cholestatic jaundice



OVERVIEW

Definition.

Cholestatic jaundice is one of the etiologic classifications of jaundice.

Cholestatic jaundice refers to jaundice caused by obstruction of bile flow or production due to a variety of reasons, resulting in cholestasis, which is characterized by yellowing of the skin and mucous membranes, yellow staining of the sclera, dark urine, and itching of the skin.

Classification

Intrahepatic cholestatic jaundice

Intrahepatic obstructive cholestasis: mostly seen in parasitic diseases, cancer embolism, intrahepatic sedimentary stones and other diseases.

Intrahepatic cholestasis: most commonly seen in diseases such as drug-induced cholestasis, viral hepatitis, intrahepatic cholestasis in pregnancy, and primary biliary cirrhosis.

Extrahepatic cholestatic jaundice

Also known as surgical jaundice and extrahepatic obstructive jaundice, it can be seen in biliary obstruction caused by tumor, roundworm, inflammation and edema, stenosis (including postoperative complications, congenital developmental defects, and compression by foreign masses), and choledochal stones.

Etiology

Causes

Intrahepatic cholestatic jaundice

Prolonged heavy alcohol abuse may lead to infiltrative damage of liver cells, impairment of normal function of liver cells, circulatory disorders such as bile secretion and excretion, and consequent cholestasis.

After hepatitis virus infection, long-term chronic hepatocellular injury, cholestasis occurs.

Many drugs can cause acute intrahepatic cholestasis, which may or may not be accompanied by an inflammatory response, and may be related to the body’s metabolic response to the drug.

Common ones include oral contraceptives, amoxicillin clavulanic acid, acetaminophen, and chloropropamide.

Cholestatic jaundice in pregnancy, also known as idiopathic jaundice in pregnancy, is not uncommon during pregnancy and may be related to acute fatty liver in pregnancy, concomitant biliary tract infections, and viral infections.

The etiology of the disease is not clear, and may be related to autoimmune reaction, presenting as progressive, destructive, non-suppurative cholangitis minor in the liver, progressing gradually to cholestatic disease.

A large amount of fat in food enters the body through hydrolysis, absorption, the formation of celiac particles, through the process of decomposition, oxidation, energy release, etc., the formation of excessive triacylglycerol, affecting the normal physiological functions of blood triglycerides, cholesterol, etc., lipid metabolism disorders can ultimately lead to progressive cholestasis.

Extensive hepatocellular lesions, destruction of the normal structure of the bile ducts or external compression lead to cholestasis.

Such etiologies include lymphoma, tuberculosis, and amyloidosis.

Extrahepatic cholestatic jaundice

Mostly seen in the obstruction of stones, parasites and other foreign bodies in the common bile duct, forming mechanical obstruction, leading to bile circulation obstruction and cholestasis.

It mostly occurs in the head of the pancreas, and with the progressive enlargement of the tumor, the lumen of the common bile duct and pancreatic duct can be compressed and narrowed, bile circulation is impaired, and jaundice occurs.

It is related to bile duct stones, bile duct parasites, bile duct scarring and narrowing, etc. Acute cholangitis occurs due to bile duct obstruction, infection, compression and other bile circulation obstruction, and in severe cases, it can be manifested as acute obstructive septic cholangitis.

Compression of the bile duct leads to obstruction of bile circulation, resulting in sludge disease. Such factors include pancreatic pseudocysts and tumors.

Risk factors

The following risk factors are associated with cholestatic jaundice.

Heavy alcohol consumption.

Hepatitis virus infection.

Pregnancy.

Various gastrointestinal diseases: pancreatic cysts, gallstones.

History of surgery: especially biliary surgery.

Tumors of the digestive tract: e.g., tumors of the liver, gallbladder, and pancreas.

Heredity: family history of abnormal bile duct structure.

Drug history: history of use of drugs that damage liver cells, history of drug abuse.

Drug use.

Symptoms

Major Symptoms

Skin and mucous membrane color: including skin, sclera, etc. It may be light yellow initially, gradually progressing to dark yellow, and in severe cases, dark yellow or even yellowish green.

Skin itching: itching is not obvious when jaundice symptoms are mild, and is more common when jaundice worsens.

Bradycardia: mostly seen in more severe cases of jaundice.

Deepening of urine color: it gradually deepens with the progress of jaundice.

Stool color becomes lighter: in severe cases, it is white clay color.

Digestive symptoms: loss of appetite, nausea, vomiting, diarrhea are common.

Other symptoms

Fever: In viral hepatitis, jaundice and fever may appear successively.

Epigastric pain: severe pain in the epigastric region may occur in bile duct stones and ascariasis. In viral hepatitis or hepatocellular carcinoma, it is usually a persistent dull pain in the right upper abdomen.

Enlargement of liver and spleen: In viral hepatitis or biliary tract obstruction, liver and spleen are usually mildly to moderately enlarged with moderate texture. In hepatocellular carcinoma, the liver will be obviously enlarged, irregular in shape and hard in texture.

Enlarged gallbladder: the gallbladder will be enlarged when the common bile duct is blocked by stone, inflammation or tumor, or pancreatic head cancer.

Enlarged spleen: it can be seen in decompensated stage of liver cirrhosis.

Abdominal fluid accumulation: Liver cancer, decompensated cirrhosis leading to hypoproteinemia, abdominal fluid accumulation (ascites) will occur.

Consultation

Department of Medicine

Gastroenterology

When there is unexplained yellowing of the skin and sclera, itching of the skin, etc., it is recommended to consult the Department of Gastroenterology or the Department of Hepatology promptly.

General Surgery

When jaundice with epigastric pain, fever, etc., or a history of gallstones or gastrointestinal tumors, jaundice or worsening of symptoms occurs, you may seek medical attention in the Department of General Surgery or Department of Hepatobiliary Surgery.

Preparation for medical treatment

Consultation: Registration, Preparation of Documents, Frequently Asked Questions

Tips for medical consultation

Try to keep a record of symptoms, duration and previous treatment of hepatobiliary diseases for your doctor’s reference.

Take pictures of abnormal skin symptoms, such as skin color changes and scratches.

Preparation Checklist

In particular, you should pay attention to the time of symptom onset, special manifestations, etc.

Is there any manifestation of dark urine, yellow sclera, yellow skin, etc.?

Is there fever?

Is there skin itching?

Is there any abdominal pain, its location, duration and severity?

Is there diarrhea and is the stool light in color?

When did the jaundice appear and how long did it last?

Is there a history of jaundice?

Any gallstones, hepatitis, cirrhosis, autoimmune disease, hemolytic disease, cancer?

Is there a history of surgery for hepatobiliary disease?

Is there a history of drug use, with specific names, dosages, and durations?

Is there a long history of heavy alcohol consumption?

Any history of drug injection, blood transfusion?

Test results in the last six months, which can be brought to the doctor’s office.

Laboratory tests: blood routine, blood biochemistry, hepatitis virology.

Imaging examination: abdominal ultrasound, CT, MRI, etc.

Medication in the last 3 months, if there is any medicine box or package, you can bring it to the doctor

Bile acid-lowering drugs: ursodeoxycholic acid, S-adenosylmethionine.

Drugs of the beta class: Fenofibrate, Benzafibrate.

Drugs for itching: calamine.

Diagnosis

Diagnosis is based on

medical history

Possible viral hepatitis, alcoholic hepatitis, cirrhosis.

Past history of gastrointestinal tumors, biliary tract surgery.

Long-term use of oral contraceptives, amoxicillin clavulanic acid, acetaminophen, and other drugs that cause cholestasis.

Past history of long-term alcoholism, blood transfusion, drug addiction.

Clinical manifestations

Patients may have symptoms such as yellowing of sclera and skin mucosa, deepening of urine color, lightening of stool color, and itching of skin.

Some patients have abdominal pain, fever, nausea, vomiting, diarrhea, loss of appetite and other symptoms.

Some patients develop central protrusions in the face, neck, chest, back and hands, surrounded by capillaries extending outward in a radial pattern, resembling spiders.

If the disease progresses to cirrhosis, there may be hepatosplenomegaly, and the liver may shrink in the advanced stage, with positive mobile turbid sounds in the abdomen.

In case of extrahepatic bile duct obstruction, there may be palpable enlarged gallbladder or tumor mass in the upper abdomen.

Laboratory tests

Changes in blood cells (red blood cells, white blood cells, platelets), hemoglobin, etc. may be detected.

Mild to moderate anemia may be present in longer term disease.

Reflects characteristic manifestations of cholestasis.

Elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) are the most characteristic early manifestations of cholestasis. Cholestatic liver disease is diagnosed if ALP exceeds 1.5 times the upper limit of normal and GGT exceeds 3 times the upper limit of normal.

Cholestasis can cause elevated bilirubin, with a marked increase in direct bilirubin (CB); direct bilirubin to total bilirubin ratio (CB/STB) > 0.5.

It is possible to know whether there is hepatitis virus infection and whether the jaundice is caused by viral hepatitis.

Need to check for hepatitis virus, herpes virus and cytomegalovirus infection.

Cholestatic jaundice usually presents with a strong positive urine bilirubin test and decreased or absent urinary cholagens.

Fecal bile may be detected in the stool routine. The appearance of the stools is mainly light in color or white clay-like stools.

Cholestatic jaundice usually presents with decreased or absent fecal cholagens.

Imaging

Ultrasound can determine the nature of jaundice and the location of biliary obstruction based on the presence, location and degree of bile duct dilatation.

Intrahepatic bile ducts >4 mm in diameter and extrahepatic bile ducts >10 mm in diameter suggest bile duct dilatation; dilatation of the common bile duct and above suggests obstruction of the lower end of the common bile duct or the jugular area.

It can show the cause and site of cholestasis, and can detect the site of bile duct dilatation and stones.

The examination can rule out extrahepatic bile duct obstruction and gallbladder cancer.

It can understand the morphology and structure of the liver, bile and pancreas and their internal stones, tumors, obstruction and dilatation.

MRCP can show the image of the whole biliary system. For example, the image of primary sclerosing cholangitis shows generalized or limited narrowing of the bile ducts, which is obvious at the bifurcation of the hepatic ducts, with fewer and stiffer and thinner bile duct branches, or segmental narrowing.

Endoscopy

ERCP directly observes the bile duct morphology.

In the case of cholestasis, the negative image of stones in the bile ducts, bile duct stenosis and proximal bile duct dilatation can be observed, or the biliary tree can be incompletely displayed, a certain part of the bile ducts does not appear, and the left and right bile ducts are asymmetrically shadowed.

Pathologic examination

The basic pathologic changes of intrahepatic cholestasis show intrahepatocellular bile siltation, feathery degeneration of hepatocytes, accompanied by dilatation of capillary bile ducts and bile plug formation. In severe cases, the dilated capillary bile ducts containing bile plugs are the center, and the hepatocytes are arranged in the form of adenoidal vesicles, forming bile wreaths.

The pathology of extrahepatic obstructive cholestasis is characterized by intrahepatic bile lakes with biliary granuloma formation around the portal area, and prolonged extrahepatic obstruction may cause secondary intrahepatic cholestasis. Later stages may cause fibrosis in the portal area and even biliary cirrhosis.

Differential diagnosis

Hepatocellular jaundice

In cholestatic jaundice, serum direct bilirubin is markedly elevated, whereas in hepatocellular jaundice, it is characterized by an elevated serum direct bilirubin/total bilirubin ratio, but the elevation is not as pronounced as in cholestatic jaundice.

Hepatocellular jaundice often has a history of hepatitis or cirrhosis, with moderate increases in both CB and UCB, and normal or mildly increased urobilinogen. It should also be differentiated by a combination of imaging, other serologic tests, and even a hepatic puncture biopsy.

Hemolytic jaundice

Hemolytic jaundice is usually characterized by anemia, mild jaundice, lemon color of skin and mucous membranes, and inconspicuous itching of the skin. mild increase in CB, marked increase in UCB, CB/STB <0.2, negative urine bilirubin test, and marked increase in urobilinogen. Acute hemolytic jaundice was manifested by hemoglobinuria, positive occult blood test; anemia, increased reticulocytes, and exuberant proliferation of bone marrow erythrocyte series were detected in routine blood tests.

Cholestatic jaundice can cause elevated bilirubin, dominated by markedly elevated direct bilirubin (CB); direct bilirubin to total bilirubin ratio (CB/STB) > 0.5.

Treatment

Treatment aim: relieve cholestasis symptoms, improve liver function, prevent and reduce complications.

Treatment principle: The treatment of cholestasis is mainly to remove the cause and symptomatic treatment. Specific methods need to be evaluated according to the cause of the disease, the severity of the disease, etc., and drug treatment or other treatments can be chosen.

Treatment of the cause

When caused by stones, tumors, etc., surgery, endoscopic removal of stones or surgical removal of tumors can be performed to relieve obstruction.

Drug-induced cholestasis requires timely discontinuation of the relevant drugs.

Alcoholic liver disease should quit drinking actively.

Viral hepatitis can be treated with appropriate antiviral therapy.

Autoimmune liver disease can be relieved by glucocorticoids and/or immunosuppressants.

Fatty liver disease is treated with diet, exercise and lifestyle interventions.

Symptomatic treatment with medications

Hepatoprotective drugs

Commonly used drugs include: ursodeoxycholic acid, S-adenosylmethionine.

Drug Indications:

Action of the drug:

Precautions for use of the drug: during the treatment period, according to the condition, check the liver function every 1 to 2 weeks and monitor changes in biochemical indicators.

Drugs for itching

Common drugs include: kolestenamide, rifampicin [7].

Drug indications: cholestatic pruritus.

The effect of the drug: by reducing the absorption of bile acids, reduce the symptoms of itching.

Precautions for the use of the drug: note that it should be taken at an interval of 4-6h with other drugs to avoid affecting the absorption of other drugs.

Surgery

ERCP

Indications: Smaller biliary stones or obstructive cholestasis caused by biliary foreign bodies.

Contraindications: severe coagulation disorders, poor cardiopulmonary function, severe infection.

Surgical modalities: balloon dilatation, endoscopic papillary sphincterotomy and stent placement [8].

Liver transplantation

Indications: Liver transplantation can be considered for those who have very severe symptoms caused by liver disease, and whose disease has progressed to an end stage and is difficult to correct, such as severe pruritus, advanced cirrhosis, and hepatocellular carcinoma [9].

Contraindications: severe allergic constitution. Severe cardiopulmonary disease, inability to tolerate surgery.

Replacement of the original diseased liver, restoration of all normal physiologic functions.

Surgery

Indications: Obstructive diseases that cannot be resolved by interventional procedures or have poor results, such as biliary tract stones and tumors.

Contraindications: acute stage of systemic infection. Severe cardiopulmonary disease, unable to tolerate surgery. Those with a history of severe allergy or others who cannot tolerate anesthesia.

Characteristics: It can be more intuitive and clear to clarify the etiology and classification of cholestasis, and provide effective treatment, such as stone removal, biliary tract reconstruction, biliary drainage, and removal of the mass [10].

Prognosis

The prognosis corresponding to cholestatic jaundice due to different etiologies is different and varies greatly.

Cure

The symptoms of jaundice due to stone, inflammatory, parasitic, pregnancy and other etiologies are mild and can be recovered by removing the etiology.

Viral hepatitis, cirrhosis, early-stage tumors and other severe diseases can be effectively improved and slowed down by active treatment.

For severe cases such as decompensated cirrhosis and advanced tumors, life may be endangered due to untimely treatment.

Prognostic factors

Tobacco, alcohol, some drugs and other risk factors may increase the prognosis and aggravate the disease.

Regular review and active treatment can effectively improve the prognosis and quality of life.

Hazards

Cholestatic jaundice is caused by a variety of etiologic factors. If left untreated, it may lead to serious life-threatening conditions such as decompensated cirrhosis and advanced hepatocellular carcinoma.

Bile can lose its normal physiological function due to long-term stasis, affecting the normal digestion, absorption and metabolism of food.

Long-term stagnant bile may also cause pain, anemia, high fever, etc., affecting daily life and work.

Daily

Daily Management

Dietary management

Stop smoking and strictly prohibit alcohol.

Balanced nutrition, diet should be low fat, high protein, light and easy to digest, avoid spicy and stimulating food.

Reduce the intake of high-fat and greasy food, such as fatty meat, high-fat desserts, barbecue and fried food.

Consume more fresh vegetables and fruits.

Life Management

Keep a regular routine and avoid staying up late.

Keep the skin of itchy area clean and dry, avoid scratching and infection.

Choose regular, scientific and moderate physical exercise according to your personal situation.

Psychological support

Receive professional health education, understand the knowledge related to the disease, and correct the wrong viewpoints about the disease.

Actively cooperate with the treatment and avoid negative treatment.

Learn to regulate emotions, release pressure and talk to others.

Prevention

There is no specific prevention method for this disease, but the occurrence of this disease can be reduced to a certain extent through the following measures:

Regular medical checkups to detect bile duct stones, inflammation, stenosis, tumors, parasites or other pathologies that can cause bile duct obstruction, and active treatment can effectively prevent cholestatic jaundice.

For cholestatic jaundice caused by viral hepatitis, it can be prevented by vaccination, avoiding blood transfusion, unclean sex and other high-risk behaviors.

Control weight and avoid obesity.