1 Modern Understanding of Liver Cancer

1 Modern Understanding of Liver Cancer

Primary carcinoma of the liver (PLC) is one of the common malignant tumors of the digestive system, with high incidence in Southeast Africa and Asia. Both its incidence and mortality rates are on the rise globally. Liver cancer predominantly affects middle-aged men, with a male-to-female incidence ratio of (2–5):1[5]. It is highly malignant and progresses rapidly, with a postoperative recurrence rate as high as 50% within two years[6]. Primary liver cancer has an insidious onset, with pain in the hepatic region being a common symptom. By the time the disease reaches the middle or late stages, patients often exhibit progressive hepatomegaly, jaundice, signs of cirrhosis, systemic manifestations of malignancy, symptoms of metastatic lesions, and paraneoplastic syndromes, among other clinical features.

1.1 Etiology and Pathogenesis of Liver Cancer

The causes of liver cancer vary across different regions, but they are generally associated with the following factors:

1.1.1 Hepatitis Viruses

The hepatitis viruses currently recognized as being linked to liver cancer are hepatitis B virus (HBV) and hepatitis C virus (HCV)[7]. Among them, HBV infection is the primary risk factor for liver cancer in China. Su Hongying [8] and others conducted an etiological risk factor analysis on 224 cases of primary liver cancer, revealing that the HBV infection rate in the primary liver cancer group was significantly higher than in the control group (excluding patients hospitalized due to liver disease or conditions with obvious gender bias). Chronic HBV carriers had a 27.4-fold higher risk of developing liver cancer compared to non-carriers, while those with a history of hepatitis B had a 57.6-fold higher risk than those without such a history. Studies have shown that vaccination against hepatitis B can greatly reduce the incidence of liver cancer[9]. HCV infection also plays a significant role in the development of liver cancer in developed countries[10].

1.1.2 Aflatoxin

Aflatoxin is a highly toxic secondary metabolite produced by the metabolism of Aspergillus flavus and Aspergillus parasiticus, mainly generated during the moldy process of grain foods such as wheat, peanuts, and corn[11]. Regions worldwide with high aflatoxin contamination are also high-incidence areas for liver cancer, with aflatoxin B1 (AFB1) being the most important contaminant. Aflatoxin has strong "three-effect" properties: carcinogenicity, mutagenicity, and teratogenicity[12]. Research has shown that aflatoxin exhibits multi-system toxicity affecting the liver, immune system, and blood, causing hemorrhage and necrosis of hepatocytes, inhibiting DNA and RNA synthesis, and acting as a potent carcinogen[13]. The carcinogenic effect of aflatoxin on the body is related to its ability to induce mutations in the tumor suppressor gene P53[14].

1.1.3 Water Pollution

An epidemiological survey conducted in Qidong, Jiangsu Province—a high-incidence area for liver cancer in China—on the relationship between drinking water and liver cancer revealed that residents who drank water from ditches and ponds had a significantly higher liver cancer mortality rate than those who drank deep well water. Some literature suggests that cyanobacterial toxins in water are associated with the occurrence of liver cancer[15], with the main toxic effects of cyanobacterial toxins including liver damage and neurotoxicity.

1.1.4 Alcohol Consumption and Smoking

Su Xiang [16] analyzed the causes of liver cancer in 120 cases and found that 33.3% (40 cases) of the patients had a history of alcohol consumption, while 30.0% (36 cases) had a history of smoking. Numerous epidemiological surveys have shown that in regions with low HBsAg prevalence, alcohol is the factor most closely associated with liver cancer development besides hepatitis viruses, making long-term drinkers a high-risk group for primary liver cancer. Li Yan et al. [17] surveyed 1,057 cases of primary liver cancer in Jilin Province and found that alcohol consumption had a significant impact on both HBV-infected and HCV-infected individuals, increasing their risk of developing liver cancer. Alcohol can lead to fatty degeneration of hepatocytes and, when combined with HBV or HCV infection, further increases the incidence of primary liver cancer[18]. Smoking also significantly promotes the development of liver cancer, with a clear positive correlation between smoking and the risk and mortality rate of liver cancer[18]. Chemical substances in tobacco smoke, such as nicotine, nitrosamines, polycyclic aromatic hydrocarbons, and cocaine, can be activated and metabolized in the liver, directly damaging the organ and causing liver cancer.

1.1.5 Genetic Factors and Other Factors

Genetic factors are an important cause of liver cancer, even more prominent than in other types of tumors. A survey of family members in a Yao ethnic minority village in Guangxi Province, where two or more cases of liver cancer occurred among relatives, revealed a clear familial clustering of liver cancer cases in the area. Over the past twenty years, families with two or more liver cancer patients accounted for 62.5% of all liver cancer families, with some families reporting as many as four cases[19]. In addition, cirrhosis, fatty liver, diabetes, consumption of salt-preserved foods[20], and obesity are all Research on Pei Zhengxue's Series of Formulas

risk factors for liver cancer.

1.2 Treatment of Liver Cancer