Summary: Risk factors for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver cancer, which is the third leading cause of cancer-related deaths in the world in 2019. There are about 841000 new cases and 782000 deaths each year.HCC incidence rate is about 10.1 cases /10 million people - year.globally, 80% of HCC cases occur in sub Saharan Africa and East Asia.the main risk factors for HCC vary from region to region.is noteworthy that the incidence rate of HCC depends not only on race / ethnicity, gender, age, geographic / demographic factors, but also on several risk factors, such as cirrhosis, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive drinking, non-alcoholic fatty liver disease (NAFLD), obesity, diabetes, metabolic syndrome and environmental toxicity.according to the current research progress, the risk factors of HCC are summarized as follows.cirrhosis is the main risk factor for HCC, and about 80% of HCC occurs on the basis of cirrhosis.compared with patients without cirrhosis, the risk of HCC in patients with cirrhosis was increased by more than 30 times.according to a study using the U.S. Census and the national mortality database, age standardized cirrhosis related mortality increased from 19.77 cases / 100000 in 2007 to 23.67 cases / 100000 in 2016, with an annual growth rate of 2.3% (95% confidence interval: 2.0-2.7).in order to reduce the incidence and mortality of liver cancer, patients with liver cirrhosis should strengthen early prevention, early diagnosis and early treatment.HBV infection is the main cause of HCC in Asia.patients with chronic HBV infection may have a 5-100 fold increased risk of HCC.in the early stage, HBV infection is asymptomatic, 15% - 40% of patients with chronic hepatitis B will progress to cirrhosis or cirrhosis related complications in their lifetime, and the elderly male patients have the highest risk.the mortality rate of HBV related cirrhosis decreased by 1.1% on average from 2007 to 2016.globally, a total of 44% of HCC cases can be attributed to chronic HBV infection, most of which occur in East Asia.compared with HBV infection, chronic hepatitis C virus (HCV) infection increases the risk of HCC by 15-20 times.the incidence of HCV related HCC is 1% - 3% after 30 years of infection, mainly in patients with advanced liver fibrosis or cirrhosis. Once cirrhosis develops, the annual incidence of HCC is 2% - 4%. lifestyle factors (drinking and smoking) drinking as a major risk factor or in combination with HBV, HCV or diabetes may increase the risk of HCC. drinking more than 80g per day for 10 consecutive years has a five fold increased risk of HCC. between 2007 and 2016, the mortality rate of alcoholic liver disease (ALD) cirrhosis increased by an average of 4.5% per year. around the world, about 26% of HCC cases can be attributed to alcohol consumption. men drink more alcohol than women. cigarettes contain more than 4000 chemicals, which may have various toxicity, mutagenicity and carcinogenicity. several epidemiological studies have shown that smoking is a minor risk factor in HCC progression. some chemicals in tobacco, such as 4-aminobiphenyl and polycyclic aromatic hydrocarbons, can produce active substances that cause HCC. currently, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with a global prevalence of 25%. NAFLD is generally considered as a non progressive liver steatosis and is rarely associated with liver complications. however, at least 20% - 30% of NAFLD patients are accompanied by necrotizing inflammation and fibrosis, 10% - 20% of patients can progress to cirrhosis, and some patients can further progress to HCC. in addition, 20% of NAFLD related HCC had no evidence of cirrhosis. however, NAFLD patients are significantly less at risk of HCC than patients with hepatitis C, hepatitis B, and alcoholic cirrhosis. obesity 9% of HCC cases in the world are caused by obesity. obesity is a metabolic disorder that increases the risk of HCC through chronic inflammation. Br / > higher levels of triglycerides and triglycerides in plasma were associated with higher levels of triglycerides . obesity not only induces carcinogenic chronic inflammation, but also changes the endocrine system, which may increase the risk of NAFLD and HCC. the increased prevalence of Nash partly contributes to the progression of obesity and obesity related diseases, which in turn increases the risk of HCC. the exact mechanism of association between obesity and HCC risk is unclear. however, recent studies have shown that there are several molecular pathways for obesity related HCC. these factors include insulin resistance, adipose tissue remodeling, proinflammatory cytokines and adipokines secretion, chronic inflammation and changes in intestinal microbiota that lead to elevated insulin and insulin-like growth factor levels. diabetes and metabolic syndrome diabetes and metabolic syndrome are all associated with an increased incidence rate of NAFLD and NASH, which eventually increases the risk of cirrhosis and HCC. about 7% of HCC cases in the world can be attributed to diabetes. a recent study estimated that patients with a history of diabetes had a 2-3-fold increased risk of developing liver cancer. according to the US data, type 2 diabetes is associated with an increased risk of HCC (HR, 4.59; 95% CI, 2.98 – 7.07), which increases with the duration of diabetes mellitus and with metabolic diseases, and hepatitis C in the elderly and women may increase this risk. studies have shown that metformin (1000 mg / D) reduces the risk of HCC, suggesting that metformin can be used as a prophylactic to improve the risk of HCC in patients with type 2 diabetes. a better understanding of the genetic and epigenetic changes of obesity may provide new targets for the treatment of HCC. environmental toxin aflatoxin (AF) is a secondary metabolite produced by Aspergillus flavus and Aspergillus parasitica, and it is a kind of strong toxic substance. aflatoxin B1 (AFB1) is the most common and one of the strongest known chemical carcinogens in naturally contaminated foods. aflatoxin B1 exposure is an important factor leading to HCC. mutation of tumor suppressor gene p53 can be found in individuals exposed to high levels of AFB1. pollution of groundwater by trichloroethylene (TCE), cadmium, lead, nickel, thallium and arsenic, as well as human exposure to organic solvents such as toluene, benzo [a] pyrene and xylene, all showed increased risk of HCC. occupational exposure to chemicals such as dichlorodiphenyltrichloroethane (DDT) and nitrosamines is another risk factor for HCC. these substances play a carcinogenic role by regulating the cyp3a1 gene and shortening telomeres (maintaining chromosome integrity by capping the ends of each DNA strand). 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