Causes
There are many causes of cirrhosis, which can be categorized as viral hepatitis cirrhosis, alcoholic cirrhosis, metabolic cirrhosis, cholestatic cirrhosis, hepatic venous reflux obstruction cirrhosis, autoimmune cirrhosis, toxic and pharmacologic cirrhosis, nutritional cirrhosis, cryptogenic cirrhosis and so on.
1.Viral hepatitis
Currently in China, viral hepatitis, especially chronic hepatitis B and C, is the main factor causing portal cirrhosis.
2. Alcoholism
Long-term heavy alcohol abuse is one of the factors causing cirrhosis.
3. Nutritional disorders
Most scholars recognize that malnutrition reduces the resistance of hepatocytes to toxic and infectious factors and becomes an indirect cause of cirrhosis.
4. Industrial poisons or drugs
Prolonged or repeated exposure to arsenic-containing pesticides, carbon tetrachloride, yellow phosphorus, chloroform, etc., or long-term use of certain drugs such as bisacodyl, isoniazid, octocrylophene, tetracycline, aminomethyltrexate, methotrexate and methyldopa, can produce toxicity or drug-induced hepatitis, which can lead to cirrhosis. Aflatoxin can also cause toxic damage to liver cells, causing cirrhosis.
5. Circulatory disorders
Chronic congestive heart failure, chronic constrictive pericarditis can make the liver long-term stagnation and hypoxia, causing hepatocellular necrosis and fibrosis, called stasis cirrhosis, also known as cardiogenic cirrhosis.
6. Metabolic disorders
such as hemochromatosis and hepatomegaly (also known as Wilson's disease).
7. Biliary stasis
The high concentration of bilirubin in extrahepatic bile duct obstruction or intrahepatic bile stasis has a damaging effect on the liver cells, and cirrhosis can occur in the long run, and the person who is caused by intrahepatic bile stasis is called primary biliary cirrhosis, and the person who is caused by extrahepatic bile duct obstruction is called secondary biliary cirrhosis.
8. Schistosomiasis
Schistosomiasis due to the eggs in the confluence area to stimulate connective tissue proliferation into schistosomiasis liver fibrosis, can cause significant portal hypertension, also known as schistosomiasis cirrhosis.
9. Unknown cause
Part of the cirrhosis cause is unknown, called cryptogenic cirrhosis.
Clinical manifestations
1. Compensatory stage (generally Child-Pugh class A)
Can have clinical manifestations of hepatitis, and can be insidious. There may be mild fatigue, abdominal distension, mildly enlarged liver and spleen, mild jaundice, liver palms, spider nevus.
2. Loss of compensation (generally Child-Pugh class B or C)
Hepatic impairment and portal hypertension syndrome.
(1) Systemic symptoms: weakness, emaciation, dark color, low urine output, and lower limb edema.
(2) Gastrointestinal symptoms: loss of appetite, abdominal distension, gastrointestinal dysfunction and even malabsorption syndrome, hepatogenic diabetes mellitus, polyuria, polyphagia and other symptoms.
(3) Bleeding tendency and anemia Gum bleeding, epistaxis, purpura, anemia.
(4) Endocrine disorders Spider nevi, liver palms, skin pigmentation, menstrual disorders in females, gynecomastia, parotid gland enlargement.
(5) Hypoproteinemia Double lower extremity edema, oliguria, abdominal effusion, hepatic pleural effusion.
(6) Portal hypertension Splenomegaly, hypersplenism, establishment of portal collateral circulation, esophago-gastric fundus varices, abdominal wall varices.
Examinations
1. Laboratory tests
(1) Blood routine Decrease in hemoglobin (blood pigment), platelets, and white blood cell count.
(2) Liver function tests Mild abnormalities in the compensated stage, decreased serum protein, increased globulin, and A/G inversion in the decompensated stage. Prolonged prothrombin time and decreased prothrombin activity. Transaminases and bilirubin are elevated. Total cholesterol and cholesterol lipids are decreased and blood ammonia may be elevated. Amino acid metabolism is disturbed and branch/aromatic ratio is imbalanced. Elevated urea nitrogen, creatinine. Electrolyte disorders: low sodium, low potassium.
(3) Pathogenetic examination HBV-M or HCV-M or HDV-M positive.
(4) Immunologic examination ①Immunoglobulin IgA, IgG, IgM may be elevated. ②Autoantibodies Anti-nuclear antibody, anti-mitochondrial antibody, anti-smooth muscle antibody, anti-hepatic lipoprotein membrane antibody may be positive. ③ Other immunologic tests Decreased complement, decreased rate of rose bengal knot formation and gonorrhea, decreased CD8(Ts) cells, and decreased function.
(5) Fibrosis tests PIIIP value increases, prolyl hydroxylase (PHO) increases, monoamine oxidase (MAO) increases, and serum laminin (LM) increases.
(6) Peritoneal fluid examination: For those who have recently developed peritoneal fluid, or for those whose original peritoneal fluid has increased rapidly for unknown reasons, abdominal puncture should be performed, and the peritoneal fluid should be drawn for routine examination, measurement of adenosine deaminase (ADA), bacterial culture, and cytologic examination. In order to increase the positive rate of culture, the sampling operation of peritoneal fluid culture should be carried out at the bedside, using blood culture bottles to do aerobic and anaerobic bacterial culture respectively.
2. Imaging examination
(1) X-ray examination Barium esophagogastric fundus contrast, visible esophagogastric fundus veins appear worm-like or earthworm-like varicose changes.
(2) B-mode and color Doppler ultrasonography Thickening of liver periosteum, non-smooth surface of liver, enhanced echogenicity of liver parenchyma, roughness and unevenness, widening diameter of portal vein, splenomegaly, and accumulation of fluid in the abdominal cavity.
(3) CT examination Liver lobes were disproportionate, with decreased density and nodular changes, widened portal, splenomegaly, and abdominal effusion.
3. Endoscopy
Can determine the presence or absence of esophageal-fundal varices, and the positive rate is higher than that of barium meal X-ray. It can also help to understand the extent of the varices and assess the risk of bleeding. Esophageal-fundal varices are the most reliable indicator for the diagnosis of portal hypertension. In complication with upper gastrointestinal bleeding, emergency gastroscopy can identify the site and cause of bleeding and provide hemostatic treatment.
4. Liver biopsy
Liver puncture biopsy can confirm the diagnosis.
5. Laparoscopy
Can directly observe the liver, spleen and other abdominal organs and tissues, and can take biopsies under direct vision, which is valuable for those who have difficulty in diagnosis.
6. Portal pressure measurement
The difference between the wedge pressure of the hepatic vein and the free pressure was measured by jugular vein cannulation, and the difference between the two was the hepatic venous pressure gradient (HVPG), reflecting the pressure in the portal vein. Normal is more less than 5mmHg, more than 10mmHg is portal hypertension.
Diagnosis
It is not difficult to diagnose decompensated cirrhosis, and it is more difficult to diagnose early cirrhosis.
1. Compensated stage
History and symptoms of chronic hepatitis can be used for reference. If there are typical spider nevi, liver palm should be highly suspicious. Hard or non-smooth liver and (or) splenomegaly >2cm, hard, without other reasons to explain, is the basis for diagnosis of early cirrhosis. Liver function may be normal. Protein electrophoresis may or may not be abnormal, and elevated monoaminoxidase and serum P-III-P help in the diagnosis. If necessary, liver puncture pathologic examination or laparoscopy to confirm the diagnosis.
2. Loss of compensation stage
Symptoms, signs, and laboratory tests are more significant manifestations, such as abdominal fluid, esophageal varices. Obvious splenomegaly with hypersplenism and abnormal liver function tests, it is not difficult to diagnose. However, it is sometimes necessary to distinguish it from other diseases.
Differential diagnosis
1. Hepatosplenomegaly
If hematological and metabolic diseases cause hepatosplenomegaly, liver puncture biopsy can be done if necessary.
2. Abdominal fluid accumulation
The abdominal fluid accumulation has various etiologies, such as tuberculous peritonitis, constrictive pericarditis, chronic glomerulonephritis and so on. According to the history and clinical manifestations, relevant examinations and abdominal fluid examination, it is not difficult to differentiate from cirrhosis abdominal fluid, and laparoscopy can often confirm the diagnosis if necessary.
3. Complications of liver cirrhosis
such as upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome and other differential diagnosis.
Complications
Cirrhosis often causes complications that lead to death. Upper gastrointestinal bleeding is the most common complication of cirrhosis, while hepatic encephalopathy is the most common cause of death in cirrhosis. Hepatic encephalopathy, infected hepatitis, primary hepatocellular carcinoma, hepatorenal syndrome, portal vein thrombosis, respiratory injury, and abdominal effusion.
Treatment
Cirrhosis is a liver dysfunction due to disorganization. There is currently no cure. It mainly lies in early detection and stopping the progression of the disease.
(A) Treatment for cirrhosis
1. Supportive treatment
Input hypertonic glucose solution intravenously to replenish calories, and vitamin C, insulin, potassium chloride and so on can be added in the infusion. Pay attention to maintain water, electrolyte, acid-base balance. In the more serious cases, albumin and fresh plasma can be imported.
2. Hepatitis active stage
Can be given to protect the liver, lower the enzyme, yellowing and other treatments: such as hepatic tylenol, vitamin C. If necessary, intravenous infusion therapy, such as hepatocyte growth promoter, reduced glutathione, glycyrrhetinic acid preparations.
3. Oral drugs to reduce portal pressure
(1) Cardiac glycosides should be given in increments, starting with a small amount.
(2) Nitrates such as analgesics.
(3) Calcium channel blockers, such as cardioplegia, can be given sublingually in an emergency.
(4) Supplementation of B vitamins and digestive enzymes, such as Vicodin and Dagi.
(5) the treatment of hypersplenism can be taken to raise the white blood cells and platelets of drugs (such as lixisheng, shark liver alcohol, aminopeptide, etc.), if necessary, the feasibility of splenectomy or splenic artery embolization treatment.
(6) the treatment of abdominal fluid ① general treatment, including bed rest, restriction of water, sodium intake. ② diuretic treatment such as dihydroclonidine, every other day or once or twice a week. Amphotericin, taken after meals. The main use of amphotericin and tachycardia. If the diuretic effect is not obvious, the amount can be gradually increased. Diuretic treatment is appropriate to lose no more than 0.5 kg of body weight per day, so as not to induce hepatic encephalopathy and hepatorenal syndrome. If ascites subsides gradually, diuretics can be gradually reduced. (iii) Repeated massive release of peritoneal fluid plus intravenous infusion of albumin For treatment of refractory peritoneal fluid. Release peritoneal fluid 3 times a day or weekly, at the same time, intravenous infusion of albumin. ④ Increase plasma colloid osmotic pressure Regular small and multiple intravenous infusions of plasma or albumin every week. ⑤ Concentration of peritoneal fluid reflux Used for the treatment of refractory peritoneal fluid, or patients with hypovolemic state, hyponatremia, hypoproteinemia, and hepatorenal syndrome, as well as patients with a large amount of peritoneal fluid due to various reasons in urgent need of symptomatic relief. (6) Peritoneal-jugular venous drainage, i.e., PVS, is an effective treatment for cirrhosis and peritoneal effusion. However, its application is greatly restricted due to its many complications, such as fever, bacterial infection, pulmonary edema, and so on. (7) Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce portal pressure, with little trauma and high safety. It is suitable for esophageal variceal hemorrhage and refractory peritoneal effusion, but easy to induce hepatic encephalopathy.
(7) Surgical treatment of portal hypertension Indications are ruptured esophageal - fundic varices bleeding, ineffective by non-surgical treatment; giant spleen with hypersplenism; esophageal varices bleeding high-risk patients. Including portal-caval vein shunt, portal-serial vein shunt and splenectomy.
(8) Liver transplantation Applicable to end-stage liver disease for which conventional medical and surgical treatment is ineffective. It includes irreversible abdominal effusion; portal hypertension with upper gastrointestinal bleeding; severe hepatic impairment (Child classification C); development of hepatorenal syndrome; development of progressively worsening hepatic encephalopathy; and liver cirrhosis based on complication of hepatocellular carcinoma.
(2) Antiviral therapy for hepatitis B cirrhosis
1. General indications
include: ① HBeAg-positive patients with HBV-DNA ≥105 copies/ml (equivalent to 20,000 IU/ml); HBeAg-negative patients with HBV-DNA ≥104 copies/ml (equivalent to 2,000U/ml); ② ALT ≥2×ULN; if treated with IFN, ALT should be ≤10×ULN, and serum total bilirubin should be ﹤2×ULN; ③ALT﹤2×ULN, but liver histology shows KnodellHAI≥4, or inflammatory necrosis≥G2, or fibrosis≥S2.
For those who are persistently HBV-DNA-positive and fail to meet the above treatment criteria but have one of the following circumstances, they also Antiviral therapy should be considered: ① For those with ALT > ULN and age > 40 years old, antiviral therapy should also be considered (Ⅲ); ② For those with ALT persistently normal but older (> 40 years old), they should be closely followed up, preferably with liver tissue biopsy; if liver histology reveals Knodell HAI ≥ 4, or inflammatory necrosis ≥ G2, or fibrosis ≥ S2, antiviral therapy should be given aggressively (Ⅱ); ③ Dynamic observation of HBV-DNA positive patients with HBV-DNA and less than the above treatment criteria, but with one of the following conditions, antiviral therapy should also be considered (Ⅲ). II); (iii) if evidence of disease progression (e.g., splenomegaly) is detected by dynamic observation, liver histology is recommended, and antiviral therapy should be given if necessary (III).
Therapeutic drugs include interferon (regular interferon, long-acting interferon) and nucleoside (acid) analogs (lamivudine, adefovir, tebivudine, entecavir, tenofovir, clavudine, etc.).
(C) Other treatments
1. Immunomodulatory therapy
Thymopeptide and alpha thymosin are commonly used in acute and chronic hepatitis B to regulate the body's immunity.
2. Traditional Chinese medicine and Chinese medicine preparation treatment
Hepatoprotective therapy is effective in improving clinical symptoms and liver function indexes.
(D) Treatment of complications
1. Spontaneous peritonitis
Antibacterial drugs mainly targeting Gram-negative bacilli and taking Gram-positive cocci into account are used. Such as three generations of cephalosporin, ciprofloxacin and so on. According to the results of drug sensitivity and the patient's response to treatment to adjust antibacterial drugs. The duration of medication is 1 to 2 weeks.
2. Hepatorenal syndrome
Improvement of renal function depends on the improvement of hepatic function, so the treatment focuses on the treatment of liver primary disease. On this basis, further treatment. ①Rapidly control upper gastrointestinal hemorrhage, infection and other predisposing factors. ②Control the amount of fluid infusion to maintain water, electrolytes and acid, alkali balance. (③) Volume expansion treatment with dextrose anhydride, albumin, plasma, whole blood and its own peritoneal fluid concentration reflux, etc., with less or no saline. Can be combined with diuretics and small doses of cardiotonic drugs. ④ Application of vasoactive drugs such as dopamine and prostaglandin E2 can improve renal blood flow and increase glomerular filtration rate. ⑤ Dialysis treatment includes hemodialysis and peritoneal dialysis, which is suitable for acute cases, those who have the possibility of liver regeneration, or those who have the possibility of liver transplantation. Otherwise it just prolongs the process of patient's death. ⑥ Surgical treatment and liver transplantation, transjugular intrahepatic portosystemic shunt is suitable for those with cirrhosis accompanied by intractable ascites complicating hepatorenal syndrome. However, the results are not yet satisfactory. Postoperative dialysis is still needed. Liver transplantation is currently recognized as the most effective treatment. (7) Other treatments: avoid strong diuresis, simple massive release of ascites and the use of drugs that impair renal function.
3. Hepatic encephalopathy
① Eliminate the triggers, low protein diet. ② correction of ammonia poisoning: oral lactulose, lactulose can acidify the intestinal tract, keep the stool, change the intestinal pH, so that the intestinal ammonia production and absorption of ammonia to reduce, and can reduce endotoxemia and other toxic substances absorption. Generally used in combination with monosodium glutamate to offset side effects and enhance efficacy. Potassium magnesium aspartate: it can combine with ammonia to form asparagine and have de-ammonia effect. (iii) Branched-chain amino acid therapy, antagonizing correlative toxins. ④Actively prevent cerebral edema. ⑤All kinds of stubborn, serious hepatic encephalopathy, end-stage liver disease feasible artificial liver, liver transplantation.
4. Esophageal - fundal varices rupture bleeding
If not timely rescue, can be life-threatening. Establishment of hemodynamic monitoring, volume expansion, blood transfusion, lowering portal pressure (growth inhibitor, octreotide, nitroglycerin + posterior pituitary hormone), hemostasis, acid suppression, triple lumen tube compression for hemostasis, endoscopic treatment, gastric coronary vein embolization, surgery, transjugular intrahepatic portal venous stenting shunt.
5. Treatment of primary hepatocellular carcinoma
At present, individualized treatment of hepatocellular carcinoma can be applied by surgery, intervention (vascular embolization + CT-guided local ablation), local radiotherapy (γ-knife, linear gas pedal, three-dimensional conformal radiotherapy) and other therapeutic means. Ricardin, Sorafenib, gene therapy, biotherapy, etc. can also be used.
Prognosis
The prognosis of cirrhosis is related to the etiology, the degree of liver function compensation and complications. Alcoholic cirrhosis, biliary cirrhosis, hepatic stasis and other causes of cirrhosis, if the cause of cirrhosis can be eliminated before cirrhosis progresses to the decompensated stage, the lesion can tend to be quiescent, compared with viral hepatitis cirrhosis and cryptogenic cirrhosis, etc. Child-Pugh grading is closely related to the prognosis, grade A is the best, grade C is the worst. The cause of death is often hepatic encephalopathy, hepatorenal syndrome, rupture and bleeding of esophageal= fundic varices and other complications. The development of liver transplantation has significantly improved the prognosis of patients with cirrhosis.
Prevention
Prevention of this disease should first emphasize the prevention and treatment of viral hepatitis. Early detection and isolation of patients to give active treatment. Attention to diet, rational nutrition, abstinence from alcohol, strengthen labor health care, avoid all kinds of chronic chemical poisoning is also a positive measure of prevention. For those who are suspected to have cirrhosis due to the above causes, they should undergo a comprehensive physical examination and relevant laboratory tests in time, so as to get reasonable and active treatment in the compensated stage and prevent the development to the uncompensated stage. Regular physical examination, while avoiding various triggers, prevention and treatment of possible complications.