How can treating tuberculosis cause liver failure?

This is the 3389th article of Da Yi Xiao Hu

Drug-induced liver injury refers to liver injury induced by various chemical drugs, biological agents, traditional Chinese medicines, natural medicines, health products, dietary supplements and their metabolites and even excipients. After most drug-induced liver injuries occur, liver function can be restored if the drug is stopped in time and liver protection treatment is given, but a small number of patients have a rapid progression of the disease and may suffer from acute liver failure or even death.

The following case is a real case that happened in my department a few years ago. Due to drug-induced liver damage, the patient eventually underwent a liver transplant.

one

Xiao Ma is in her 30s and is a mother of a 10-year-old child. She and her husband love each other very much. The two have been running an ethnic-style hotel in a popular tourist attraction for many years and live a happy life.

But in the past month, Xiao Ma felt something strange about his body: a little tired, a slight dry cough, no appetite, and nothing tasted good. Xiao Ma thought he had a cold, so he found some leftover cold medicine at home and took it sporadically for a few days. However, the above discomfort did not get better, but some abnormalities appeared: he sweated more than before, especially after waking up from a nap, his skin was sweaty, and his underwear felt damp.

Xiao Ma wanted to go to the hospital to check if she was sick, but because she had to run the hotel business, take care of the children, and take care of the family's food and drink, she was busy all day, so she kept putting off going to the hospital. Until one day after dinner, Xiao Ma felt very sleepy and weak. She didn't eat dinner, and she didn't take care of her son doing homework. She went to bed early with her clothes on.

After finishing his homework, the child wanted to find his parents to sign it. He couldn't find his mother, so he found his father, Xiao Zheng. Xiao Zheng thought it was a bit strange because his wife had always been the one who looked after the child while he was doing his homework. She would usually say hello when she went out. Xiao Zheng called his wife but she didn't answer, so he looked everywhere and finally found his wife sleeping in the bedroom.

Xiao Zheng lifted the quilt and saw that his wife seemed sick, with red cheeks and a hot forehead, as if she had a fever. Xiao Zheng panicked and quickly rummaged through the boxes to find the thermometer his son had used when he was sick and put it under his wife's armpit. A few minutes later, he took out the thermometer and saw that it was 38.1℃. His wife really had a fever. He hurriedly found antipyretic and cold medicine for his wife, asked her to take it with warm water, and then helped her lie down.

After taking the medicine, Xiao Ma continued to sleep. He woke up in the middle of the night and felt that his fever had subsided and he felt more energetic. He seemed a little hungry, so he got up to find something to eat to fill his stomach.

two

The next day, Xiao Zheng entrusted the hotel business to his parents and took his wife to the hospital. The outpatient doctor admitted Xiao Ma to the hospital for "fever investigation".

After being hospitalized, the doctor did not use any special medicines, but mainly did examinations, including drawing blood, collecting urine, feces and sputum, and also doing B-ultrasound and CT scans. Xiao Ma had never had such a detailed physical examination before.

Three days later, the results came out. Dr. Jiang, the attending physician, told Xiao Ma that she had secondary pulmonary tuberculosis. Xiao Ma couldn't believe her ears. She knew about pulmonary tuberculosis a few years ago. At that time, one of her relatives had pulmonary tuberculosis. The doctor said that it was contagious and drug-resistant. After several years of treatment, it was not completely cured. One day, she suddenly coughed up blood and died. Xiao Ma was scared when she thought about it. How could she get this disease?

Fortunately, Dr. Jiang said that her tuberculosis was not contagious, and that the initial treatment of tuberculosis was relatively mature, with some old drugs that had been used for many years. However, Dr. Jiang emphasized that some anti-tuberculosis drugs have side effects such as liver damage, and required her to have blood drawn at least every two weeks for the first three months of anti-tuberculosis treatment, especially for liver function, and to promptly detect and treat any abnormalities; and to have a chest CT scan every 2-3 months to check the absorption of the lesions.

Dr. Jiang also told Xiao Ma that she must take the medicine on time for at least six months, and then decide whether to stop taking the medicine based on the absorption of the lesions assessed by lung CT scan. In addition, she should pay attention to strengthening nutrition, avoid overwork, and maintain a good immune status, which will help her recover from the disease.

After taking anti-tuberculosis drugs for a week, Xiao Ma no longer felt feverish, her previous fatigue and other symptoms gradually disappeared, and her appetite gradually improved. Two weeks later, she followed the doctor's advice to go to the hospital for a follow-up examination, and the results showed that she was normal, so Xiao Ma continued to take the medicine.

Because it was the peak tourist season, the hotel was doing very well. Xiao Ma and his wife, together with the help of his father-in-law and mother-in-law, still felt very busy. He had not stopped taking anti-tuberculosis drugs, but had forgotten about the follow-up examination.

After taking the medicine for another month, Xiao Ma felt unwell and had symptoms such as nausea, vomiting, fatigue and weakness, and the symptoms gradually worsened. Xiao Ma thought that her recent irregular meals had caused a recurrence of her stomach disease. She found some stomach medicine and took it for two meals, but the above symptoms did not improve, and the color of her urine seemed to turn yellow. Xiao Ma did not take it seriously.

A few days later, after getting up early in the morning, Xiao Ma looked in the mirror and found that her face was a little yellow, and the whites of her eyes were also yellow. She was very nervous and worried that something had happened to her again, so she called her husband and rushed to the hospital.

Xiao Ma found Dr. Jiang, the doctor who was in charge of Xiao Ma's last visit. Dr. Jiang took one look at Xiao Ma's expression and said, "This is bad. You have to stop taking anti-tuberculosis drugs first. You may have liver damage related to tuberculosis drugs."

Dr. Jiang took a blood test on Xiao Ma and the results came out in the afternoon. She saw many upward arrows on the test report and many indicators were far beyond the normal range.

Xiao Ma showed the test results to Doctor Jiang, who shook his head as he read them. "I told you a long time ago that you need to have a follow-up check at least 2 weeks after treatment. Why didn't you come on time? You have acute drug-induced liver injury, and there are signs of liver failure. You need to be hospitalized immediately."

And so, Xiao Ma was hospitalized for the second time.

three

This time, Dr. Jiang required Xiao Ma to strictly stay in bed and rest except for washing her face, brushing her teeth, and going to the toilet. He also asked her to eat a light diet, mainly porridge, rice noodles, and pasta. He also said that because her liver function was severely damaged, blood tests would be done every day to adjust the treatment plan as appropriate.

However, despite strictly following Dr. Jiang's advice and cooperating with the treatment, Xiao Ma's symptoms did not improve. He still felt tired and weak, suffered from frequent nausea and vomiting, his urine became increasingly yellow, and his skin turned completely yellow. He was almost like a little "golden man".

On the third day, Dr. Jiang arranged for Xiao Ma to undergo a blood transfusion. Dr. Jiang said that this method is called artificial liver plasma exchange, which means drawing her blood out of the body, separating and discarding her plasma, and then injecting an equal amount of fresh frozen plasma into her body. The purpose is to excrete toxic substances produced by the metabolism that the liver cannot complete detoxification, purify the blood, improve the microenvironment, and facilitate the regeneration of liver cells.

Two days later, she received another artificial liver treatment, but Xiao Ma's condition did not improve. She became increasingly listless and had no appetite. She only drank a small amount of porridge every day. The color of her urine was like strong tea.

One week into the hospital stay, Dr. Jiang called Xiao Ma's husband, Xiao Zheng, to the doctor's office again to discuss the condition with him. Dr. Jiang told Xiao Zheng that Xiao Ma's condition was progressing rapidly, and that conservative treatment had not been effective, and that it had progressed to the late stage of liver failure. If conservative treatment continued, the effect would not be good, and it was recommended that he actively prepare for a liver transplant.

Dr. Jiang had talked to Xiao Zheng about his wife's condition many times before, and had said that if conservative treatment did not work, liver transplantation should be considered. Xiao Zheng thought the doctor was exaggerating to scare him, and never thought that a liver transplant would actually be necessary.

Four

Xiao Zheng was very confused. His wife only had tuberculosis and was being treated. How could she suddenly develop liver failure and need a liver transplant?

Doctor Jiang patiently explained to Xiao Ma: "To put it in an analogy, the liver is like a large chemical processing plant for the human body. Various substances, including food absorbed by the gastrointestinal tract, must be processed by the liver before they can take effect; some waste products produced by metabolism, as well as foreign drugs or poisons, must also be processed and detoxified by the liver. However, some drugs or their metabolites can directly cause liver damage; in addition, some individuals lack enzymes that detoxify certain drugs, poisons and their metabolites due to congenital genetic factors, or the enzymes are dysfunctional, which can also cause drugs to accumulate in the body and cause liver damage; some drugs or metabolites can also change the antigen structure of the liver, thereby triggering the body's autoimmune attack and causing immune liver damage."

Doctor Jiang took a sip of water and continued, "Rifampicin, pyrazinamide and isoniazid in anti-tuberculosis drugs are common drugs that cause liver damage, and the incubation period of common drug-induced liver damage is mostly within 3 months. Therefore, we require patients taking anti-tuberculosis drugs to have their liver function checked every 2 weeks within the first 3 months, and if there is any abnormality, it must be discovered and treated in time. However, Xiao Ma did not come for a follow-up check in time, and she did not stop taking the drug in time even though she had symptoms of liver damage, so her condition was delayed. At present, the disease is progressing very rapidly, and the liver cells are necrotic very quickly. The body has no time to repair it. The entire liver fiber scaffold has collapsed, and the liver volume has significantly shrunk. Now, only a liver transplant can save her life."

After listening to Dr. Jiang's introduction, Xiao Zheng gradually understood how his wife's liver failure occurred. He was determined to do his best to save his wife no matter how much it cost.

five

The doctor from the liver transplantation department came to consult soon and told Xiao Zheng to register as soon as possible and prepare the fees to wait for the liver source. Fortunately, the couple had a lot of savings from their business over the years, so it was not difficult to come up with the money for the liver transplant. Xiao Zheng registered at the liver transplantation department that day and prepared the fees.

Xiao Ma had his third artificial liver blood purification treatment. Dr. Jiang said it was a transitional treatment before waiting for a liver transplant. Two days later, a liver was finally found, and Dr. Jiang arranged for Xiao Ma to be transferred to the liver transplant department.

Xiao Ma successfully completed the liver transplant and recovered smoothly without any complications. Two days after the transplant, Xiao Ma was transferred out of the ICU and stayed in the liver transplant department for 18 days. After reexamination, his liver function and other indicators basically returned to normal.

Under the guidance of Dr. Jiang, Xiao Ma adjusted the anti-tuberculosis treatment drugs.

After being discharged from the hospital, Xiao Ma rested at home for a while and felt back to normal in all aspects.

After that, Xiao Ma took the doctor's words as an imperial edict, took anti-rejection and anti-tuberculosis drugs on time every day, and went to the hospital on time to monitor blood drug concentrations, liver function, etc. He never dared to be careless again.

Drug-induced liver injury is very common in clinical practice. It is known that there are more than 1,100 drugs on the market worldwide with potential hepatotoxicity, including common non-steroidal anti-inflammatory drugs (antipyretics and analgesics), anti-infective drugs (including anti-tuberculosis drugs), anti-tumor drugs, central nervous system drugs, cardiovascular system drugs, metabolic disease drugs, hormone drugs, certain biological agents and traditional Chinese medicine, natural medicine, health products, dietary supplements, etc.

In developed countries in Europe and the United States, non-steroidal anti-inflammatory drugs, anti-infective drugs, herbal medicines and dietary supplements are common causes of drug-induced liver injury. Among them, acetaminophen (paracetamol) is the main cause of acute liver failure.

Traditional Chinese medicine, natural medicine, health products, and dietary supplements are receiving increasing attention around the world as causes of drug-induced liver injury.

A prospective study in Iceland in 2013 showed that dietary supplements accounted for 16% of the causes of drug-induced liver injury in the country, and data on drug-induced liver injury in the United States showed that dietary supplements accounted for more than 20% of the causes of drug-induced liver injury. There are reports in China that related drugs are involved in drug-induced liver injury: traditional Chinese herbal medicine (23%), anti-infective drugs (17.6%), anti-tumor drugs (15%), hormone drugs (14%), cardiovascular drugs (10%), non-steroidal anti-inflammatory drugs (8.7%), immunosuppressants (47%), sedatives and neuropsychiatric drugs (2.6%), etc.

Traditional Chinese medicines, natural medicines, health products, dietary supplements that are frequently reported to be related to liver damage include Polygonum multiflorum, Radix Notoginseng, and certain compound preparations for the treatment of osteoporosis, arthritis, vitiligo, psoriasis, eczema, acne, etc. However, due to the complexity of the ingredients, it is difficult to determine which ingredients cause liver damage.

Here, as a hepatologist, I would like to remind you:

“Medication-induced liver disease” is not uncommon, so be cautious when taking “medicine”!

Author: Department of Hepatology II, Shenzhen Third People's Hospital

Wang Fang