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Hepatocellular carcinoma (HCC) refers to cancer that originates in the liver, which is distinguished from "secondary" liver cancer that spreads from other organs to the liver. Hepatocellular carcinoma, which accounts for 90% of all primary liver cancers, is the sixth most common cancer in the world and the second leading cause of cancer death [1]. It has the highest incidence in East Asia and other regions where HBV is prevalent.
Asia and sub-Saharan Africa are the areas with the highest incidence of HCC and are also high-risk areas of HBV infection. HBV and aflatoxin together influence the occurrence of HCC in Africa. It is estimated that aflatoxin B1 is a cofactor in 60% of liver cancer cases in Sudan.
In North America, Europe, and Japan, hepatitis C is the leading cause of liver cancer.
The situation in some countries is as follows:
This image is from the literature Hepatitis B and Hepatocellular Carcinoma [2]
Figure 1 The global burden of HCC
The liver is the largest internal organ in the human body. It is of great significance to human health. It has several important features:
Hepatocellular carcinoma is the most common type of liver cancer in adults. It is usually diagnosed in people aged 50 or older.
The etiology of liver diseases is diverse, including chronic viral infection of hepatitis b or hepatitis c virus, alcohol toxicity, autoimmune and cholestasis liver diseases, and metabolic factors [3].
Hepatocellular carcinoma is more common in men than in women [4]. But one of the subtypes, the fibroblast, which is very rare and accounts for less than 1% of HCC, is more common in women.
Liver cancer often occurs in the context of chronic hepatitis. Chronic (long-term) infection with either hepatitis b virus (HBV) or hepatitis C virus (HCV) is the most common risk factor for liver cancer [5] [6].These infections cause cirrhosis of the liver. Hepatitis C-induced progressive hepatic fibrosis and aging are recognized as high-risk conditions for liver cancer development [7].
Cirrhosis [8] is a disease in which liver cells are damaged and replaced by scar tissue. Most liver cancer patients have signs of cirrhosis.
Alcoholism [9] is one of the main causes of liver cirrhosis, which in turn increases the risk of liver cancer.
Obesity can lead to nonalcoholic fatty liver disease, and people with nonalcoholic fatty hepatitis (NASH) can develop cirrhosis of the liver. Studies have shown that there is a close relationship between neuromodulation, endocrinology and liver cancer in obese patients [10].
The high risk of diabetes may be due to high insulin levels in diabetics or liver damage caused by diabetes. The choice of antidiabetic treatment may affect the development of liver cancer. Insulin therapy has been reported to increase the risk of liver cancer, while metformin seems to reduce the risk of liver cancer [11].
Hemochromatosis, which causes the liver and other organs to store excess iron. People with the disease can develop hepatocellular carcinoma.
Aflatoxin: Long-term exposure to aflatoxin is a major risk factor for liver cancer.
Vinyl chloride and cerium oxide: Exposure to these chemicals increases the risk of hepatic angiosarcoma.
Arsenic: Long-term consumption of arsenic-contaminated water increases the risk of certain types of liver cancer.
Diseases that increase the risk of liver cancer include:
Porphyria cutanea tarda.
Wilson disease.
Alpha1-antitrypsin deficiency.
Tyrosinemia.
Glycogen storage diseases.
Smoking [12] increases the risk of liver cancer
Recent findings suggest that adeno-associated virus 2 (AAV2) infection is a new cause of this disease, especially in people without cirrhosis [13].
Figure 2 The impact factors and processes of HCC
In the early stages of hepatocellular carcinoma, there may be no symptoms. As cancer progresses, the following symptoms may occur:
A lump or pain on the right side of the abdomen.
Abdominal swelling or effusion.
Loss of appetite.
Unexplained weight loss.
Nausea and vomiting.
Weakness or extreme fatigue.
Yellowing of the skin and eyes (jaundice).
Fever.
Abnormal bruises or bleeding.
Abdominal vein dilatation.
Early diagnosis of hepatocellular carcinoma is of great value for the treatment and prognosis of patients with hepatocellular carcinoma.
People who have (or may have) liver cancer need more tests.
The test can show that tumors are growing in the liver and can be tested for cancer if needed.
Abdominal CT scans can help identify many types of liver tumors. CT scans can also be used to direct a biopsy needle to precisely enter a suspected tumor.
MRI scans can sometimes distinguish between benign and malignant tumors. They can also be used to look at blood vessels inside and outside the liver and to see if liver cancer has spread.
Angiography can be used to show the arteries that supply blood to liver cancer. It can also be used to guide nonsurgical treatments, such as embolization.
Bone scans can see if cancer has spread to the bone.
A biopsy is a sample taken from a tissue to see if it is cancer.
Adult AFP levels can often rise due to liver disease, liver cancer or other cancers.
AFP levels can help identify possible treatment options and evaluate treatment outcomes.
Clotting test: prothrombin time (PT) is used to test the ability of the liver to produce clotting factors.
Viral hepatitis test: check for hepatitis b and c in the blood.
Kidney function tests: include blood urea nitrogen (BUN) and creatinine levels.
Whole blood cell count (CBC): measures red, white, and platelet levels.
Sensitive biomarkers may help early detection of chronic hepatitis patients.
AFP (> 400 ng / mL) is the most commonly used biomarker for liver cancer, but its sensitivity and accuracy are not high, and half of the patients have not detected liver cancer. Another marker is des-gamma-carboxyprothrombin (DCP), however, elevated DCP may be due to other reasons, and normal DCP does not exclude HCC.
Recent studies have shown that serum microRNA is a promising method for monitoring liver function [14].
Targeted prevention according to risk factors for hepatocellular carcinoma.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) can spread from person to person by sharing contaminated needles and non-protective sex. Therefore, not sharing needles and using safer sexual practices (such as continuous condom use) can prevent some cancers.
Vaccination and antiviral therapy will have a positive impact [15].Vaccination can reduce the risk of hepatitis and liver cancer. Interferon-based regimen has been the mainstay of anti-hepatitis c therapy [16].
Blood transfusions are also a source of hepatitis infection. Rigorous testing of blood Banks is needed to reduce the risk of transmission through this route.
Drinking and smoking both increase the risk of liver cancer.
Avoiding obesity is another way to help prevent liver cancer. Obese people are more likely to develop fatty liver and diabetes, both of which are associated with liver cancer.
Hemochromatosis screening and timely treatment should be carried out for hemochromatosis family members.
Treatment depends on the extent of cancer progression.
The most commonly used liver cancer comprehensive staging tool in the world is the Barcelona Clinical Liver Cancer (BCLC) system.
The best treatment opportunity for hepatocellular carcinoma is resection. When the tumor is single and less than 2 cm, the survival rate after resection is close to 70%. However, only 10% of patients met the criteria at the time of discovery. Therefore, early diagnosis is essential to improve prognosis.
The criteria for determining whether a liver cancer patient is eligible for a liver transplant are very different worldwide. However, MC remains the benchmark for patient selection [17].
During liver transplant surgery, the entire liver is removed and replaced with a healthy liver. After the transplant, you need to continue taking the drug to prevent the body from rejecting the new liver.
However, the current status is that the number of patients waiting for liver transplantation each year exceeds the number of patients undergoing liver transplantation.
Ablation therapy removes or destroys tissue.
Radiofrequency ablation (RFA) [18]: the first line of ablation technique, which involves the use of a special needle to insert directly into the skin or through the abdominal incision to reach the tumor. High-energy radio waves heat needles and tumors that kill cancer cells.
Microwave therapy: A therapy that exposes a tumor to high temperatures generated by microwaves. This can destroy and kill cancer cells.
Percutaneous injection of ethanol: using ethanol kill cancer cells. The local control effect of ethanol injection is poor [19].
Cryoablation: A therapy that uses instruments to freeze and destroy cancer cells.
Electroporation treatment: An electrical pulse is sent through an electrode placed in a tumor to kill cancer cells. Electroporation therapy is being studied in clinical trials.
Embolization therapy: Embolization treatment is to block or reduce the flow of blood through the hepatic artery to the tumor. Thereby inhibiting the growth of the tumor.
Targeted therapy is a method that uses drugs or other substances to specifically recognize and attack specific cancer cells without harming normal cells.
Hepatocellular carcinoma is associated with abnormal activation of multiple cellular signaling pathways [20], which leads to the complexity of its etiology. The current therapeutic targets for hepatocellular carcinoma include:
Figure 3 The targets involved in hepatocellular carcinoma
Cell membrane receptors: such as tyrosine kinase receptor, vascular endothelial growth factor receptor.
Growth factors: Wnt/beta-catenin, Ras /Raf /MEK /ERK and PI3K /Akt /mTOR.
Cell cycle regulatory proteins: p53, p16 /INK4, cyclin /CDK complex.
Unfortunately, currently there are so few clinically effective HCC targeted therapies that multiple kinase inhibitors are the only HCC therapy drugs approved by FDA.
Sorafenib is currently approved as a first-line systemic therapy for unresectable liver cancer [21]. It is a multi-kinase inhibitor and is the only advanced HCC-targeted drug currently marketed in the United States and the European Union.
Sorafenib inhibits kinases such as RAF kinase, VEGFR-2, VEGFR-3, PDGFR-β, KIT and FLT-3. It can also directly inhibit tumor growth through the RAF / MEK / ERK signaling pathway; it also inhibits tumor cell growth indirectly by inhibiting VEGFR and PDGFR.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill or prevent cancer cells from growing.
Studies on microflora and HCC have found that in the mouse model of liver cancer induced in the laboratory, intestinal microorganisms influence the development of tumors and induce the occurrence of tumors [22].One study found that a specific probiotics (inulin type fructan) can reduce the proliferation of hepatocellular carcinoma cells in mice by stimulating the production of short-chain fatty acid propionate [23].
Even after liver cancer treatment is completed, you still need some tests, such as alphafetoprotein (AFP) level, liver function test (LFTs) and so on.
Patients after liver transplantation need to take medication to prevent rejection.
References
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