liver dysfunction



Overview of Liver Function Tests

Definition

Abnormal liver function refers to abnormal liver function tests caused by changes in the physiological and biochemical functions of the liver due to pathogenic factors such as infection, drugs or toxins, alcohol, autoimmune diseases, genetic metabolic diseases, etc. [1-3].

The liver plays an important role in the metabolism of proteins, amino acids, sugars, lipids, vitamins, hormones and other substances in the body, and also has the functions of secretion, excretion, biotransformation, and metabolism of bilirubin and bile acids.

Liver function test is a group of related biochemical indicators, mainly including aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), bilirubin, albumin, plasminogen time (PT), etc. These indicators have different clinical significance, and the comprehensive combination of these indicators can reflect the state of liver synthesis, secretion and metabolism function and liver injury.

Causes

Causes

The following factors can lead to hepatocellular injury, thus causing abnormal liver function [1-2]:

Infection

Viruses

Viral infections: include hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Hepatitis B virus is the most common.

Other viruses: EBV, cytomegalovirus (CMV), coxsackie virus, herpes simplex virus, and herpes zoster virus.

Bacteria

Including Streptococcus, Staphylococcus aureus, E. coli, Borrelia burgdorferi, etc.

Parasites

Including Trematode, Ascaris lumbricoides, Amoeba, Schistosoma japonicum, Echinococcus granulosus, etc.

Fungi

Including Aspergillus flavus, Aspergillus miscellaneous, etc.

Drugs or poisons

Drugs

There are many drugs that may cause liver function abnormalities clinically, such as azithromycin, cephalosporins, ethambutol, rifampicin, fluconazole, voriconazole, atorvastatin, chemotherapeutic drugs, aspirin and other western drugs and Chinese medicines such as He Shou Wu, Lei Gong Teng and Panax Ginseng.

Poisons

Such as phosphorus, trinitrotoluene, arsenic, mercury, acetaldehyde, etc.

Alcohol

Alcohol is one of the common causes of abnormal liver function [6].

Autoimmune diseases

Including autoimmune hepatitis, dry syndrome, systemic lupus erythematosus, etc [5].

Inherited metabolic diseases

Including Wilson’s disease, hemochromatosis, α1-antitrypsin deficiency, etc.

Vascular diseases

Including Bard-Ge (Ki) Yali syndrome, hepatic small vein occlusive disease, ischemic liver injury, etc.

Siltation diseases

Chronic right heart failure, constrictive pericarditis, etc. can lead to hepatic siltation, followed by abnormal liver function.

Tumor diseases

Including primary hepatocellular carcinoma and tumor infiltration in other parts (e.g. when lung, gastrointestinal tumor, lymphoma, etc. involve the liver).

Endocrine diseases

Including abnormal lipid metabolism, hyperthyroidism, adrenal insufficiency, etc.

Others

Strenuous exercise, celiac disease, anorexia nervosa, idiopathic inflammatory myopathy, and acute fatty liver in pregnancy can also lead to abnormal liver function [7].

Risk factors

People with any one or more of the following risk factors are at high risk for liver function abnormalities [1].

Adverse dietary habits: for example, long-term high-fat diet can lead to liver steatosis, causing liver function abnormalities [10].

Excessive exertion: including strenuous exercise, staying up late, high mental tension, and excessive work pressure can cause liver function abnormalities.

Symptoms

Main symptoms

The onset of the disease is usually more insidious, often no obvious symptoms or mild symptoms, some patients are only found during physical examination, with the progression of the disease, the following symptoms can appear:

Liver pain

Pain in the right subcostal area or right upper abdomen may be present.

The pain is mostly manifested as distension or vague pain.

poor appetite

Reduced food intake, lack of appetite, and anorexia (not wanting to eat greasy food or nausea and vomiting after eating greasy food) may be present.

Weakness

Generalized weakness and mental depression may occur.

Jaundice

Yellowing of the skin and sclera, itching of the skin, and tea-colored urine may occur.

Complications

Blood clotting dysfunction

Liver is the synthesis place of many clotting factors in the body, when liver function is seriously abnormal, it can lead to clotting factor synthesis disorder, causing coagulation dysfunction.

Skin petechiae, ecchymosis, purpura, bleeding gums, nosebleed, black stools and other manifestations can be seen.

Hypoproteinemia

Liver is the place of protein synthesis in the body, when the liver function is seriously abnormal, it can lead to protein synthesis disorder, causing hypoproteinemia. Hypoproteinemia can lead to the decrease of plasma colloid osmotic pressure, causing ascites, pleural fluid, and subcutaneous edema of the low-hanging parts.

Abdominal distension, chest tightness, shortness of breath, and lower extremity edema may occur.

Gastric fundus-esophageal varices

When progressing to cirrhosis, fundic-esophageal varices can be induced, which can easily lead to gastrointestinal hemorrhage.

There may be manifestations such as vomiting blood, black stool and blood in stool.

Hepatic encephalopathy

Serious abnormal liver function may lead to metabolic disorder and induce hepatic encephalopathy.

There may be confusion, drowsiness, convulsions, consciousness disorder and other manifestations.

Consultation

Department of Medicine

Gastroenterology

If symptoms such as pain in the liver area, loss of appetite, fatigue, or jaundice occur, it is recommended to consult a doctor promptly.

If the physical examination reveals abnormal liver function, it is recommended to consult a doctor promptly.

Department of Infectious Diseases

Infectious diseases such as viral hepatitis and parasitic diseases are recommended to consult the Department of Infectious Diseases.

Preparation for medical treatment

Consultation: Registration, Preparation of documents, Frequently Asked Questions

Tips for medical treatment

It is recommended to have an empty stomach before visiting the doctor so that the doctor can complete the relevant examinations.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Are there any symptoms of pain in the right side of the lower ribs or right upper abdomen?

What is the nature of the pain (e.g. swelling, vague pain, etc.)? How long does it last?

Is there any symptom of reduced food intake, no desire to eat, anorexia of oil?

Are there any symptoms such as generalized weakness, lack of energy?

Are there any symptoms such as yellowing of the skin and sclera, itching of the skin, tea-colored urine, etc.?

How long have these symptoms been present?

List of medical history

Is there any history of infectious diseases such as viral, bacterial infections, parasites, fungi, etc.?

Has there been any use of azithromycin, cephalosporins, ethambutol, rifampicin, fluconazole, voriconazole, atorvastatin, chemotherapeutic drugs, aspirin, heshouwu, rehmannia glutinosa, panax ginseng, or other medications that may cause abnormal liver function?

Have you been exposed to phosphorus, trinitrotoluene, arsenic, mercury, acetaldehyde, and other poisons that may cause abnormal liver function?

Is there any alcohol consumption?

Any history of autoimmune diseases such as autoimmune hepatitis, dry syndrome, systemic lupus erythematosus?

Is there a history of inherited metabolic diseases such as Wilson’s disease, hemochromatosis, α1-antitrypsin deficiency, etc.?

Any history of chronic right heart failure, constrictive pericarditis, etc.?

Is there a history of primary hepatocellular carcinoma and tumor infiltration from other sites (e.g., lung, gastrointestinal tumors, lymphomas, etc. when they accumulate in the liver)?

Is there a history of abnormal lipid metabolism, hyperthyroidism, adrenal insufficiency, etc.?

Any history of strenuous exercise, celiac disease, anorexia nervosa, idiopathic inflammatory myopathy, acute fatty liver in pregnancy?

Checklist

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

Laboratory tests: liver function tests, coagulation function, hepatitis series tests, etc.

Imaging tests: liver ultrasound, abdominal CT, etc.

Medication List

Medications used in the last 3 months, if there is a box or package of medication, you can bring it to the doctor

Hepatoprotective drugs: glycyrrhizic acid preparations, reduced glutathione, bicyclic alcohol, etc.

Glucocorticoids: methylprednisolone sodium succinate, prednisone, etc.

Antiviral drugs: Entecavir, Tenofovir, Vipatavir, etc.

Diagnosis

Diagnosis is based on

Medical history

The following medical history may have preceded the onset of the disease:

Any history of infectious diseases such as viral, bacterial infections, parasites, fungi, etc.?

Use of azithromycin, cephalosporins, ethambutol, rifampicin, fluconazole, voriconazole, atorvastatin, chemotherapeutic agents, aspirin, He Shou Wu, Lei Gong Teng, Panax Ginseng, and other medications that may lead to abnormalities in liver function.

Have been exposed to phosphorus, trinitrotoluene, arsenic, mercury, acetaldehyde, and other poisons that may cause abnormal liver function.

Have alcohol consumption.

Have a history of autoimmune diseases such as autoimmune hepatitis, dry syndrome, systemic lupus erythematosus.

Have a history of inherited metabolic diseases such as Wilson’s disease, hemochromatosis, and alpha1-antitrypsin deficiency.

Any history of Bard-Ge (Ki) Yali syndrome, hepatic small vein occlusive disease, ischemic liver injury, etc.?

Any history of chronic right heart failure, constrictive pericarditis, etc.

History of primary hepatocellular carcinoma and tumor infiltration from other sites (e.g., lung, gastrointestinal tract tumors, lymphomas, etc. when they accumulate in the liver).

History of abnormal lipid metabolism, hyperthyroidism, and adrenal insufficiency.

History of strenuous exercise, celiac disease, anorexia nervosa, idiopathic inflammatory myopathy, and acute fatty liver in pregnancy.

Clinical manifestations

Symptoms

There may be pain in the liver area, poor appetite, fatigue, itching of the skin, and tea-colored urine.

Signs

The following signs may be present:

There may be yellowing of the skin and sclera.

After progression to cirrhosis, there may be signs such as hepatic palms (flaky congestion of the skin at the interstices of the big and small fishes at the roots of the thumb and little fingers of the palms of the hands, which turn pale white when pressure is applied), spider nevus (the appearance of radial branches of small blood vessels in the form of spiders on the face, neck, upper chest, shoulders, and upper limbs, etc.), varicose veins of the abdominal wall, and a positive mobile turbid tone.

Chronic right heart failure and constrictive pericarditis may result in jugular venous filling or angulation.

Proptosis and goiter may be seen in hyperthyroidism.

Muscle atrophy and joint deformities may be seen in autoimmune diseases.

Laboratory Tests

Liver Function Tests

Purpose: To determine liver function.

Significance: Elevation of one or more indicators such as aminotransferase, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, albumin, etc. may occur.

The most commonly used are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatocellular damage and necrosis caused by viral hepatitis, liver injury from drugs or toxins, alcoholic liver disease, ischemic liver disease, and autoimmune hepatitis are all factors that can lead to elevation of aminotransferase.

Poor bile excretion results in elevated levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and 5′-nucleotidase.

Serum bilirubin measurements include total bilirubin (TB), bound bilirubin (CB), and unconjugated bilirubin (UCB). Clinically, serum TB, CB, and UCB can be used to distinguish hemolytic diseases from hepatobiliary diseases.

Indicators reflecting the synthesis function of the liver mainly include albumin and prealbumin; in addition, II, V, VII, IX coagulation factors are synthesized in the liver, and changes in the levels of these coagulation factors and their biological activities are followed by changes in the prothrombin time (PT).

The level of albumin can reflect the synthesis and reserve function of the liver in a certain period of time. Under the premise of normal diet and exclusion of abnormal renal function, the decrease of albumin is mainly seen in many kinds of chronic liver diseases, such as end-stage liver disease and cirrhosis, etc., and the degree of its decrease is positively proportional to the degree of damage to the synthesis function of the liver.

Serum markers of liver fibrosis include hyaluronic acid (HA), a noninvasive indicator of the degree of hepatic fibrosis and a basis for early diagnosis of fibrosis. Serum HA levels are significantly elevated in chronic hepatitis, liver fibrosis, and cirrhosis.

Coagulation function

Purpose: To know whether there is coagulation function abnormality.

Significance: Different degrees of coagulation dysfunction can occur.

Hepatitis Series Tests

Purpose: To know whether there is hepatitis virus infection.

Significance: Positive antibodies may be present if viral hepatitis is present.

Autoimmune Antibodies

Purpose: To detect the presence of autoimmune diseases.

Significance: Positive antibodies may be seen when autoimmune diseases are present.

Imaging

Liver ultrasound

Purpose: It is the most common and important examination, which can understand the shape and morphology of the liver [8].

Significance: It can find the etiology and clues of liver tumor, biliary obstruction, fatty liver, etc.

Abdominal CT or magnetic resonance imaging (MRI)

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

Liver puncture biopsy

Liver tissue biopsy can be used to clarify the cause of the disease and guide treatment.

Differential Diagnosis

Liver function abnormality is a common biochemical change in clinic, mainly seen in viral hepatitis, fatty liver, bile duct obstruction, drug-induced hepatitis, autoimmune liver disease and other diseases of hepatobiliary system. The differential diagnosis of each etiology relies on detailed history taking, seropathology, immunology and imaging examination, and most of the diseases are not difficult to differentiate.

For a few cases of unexplained liver function abnormalities, liver puncture biopsy is necessary for diagnosis, and in a very small number of cases, genetic testing is required to obtain a final diagnosis.

Treatment

Aim of treatment: timely correction of liver function abnormalities and prevention of complications.

Treatment principle: identify the specific causes of the disease, and adopt different treatments according to different manifestations and causes, such as liver preservation, anti-virus, anti-inflammatory and other treatments.

General treatment

Attention should be paid to rest, avoid exertion and strenuous exercise. Transient transaminase elevation caused by strenuous exercise, fatigue, poor sleep, etc. can be recovered on its own without medication.

Promptly remove the cause of the disease, such as stopping medication immediately when it is caused by drugs, or stopping alcohol abuse immediately when it is caused by alcoholism.

Medication

Hepatoprotective drugs

Indications: patients with abnormal liver function.

Effects: Can protect and repair damaged liver cells.

Commonly used drugs: glycyrrhizic acid preparation, reduced glutathione, bicyclic alcohol, polyene phosphatidylcholine and so on.

Glucocorticoid

Indications: For patients with severe diseases and those caused by autoimmune diseases.

Effects: It can reduce the damage of inflammatory reaction to liver cells; it can inhibit autoimmune reaction.

Commonly used drugs: methylprednisolone sodium succinate, prednisone and so on.

Immunosuppressant

Indications: for autoimmune diseases.

Effects: inhibit autoimmune reaction.

Commonly used drugs: methotrexate, cyclophosphamide, tacrolimus, etc. [11].

Antiviral drugs

Indications: Applicable to those caused by viral hepatitis.

Effects: Inhibit the replication of hepatitis virus.

Commonly used drugs: entecavir, tenofovir, vipatasvir, etc.

Prognosis

Cure

The prognosis depends on the cause of the disease, the severity of the disease and whether the treatment is timely or not, which is briefly summarized as follows:

For mild liver function abnormalities caused by overwork, abnormal lipid metabolism, etc., they can recover on their own by resting, improving eating habits and losing weight.

For liver function abnormalities caused by infections, drugs or poisons and other etiologies, the prognosis is mostly fair after timely treatment, but some of the untimely treatment or more severe conditions may progress to cirrhosis or even induce liver failure, with poor prognosis [9].

For liver function abnormalities caused by malignant tumors, hereditary metabolic diseases, autoimmune diseases and other diseases with poor prognosis themselves, the condition is difficult to control and the prognosis is poor.

Daily

Daily management

Dietary management

Avoid spicy and stimulating food (e.g. chili, mustard, etc.), high-fat food (e.g. animal offal, fried food, etc.).

It is advisable to eat more fresh fruits and vegetables, meat, eggs and other foods to maintain balanced nutrition; however, protein intake should be appropriately restricted in severe liver function abnormalities to avoid inducing hepatic encephalopathy.

Life management

Attention should be paid to rest, avoiding exertion and strenuous exercise, and activities can be resumed gradually only after the condition improves.

Strictly abstain from alcohol.

Follow-up examination

Follow the doctor’s instructions for regular review, so that the doctor can assess the condition and adjust the treatment plan.

The time of follow-up examination should be determined by the doctor according to the patient’s condition.

Follow-up examinations generally include liver function, coagulation function and liver ultrasound.

Prevention

Control weight and avoid obesity.

Avoid high-fat diet.

Avoid eating moldy food.

Avoid drinking alcohol.

Avoid overwork.

Medications should be used under the guidance of a doctor.

Have regular medical checkups and seek medical advice when abnormal liver function is detected.