Hepatocellular carcinoma is a primary malignant liver lesion (hepatic cell carcinoma) characterized by rapid progression and an unfavorable prognosis. Signs of this pathology are hepatomegaly, symptoms of compression of the portal vein and the common hepatic duct, dyspeptic phenomena and intoxication syndrome. Diagnosis is based on ultrasound, CT and MRI of the liver, histological confirmation of malignant neoplasm and determination of elevated (more than 400 ng/ml) levels of alpha-fetoprotein in the blood. Complex treatment: radical removal of the tumor and chemotherapy.
Meaning
Hepatocellular carcinoma is a primary liver cancer, one of the most common oncological diseases, the frequency of which continues to grow steadily. Among all liver tumors, this form is diagnosed in more than 80% of cases. The incidence of primary liver cancer is 5-6 cases per 100 thousand population. The complexity of the pathology lies in its rapid progression: in some forms of hepatocellular carcinoma, only a few months pass from the moment of the appearance of a bright clinical picture to a fatal outcome. Latent forms are often recorded when symptoms appear already when the formation reaches a significant size and the presence of distant metastases.
Causes of hepatocellular carcinoma
The direct connection of the development of hepatocellular carcinoma with chronic liver diseases caused by hepatitis C, B viruses, as well as alcoholic illness and cirrhosis has been proved. In the etiology of the tumor, an important role is assigned to an unbalanced diet with insufficient protein intake, repeated liver injuries, autoimmune diseases and portal hypertension. The presence of dysplastic nodes or adenomatous liver hyperplasia in the patient is considered as a precancerous condition.
Risk factors include male sex, hemochromatosis, non-alcoholic fatty liver disease (with obesity), parasitic diseases (schistosomiasis, opisthorchiasis and others). The effect of carcinogenic substances (polychlorinated biphenyls, hydrocarbon solvents, organic pesticides, aflatoxins of food products), tobacco smoking (the risk increases significantly with the simultaneous use of alcohol), the use of anabolic steroids (in particular their uncontrolled use in sports) and contraceptives, the effect of arsenic (the use of water contaminated with this substance) significantly increases the likelihood of liver cancer.
Classification
In modern oncology, there are several classifications of this disease. Depending on the morphological changes, nodular, massive and diffuse hepatocellular carcinoma are distinguished. According to the generally accepted classification of malignant neoplasms (TNM), the characteristics of the primary tumor, the presence or absence of lesions of regional lymph nodes and distant metastases are determined. Based on the revealed pathomorphological changes during histological examination of the biopsy, four degrees of differentiation are distinguished: high, medium, low degree, as well as undifferentiated neoplasia.
Hepatocellular carcinoma symptoms
The clinical picture is characterized by a rapid deterioration in the general condition of the patient, significant weight loss, progressive weakness. At the beginning of the disease, there is a feeling of heaviness and pressure in the epigastric region, constant pain in the right hypochondrium. With the progression of pathology, the pain syndrome increases due to the stretching of the liver capsule, the germination of the serous membrane, surrounding tissues and organs by the tumor.
A rapid increase in the size of the liver is characteristic, its lower edge may be at the level of the navel. Hepatomegaly and the inseparable and mobile formation palpable on the surface of the liver together with it are permanent signs of hepatocellular carcinoma. Late symptoms are jaundice, ascites and dilation of the superficial veins of the abdomen. The cause of jaundice is the germination of the liver gate by the tumor and compression of the common bile duct. Ascites is formed due to a violation of blood flow in the portal vein system or its thrombosis. Dyspeptic phenomena (loss of appetite, nausea, vomiting) and an increase in body temperature are also possible.
Hepatocellular carcinoma in most cases develops against the background of existing liver disease. In patients with cirrhosis or viral hepatitis, a significant deterioration of the condition within a short period of time, the appearance of pain syndrome, a progressive increase in liver size, as well as the appearance of ascites and jaundice resistant to the treatment, allows to suspect the presence of a malignant neoplasm.
Depending on the prevailing symptoms, there are six variants of the clinical course of hepatocellular carcinoma. The most common hepatomegaly variant occurs, in which the leading sign is an increase in the size of the liver, its significant compaction, the appearance of tuberosity in areas accessible to palpation. Patients are concerned about pain in the right hypochondrium with irradiation to the lumbar region, slight jaundice of the skin and mucous membranes, an increase in body temperature.
Cirrhosis-like course is characterized by slow progression without a significant increase in the size of the liver. The pain syndrome is less pronounced, in most cases ascites resistant to therapy develops. In this form, the tumor is usually small, about three centimeters in diameter, but despite this, the formation squeezes the branches of the portal vein and significantly disrupts portal blood flow.
The cystic variant resembles the hepatomegaly in clinical manifestations, but develops more slowly; during MRI of the liver, rounded cavities are determined. Hepatonecrotic (abscess-like) type of neoplasm develops with necrotizing tumor nodes and is accompanied by a significant increase in body temperature, signs of intoxication, pronounced hepatomegaly and pain syndrome.
The obturation form occurs when the common bile duct is compressed and is characterized by the early development of jaundice with a gradual increase in formation. In 10% of cases, hepatocellular carcinoma occurs in a disguised form, when the first manifestations of the disease are caused by distant metastases, and liver enlargement, jaundice and ascites occur in the terminal stage.
Diagnostics
When examining patients with hepatic cell carcinoma, hypochromic anemia, leukocytosis with neutrophil shift, sharply increased ESR are determined in laboratory tests. When evaluating liver samples, an increase in the activity of alkaline phosphatase, GGT is detected. An important diagnostic criterion is an increase in the level of alpha-fetoprotein in the blood of patients with liver pathology above 400 ng / ml (the level of this substance correlates with the size of the tumor formation). Alpha-fetoprotein analysis in combination with liver ultrasound is performed every six months to assess the course of pathology, the effectiveness of treatment and prognosis.
Ultrasound of the abdominal organs serves as a highly informative method, allows you to detect nodular formations, assume their malignant nature, evaluate changes in the parenchyma of the organ. CT and MRI of the liver are prescribed by an oncologist for detailed visualization of the formation with determination of the size, extent of the process, the growth of the tumor into the portal vein system, hepatic ducts or neighboring organs. A mandatory diagnostic method is a puncture biopsy of the liver with a histological examination of the tissues and determination of the type of tumor and the degree of differentiation.
The criteria for verifying the diagnosis of hepatocellular carcinoma are characteristic histological signs, the coincidence of the results of two non-invasive methods of examination (ultrasound and CT or MRI of the liver) and an increase in alpha-fetoprotein of more than 400 ng / ml. Differential diagnosis is carried out with metastatic liver damage.
Hepatocellular carcinoma treatment
If hepatic cell carcinoma is detected, a combined treatment is carried out, including radical surgical removal of the tumor and chemotherapy. The operation consists in removing a segment (segmental resection) or lobe (lobectomy) of the liver, with a significant spread of the formation, liver transplantation is indicated. Patients with no more than three lesions with a diameter of up to 3 centimeters are given percutaneous injections of ethanol into tumor formations. In the absence of extrahepatic manifestations, the effectiveness of this method is about 80%.
Removal of the tumor can also be carried out by methods of thermal exposure: radiofrequency, laser-induced thermal ablation, as well as thermotherapy induced by high-frequency waves. In addition, with hepatocellular carcinoma, the method of introducing gelatin foam into the vessels (embolization) is used, while blood access to the tumor stops and its necrotizing occurs.
It is possible to inject through the hepatic artery directly into the tumor an oily contrast agent mixed with chemotherapeutic drugs and having the ability to accumulate formation cells. Local chemotherapy has a much higher efficiency in this pathology than systemic. Methods of genetic immunotherapy and oncogen suppression are also used.
Prognosis and prevention
Primary liver cancer refers to prognostically unfavorable diseases. The prognosis is determined by the degree of differentiation of tumor cells, the course variant, and the timeliness of disease detection. Prevention consists in excluding the effects of carcinogenic substances (in particular alcohol, especially in patients with viral liver damage), vaccination against hepatitis B, prevention of infection with hepatitis C virus, timely diagnosis of liver diseases and early effective treatment of all chronic hepatological diseases.
Literature
- Llovet, J. M. et al. Hepatocellular carcinoma. Nat. Rev. Dis. Prim. 2, 16018 (2016). – link
- Villanueva, A. Hepatocellular carcinoma. N. Engl. J. Med. 380, 1450–1462 (2019). – link
- International Agency for Research on Cancer. GLOBOCAN 2018. IARC
- Akinyemiju, T. et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level. JAMA Oncol. 3, 1683 (2017). – link
- Kanwal, F. et al. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology 153, 996–1005.e1 (2017). – link