From Western medicine to Chinese medicine, how much drug-induced hepatitis can be read in one article

Author: Wang Mingming, Chief Physician, Shandong Public Health Clinical Center (formerly Jinan Infectious Disease Hospital).

This article is authorized by the author to be published by Yimaitong, please do not reprint
it without authorization.

Drug-induced hepatitis refers to liver damage caused by various drugs, health products and dietary supplements, including prescription and over-the-counter Western medicines and traditional Chinese herbal medicines
.
At present, more than 1,100 drugs on the market are known to have potential hepatotoxicity, covering a wide range of aspects, including non-steroidal anti-inflammatory drugs, anti-infective drugs, anti-tumor drugs and drugs for metabolic diseases
.
Among traditional Chinese herbal medicines, there are also a few that can cause liver damage, among which He Shou Wu and Tu Sanqi are the most eye-catching
.
The reason for the high incidence of drug-induced hepatitis is related to the function of the liver itself, and most drugs need to be metabolized by the liver after entering the human body, or the activity is enhanced, or the activity is weakened, or non-toxic chemical components are formed to be excreted from the body, so liver cells are easily damaged
.

I don't know when there was a saying circulating on the Internet: "Putting aside the dose and talking about toxicity is hooliganism"
.
This sentence is not scientific, because the toxic effects of drugs are not all related to the dose of the drug, and some have nothing to do with
the dose.
There are two aspects
to the pathogenesis of drug-induced hepatitis.

First, it is related to the dose of the drug, the drug can directly act on liver cells, the larger the dose
, the greater the damage.
For example, we know that rifampicin anti-tuberculosis treatment can cause liver damage, and the longer the drug is used, the more serious
the liver damage.
This drug-induced hepatitis is usually foreseeable and avoidable, and we call it intrinsic drug-induced hepatitis
.
Direct hepatotoxicity of drugs can cause inflammatory injury and death
of hepatocyte cells through a variety of molecular or immune mechanisms.

The second is not related to the dose of the drug, but related to the specific constitution of the individual, and we can understand it as a special allergic reaction, which occurs in the
liver.
For example, most people do not respond to acetaminophen, but a very small number of people are particularly sensitive to acetaminophen, and eating one tablet can cause serious liver damage
.
This drug-induced hepatitis is unforeseeable and inevitable, and we call it idiosyncratic drug-induced hepatitis
.
Its pathogenesis is mostly related to the gene polymorphisms of individual drug-metabolizing enzymes (phase I metabolizing enzymes such as cytochrome P450 and a variety of phase II.
metabolizing enzyme systems), transmembrane transporters and solute transporters, and these gene polymorphisms and their epigenetic characteristics lead to abnormal function of these enzymes or transporters, thereby increasing the susceptibility of individuals to drug damage
.

The clinical manifestations of drug-induced hepatitis are different, mild cases may not have any symptoms, and only transaminases are found to be elevated in laboratory tests; Severe cases may have severe gastrointestinal symptoms, jaundice, and significant abnormalities
in liver function.
The onset of onset and urgency are related to
the type of disease.

Acute drug-induced hepatitis can begin within 1 day or a few days of administration, but most begin within 1 week to 1 month
.
It may present with gastrointestinal symptoms such as nausea, vomiting, decreased appetite, and bloating, and may present with jaundice, petechiae and ecchymosis of the skin, elevated liver enzymes, and elevated
bilirubin.

Chronic drug-induced hepatitis can begin months
to 1 year after medication.
It can be manifested as long-term fatigue, poor appetite, abdominal distention, bruising, skin itching, etc.
, and as the disease progresses, there may be manifestations of portal hypertension in cirrhosis, ascites, splenomegaly, esophageal and gastric varices, etc
.

There is no specific diagnostic method for drug-induced hepatitis, mainly in combination with drug history, for exclusive diagnosis
.
When abnormal liver function is found, viral hepatitis, Epstein-Barr virus and cytomegalovirus infection should be ruled out first, and corresponding etiological examinations should be performed; Secondly, attention should be paid to excluding autoimmune liver disease, alcoholic liver disease, fatty liver disease, and various metabolic liver diseases (such as copper metabolism disorders, iron metabolism disorders), and corresponding laboratory tests
should be performed.
After excluding these conditions, the diagnosis
of drug-induced hepatitis can be considered in conjunction with the patient's clear medication history.

It should be emphasized that many infectious diseases themselves may also be complicated by liver damage and elevated transaminases, and we cannot simply think that it is liver damage
caused by the drug because the patient has used a certain drug (or antipyretic analgesics, or Chinese proprietary medicines that clear heat and detoxify).

1.
Once drug-induced hepatitis is diagnosed or suspected, the relevant suspected drugs should be stopped in time, which is the best option
to stop the development of drug-induced hepatitis.
However, when stopping the drug, it should be considered that the primary disease may be aggravated after stopping the drug, so it is necessary to pay attention to weighing the pros and cons and making the correct trade-off
when making decisions.

2.
Active hepatoprotective treatment, commonly used drugs include N-acetylcysteine, glycyrrhizic acid preparation, schisandra preparation, silymarin, adenosylmethionine, ursodeoxycholic acid and polyene phosphatidylcholine
.
These drugs can promote the regeneration of liver cells, fight antioxidant free radicals, stop the development of inflammation, and have the effect
of improving liver function.
There is no evidence-based evidence for the use of adrenocortical hormones, and contraindications
should be strictly excluded when used.

3.
For severe liver damage and liver failure, artificial liver therapy or liver transplantation
can be given.

4.
The prevention of drug-induced hepatitis, the focus is not to use drugs indiscriminately, do not eat health care products, do not believe in home remedies, especially patients with liver disease foundation should try to avoid drugs with liver toxicity
.

1.
Nonsteroidal anti-inflammatory drugs are commonly paracetamol and ibuprofen, causing hepatocytotoxicity is mainly caused by the production of toxic free radical metabolites in the process of biotransformation, overdose and drinking alcohol during medication (alcohol will induce and aggravate the hepatotoxicity of antipyretic analgesics) will increase the risk of
liver damage.
In developed countries in Europe and the United States, acetaminophen is the most important cause
of acute liver failure.

2.
Anti-infective drugs: rifampicin and erythromycin as examples
.
Rifampicin is an inducer of liver enzymes that can promote the metabolism of drugs in the liver, but it itself has a direct hepatotoxic effect, interferes with the uptake of bilirubin and excretion of bile acid by hepatocyte membranes and receptor proteins, and causes an increase
in indirect bilirubin and bile acid.
Erythromycin is mainly metabolized by the liver, binds to hepatic metabolic enzymes, can inhibit the activity of hepatic cytochrome P450, and affect the metabolism
of other drugs in vivo.
Liver damage in some patients may also be associated with
hypersensitivity reactions to esters.

3.
He Shou Wu He Shou Wu is a traditional Chinese medicine whose effects include nourishing the essence and blood, detoxifying, and moisturizing the intestines and laxative
.
However, studies have shown that He Shou Wu contains anthraquinone derivatives, which contain important hepatotoxic substances
such as emodin, chrysa phenol and rhebarbhanic acid.
If the dose of He Shou Wu is taken at or exceeds the normal dosage by 50 times and the medication time is more than 3 months, transaminases may generally be elevated
.
If it is really necessary, the daily dosage of He Shou Wu should not exceed 1.
5g, and the daily dosage of He Shou Wu should not exceed 3.
0g
.

4.
Pharmacological studies have shown that Panax notoginseng contains pyrrolosidine alkaloids (PAs), which have a variety of toxic effects
.
The liver is the main target organ for the toxicity of PAs, which can cause damage to the ultrastructure of hepatic sinus endothelial cells, blood sinus blockage, endothelial cell damage, etc.
, causing hepatic sinus obstruction syndrome, resulting in portal hypertension
.

References:

[1] Pharmaceutical Hepatology Group, Hepatology Branch of Chinese Medical Association.
Guidelines for the diagnosis and treatment of drug-induced liver injury.
2015; 23(11):810-820.

[2] YU Xin, LI Xiaobing, HE Xiaojing, et al.
Mechanism of drug-induced liver injury, Chinese Journal of Hospital Pharmacy.
2017; 37(10):895-899.

[3] WANG Ruishi, WANG Qingwen.
Hepatotoxicity of the drug, 2004; 13(5): 458-462.

[4] LI Yan, ZHAO Guangchen.
Research Progress on Anti-tuberculosis Drug-induced Liver Damage, People's Military Medicine, 2019; 46(3):278-281.

[5] Hepatobiliary Disease Collaborative Group, Gastroenterology Branch of Chinese Medical Association.
Expert consensus opinion on the diagnosis and treatment of pyrrole alkaloid-associated sinus obstruction syndrome (Nanjing, 2017), Chinese Journal of Digestion, 2017; 37(8):513-520.