Overview
胆汁淤积性肝病是以胆汁淤积为主要表现的肝脏疾病
可出现皮肤瘙痒、黄疸、乏力、粪便恶臭、夜盲、骨痛等症状
可采取病因治疗、对症治疗，必要时采用非生物型人工肝或肝移植治疗
原发病治愈后通常预后良好，严重慢性胆汁淤积性肝炎可进展为肝衰竭
What is cholestatic liver disease?
Definition
Cholestasis is a disease of the hepatobiliary system caused by a series of organic damage, metabolic imbalance and dysfunction due to various causes inside and outside the liver, including obstacles to the formation, secretion and excretion of bile, which fails to flow into the duodenum, accumulates in the liver and flows back into the bloodstream.
Classification
按照胆汁淤积发生部位分类
Extrahepatic cholestatic liver disease: caused by lesions or obstruction of the septal bile ducts, regional bile ducts, segmental bile ducts, right and left hepatic ducts, common bile duct to the jugular abdomen.
Intrahepatic cholestatic liver disease: caused by hepatocellular dysfunction or lesions or obstruction of intrahepatic bile ducts (capillary bile ducts, fine bile ducts, interlobular bile ducts).
按照发病时间分类
Acute cholestatic liver disease: cholestasis lasting less than 6 months.
Chronic cholestatic liver disease: cholestasis lasting more than 6 months.
Morbidity
The incidence of cholestatic liver disease is not yet known.
The results of a survey in Shanghai showed that the total incidence of cholestasis in 4660 hospitalized patients with chronic liver disease was 10.26%, and the incidence of cholestasis in patients with chronic liver disease has a tendency to increase with age.
Questions you may be concerned about
Can cholestatic liver disease be cured?
Whether cholestatic liver disease can be cured is related to the primary disease.
Extrahepatic cholestatic liver disease can recover quickly when the obstruction is removed. Some cholestatic liver diseases caused by viral hepatitis can be cured after antiviral treatment.
Cholestasis due to autoimmune liver disease and inherited metabolic disease can be in long-term remission or progressive development with effective drug treatment. If the condition is severe, all of them can eventually lead to biliary cirrhosis and liver failure with a poor prognosis.
What are the symptoms of cholestatic liver disease?
In the early stage, there may be no obvious symptoms. Some patients have non-specific symptoms such as fatigue, loss of appetite, nausea and epigastric discomfort.
With the aggravation of cholestasis, clinical symptoms related to cholestasis, such as jaundice, itchy skin, steatorrhea, etc., may appear.
Chronic cases may show impaired absorption of fat and fat-soluble vitamins. Foul-smelling feces, night blindness, bone pain, easy bleeding and other manifestations may occur. Male patients may have testicular atrophy, decreased libido, impotence and other manifestations.
What kind of medicine should I take for Cholestatic Liver Disease?
The drug treatment of cholestatic liver disease is mainly divided into cause-specific treatment and symptomatic treatment.
Causative treatment: ursodeoxycholic acid can treat primary biliary cholangitis; glucocorticoids can treat patients with autoimmune liver disease; alcoholic liver disease needs to quit drinking in time; viral hepatitis needs to be antiviral treatment; drug liver disease needs to stop the use of liver damage drugs in time.
Symptomatic treatment: such as itchy skin can be used kolexamine, vitamin deficiency needs to supplement vitamins, osteoporosis need to supplement calcium, and so on.
Causes
Causes
Intrahepatic cholestatic liver disease
Hepatocellular cholestatic liver disease: any disease that causes damage to liver cells is a possible cause, such as septicemia, viral hepatitis, pharmacological liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, intrahepatic cholestasis in pregnancy.
Cholangiocellular cholestatic liver disease: etiologies include autoimmune liver disease, drug-induced cholangiopathy, bile duct wall developmental abnormalities (e.g., cholestatic malformation and Karolyi syndrome), and secondary sclerosing cholangitis.
Mixed cholestatic liver disease: injury to both hepatocytes and bile duct cells.
Extrahepatic cholestatic liver disease
The main causes include bile duct stones, tumors, pancreatic diseases, bile duct parasitosis, and congenital bile duct malformations (e.g., congenital extrahepatic biliary atresia).
Other.
Primary sclerosing cholangitis may involve both intra- and extrahepatic bile ducts, which can lead to both intrahepatic and extrahepatic cholestatic liver disease.
Symptoms
Main Symptoms
Early symptoms
There may be no obvious discomfort in the early stage.
Some patients have non-specific symptoms such as fatigue, loss of appetite, nausea, epigastric discomfort and fatigue.
Cholestasis Symptoms
With the aggravation of cholestasis, clinical symptoms related to cholestasis, such as jaundice, itchy skin, steatorrhea, etc., may appear.
Symptoms of impaired absorption of fat and fat-soluble vitamins
Chronic cases may show impaired absorption of fat and fat-soluble vitamins.
Foul-smelling feces, night blindness, bone pain, susceptibility to fracture, and susceptibility to bleeding may be present.
Male patients may have testicular atrophy, decreased libido, impotence and other manifestations.
Other symptoms
Some patients may also have skin pigmentation.
Complications
Cirrhosis
Cirrhosis can either be the cause of or develop from cholestatic liver disease.
Patients may present with jaundice, abdominal distension, ascites, vomiting of blood, and black stools.
Liver failure
Severe cholestatic liver disease can lead to liver failure.
Patients may present with severe nausea, vomiting, abdominal distension, and even symptoms of hepatic encephalopathy such as altered consciousness and coma.
Consultation
Department of Medicine
Gastroenterology
It is recommended to consult a doctor if you have abnormal liver function indexes during physical examination, or if you have symptoms such as itching, fatigue, jaundice and loss of appetite for unknown reasons.
Emergency Medicine
It is recommended to seek medical treatment immediately when symptoms such as severe abdominal distension, vomiting, change in consciousness, coma, etc. appear.
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of documents, common problems
Tips for seeking medical treatment
Before seeking medical treatment, try to keep a record of the symptoms you have experienced, their duration, etc. for the doctor’s reference.
Preparation Checklist
症状清单
Pay particular attention to the time of onset of symptoms, special symptoms, etc.
Where is the discomfort? How long has the discomfort lasted?
How many times a day do you pass stools and urine, and is there any change in color?
How has your appetite been recently?
Do you drink alcohol? How much do you drink every day? How long have you been drinking?
Has there been any recent change in weight?
Have you been diagnosed with any other illnesses recently?
Have you had any tests and what were the results?
Have you taken any medications recently?
病史清单
Any previous illnesses of the hepatobiliary system?
Has anyone in the family experienced similar symptoms?
检查清单
Test results in the last 6 months to bring to the doctor
Blood test, urine test, stool test
Liver function, blood lipids
Virology
Coagulation tests
Autoantibody test
Abdominal ultrasound, abdominal CT, abdominal MRI, transendoscopic retrograde cholangiopancreatography (ERCP), ultrasound endoscopy
用药清单
Medication in the last 3 months, if available, bring the box or package with you to the doctor’s office.
Hepatoprotective medications: liver protection tablets, silymarin
Antibacterial drugs: cefuroxime, amoxicillin, vancomycin
Glucocorticoids: dexamethasone, prednisone acetate
Immunosuppressants and antitumor drugs: azathioprine, cyclosporine, infliximab, cisplatin
Chinese medicine: He Shou Wu, Tu San Qi
Diagnosis
Diagnosis is based on
Medical history
Suffering from liver diseases such as viral hepatitis, drug-induced liver injury and cirrhosis.
Someone in the relatives suffers from cholestatic liver disease.
Clinical manifestations
Early stage may be asymptomatic, or there may be symptoms such as malaise, loss of appetite, easy fatigue, etc. With the aggravation of the disease, there may be itching of the skin, jaundice and other symptoms.
The liver, spleen and superficial lymph nodes throughout the body are enlarged.
Laboratory tests
肝功能检查
Cholestatic liver disease can lead to impaired liver function, and liver function tests can be performed to understand the impairment of liver function.
Elevated direct and indirect bilirubin can be seen.
Elevated serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) are the most characteristic manifestations of early cholestatic liver disease.
Precautions: No food after 8:00 p.m. and no water after 12:00 p.m. the night before the test until the blood draw is completed.
血脂检查
Elevated serum cholesterol, phospholipids, and triglycerides may be present.
Serum lipoproteins may be abnormal.
Precautions: Maintain a normal diet for two weeks prior to the lipid test, do not exercise strenuously the day before the test, do not eat after 8:00 p.m. the night before, and do not drink after 12:00 p.m. until the blood draw is complete.
自身抗体检查
It may help to clarify the cause of cholestasis.
Positive serum anti-mitochondrial antibodies (AMA), anti-nuclear antibodies (ANA), anti-SP100 antibodies, and anti-nuclear pore membrane protein antibodies suggest the possible presence of primary biliary cholangitis.
病毒学检查
Detection of hepatitis virus-related antibodies/antigens, genetic material (DNA, RNA)
May clarify the presence of viral hepatitis and help determine the cause of cholestatic liver disease.
血常规
To find out the changes in red blood cells, white blood cells, platelets, etc.
Can assess bleeding or anemia, determine the presence of infection, and assess coagulation.
凝血功能检查
Patients with cholestatic liver disease can have coagulation disorders, and coagulation tests can help in the diagnosis and treatment plan.
They usually include activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), prothrombin time (TT), international normalized ratio (INR), and prothrombin activity (PTA).
胆汁酸代谢检查
Bile acids have a high sensitivity and specificity for the diagnosis of cholestasis, and serum total bile acids are elevated in sludge hepatitis.
Imaging
腹部CT
Valuable in the diagnosis of biliary obstructive lesions.
Precautions
腹部增强CT检查前需要空腹，检查前一晚晚饭后需要禁止饮食与饮水。
检查前须去除随身携带的金属物品，如头饰、发夹、钥匙等。
磁共振胰胆管造影（MRCP）
It can safely and non-invasively show the condition of pancreatic and biliary tracts and determine the cause of cholestatic liver disease.
Precautions
带有心脏起搏器，人工心脏金属瓣膜，体内有金属或磁性物植入史及早期妊娠的受检者，不能进行检查。
检查前至少禁食4小时，除去项链、耳环、手机、手表、计算器、磁卡、活动假牙、假肢、义眼等。
对对比剂过敏者，须提前告知医生。
腹部超声
It can initially determine whether there is obstruction and dilatation of the bile ducts inside and outside the liver, and can distinguish between intrahepatic and extrahepatic cholestasis.
Precautions: Fasting is required the night before the examination; adjust the body position as prescribed by the doctor during the examination.
超声内镜（EUS）
Ultrasound endoscopy is to send the ultrasound probe into the body through the gastroscope, and check the biliary tract and extrahepatic bile duct obstruction through the ultrasound probe.
Precautions: Fasting and water fasting 6 hours before the examination.
经内镜逆行胰胆管造影（ERCP）
ERCP is the gold standard for diagnosing and treating extrahepatic biliary obstruction.
However, ERCP is an invasive test and may cause complications such as post-ERCP pancreatitis, bleeding and cholangitis.
瞬间弹性成像
Transient elastography is a non-invasive examination, based on ultrasonography, which has the advantages of convenience, speed, and the ability to repeat the examination many times.
It is able to determine liver fibrosis and cirrhosis, and is helpful in determining the cause and severity of cholestatic liver disease.
Genetic testing
Patients who cannot determine the cause of cholestatic liver disease by other diagnostic methods may choose genetic testing to determine the presence of hereditary liver diseases.
Pathologic examination
For those who are unable to determine the cause of the disease, cholestatic liver disease may be diagnosed by obtaining a biopsy of liver tissue by puncture.
Diagnostic Criteria
The diagnostic criteria and specific indicators of cholestatic liver disease have not yet been standardized, and the recommendations of the Expert Diagnostic Working Group of the 2009 European Association of the Society of Hepatology (EASL) Clinical Practice Guidelines for the Management of Cholestatic Liver Disease are used in clinical practice.
It is recommended that serum alkaline phosphatase (ALP) exceeds 1.5 times the upper limit of normal and gamma glutamyl transpeptidase (GGT) exceeds 3 times the upper limit of normal to diagnose cholestatic liver disease.
Differential diagnosis
Hereditary hyperbilirubinemia, hemolytic disease
Similarity: both have jaundice.
Differences: hereditary hyperbilirubinemia and hemolytic disease can be differentiated by the fact that only bilirubin is elevated, but bile acids, serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) are not elevated.
Treatment
Etiologic treatment
Extrahepatic cholestatic liver disease
Extrahepatic obstruction can be relieved by endoscopic intervention and surgical treatment with stone removal, stent placement, or tumor resection.
经内镜逆行性胰胆管造影（ERCP）
Placement of a stent and duodenal papillary sphincterotomy (EST) may be performed simultaneously to remove the stone and improve the obstruction.
This treatment carries the risk of causing pancreatitis and is contraindicated in the presence of severe coagulation disorders, cardiopulmonary or renal insufficiency, and acute episodes of pancreatitis.
开腹手术
Patients with stone obstruction who fail endoscopic retrograde cholangiopancreatography may undergo open surgery to remove the stone.
In patients with tumor, the tumor can be removed by open surgery to relieve the obstruction.
Intrahepatic cholestatic liver disease
Ursodeoxycholic acid can treat primary biliary cholangitis.
Glucocorticoids can be used in some patients with autoimmune liver disease.
Pharmacologic liver disease requires prompt cessation of liver-injuring drugs.
Alcoholic liver disease requires prompt abstinence from alcohol, and severe cases can be treated with glucocorticoids.
Viral hepatitis requires antiviral treatment, which can be done with nucleoside (acid) analogs or interferon.
Symptomatic treatment
Itchy skin
Commonly used drugs include colesevelam, pregnane X receptor agonists (e.g., rifampicin), opioid receptor antagonists (e.g., naltrexone), and 5-hydroxytryptamine receptor antagonists (e.g., trasylol).
Colestenolamine has an odor and adverse effects, including gastrointestinal, and prolonged use can lead to fat-soluble vitamin deficiencies.
Rifampicin and naltrexone have a certain degree of liver and kidney toxicity, and liver and kidney functions need to be followed up during treatment.
For those who fail to receive the above treatments, ultraviolet irradiation, plasma exchange, extracorporeal albumin dialysis and nasobiliary drainage may be considered.
Fat-soluble vitamin deficiency
Patients with cholestatic liver disease need regular vitamin A, D, E, and K supplementation.
Osteoporosis
Patients need regular calcium and vitamin D supplements to prevent osteoporosis.
Patients who have developed osteoporosis may be treated with raloxifene in combination with alendronate.
Fatigue
Currently there is no effective treatment to improve the patient’s fatigue.
Treatment with selective 5-hydroxytryptamine 3-receptor antagonists (e.g., ondansetron), opioid receptor antagonists, and modafinil, a central nervous system stimulant, is an option.
Other treatments
When the disease progresses to liver failure, liver damage is severe and the liver loses its function, requiring treatment with abiotic artificial liver or liver transplantation.
Non-biological artificial liver
By removing all kinds of harmful substances and replenishing essential substances through extracorporeal devices, it can temporarily replace part of the function of the liver and create conditions for regeneration of liver cells and recovery of liver function, or wait for the opportunity to undergo liver transplantation.
Indications: patients with cholestatic liver disease whose condition has progressed to liver failure or waiting for liver transplantation, and whose prothrombin activity is between 20%~40% is suitable.
Relative contraindications: patients with severe active bleeding or disseminated intravascular coagulation; those who are highly allergic to blood products or medicines used in the treatment process, such as plasma, heparin, and fischer’s protein; those with circulatory failure; those with cardio-cerebral infarction in a non-stable stage; and those in late pregnancy.
Complications: There may be bleeding, coagulation, hypotension, secondary infections, allergic reactions, imbalance syndrome, hypercitratemia, etc.
Liver transplantation
Indications: other treatments are ineffective and the condition is still deteriorating.
Contraindication
4个及以上器官功能衰竭（肝、肾、肺、循环、脑）。
脑水肿并发脑疝。
循环功能衰竭：需要2种及以上血管活性物质维持，且对血管活性物质剂量增加无明显反应。
肺动脉高压：平均肺动脉压力大于50mmHg。
严重的呼吸功能衰竭：需要最大程度的通气支持[吸入氧浓度（FiO2）≥0.8，高呼气末正压通气（PEEP）]或者需要体外膜肺氧合（ECMO）支持。
持续严重的感染：细菌或真菌引起的脓毒血症，感染性休克，严重的细菌或真菌性腹膜炎，组织侵袭性真菌感染，活动性肺结核。
持续的重症胰腺炎或坏死性胰腺炎。
营养不良及肌肉萎缩引起的严重虚弱状态需谨慎评估肝移植。
Long-term immunosuppressant is needed after liver transplantation, preventing infection, quitting smoking and drinking, and regular review.
Prognosis
Cure
Prognosis depends on the original disease.
Extrahepatic cholestasis can recover quickly after relief of obstruction.
Some cholestatic liver diseases caused by viral hepatitis may recover spontaneously.
Cholestasis due to autoimmune liver disease may resolve in the long term with effective drug therapy, while cholestasis due to inherited metabolic diseases tends to be progressive.
Severe chronic cholestasis due to various diseases can eventually lead to biliary cirrhosis and liver failure with a poor prognosis.
Harmfulness
Weakness and itchy skin caused by cholestatic liver disease may have some impact on the patient’s work life.
Severe chronic cholestatic liver disease can lead to cirrhosis and liver failure, which can be life-threatening.
Daily
Daily Management
Dietary management
Consume low-fat, high-protein, vitamin-rich and easily digestible food.
Avoid oily, spicy and irritating foods.
If you have osteoporosis, eat more food with high calcium content such as shrimps.
Eat more fresh fruits and vegetables.
Avoid drinking alcohol.
Life management
Keep a good state of mind and avoid excessive excitement or tension.
Pay attention to rest and ensure sufficient sleep.
Get more sunshine to help calcium absorption.
Wear loose clothes and minimize scratching when itching to avoid breakage and infection.
Follow-up
Follow the doctor’s instructions for regular follow-ups, and bring along your personal medical records and examination reports.
If the symptoms do not decrease, or even worsen, you need to consult a doctor.
If there is any other discomfort, inform the doctor of the symptoms in detail for timely diagnosis.
Prevention
Actively treat the primary disease and avoid triggering factors, such as abstaining from alcohol, avoiding the use of hepatotoxic drugs and so on.
Take medication as prescribed by the doctor, and consult the doctor if any abnormality occurs during the medication; for medications that may have hepatotoxicity, liver function should be checked regularly as prescribed by the doctor during the medication.
Avoid staying up all night, and practice a good work routine.
Eat a light diet and less greasy food.
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