Hepatocellular carcinoma: diagnosis

Biochemical changes

Biochemical changes may not differ from those in cirrhosis. Significantly increased activity of alkaline phosphatase and serum transaminases.

With the electrophoresis of serum proteins, an increase in the level of y and alpha ₂ -fractions of globulins is noted. A rare finding is myeloma type serum macroglobulin.

Serologic markers

A-Fetoprotein whey

Alpha fetoprotein is a protein that is normally found in the fetal blood serum. After 10 weeks after birth, its concentration does not exceed 2 0 ng / ml and remains at this level in an adult throughout life. Some patients with hepatocellular carcinoma show a progressive increase in the concentration of a-fetoprotein, although in some cases its level remains normal. Detection of an elevated level of a-fetoprotein at the first examination of a patient with cirrhosis of the liver indicates a high probability of developing hepatocellular carcinoma during subsequent observation. A group of high risk of developing hepatocellular carcinoma is a patient with cirrhosis of the liver caused by HBV or HCV infection, in which the serum a-fetoprotein level exceeds 2 0 ng / ml or transiently increases to 100 ng / ml and higher. In patients with repeated increases in the level of a-fetoprotein up to 100 ng / ml and more, the incidence of hepatocellular carcinoma during the 5-year follow-up period is 36%.

A slight increase in the level of a-fetoprotein is often found in acute and chronic hepatitis and liver cirrhosis, which can cause difficulties in diagnosis.

The level of a-fetoprotein usually correlates with the size of the tumor, but exceptions are possible. Nevertheless, there is a close relationship between the time interval, during which there is a twofold increase in the level of a-fetoprotein, and a period of increasing the size of the tumor by a factor of 2. After resection, as well as after liver transplantation, the level of a-fetoprotein decreases. Preservation of a slightly elevated level of a-fetoprotein indicates an incomplete removal of the tumor, and its progressive increase - for its rapid growth. To evaluate the effectiveness of therapy, it is expedient to determine the level of a-fetoprotein in dynamics.

The structure of circulating a-fetoprotein in patients with hepatocellular carcinoma differs from that of cirrhosis. The study of a-fetoprotein fractions plays an important role in the differential diagnosis of hepatocellular carcinoma and liver cirrhosis, as well as for the prognosis of the development of hepatocellular carcinoma.

With fibrolamellar and cholangiocellular cancer, the level of a-fetoprotein usually does not exceed the norm. With hepatoblastoma, it can be very high.

The level of carcinoembryonic antigen is especially high with metastatic liver damage. Because of its non-specificity, this indicator does not play a significant role in the diagnosis of hepatocellular carcinoma. The increase in serum a ₁ -antitrypsin and acid α-glycoprotein concentration is also a nonspecific sign.

The increase in serum ferritin concentration in hepatocellular carcinoma is more likely due to its production by a tumor than by liver necrosis. An increase in the ferritin level is observed with any active hepatic-cell lesion and does not necessarily indicate hepatocellular carcinoma.

Des-y-carboxyprotrombin (des-y-KPT) is a vitamin K-dependent precursor of prothrombin, synthesized by normal hepatocytes, as well as cells of hepatocellular carcinoma

An increase in the level of this factor to 100 ng / ml and more indicates a possible hepatocellular carcinoma. With chronic hepatitis, cirrhosis and metastatic liver damage, the level of des-y-CBT is normal. The specificity of this indicator is higher than that of a-fetoprotein, however, sensitivity is not sufficient for the diagnosis of small tumors.

The level of serum aL-fucosidase in hepatocellular carcinoma is increased, but the mechanism of this increase is unclear. The determination of the level of this enzyme can be used in the early diagnosis of hepatocellular carcinoma in patients with cirrhosis of the liver.

Hematologic changes

The number of leukocytes usually exceeds 10 • 10 ⁹ / l; 80% are neutrophils. Sometimes there is eosinophilia. It is possible to increase the number of platelets, which is not characteristic of uncomplicated cirrhosis of the liver.

The number of erythrocytes is usually normal, anemia is poorly expressed. In 1% of patients, erythrocytosis is observed, probably due to increased production of the erythropoietin tumor. The concentration of erythropoietins in the serum can be increased even with normal hemoglobin and hematocrit.

Possible disruption of the function of the coagulation system of blood. Fibrinolytic activity decreases. This is due to the release of a tumor into the vascular bed of a fibrinolysis inhibitor. Perhaps this explains the increase in the level of fibrinogen in the serum.

Disfibrinogenemia reflects a return to the fetal form of fibrinogen. Matte-vitreous cells in hepatocellular carcinoma may contain and produce fibrinogen.

Markers of hepatitis viruses

A study of HBV and HCV markers should be carried out. Exclude hepatitis B and C.

Tumor localization

X-ray can detect calcifications.

Liver scanning

Isotope scanning reveals tumors with a diameter of more than 3 cm in the form of a filling defect.

With ultrasound, the echogenicity of the liver can be either elevated or decreased. The tumor is hypoechoic, with fuzzy contours and non-uniform echoes. The diagnosis can be confirmed by sight biopsy. The sensitivity and specificity of the method are quite high. False positive results of the study in cirrhosis due to increased echogenicity of large nodes. Ultrasound is of particular value in the screening survey, it can detect lesions of less than 2 cm in diameter.

With computed tomography (CT), hepatocellular carcinoma appears as a foci of reduced density. CT often does not allow to determine the size and number of tumors, especially in the presence of cirrhosis. It is also important to conduct a study with contrasting. The picture with hepatocellular carcinoma is mosaic, multiple nodes with different degrees of signal weakening and clearly defined partitions separating the tumor mass are visible. The tumor can be encapsulated. Often observed fatty degeneration of the liver. There may be infiltration of the portal vein and the presence of arterioportal shunts.

Iodolipol, injected into the hepatic artery, is removed from the healthy tissue, but remains almost constantly in the tumor, due to which on computer tomograms obtained after 2 weeks after the administration of the contrast medium, it is possible to detect even small tumor foci with a diameter of up to 2-3 mm. With focal modular hyperplasia, iodolipol is also delayed, but unlike hepatocellular carcinoma, it is removed from the hyperplastic nodes within 3 weeks.

Magnetic resonance imaging (MRI) makes it possible to obtain somewhat sharper images in focal pathology than CT scans. This method is especially valuable in the presence of concomitant fatty liver. On T1-weighted images, the tumor has the appearance of a normal density, bordered by a belt of reduced intensity. T2-weighted images clearly reveal a difference in the density of normal liver tissue and tumor, as well as tumor growth of the vessels and satellite foci.

Intravenous administration of iodine-containing (gadolinium salt) or magnesium-containing contrast medium (Mnd PDP) improves the detection of hepatocellular carcinoma. The introduction of super-magnetic iron oxide during the investigation in T2-mode is safe and raises the effectiveness of the study.

Angiography of the liver

Angiography can detect liver cancer, establish its localization, resectability, and monitor the effectiveness of treatment. The tumor is supplied with blood from the hepatic artery, so it can be detected using selective arteriography with the introduction of contrast material into the celiac trunk or the superior mesenteric artery. Super selective infusion angiography is especially valuable for the detection of small tumors. Selective digital subtractive angiography with intra-arterial administration of contrast medium allows detecting tumors with a diameter of 2 cm or less, which eventually evolve from isovascular to hypervascular.

Computer arterioportography reveals a decrease in portal blood flow in the tumor node.

Differential diagnosis of hepatocellular carcinoma and regeneration sites with cirrhosis presents certain difficulties. The results of angiography may depend on the anatomical structure of the tumor. Its vascular pattern has a bizarre character, focal congestions of contrast medium, dilatation and displacement of vessels, which can be sclerized, fragmented, have an uneven lumen. Often there are arteriovenous shunts, through which the portal vein can retrograde contrast. When the tumor grows, the portal vein can be deformed.

Doppler ultrasound reveals intravascular spread of the tumor. The sprouting of the portal vein is confirmed by the presence of an arterial wave in the portal bloodstream, which spreads in the hepatofugal direction. The maximum velocity of blood flow during systole is increased, a significant increase is noted in the presence of an arteriovenous shunt or the growth of a tumor into the portal vein. Doppler ultrasound allows differential diagnosis with hemangioma.

Puncture liver biopsy

If small focal lesions are detected by ultrasound or CT, it is necessary to histologically verify the diagnosis. If possible, liver biopsy should be performed under visual control. There is the possibility of spreading the tumor along the needle, but this complication is rare.

Cytological examination of the material obtained with aspiration biopsy with a thin needle N22, allows to diagnose tumors with a low and moderate degree of differentiation. However, it is not easy to identify highly differentiated liver cancer with the help of a cytological study.

Screening examination

Asymptomatic hepatocellular carcinoma of small size in patients with cirrhosis of the liver can be diagnosed by screening of high-risk groups or was found accidentally when using visualization diagnostic methods in the study of a liver removed during transplantation. Early diagnosis of hepatocellular carcinoma is important, as it increases the likelihood of favorable outcomes after resection or liver transplantation. The annual survival rate of untreated patients with compensated liver cirrhosis (group A according to the Childe system of criteria) and asymptomatic course of hepatocellular carcinoma is 90%, while a similar figure for patients with clinical manifestations of the disease is only 4 0%. The success of treatment depends on the rate of tumor growth. Therapy is more effective in Japanese, whose tumor is growing more slowly than in South Africa.

Screening is indicated among patients at high risk of developing hepatocellular carcinoma. They include men over 40 with the presence of HBsAg or anti-HCV antibodies in the serum, as well as those suffering from chronic liver diseases, especially cirrhosis with large regeneration sites. Ultrasound is a more sensitive research method than CT. Usually, after them, a needle aspiration liver biopsy is performed with a thin needle. Samples from non-tumor tissue should also be obtained to detect concomitant cirrhosis and to determine its activity.

Every 4-6 months, the serum a-fetoprotein level is determined, especially if it was initially elevated, and also when large regeneration sites are detected. The normal level of a-fetoprotein in the serum does not exclude the presence of hepatocellular carcinoma.

The value of this screening varies depending on the country in which it is conducted. So, in Japan, where hepatocellular carcinoma due to slow growth is small and often encapsulated, the value of screening is great. At the same time, its practical value is minimal in the countries of South Africa, where hepatocellular carcinoma is characterized by rapid growth and high malignancy. European countries in this respect occupy an intermediate position. Conducting a preventive survey of the population depends on the level of development of the country's economy. In Japan, procedures such as ultrasound and determining the level of a-fetoprotein are widely available and are free of charge. However, in most other countries of the world there are no such opportunities. The prognosis for hepatocellular carcinoma is so poor that, where the cost of the examination is an important factor, there is a restrained attitude towards the screening survey, as there is no firm belief that it will help reduce the death rate in this disease.

[1], [2], [3]