OVERVIEW
Symptoms are mild and lack specificity, and may be characterized by mild fatigue, emaciation, loss of appetite, abdominal distension, etc.
Abdominal ultrasound is a simple method to diagnose the compensated stage of cirrhosis.
Treatment includes supportive therapy, symptomatic therapy, liver preservation therapy, etc.
Median survival is more than 12 years
Definition
Cirrhosis can be categorized into compensated phase, decompensated phase, re-compensated phase and cirrhosis reversal in China [1-4].
The compensated phase of cirrhosis is generally also known as the early stage of cirrhosis, which is characterized by normal or mildly abnormal liver function tests, in Child-Pugh class A, and insignificant portal hypertension [2].
Patients in the compensated stage have mild symptoms and lack of specificity, which may be manifested as mild fatigue, emaciation, loss of appetite, abdominal distension, anorexia of oil, epigastric discomfort and vague pain in the right upper abdomen [3].
Some patients have no obvious symptoms and are found incidentally during normal physical examination or examination due to other diseases. On physical examination, some patients can palpate a hard textured liver with blunt edges.
Abdominal ultrasound (ultrasound) is an easy way to diagnose cirrhosis, but there are usually no abnormal manifestations in the compensated phase of cirrhosis [4-5].
Morbidity
The compensated phase of cirrhosis is the early stage of liver cirrhosis, and there is no authoritative morbidity data because the boundary between the compensated and decompensated phases is unclear.
In China, cirrhosis is a relatively common disease of the hepatobiliary system. Cirrhosis accounts for 1% of the total number of hospitalized patients in the same period.
Cirrhosis is most common in men between the ages of 20 and 50.
The main populations of cirrhosis in China are patients with chronic hepatitis B and metabolic fatty liver disease as well as people with chronic alcoholism.
The annual incidence of cirrhosis in China is about 17.1/100,000 people.
Causes
Causes
The etiology of the compensated stage of cirrhosis is no different from that of other stages of cirrhosis.
Common causes of cirrhosis include viral hepatitis, long-term alcohol consumption, abnormal fat metabolism liver disease, toxins or drugs causing liver injury, parasitic infections such as schistosomiasis, metabolic liver disease and autoimmune liver disease [4].
Rare factors include obstruction of hepatic venous return (e.g., chronic right heart failure, Buga syndrome, hepatic sinusoidal obstruction syndrome).
Very rarely, the cause is unknown and is called idiopathic cirrhosis.
For more information on the causes of cirrhosis, please refer to the Causes of Cirrhosis section.
Pathogenesis
When liver cells are attacked by pathogenic factors for a long period of time, necrosis will occur, and in the process of repairing liver cells, fibrosis and proliferation will occur, extracellular matrix will be deposited, resulting in cirrhosis.
Microscopic manifestations include massive necrosis of hepatocytes, nodular regeneration of residual hepatocytes, proliferation of connective tissue with fibrous septum formation, destruction of the normal hepatic lobular structure, and pseudolobule formation.
Symptoms
Main Symptoms
Asymptomatic
A small percentage of patients with compensated cirrhosis may be asymptomatic.
Mild symptoms
Most patients have mild symptoms and poor specificity.
They manifest as mild fatigue, emaciation, loss of appetite, abdominal distension, aversion to greasy food, epigastric discomfort and vague pain in the right upper abdomen [3].
Some of them have symptoms such as dyspepsia, diarrhea and irregular bowel movements, which are mostly intermittent, often occurring with exertion, stress or accompanying other illnesses, and can be relieved by rest and medications that help digestion [6-7].
Other symptoms
In some cases, liver palms (reddening of the skin on the palms of the hands near the wrist joints, which fades when pressure is applied) and spider nevi (vascular naevi formed by dilation of the ends of small arteries in the skin, which resemble spiders) may be present.
Whether the liver is enlarged or not depends on the different types of cirrhosis, and the spleen is often mildly or moderately enlarged due to portal hypertension.
Consultation
Department of Medicine
Gastroenterology
If you experience symptoms such as mild fatigue, weight loss, loss of appetite, bloating, aversion to greasy food, epigastric discomfort and vague pain in the right upper abdomen, we recommend that you consult a doctor promptly.
Hepatology
When you are diagnosed with cirrhosis in the compensated stage, you can also visit the Department of Hepatology to receive specialized treatment.
Preparation
Preparing for your visit: registering, preparing documents, and frequently asked questions
Tips for medical treatment
Before visiting the doctor, try to record the symptoms you have experienced, their duration, etc. for the doctor’s reference.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Where is the discomfort? How long has the discomfort lasted?
Any change in stool color?
How has your appetite been recently?
Any recent change in weight?
Have you had any tests and what were the results?
Have you taken any medications recently?
Medical History List
Any previous diseases of the hepatobiliary system?
Has anyone in the family experienced similar symptoms?
What is your occupation?
Do you drink alcohol? How long have you been drinking alcohol? What is the daily amount of alcohol consumed?
Any recent blood transfusions or use of blood products?
Checklist
Test results for the last six months, which can be brought to the doctor’s office
Routine blood test, routine urine test, routine stool test
Liver function, blood lipid, liver fibrosis index test
Virology test
Coagulation function test
Autoantibody test
Abdominal ultrasound, abdominal CT, abdominal MRI
Liver puncture biopsy pathology report
Medication List
Medication used in the last 3 months, if available, bring the box or package with you to the doctor’s office.
Hepatoprotective drugs: Liver tablets, Silymarin
Antibacterial drugs: cefuroxime, amoxicillin, vancomycin
Glucocorticoids: dexamethasone, prednisone acetate
Diuretics: furosemide, spironolactone
Diagnosis
Diagnostic basis
The diagnosis of cirrhosis of the liver needs to be based on the history, clinical manifestations, physical examination, laboratory tests and imaging tests.
Medical history
The patient may have the following medical history:
History of viral hepatitis and fatty liver.
Chronic alcohol consumption.
Family history of cirrhosis.
Clinical manifestations
There are systemic symptoms such as fatigue and emaciation, digestive symptoms such as abdominal distension and loss of appetite.
There are signs such as liver palms and spider nevus.
Some patients have characteristic manifestations of cirrhosis such as hepatosplenomegaly and tenderness to percussion in the liver area.
Laboratory examination
Etiologic examination
Etiologic tests help to diagnose the cause of cirrhosis and provide treatment options for follow-up.
Hepatitis B five indexes test, Hepatitis B virus DNA (HBV-DNA) test.
Hepatitis C virus (HCV-RNA) test and genotyping.
Serum copper, copper blue protein test, serum iron test.
Autoantibody test.
Routine blood tests
Cirrhosis, if combined with hypersplenism, may have decreased white blood cell count and platelet count.
Urine routine
Abnormal urinary bilirubin and urobilinogen indexes have significance in determining the jaundice caused by liver cirrhosis.
Stool routine
Fecal occult blood test is useful in determining gastrointestinal bleeding caused by liver cirrhosis.
Liver function test
Liver function tests such as serum bilirubin, serum albumin, serum enzymes and blood ammonia can help diagnose liver cirrhosis by finding out whether the liver is in normal working condition.
Liver Fibrosis Indicator Test
Elevated values of Pre-III collagen peptide (PIIIP), prolyl hydroxylase (PHO), monoamyl oxidase (MAO), serum laminin (LM), as well as hyaluronic acid and laminin, indicate the presence of hepatic fibrosis, which is helpful for the diagnosis of liver cirrhosis.
APRI score
Recent studies have used the APRI score for the diagnosis of cirrhosis.
Definition: APRI is the aspartate aminotransferase (AST) and platelet (PLT) ratio index.
Calculation method: APRI = [(AST test value/upper limit of normal value) × 100] /PLT (109/L).
Evaluation criteria: When APRI is greater than 2, it suggests the presence of cirrhosis.
Imaging
Ultrasonography
Abdominal ultrasound is an easy way to diagnose cirrhosis.
Ultrasound Doppler examination can detect changes such as decreased portal vein flow velocity and reversal of portal vein flow.
CT or magnetic resonance imaging
It can be used for the evaluation of liver fibrosis and cirrhosis, but has low sensitivity for the diagnosis of liver fibrosis and high sensitivity and specificity for the diagnosis of cirrhosis.
Three-dimensional angiographic reconstruction clearly shows the vascularization and thrombosis of the portal venous system and allows calculation of liver and spleen volumes [8-9].
Liver transient elastography
Liver fibrosis can be assessed and the degree of fibrosis graded.
This test is one of the preferred modalities currently used to monitor the progression of cirrhosis. It is fast, convenient and safe.
The normal reference value is 2.8-7.4 kilopascals (kPa), and more than 17.5 kPa is indicative of cirrhosis [10].
Pathologic examination
Liver biopsy (liver biopsy) is the “gold standard” for the diagnosis and evaluation of early cirrhosis and the degree of inflammatory activity in cirrhosis due to different etiologies.
Cirrhosis is defined histologically as a disorganization of the lobular structure caused by the encirclement of the lobules by fibrous septa, nodular regeneration of hepatocytes, and the formation of pseudo-lobular structures.
When the cause of cirrhosis is eliminated or suppressed and the inflammatory lesions subside, some cirrhosis may show some degree of histologic reversal [11-12].
Endoscopy
Gastroscopy and colonoscopy are the “gold standard” for screening for varicose veins in the gastrointestinal tract and assessing the risk of bleeding [13].
In 90% of cirrhotic patients, varices occur in the esophagus and/or fundus of the stomach. Gastroscopy can directly observe whether there are varices in the esophagus and fundus of the stomach, understand the degree and extent of varices, and determine whether there is portal hypertensive gastropathy.
About 10% of patients with cirrhosis have varicose veins in rare areas such as the duodenum, small intestine and large intestine, which are called “ectopic varicose veins”.
Diagnostic criteria
The diagnosis of compensated cirrhosis is based on any of the following four aspects.
Histology
Histology is consistent with the diagnosis of cirrhosis.
Endoscopic aspect
Endoscopy shows esophagogastric varices or ectopic varices in the GI tract, except for non-cirrhotic portal hypertension.
Imaging
Imaging tests such as ultrasound, LSM or CT suggest features of cirrhosis or portal hypertension: e.g., splenomegaly, portal vein ≥1.3 cm, and LSM measurements are consistent with the diagnostic thresholds for cirrhosis of different etiologies.
Laboratory tests
In the absence of histologic, endoscopic, or imaging tests, abnormalities in the following tests are suggestive of the presence of cirrhosis (2 of 4 must be met):
PLT < 100 x 109/L with no other explanation;
Serum ALB < 35 g/L, excluding other causes such as malnutrition or renal disease;
INR > 1.3 or prolonged PT (discontinuation of thrombolytic or anticoagulant drugs for more than 7 d);
AST/PLT ratio index (APRI): adult APRI score > 2 [14]. The effect of factors such as enzyme-lowering drugs on APRI needs to be noted.
Cirrhosis according to the presence or absence of complications such as ascites, esophageal variceal bleeding, hepatic encephalopathy, etc., foreign guidelines have also classified the compensated stage of cirrhosis into stage 1a, stage 1b and stage 2 [15].
Differential diagnosis
Differential with diseases causing hepatosplenomegaly
Malaria
Similarities: both can present with hepatosplenomegaly and both may be preceded by a history of blood transfusion.
Differences: malaria is preceded by a history of living in a malaria-endemic area, or a history of mosquito bites, etc.; typical intermittent chills, profuse sweating, etc. may also be present, and intermittent episodes have a certain regularity; Plasmodium vivax may be detected by laboratory tests.
Malignant histiocytosis
Similarities: both may present with hepatosplenomegaly, jaundice and abnormal liver function.
Differences: Bone marrow smear or other histopathologic findings of malignant histiocytosis include abnormal histiocytes and multinucleated giant histiocytes.
Hepatocellular carcinoma
Similarity: Early stage of liver cancer is relatively insidious, with no specific symptoms. With the progression of the disease, symptoms such as pain in liver area, hepatosplenomegaly, yellowing of skin and sclera may appear.
Differences: Liver cancer may be accompanied by malignant disease, manifested by extreme emaciation. Differential diagnosis can be made by imaging and pathological examination.
Differences with diseases causing ascites
Cardiogenic ascites
Similarity: both can present with ascites.
Differences: Patients with cardiogenic ascites may show signs of heart failure, i.e. sedentary breathing, coughing up pink foamy sputum.
Carcinogenic ascites
Similarity: Ascites can occur in both advanced liver cancer and decompensated cirrhosis, and the mechanisms are similar.
Difference: Hepatocellular carcinoma may be accompanied by elevated alpha-fetoprotein value, whereas cirrhosis usually does not. It can be differentiated by imaging and pathologic examination.
Treatment
Aim of treatment: For patients with cirrhosis in the compensated stage, treatment is aimed at delaying the loss of hepatic function, preventing hepatocellular carcinoma, and striving for the reversal of lesions.
Treatment principle: comprehensive treatment, personalized treatment for patients’ conditions. In the early stage, the main supportive therapy, hepatoprotective therapy and causative therapy (treating the primary disease leading to liver cirrhosis) are adopted.
Supportive treatment
Heavy physical activity and high intensity physical exercise are not suitable, but light physical labor is allowed.
Nutritional screening and assessment are required before and during nutritional support therapy, and the principles of nutritional and dietary therapy are as follows [16].
Energy
Cirrhosis is supplied with energy at 35 kcal to 40 kcal per kilogram of body weight per day.
In obese patients, energy is reduced by 500 kcal to 800 kcal throughout the day to ensure adequate protein intake (>1.5 g per kg body weight per day) to ensure a 5% to 10% weight loss without compromising protein stores.
Protein
For compensated cirrhosis without nutritional risk and without malnutrition, the normal dietary protein supply should be 1.2 g per kg body weight per day.
If adequate nitrogen intake cannot be obtained orally, consider taking branched-chain amino acid supplements under medical supervision. Protein diet should be controlled in decompensated cirrhosis.
Fat
The supply should be 25% of total energy.
If steatorrhea occurs, the diet should be changed to a low-fat diet. Patients may also apply a medium-chain triglyceride diet under medical supervision.
Carbohydrates
Daily intake of carbohydrates should be 300 to 450 grams to ensure glycogen reserves.
Other Nutrients
Supplementation with multivitamins and trace element preparations is recommended under medical supervision, and no special treatment is needed for those without clinically significant deficiencies.
Dietary considerations
Eat small and frequent meals, those who can eat by mouth can have 4～6 meals per day (including additional meals before bedtime).
Use less or no spicy and stimulating food, and focus on a light diet (less salt, less sugar, less oil).
Those who have developed esophageal varices need to avoid hard, coarse and dry foods, such as coarse grains, cookies, ham, nuts, vegetables and fruits with high fiber; vegetables and fruits can be chopped and juiced for drinking, and nuts and nuts can be crushed and added to cooked dishes for consumption.
Hypertonic glucose solution can also be fed intravenously to replenish calories, and vitamin C, insulin, and potassium chloride can be added to the infusion.
Ascites should be limited to sodium intake (no more than 2 grams of ingested sodium per day), and attention should be paid to protein supplementation.
Hepatoprotective treatment
The principle of treatment is to protect the liver, reduce enzymes, reduce yellowing, resist liver fibrosis, and promote liver cell regeneration [17].
Western medicine
Adenosylmethionine, ursodeoxycholic acid, diammonium glycyrrhizinate can be chosen.
Intravenous infusion therapy, such as hepatocyte growth-promoting hormone, reduced glutathione, glycyrrhizic acid-based preparations, etc., if necessary.
Chinese medicine
Fuzheng Huayu capsule, Heluo Huayu pill, Compound turtle shell soft liver tablets, silymarin-like drugs can be chosen.
Etiologic Treatment
Chronic viral hepatitis
Chronic hepatitis B
Nucleoside analogs: entecavir, tenofovir or propofol tenofovir are recommended, but also tebivudine, adefovir, lamivudine, etc. [18].
Interferon: Polyethylene glycol interferon may be chosen with caution in compensated cirrhosis, or regular interferon therapy may be chosen. Interferon is contraindicated in decompensated cirrhosis.
Hepatitis C
Direct antiviral drugs (DDAs) are currently used in clinical practice [19].
Commonly used drugs include prozac (a combination of sofosbuvir and viplatasvir, also known as gitazan), asurevir, simeprevir, dalatasvir, lediprevir, and sofosbuvir.
Antiviral drugs should be selected based on viral genotyping. With a course of treatment of 8 to 12 weeks, more than 95% of hepatitis C can be completely cured.
Alcoholic cirrhosis
The principles of treatment of alcoholic liver disease are abstinence from alcohol and nutritional support, reduction of the severity of alcoholic liver disease, amelioration of pre-existing secondary malnutrition and symptomatic treatment of alcoholic cirrhosis and its complications [20].
Hepatomegaly.
Copper repellent therapy, commonly used copper repellent drugs include penicillamine and tretinoin, and oral zinc preparations (e.g., zinc acetate, zinc gluconate) [21-22].
Patients with cirrhosis should avoid copper-rich foods such as shellfish, nuts, mushrooms and animal offal.
Autoimmune hepatitis
Patients with autoimmune hepatitis can rapidly progress to cirrhosis or end-stage liver disease without clinical intervention [23].
Currently, non-specific immunosuppression: prednisone (Dragon) combined with azathioprine (AZA) therapy or prednisone (Dragon) monotherapy is used as the standard treatment regimen.
Complications
Splenomegaly with hypersplenism and gastrointestinal bleeding may occur in the compensated phase of cirrhosis, please refer to the Treatment of Cirrhosis – Treatment of Complications section for specific treatment.
Prognosis
Cure
Medication can slow down, or keep cirrhosis from worsening further, but there is no way to reverse cirrhosis.
Current antifibrotic drugs also cannot completely reverse liver fibrosis and cirrhosis, so medical treatment is not a cure for cirrhosis.
Median survival
Some studies have shown that the median survival of patients with compensated cirrhosis is more than 12 years [24].
Special reminder.
Median survival, for example, a total of 1,000 people participate in a clinical trial, the survival time of each person is ranked from smallest to largest, the 500th person’s survival time is 12 years, which indicates that the median survival of the clinical trial is 12 years.
Median survival is a statistic used in clinical research, usually based on the results of a large number of previous studies of people suffering from a particular condition, and these statistics do not predict nor represent the survival of any individual.
Hazards
The compensated phase of cirrhosis may progress to the decompensated phase of cirrhosis, posing a serious threat to the health and life of the patient.
Rupture of esophagogastric fundic varices can lead to bleeding, which manifests as vomiting of blood and dark stools, and massive bleeding can lead to shock and even death.
Cirrhosis is easily complicated by various infections due to hypersplenism and reduced immune function of the body.
About 10% to 25% of cirrhosis can eventually transform into liver cancer.
About 10% of cirrhosis can be complicated by portal vein thrombosis, which is mainly related to the slow blood flow in portal vein, portal vein hardening and other factors.
Daily life
Cirrhosis should pay attention to dietary regulation, life regulation, psychological regulation and other aspects in daily life.
Daily management
Dietary management
Diet should be light, soft, easy to digest, non-stimulating, small amount of meals, chewing and swallowing slowly [25].
Cooking should be processed finely, avoiding hard and rough foods, such as fried foods and hard fruits; if there is upper gastrointestinal bleeding, the above foods are strictly prohibited.
Staple food should be chosen softer, rice and noodles should be softer than normal, buns, steamed buns, wontons, dumplings can be (note that the filling of wontons or dumplings should be chosen with less fiber).
Recommended high-quality protein diet, such as soybeans and their products such as tofu, tofu brain, soy milk, milk and dairy products, a variety of lean meats.
Eat more vegetables and fruits with lower fiber content to replenish vitamins and minerals, such as winter squash, pumpkin, cauliflower, apples and oranges, etc. Chopping, juicing and pureeing are preferred for cooking.
Life Management
Maintain regular exercise, taking into account your own physical condition, with walking as the main focus, which should not be more than half an hour each time or more than twice a day.
Try not to go out of the house or go on long trips.
To reduce the amount and duration of exercise, and not to engage in work with high energy consumption [26].
Do not use drugs that may harm the liver as well as supplements indiscriminately.
Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, acetaminophen, indomethacin, etc.) may increase the risk of ruptured esophageal varices bleeding and should be taken with caution.
Psychological support
Maintain a positive outlook.
Family members should provide comfort and psychological guidance, as well as patient companionship and good care for advanced cirrhosis.
Prevention
Prevention of cirrhosis is mainly from etiologic prevention, early detection and treatment and adjustment of life and diet habits [26].
Active treatment of viral hepatitis, alcoholic liver disease, fatty liver and chronic heart failure and other diseases.
Newborns and high-risk groups should be vaccinated against hepatitis B for prevention.
Chronic viral hepatitis requires active antiviral treatment as prescribed by the doctor.
Stop smoking and drinking.
Avoid the use of drugs that can damage the liver.
Reasonable weight control, diversification of food types, dietary exercise phase balance, prevent the occurrence of non-alcoholic fatty liver.
Workers with long-term exposure to hepatotoxic substances such as arsenic and carbon tetrachloride need to pay attention to the environmental pollution of the workplace, and need to carry out certain occupational protection when necessary.