One article to master: non-infectious factors of elevated serum transaminases | Clinical Essentials

Author: Affiliated to Shandong University, Jinan Infectious Disease Hospital chief physician Wang Mingming This article is the author's permission NMT Medical publish, please do not reprint without authorization.

 Elevated serum transaminase may indicate liver cell damage and liver inflammation.

The factors that cause the increase of serum transaminase can be divided into infectious and non-infectious.

Common infectious factors that lead to elevated serum transaminases in clinical practice include: various viral hepatitis (including hepatotropic virus infections such as hepatitis B virus and hepatitis C virus, and non-hepatotropic virus infections such as Epstein-Barr virus and cytomegalovirus), bacterial liver abscess , Amoebic liver abscess and biliary system infection.

Non-infectious factors include: autoimmune factors, metabolic factors, tumor factors, alcohol factors, etc.

Clinically, the increase in transaminase caused by infectious factors will be paid attention to, but the onset of non-infectious factors is often hidden and easily overlooked.

This article will briefly introduce the non-infectious factors of elevated serum transaminase for reference.

1.
Autoimmune factors.
Various autoimmune diseases such as systemic lupus erythematosus, Behçet's disease, hyperthyroidism and rheumatoid arthritis can all be combined with liver damage and cause elevated serum transaminases.

For the liver itself, the most common autoimmune diseases are autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and overlapping syndromes where the above three diseases overlap.

The lesions of autoimmune hepatitis are mainly liver cells, which are more common in middle-aged women around 50 years old.

In addition to the common clinical manifestations of hepatitis, it is characterized by elevated serum transaminases to varying degrees, significantly elevated serum immunoglobulin IgG levels (>20g/L), and serum antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) , Anti-liver and kidney microsomal type I antibody (anti-LKM-1) or anti-hepatocyte cytoplasmic type I antibody (anti-LC-1) and other autoantibodies are positive.

The lesions of primary biliary cholangitis are mainly interlobular bile ducts and small bile ducts, which are more common in middle-aged and older women.

Clinically, there may be skin itching, xanthomas in the inner canthus of the upper eye, and liver function tests are characterized by intrahepatic cholestasis.

It shows that total bilirubin is increased, direct bilirubin is increased more than indirect bilirubin, and alkaline phosphatase and glutamyltransferase are significantly increased.

Serum immunoglobulin IgM was significantly increased, and serum ANA and ASMA were positive.

The lesions of primary sclerosing cholangitis are mainly intrahepatic bile ducts, a few can involve extrahepatic bile ducts, and most of them are middle-aged men around 40 years old.
Most patients also have ulcerative colitis.

Compared with primary biliary cholangitis, the incidence of primary sclerosing cholangitis is lower, but the clinical manifestations and laboratory test results of the two are similar.
Endoscopic retrograde cholangiopancreatography (ERCP) or Skin liver puncture cholangiography (PTC) can help distinguish the two.

2.
Drug factors The metabolism of drugs in the liver is divided into two phases.
The first phase is mainly to metabolize the drugs through cytochrome P450 (CYP450), so that non-polar fat-soluble compounds produce oxygen-carrying polar products and increase Water-soluble.

The second phase is to combine with polar ligands such as glucuronic acid, sulfuric acid, methyl, acetyl or sulfide under the action of CYP450 to form more water-soluble compounds, which are finally excreted in bile and urine.

CYP450 is a large family with genetic polymorphisms, so there are differences in drug metabolism between individuals.

Most drugs are metabolized by the liver, and drug-induced hepatitis is common in clinical practice.

Drug-induced hepatitis has two manifestations: one is known and predictable, the degree of liver damage is related to the dose of the drug; the other is idiosyncratic, unknown, unpredictable, and drug-related The dose is irrelevant.

The latter is actually a lack of metabolic enzymes such as CYP450, which can be understood as an individual's allergic reaction to drugs.
For example, most people use cephalosporin drugs without elevated transaminase, but a few people will experience severe liver damage. Common liver injury drugs include: (1) Western medicine: statins, anti-tuberculosis drugs, and acetaminophen and other antipyretic analgesics.

(2) Traditional Chinese medicine: Polygonum multiflorum, Tripterygium wilfordii, Chuanmeizi, Shandougen, Tusanqi and Xanthium spp.

For those with elevated transaminase for unknown reasons, attention should be paid to their medication history.

3.
Metabolic factors Metabolic-related fatty liver disease (formerly known as non-alcoholic fatty liver disease) is a disease in which fat accumulates excessively in the liver caused by multiple factors.
It is closely related to insulin resistance (IR) and genetic susceptibility.
Irrational diets such as calories and high fat are important predisposing factors for the disease.

IR can increase the liver's uptake of free fatty acids in the blood, promote the conversion of glucose to fatty acids, and lead to excessive deposition of fat in the liver, which in turn activates the endoplasmic reticulum stress response and ultimately leads to liver cell apoptosis; at the same time, free fatty acids can also promote The occurrence of liver IR triggers a vicious cycle of lipid deposition.

Most metabolic-related fatty liver diseases have no symptoms, only elevated transaminase, blood lipids and liver B-ultrasound can help diagnosis.

Hepatolenticular degeneration is a disorder of copper metabolism caused by ceruloplasmin deficiency.
A large amount of copper ions deposited in the body leads to organ dysfunction, which is an autosomal recessive genetic disease.

The main target organs are the liver and central nervous system.
The clinical manifestations are progressive liver injury, liver failure, and extrapyramidal damage.
It is more common in children and adolescents with a poor prognosis.

Decrease in serum ceruloplasmin (<0.
2 g/L), increase in 24-hour urinary copper (>100 μg in adults, >40 μg in children), and a positive corneal KF ring by slit lamp can confirm the diagnosis.

Hemochromatosis is a genetic disease.
The defective gene is located at 6P21.
3.
It is inherited in an autosomal recessive manner.
It is one of the common genetic diseases in Caucasians and is rare in my country.

The pathogenesis is that the body loses its ability to regulate iron metabolism, and iron ions in the intestine are over-absorbed and deposited in large amounts in tissues and organs such as the liver, pancreas, and heart, leading to corresponding organ dysfunction.

The patient’s characteristic manifestations are skin pigmentation, hepatomegaly, delayed porphyria skin, arthritis, and cardiac insufficiency.

The 2011 Hemochromatosis Diagnosis and Treatment Recommendations of the American Society of Liver Diseases: For patients with abnormal serum iron tests, evaluate for hemochromatosis even if there are no symptoms; for all patients with liver disease, evaluate for hemochromatosis.

Other metabolic diseases include glycogen accumulation disorder and sphingomyelin metabolism disorder, which are rare in clinical practice.

4.
Tumor factors As the disease progresses, the serum transaminase of patients with primary liver cancer and metastatic liver cancer can gradually increase, accompanied by an increase in bilirubin, which is difficult to control with general drugs until liver failure.

Patients with persistent elevated transaminase should pay attention to the investigation of liver cancer, and regularly check alpha-fetoprotein, alpha-fetoprotein heterogenes, abnormal prothrombin, liver B-ultrasound, and CT or MRI if necessary.

Hepatic hemangioma and liver cysts (to be exact) are benign lesions and generally do not cause elevated transaminase.
Those with small tumors and no obvious discomfort do not need special treatment.

5.
Alcohol Factors The chemical name of wine is ethanol, which is converted into acetaldehyde and acetic acid in turn through the metabolism of liver dehydrogenase.

The toxic effect of alcohol on the human body is mainly through conversion to acetaldehyde.

Acetaldehyde has a strong oxidizing property.
It is converted into superoxide by xanthine oxidase, leading to lipid peroxidation, destroying cell membrane structure, causing liver cell damage, and increasing transaminase.

Acetaldehyde can also combine with various proteins to form a complex (acetaldehyde complex), which acts as a new antigen stimulant and once again causes liver cell damage.

The tolerance to alcohol varies among individuals, which is mainly related to genetic heredity.

Studies on the polymorphism of the acetaldehyde dehydrogenase 2 (ALDH2) gene have shown that the G1510A mutation in the ALDH2 gene can cause the glutamic acid at position 487 of the amino acid sequence to be replaced by lysine, and GG is a homozygous wild type.
AA is a homozygous mutant, and GA is a heterozygous mutant.

Gene mutations lead to reduced ALDH2 enzyme activity, and acetaldehyde tends to accumulate in the body.

GG type ALDH2 has the strongest activity and the best tolerance to alcohol, followed by GA type, and AA type the worst.

For adult males with elevated serum transaminase, the medical history should be carefully asked to rule out alcoholic hepatitis.

6.
Poisoning factors should pay attention to organic volatile poisoning and food poisoning in daily work and life.

In food poisoning, attention should be paid to wild mushroom poisoning, string bean poisoning and fresh daylily poisoning.

Organic volatiles mainly include benzene and formaldehyde, which are easily inhaled through the respiratory tract and cause liver damage in a confined space.
They are commonly used in house decoration in daily life, such as closing doors and painting walls with paint.

Wild mushroom poisoning is seasonal and mainly occurs in the summer when mushrooms are grown.

According to the structure and toxicity of the toxin, it can be divided into cyclic peptides, orellatoxin, muscarinic, psilocybin, alloxin derivatives, lycophyllin, coprinin, etc.
The most toxic is the cyclic peptide "Amanita Toxin".

Wild mushroom poisoning mainly has two types of clinical manifestations of the mental nervous system and the digestive system.
The digestive system is mainly manifested as: nausea, vomiting, abdominal pain and diarrhea, yellow staining of the skin and sclera, and rapid increase in serum transaminase and bilirubin.

Kidney beans contain toxins such as saponin, phytohemagglutinin, trypsin inhibitors, and fresh daylily contains colchicine.
If cooked improperly, it can cause poisoning, nausea and vomiting, abdominal pain, diarrhea, and liver damage.

Conclusion There are many reasons for elevated serum transaminase, and there are many considerations for clinical diagnosis.

Among the non-infectious factors, autoimmune factors and drug factors should be excluded first, followed by metabolic-related fatty liver disease in metabolic factors.
Children should be excluded from copper metabolism disorders.
Adult men should be careful to exclude alcoholic hepatitis.
Benzene poisoning in paint is clinically common.
, Should maintain a high degree of vigilance.

There is a high incidence of food poisoning in summer and autumn, and attention should be paid.

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