foods with strong flavors, too sour, too sweet, too salty, too cold, too hot, and foods with too much gas.

　　7. Abdominal fluid should avoid foods with high salt and water content.

　　8. Those with low coagulation function, especially those with a tendency to bleed, should avoid scorpions, centipedes, and foods and traditional Chinese medicines with blood-activating and blood-removing effects.

　　Diet for primary liver cancer - Should

　　1. It is advisable to eat more foods that have a softening, dispersing, and anti-hepatocarcinoma effect, such as red beans, Job's tears, jujube, kombu, sea asparagus, kelp, clam, eel, turtle, and loach, etc.

　　2. It is advisable to eat more foods that have a protective effect on the liver: turtle, softshell turtle, clam, oyster, mulberry, dandelion greens, mushrooms, mushrooms, broad bean, and honey, etc.

　　3. Abdominal fluid should be consumed with red beans, quail eggs, kelp, green crabs, clams, black fish, crucian carp, crucian carp, and duck meat, etc.

　　4. For jaundice, foods such as horseshoe crab, crucian carp, bream, loach, crab, clam,螺, sweet potato, lotus root, lily bulb, dried tangerine, kumquat, etc., should be eaten.

　　5. For patients with a tendency towards hemorrhage, foods such as clam, tangerine, sea turtle, oyster, jellyfish, sea cucumber, cuttlefish, hairtail, hawthorn, persimmon, malan head, shepherd's purse, etc., should be eaten.

　　6. For patients with liver pain, foods such as kumquat, dried tangerine, finger citron, myrica, hawthorn, lotus root, cucumber, etc., should be eaten.

　　7. For patients with a tendency towards hepatic coma, foods such as dolichos, coix seed, arctium lappa, river clam, hippocampus, etc., should be eaten.

　　Individualized comprehensive treatment according to the different stages of liver cancer is the key to improving efficacy; treatment methods include surgery, ligation of the hepatic artery, hepatic artery chemotherapy embolization, radiofrequency, cryotherapy, laser, microwave, as well as chemotherapy and radiotherapy, and biological therapy, traditional Chinese medicine and Chinese herbal medicine treatment for liver cancer are also widely used.

　　1. Surgical Treatment

　　Surgery is the first choice and the most effective method for treating liver cancer. The surgical methods include radical liver resection, palliative liver resection, etc.

　　2. Treatment for inoperable liver cancer

　　For inoperable liver cancer, treatment methods such as ligation of the hepatic artery during surgery, hepatic artery chemotherapy embolization, radiofrequency, cryotherapy, laser, microwave, etc., can have certain efficacy. Primary liver cancer is also an indication for liver transplantation surgery.

　　3. Chemotherapy

　　For those in whom the tumor cannot be resected after laparotomy or as follow-up treatment after palliative resection of the tumor, regional chemotherapy embolization can be performed by placing a pump (subcutaneous implantable infusion device) in the hepatic artery and (or) portal vein; for those who are estimated to be inoperable, radiotherapy interventional treatment can also be performed, with selective catheterization into the hepatic artery through the femoral artery, injection of embolic agents (commonly such as iodized oil) and anticancer drugs for chemotherapy embolization, and some patients may thus obtain the opportunity for surgical resection.

　　4. Radiotherapy

　　For patients with good general condition, normal liver function, without cirrhosis, no jaundice, ascites, no hypersplenism and esophageal varices, limited tumor without distant metastasis, and not suitable for surgical resection or recurrence after surgery, comprehensive treatment mainly with radiotherapy can be adopted.

　　5. Biological Therapy

　　Commonly used ones include immunoribonucleic acid, interferon, interleukin-2, thymosin, etc., which can be used in combination with chemotherapy.