The age and sex ratio of patients varies depending on the primary disease. Hepatitis B cirrhosis, alcoholic cirrhosis and cirrhosis due to hemochromatosis are more common in men after middle age, while cirrhosis due to autoimmune hepatitis is more common in young and middle-aged women, primary biliary cirrhosis is more common in middle-aged and older women, and hepatomegaly is more common in teenagers.
The onset of cirrhosis is often slow and the symptoms are insidious. In the early stages of cirrhosis, the clinical presentation of the patient depends on the primary disease. Many patients do not have any symptoms, but some patients complain of weakness, loss of appetite, weight loss, bloating, diarrhea, pruritus (especially in patients with primary biliary cirrhosis) and hypothermia; men may have decreased libido and women may have decreased menstruation or premature amenorrhea.
Physical examination may not show any positive signs. Some patients may have a dark complexion, mild jaundice of the sclera, liver palms and spider nevi, edema of both lower limbs, and the liver is mostly inaccessible (but the liver is often enlarged in primary biliary cirrhosis and alcoholic cirrhosis), and the spleen may be enlarged to varying degrees. Some patients may have spatulate, pestle, or flat fingers. Parotid enlargement and Dupuytren’s contracture of the palm may also be seen in patients with alcoholic cirrhosis.
The two main manifestations of cirrhosis itself are chronic liver failure and portal hypertension. Chronic liver failure is mainly manifested by dysfunction of liver synthesis and metabolism and excretion. Blood biochemical tests may show decreased serum albumin level, decreased cholinesterase activity, prolonged prothrombin time, increased serum bilirubin level and increased bile acid level. The manifestations of portal hypertension are mainly: esophagogastric fundic varices and their rupture and bleeding.
In contrast, hepatic encephalopathy, ascites and its related complications (spontaneous bacterial peritonitis, hepatorenal syndrome) are common manifestations of chronic liver failure and portal hypertension. In a small number of patients with combined primary hepatocellular carcinoma, manifestations of malignancy such as pain in the liver area and significant wasting may occur.
Although cirrhosis is a local organ lesion, the consequences caused by it are still systemic diseases.
1.Digestive system
(1) Peptic ulcer: the incidence is about 20-30%, which is much higher than that of the general population. Gastric mucosa congestion, edema, mucosal erosion and duodenitis are also more common. The pathogenesis of gastrointestinal mucosal damage and ulcers in cirrhosis, especially in those with concomitant portal hypertension, is related to reduced gastric mucosal blood flow, nutritional disorders, H+ reperfusion, increased serum gastrin and increased bile reflux.
(2) Cholelithiasis: Patients with cirrhosis have an increased incidence of cholelithiasis, mainly bile pigment stones, rather than cholesterol stones. The reason for the increase in pigmented stones may be related to hemolysis and increased excretion of bile pigments. Pigmented stones in cirrhotic patients are less likely to lead to complications, such as biliary obstruction, than cholesterol stones in non-cirrhotic patients. A satisfactory explanation for this phenomenon is lacking.
2. Respiratory system
(1) Hepatopulmonary syndrome: about half of the decompensated patients present with reduced partial pressure of oxygen, with PO2 ranging from 8.0-9.3 kPa (60-70 mmHg), along with increased alveolar-arterial oxygen difference.
The main mechanisms of its occurrence are.
(i) Increased intrapulmonary NO activity causes capillary dilation forming a functional arteriovenous short circuit and an imbalance in the ventilation/perfusion ratio;
(2) the dilatation of the terminal vessels of the intrapulmonary arteries, which increases the diffusion distance of oxygen exchange; (3) the decrease of oxygen affinity of red blood cells. Clinical manifestations are gradual onset of dyspnea, cyanosis, pestle finger, especially upright hypoxia is characteristic.
(2) Pulmonary hypertension: Pulmonary hypertension occurs in patients with cirrhosis on the basis of portal hypertension, with an incidence of about 1% and more women than men. The manifestations are: dyspnea, syncope, pain in the precordial region, and hemoptysis in a few patients. The second heart sound in the pulmonary valve area is hyperactive, and murmurs can be heard at the left sternal border. Echocardiography shows an enlarged heart, often suggesting right ventricular hypertrophy. Cardiac catheterization is required to confirm the diagnosis. The cause of occurrence is not well understood and may be related to emboli and constricting substances entering the body circulation directly from the portal artery and then into the pulmonary circulation.
3.Cardiovascular system
30-60% of patients with cirrhosis may have a hyperdynamic circulatory state, characterized by increased cardiac output and reduced peripheral resistance. The possible mechanisms are: increased vasodilating factors such as NO, substance P and cardiac natriuretic factor in the body, and decreased sensitivity to vasoconstrictive substances such as endothelin and catecholamines. Despite the increase in cardiac output, patients often have a mild decrease in blood pressure due to the decrease in resistance of the body circulation.
4.Urinary system
In the late stage of cirrhosis, especially when there is a large amount of ascites, functional renal failure can occur, called hepatorenal syndrome. The main mechanism of its occurrence is the dilatation of small visceral arteries leading to insufficient effective arterial content, thus causing renal artery constriction and decreased renal blood flow. The main clinical manifestations are elevated serum creatinine without significant proteinuria and no signs of renal parenchymal damage or urinary tract obstruction. This syndrome should be distinguished from the organic renal lesions caused by HBsAg-associated nephritis.
5.Hematological system
(1) Anemia, leukopenia and thrombocytopenia: Anemia is more common in patients with cirrhosis, and its occurrence is multifactorial. Malnutrition, absorption disorders and folic acid deficiency, coupled with reduced conversion of folic acid into storage tetrahydrofolate and reduced vitamin B12 stores in the decompensated phase, can lead to macrocytic anemia. In case of iron deficiency due to blood loss, microcytic hypochromic anemia is observed.
A small number of patients have iron-rich erythrocytes due to suppressed hematopoiesis. If cirrhosis is accompanied by hypersplenism, there is a decrease in red blood cells, white blood cells (polymorphonuclear) and platelets. Hemolysis sometimes occurs in cirrhosis, especially in advanced patients, mainly due to changes in the erythrocyte membrane and increased erythrocyte fragility.
(2) Bleeding tendency: Some patients develop bleeding from the nose, gums, skin and mucous membranes. The causes are.
(i) decrease in coagulation factors due to hepatic synthesis ;
(ii) increased fibrinolytic enzymes;
(iii) diffuse intravascular coagulation;
④Thrombocytopenia due to hypersplenism.
6.Endocrine system
Sex hormone changes: In men, serum testosterone decreases and estradiol increases.
The causes are.
(1) Reduced testosterone synthesis due to reduced testicular function;
(2) Increased conversion of testosterone to estradiol in peripheral tissues;
(3) Increase in sex hormone binding globulin, which decreases free testosterone;
(4) Hypothalamic-pituitary function is suppressed. Patients thus have hypogonadism, testicular atrophy, breast development and female pubic hair distribution. Gynecomastia is mostly explained by increased sensitivity of breast tissue to estradiol; it is also thought to be caused by decreased plasma testosterone levels and decreased hepatic androgen receptor activity due to androstadienone. In female patients, this is manifested by decreased libido, low menstrual flow, menopause and breast atrophy, which may be caused by increased estrogen and decreased androgens (testosterone).
At this time, plasma estrogen (estradiol and androstenedione) levels may be normal or mildly elevated, but estrogen levels in peripheral tissues (skin, adipose tissue, muscle, bone) are significantly elevated.
Diabetes mellitus: due to the development of insulin resistance in the liver and peripheral target cells, which leads to reduced glucose tolerance and diabetes mellitus. The clinical manifestations are hypoglycemia, hyperglycemia, mild glycosuria, hyperinsulinemia, and hyperglycemia. The glucose tolerance curve is often normal at fasting, and blood glucose is still more significantly increased at 120 minutes and 180 minutes; insulin release is also increased, and ketosis and acidosis occur relatively rarely.
Hypoglycemia: Patients with advanced cirrhosis combined with severe liver failure, bacterial infection or liver cancer may show hypoglycemia.