I. Symptoms
In China, it is more common in men aged 20 to 50 years, and the onset in young adults is mostly associated with viral hepatitis (type B and C) and certain parasitic infections.
The onset and course of cirrhosis is generally slow-moving, and may also be latent for several years (2-5 years on average). Many patients are diagnosed during physical examination or sudden vomiting of blood due to esophageal varices or during dissection for other diseases, or even during autopsy. Sun Changyu, Department of Infectious Diseases, First Affiliated Hospital of Zhengzhou University
1, general symptoms: fatigue and weakness is one of the early symptoms, which is related to the degree of liver disease activity. The causes of easy fatigue and weakness are related to inadequate caloric intake due to loss of appetite as well as impaired intermediate metabolism of sugars, proteins, fats, etc., and insufficient heat production. In addition, due to liver damage or poor bile excretion, cholinesterase in the blood is reduced, affecting the normal physiological function of neuromuscular and lactic acid into hepatic glycogen is reduced, and lactic acid accumulation after muscle activity is excessive. Hypothermia may be caused by necrosis of hepatocytes, inflammatory activity or due to endotoxin produced by intestinal bacteria, which enters the body circulation through the collateral circulation without inactivation by the liver. In addition, the liver cannot inactivate thermogenic hormones, such as reduced urinary testosterone, which can also be found.
2. Gastrointestinal symptoms: There is often loss of appetite or accompanied by nausea, vomiting, abdominal distension, diarrhea and other symptoms. With liver dysfunction and portal hypertension, so that the gastrointestinal tract obstructive congestion and disruption of secretion and absorption function. Ascites or gastrointestinal bleeding occurs in the late stage.
(1) Esophagogastric fundic varices and hemorrhoidal varices: both can cause massive bleeding, among which ruptured hemorrhage from esophageal varices is common. The manifestation is vomiting a lot of bright red blood and black stool. The bleeding is often rapid and the patient can go into shock or even die. Bloody stools may be passed in cases of massive bleeding. Hemorrhoidal vein bleeding is a fresh blood stool, but it is less common.
(2) Gastric mucosal lesions: often a complication of liver cirrhosis. Those caused by portal hypertension are called portal hypertensive gastropathy. Portal hypertension causes general dilatation and distortion of the gastric mucosa and submucosal vessels (including capillaries, small arteries and small veins), resulting in arteriovenous short circuits and hemangiomas, and arterialization of submucosal veins. The characteristic endoscopic manifestation is congestive erythema, “mosaic sign” or “snakeskin sign”. Generally, on the basis of diffuse congestion and edema, scattered erythema appears, with a distinct redness in the center and fading in the periphery, and the red and white areas are contrasting and well-defined. Some of them show obvious spider nevus-like changes, often accompanied by scattered or even diffuse erosions, bleeding or small ulcers. It may cause upper gastrointestinal bleeding, which is milder than the bleeding from ruptured esophageal varices, and may be accompanied by vomiting of coffee-colored material and black stools.
(3) Peptic ulcer: in patients with cirrhosis than in normal people, its incidence is reported to be 18.6% and 17.7% in clinical autopsy, respectively, and more duodenal ulcers than gastric ulcers. The pathogenesis may be due to.
① Histidine in food is decarboxylated to form histamine, which is detoxified in the liver. In cirrhosis, the detoxification function is low, and histamine and 5-hydroxytryptamine, which are substances that promote gastric secretion and exist in the portal vein after the formation of the collateral circulation, are not inactivated by the liver and enter the body circulation directly, which increases gastric acid secretion.
When portal hypertension is present, dilation of the submucosal veins and capillaries of the upper gastrointestinal tract and stasis of blood cause mucosal microcirculation disorders, metabolic disorders, necrosis of mucosal cells, formation of erosion and bleeding, and ulceration in severe cases.
Endotoxemia is often associated with liver cirrhosis, and the intestinal tract absorbs endotoxin into the body circulation via the collateral circulation, which aggravates the destruction of the mucosal barrier and leads to ulceration and gastrointestinal bleeding.
④The storage of toxic substances in hepatorenal syndrome directly destroys the mucosal barrier.
⑤ Infection as a stress factor and ulceration occurs. Emergency endoscopy reported that upper gastrointestinal bleeding in cirrhotic patients was caused by rupture of esophageal varices in 24%-41% of cases, while non-variceal rupture bleeding in 45%-76% of cases.
(4) Reflux esophagitis: ascites patients due to increased abdominal pressure, causing regurgitation of gastric juice into the esophagus, erosion of esophageal mucosa inflammation and ruptured esophageal veins haemorrhage.
(5) Diarrhea: It is quite common, mostly with unformed stools. Due to edema of the intestinal wall, malabsorption (fat-based), niacin deficiency, etc.
(6) Biliary infection and gallstones: the combination of cirrhosis is higher than that of non-cirrhotic patients. Biliary infections are mostly chronic viral infections. The cause of gallstones is due to chronic hemolysis, giant spleen secretion of hemolysin and biliary infection and the formation of calcium bilirubin stones.
3, malnutrition manifestations: wasting, anemia, with a variety of vitamin deficiencies. Such as night blindness, rough skin, hair follicle keratinization, smooth tongue, orchitis, scrotum, seborrheic dermatitis. Pale or spatulate fingernails, polyneuritis, etc.
4. Hematological manifestations: bleeding tendency is common, caused by coagulation factor deficiency and hypersplenism thrombocytopenia resulting in bleeding spots or bruises on skin mucosa, nasal bleeding, gum bleeding, women often have excessive menstruation. In hypersplenism, there is an inhibition of blood cell production and an increase in the destruction of blood cells, resulting in a decrease in red and white blood cells and platelets. Anemia can be caused by iron, folic acid and vitamin B12 deficiency. Hemolytic anemia can be caused by hypersplenism, which is mild and not easily recognized clinically. Post-hepatitis cirrhosis can also be combined with aplastic anemia and blood disorders (thrombocythemia, acute granulocytic leukemia, slow granulocytic leukemia, chronic lymphatic leukemia, and Evans syndrome).
Bone marrow examination helps to differentiate the various anemias. There may be proliferation of plasma cells in hyperglobulinemia and active bone marrow proliferation in chronic liver failure. Patients with hemochromatosis may have excessive amounts of iron-containing heme in the bone marrow. Rare cases may appear to have echinocytic anemia.
5. Respiratory manifestations: Blood gas analysis shows that about half of the patients with decompensated cirrhosis have reduced oxygen saturation and decreased partial pressure of oxygen. Patients with cirrhosis without primary cardiopulmonary disease have arterial oxygenation deficiency, arterial hypoxemia, cyanosis, pestle finger and other syndromes called hepatopulmonary syndrome due to pulmonary vascular abnormalities. The main clinical manifestation is cirrhosis with cyanosis and pestle finger. The mechanism of occurrence is mainly due to right-to-left shunt. Pulmonary arteriovenous fistula and pleural spider nevus can be complicated by cirrhosis, which can cause venous blood to shunt directly into the pulmonary veins without gas exchange, and the patient develops significant cyanosis and hypoxemia that is difficult to correct with oxygen. The disease can be diagnosed by two-dimensional echocardiography. Indocyanine green (ICG) is used as the contrast agent, and microbubbles can be produced by proper mixing with saline. When injected from a peripheral vein, only the right heart is visualized in normal subjects, and the bubbles do not appear in the left heart. When an intrapulmonary arteriovenous shunt is present, the left atrium is delayed. 99mTc-MAA nuclear scan is also relevant for the diagnosis of intrapulmonary shunts. Because the albumin polymer has an average diameter of 20-60 µm, it is captured by alveolar capillaries after injection and cannot be seen outside the lung. When 99mTc-MAA accumulation is found on an extra-pulmonary scan, the presence of an arteriovenous shunt can be assumed. In addition, functional shunts of intrapulmonary arterioles are also closely associated with hepatopulmonary syndrome. Factors contributing to functional shunts may be increased cardiac output and vascular volume expansion; mismatch in the ratio of vasodilating to vasoconstricting substances in the lungs; and hypoxic pulmonary vasoconstriction. At the same time, the formation of collateral vessels from the portal vein to the pulmonary veins and the large amount of ascites that elevates the diaphragm and reduces the lung volume are also the causes of reduced oxygen saturation.
6. Skin manifestations: Jaundice may be present, with blood bilirubin mostly below 17.1 to 51.3 µmol/L, possibly due to hemolysis. However, most of them are caused by the inability of hepatocyte dysfunction to take up bilirubin or to bind and secrete it. If hepatocytes have inflammatory necrosis, jaundice deepens and can reach 68.4 to 85.5µmol/L or more, even up to 342.0µmol/L.
(1) Carotinemia: Normally, hepatocytes can convert carotene to vitamin A. Due to decreased liver function, carotinemia occurs when large amounts of carotenoid fruits or vegetables are consumed, and the skin, palms and feet are yellow.
(2) Spider nevus: The shape of a typical spider nevus is a central elevation of 3 to 5 mm with a surrounding diameter of 2 to 3 mm, which is called the body part. The body temperature of this part is 3℃ higher than that of the surrounding area; the surrounding area is a network of blood vessels, called claws. The branches of each claw, if magnified 20 times, can be seen to have 6 to 7 small branches. Spider nevus varies in size and variety, and the first occurrence can be only 1mm in size. It is characterized by bright red color, and the direction of blood flow is from the center to the surrounding area. When the body is pressed with the tip of a large-headed needle, the surrounding vascular network disappears. Larger spider nevi may have pulsation in the center, which can be confirmed by examination and palpation.
Spider nevus is more likely to occur on the face, neck and hands, followed by the chest, arms and back, and rarely on the lips, ears, nail beds and mucous membranes; it is even more rare below the umbilicus, and the reason for this is not clear. Spider nevus can occur in normal women. However, if they are large and typical, they are mostly caused by liver disease. The presence of spider nevus in male patients has more diagnostic significance for liver disease.
(3) Liver palm: usually in the size of the fissure, the skin there is red. In severe cases, the tips of each finger and even the palm are red. This is because of the concentration of arterial and venous anastomotic branches in these areas. The same manifestations can also be seen in rheumatoid arthritis and pregnancy.
(4) Capillary dilatation: The principle is the same as that of spider nevus, which mostly occurs on the face and lower extremities, with fine branches and bright red color.
(5) Nails: There may be white transverse lines (Muehrcke line.) Terry has described white nails in liver cirrhosis.
(6) Facial appearance of liver disease: the face is mostly dark and dirty-like without luster, probably due to secondary hyperalgesia or the liver’s inability to metabolize melanocyte-stimulating hormone. In addition to the face, the palm texture and skin folds may also have pigmentation.
7. Endocrine system: menstrual disorders in women. Male hypogonadism, impotence, testicular atrophy and male breast feminization.
8.Glucose metabolism: cirrhosis combined with diabetes mellitus is higher than non-cirrhotic patients. Hypoglycemia may also occur when liver function is severely impaired, which can be relieved by eating.
9, electrolyte metabolism.
(1) Low potassium: It is a common phenomenon in cirrhosis. Increased aldosterone easily causes potassium excretion. The application of diuretics often causes electrolyte disorders and produces hypokalemia. If there is vomiting, diarrhea can lead to a large amount of potassium loss. The renal tubules have a poor ability to reabsorb potassium and a strong ability to reabsorb sodium. When there is alkalosis, the renal tubules can eliminate a large amount of potassium even though the patient is already in a severe state of potassium deficiency, which increases the pH gradient inside and outside the cells. The intracellular K
exchange with extracellular H, which lowers the intracellular pH and easily causes ammonia absorption and induces hepatic encephalopathy.
(2) Hyponatremia: edema and ascites can cause dilutional hyponatremia; the application of diuretics can cause sodium deficiency hyponatremia. It is a common phenomenon in cirrhosis.
10. Liver and spleen condition: The size, hardness and smoothness of the liver and spleen in cirrhosis vary with the early and late stage of the disease. The nature of the liver is related to the amount of fat infiltration in the liver and the degree of hepatocyte regeneration and connective tissue proliferation and contraction. In early stages, the liver is large, smooth and moderately hard, 1 to 3 cm below the rib cage. in late stages, it is shrunken, hard, with a nodular uneven surface and sharp edges. When the subcostal area is not palpable, it is mostly palpable under the raphe and usually without pressure pain. There may be pressure pain if inflammation is present. Most patients have splenomegaly, which can be palpated under the ribs, usually more than 2 cm. In advanced stages, the spleen may be enlarged and flattened to the umbilicus, sometimes as a giant spleen. There is no pressure pain and the surface is smooth. If accompanied by peri-splenitis or splenic embolism, there may be pressure pain.
11, ascites: the appearance of ascites often indicates that cirrhosis has entered an advanced stage, which is a manifestation of loss of compensation. Before the appearance of ascites, there is often abdominal distension, followed by the gradual appearance of ascites. Short-term appearance of large amounts of ascites often have causes to find, such as upper gastrointestinal bleeding, infection, portal vein thrombosis, surgery and so on.
12, pleural effusion: ascites patients with pleural effusion is not uncommon, about 5% to 10%, mostly right-sided, less bilateral, simple left pleural effusion is rare. The reasons for the occurrence of pleural effusion may include hypoproteinemia; the opening of the odd vein and semi-odd vein, which increases the pressure; the increase of hepatic lymph flow leads to the expansion, sludge and rupture of the pleural lymphatic vessels, which causes the lymphatic fluid to overflow; the increase of abdominal pressure, the thinning of the diaphragm tendons to form orifices, then the ascites flows into the chest cavity. However, because the resistance decreases in cirrhosis, one should be alert to pleurisy caused by tuberculous infection.
13. Neuropsychiatric symptoms: If symptoms such as drowsiness, excitement and xerostomia appear, the occurrence of hepatic encephalopathy should be alerted.
According to the clinical manifestations and liver function, cirrhosis can be divided into compensated and decompensated stages.
II. Diagnostic criteria
The diagnosis of decompensated cirrhosis is not difficult, and the early diagnosis of cirrhosis is more difficult.
1. Compensated stage: History and symptoms of chronic hepatitis are available for reference. If there are typical spider nevus and liver palm should be highly suspected. Hard or unsmooth liver texture and/or splenomegaly >2cm with hard texture without other reasons to explain is the basis for the diagnosis of early cirrhosis. Liver function may be normal. Protein electrophoresis may be abnormal, and elevated monoamine oxidase and serum P-III-P are helpful for diagnosis. If necessary, liver puncture pathology or laparoscopy can help to confirm the diagnosis.
2. Loss of compensation stage: symptoms, signs, and laboratory tests are more significant, such as ascites and esophageal varices. Obvious splenomegaly with hypersplenism and abnormal liver function tests, etc., is not difficult to diagnose. However, sometimes it needs to be differentiated from other diseases.
Classification
The formation and development of cirrhosis are mostly slow (except for acute severe hepatitis and sub-severe hepatitis where cirrhosis occurs within a short period of time), the liver has a strong regenerative capacity and a large compensatory capacity, and there is often a fairly long compensatory period. If the compensatory phase of cirrhosis is detected in time and the progress of the disease is controlled, it is possible to keep the patient in the compensatory phase for a long time.
(1) Substitute stage (early or occult stage): no obvious clinical manifestations, or even no discomfort, as in normal people. It is occasionally detected during health examination or during caesarean operation for other diseases, or discovered by sudden gastrointestinal bleeding as well as by abdominal examination and post-mortem autopsy. At this stage, there may be less obvious digestive symptoms such as loss of appetite, nausea, abdominal distension, unformed stools, etc. There may also be general symptoms such as pain in the liver area, wasting, and weakness. Physical examination may reveal spider nevus, liver palm, large liver and spleen, and hard texture. There is usually no pressure pain, and liver function tests may be within the normal range or only mildly abnormal. It is mostly seen in small nodular cirrhosis, which progresses slowly and finally enters the decompensated stage with complications such as vomiting blood or ascites.
(2) Loss of compensation stage (late stage): manifesting various symptoms and signs of cirrhosis. Various complications often appear, such as ascites, vomiting blood, jaundice, hepatic encephalopathy, etc. Liver function tests show obvious abnormalities. It is mostly seen in large nodular cirrhosis, where the lesions continue to progress and end up with liver failure.