Hepatocellular carcinoma - Symptoms

The symptoms of hepatocellular carcinoma are quite polymorphic. The course of the disease may be asymptomatic; in this case, patients only show signs of liver cirrhosis. The tumor may be diagnosed accidentally. However, the clinical manifestations may be so vivid, and liver failure so pronounced, that the clinical picture resembles that of a liver abscess. The spectrum of manifestations lies between these two extreme clinical forms of the disease.

Age. Hepatocellular carcinoma can develop at any age. Among Chinese and Bantu people, the disease is most common in people younger than 40. In temperate climates, patients with hepatocellular carcinoma are usually older than 40.

Gender. Men get sick 4-6 times more often than women.

Associated cirrhosis. It is necessary to diagnose liver cirrhosis in a timely manner. Hepatocellular carcinoma may be suspected in a patient with cirrhosis if the condition worsens or pain appears in the right hypochondrium, as well as if a palpable tumor originates from the liver. Hepatocellular carcinoma should also be excluded in cases where there is no improvement with adequate treatment of ascites, bleeding from esophageal varices, or precoma in a patient with liver cirrhosis.

Rapid deterioration in the condition of a patient with hemochromatosis or chronic liver disease with the presence of HBsAg or anti-HCV antibodies in the serum indicates the possible development of hepatocellular carcinoma.

Patients complain of weakness and a feeling of discomfort and pressure in the upper abdomen. Weight loss is noted. Temperature rarely exceeds 38 °C.

Pain is common in patients with hepatocellular carcinoma, but only rarely is it severe.

Usually it is a dull constant pain in the epigastric region, right hypochondrium or back. Intense pain indicates perihepatitis or diaphragmatic damage.

Gastrointestinal dysfunction is common in hepatocellular carcinoma. It manifests itself as loss of appetite, flatulence, and constipation. The first symptom of the disease may be diarrhea, which is caused by cholestasis or the production of active substances by the tumor, such as prostaglandins.

Shortness of breath is a late symptom caused by the large size of the tumor, which presses on the diaphragm or grows into it, or by metastases to the lungs.

Jaundice is rarely intense and usually does not depend on the size of the tumor. In rare cases, the tumor may look like a polyp on a stalk, be located inside the bile duct and cause mechanical jaundice. The tumor can grow into the common bile duct. In this case, tumor masses can be found in the lumen of the duct, and hemobilia can be the immediate cause of death.

Sometimes, as a result of necrosis of the central part of the tumor, fever and leukocytosis appear; in this case, the clinical picture resembles that of a liver abscess.

The liver increases in size not only downwards, into the abdominal cavity, but also in the direction of the chest cavity. In the right hypochondrium, a dense tumor-like formation with an uneven surface emanating from the liver can be palpated. If the left lobe is affected, the tumor is palpated in the epigastric region. Sometimes several tumor nodes are palpated. The pain can be so pronounced that it makes palpation difficult.

Friction noise may sometimes be heard over the tumor as a result of perihepatitis. Arterial noise over the tumor is a consequence of the expansion of the arterial network supplying the tumor with blood. In the absence of acute alcoholic hepatitis, this noise indicates hepatocellular carcinoma.

Ascites is found in approximately half of patients. Ascitic fluid contains a lot of protein. Malignant cells may be detected, but their interpretation in peritoneal fluid is difficult. Increased LDH activity and carcinoembryonic antigen levels in ascitic fluid are possible. It may be stained with blood. Tumor rupture leads to hemoperitoneum. The latter may develop gradually or manifest as an acute abdomen with severe pain syndrome. The prognosis for such patients is very poor.

Portal vein thrombosis aggravates ascites. Occlusion of the hepatic veins may develop. Tumor growth into the right atrium and esophageal venous plexuses is possible.

Esophageal variceal bleeding is a common and usually fatal complication. Failure to stop variceal bleeding in a patient with liver cirrhosis is often due to hepatocellular carcinoma growing into the portal vein.

Clinical manifestations of metastases

Metastases may be found in the lymph nodes, especially the right supraclavicular nodes, which can be palpated. Metastasis to the lungs may be accompanied by the appearance of pleural effusion. Massive pulmonary embolism causes dyspnea and pulmonary hypertension. Severe arteriopulmonary shunting may develop. Bone metastases are usually found in the ribs and spine. Metastatic lesions of the brain manifest as symptoms of a brain tumor.

Systemic manifestations of hepatocellular carcinoma

Severe endocrine disorders are observed more often in hepatoblastoma in children than in hepatocellular carcinoma in adults.

Painful gynecomastia associated with increased secretion of estrogens is possible.

Hypercalcemia is sometimes caused by pseudohyperparathyroidism. The tumor may contain a substance that resembles parathyroid hormone (PTH); serum PTH levels are elevated. Hepatic artery embolization may be effective.

Hypoglycemia occurs in 30% of patients. It may be caused by extremely rapid tumor growth, usually undifferentiated, which is accompanied by an increased need for glucose. Occasionally, hypoglycemia develops in patients with a slowly progressing tumor. In this case, the activity of G-6-phase and phosphorylase in the tumor is reduced or absent, while the glycogen content in the tumor and adjacent tissue increases. This indicates that hypoglycemia is caused by an acquired disorder of glycogen metabolism with its increased accumulation. In such patients, it is extremely difficult to normalize the blood glucose level even when eating food with a high carbohydrate content.

In patients with severe recurrent hypoglycemia, the level of high-molecular-weight insulin-like growth factor (IGF-II) in tumor tissue is 10-20 times higher than its level in normal liver. This may also contribute to the development of hypoglycemia.

Hyperlipidemia is rare in patients with hepatocellular carcinoma, but approximately one third of patients on a low-cholesterol diet have elevated serum cholesterol levels. In one patient, hyperlipidemia and hypercholesterolemia were due to the formation of abnormal beta-lipoprotein.

Hyperthyroidism may be caused by inadequate production of thyroid stimulating hormone.

Pseudoporphyria with a significant increase in the concentration of porphobilinogen in urine and serum is a consequence of the production of porphyrins by the tumor.

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