Drug-Induced Liver Injury
The liver is the body's second-largest vital organ and its largest gland, weighing about 1.36 kg and accounting for 1.5%–2.5% of body weight. The liver is the largest digestive gland in the body, with important and complex metabolic functions.
The liver has a dual blood supply from the hepatic artery and hepatic vein; hepatocytes are rich in mitochondria, with each hepatocyte containing on average about 400 mitochondria. These mitochondria are round, oval, or rod-shaped; they are particularly sensitive to hypoxia and easily damaged. The rough endoplasmic reticulum of hepatocytes is the site where various proteins and enzymes are synthesized, while the smooth endoplasmic reticulum is involved in the synthesis and breakdown of glycogen and the biotransformation of bilirubin, hormones, drugs, dyes, and toxic substances. More than 500 kinds of chemical reactions occur in the liver; animal experiments confirm that if an animal's liver is removed, it can survive at most only about 50 hours.
When we take medications to treat disease, the liver is extremely easily damaged. Drug-induced liver injury is related to several factors: first, the toxicity of the drug taken is too great; second, the course of medication is too long; third, improper use of drugs. Many patients who take health foods or health supplements of unknown composition and side effects year after year also develop drug-induced liver injury.
Cancer patients very easily develop drug-induced liver injury during treatment. Chemotherapy, targeted drugs, Chinese herbal medicines, and health supplements can all cause liver damage in cancer patients—so generally one should not take various anticancer drugs simultaneously, as this increases the risk of drug-induced liver injury.
Drugs used to treat cancer are mostly quite toxic, and cancer patients' courses of treatment are long; most cancer patients develop abnormal liver function at some stage of treatment.
Even non-toxic herbal medicines and supplements, when taken over too long a course, can likewise cause liver damage. Scholars have done statistics: among 112 single Chinese herbs with reported poisoning cases, 30 were recorded in the literature as non-toxic or not recorded as toxic, and 10 of those resulted in death. There are also case reports of liver and other organ damage caused by taking traditionally regarded non-toxic herbs such as ginseng and ganoderma (lingzhi).
The idea that Chinese herbal medicines have no toxic side effects has badly misled Chinese patients; some drug advertisements deliberately emphasize "pure natural herbal preparation, non-toxic side effects." Such publicity leads most Chinese residents to believe that herbal medicines have no side effects. In fact, among drug-induced liver injuries reported each year, those caused by herbal medicines and herbal health supplements account for about half.
Some patients with severe liver injury develop acute liver damage requiring hospitalization. Most patients with mild liver injury can recover liver function by stopping the drug. But sometimes for cancer patients, stopping the drug means death, so at such times it is necessary to pair treatment with liver-protective medications. During chemotherapy, targeted therapy, and herbal treatment for cancer, many patients develop abnormal liver function; if the situation is not particularly serious, treatment should not be suspended arbitrarily.
Both Chinese and Western medicines can cause liver damage, and health supplements—along with the various tonics patients take on their own, touted as health-promoting—can also cause liver damage. Irrational drug use or supplement abuse is the most important cause of drug-induced liver injury; patients who take health supplements or various fungal products year after year are at high risk of chronic liver damage.
Drugs and supplements should be taken under a doctor's guidance and should not be self-administered long-term. Even an effective regimen should not be used continuously without a break, otherwise liver function is easily impaired. After one chemotherapy cycle, doctors require patients to rest for a period before the next cycle, also to avoid severe bodily damage from overtreatment. When taking herbal medicines, there should also be intermittent periods; one should not take herbs continuously without a break.
I usually require patients to take the medicine for five days and rest for two; patients who have passed the danger period stop the drug for even longer. Many patients are especially worried that the cancer will progress during the drug-free period, but in fact the harm of taking medicine continuously without a break is greater than the benefit. Some terminal-stage patients recklessly abuse drugs and increase dosages regardless of consequences, ultimately inevitably developing side effects such as acute liver damage and dying prematurely.
When an internal medication is effective against a tumor, the dosage should not be arbitrarily increased either. Some drugs are harmless at low doses but cause liver damage when the dose is raised. The highly toxic arsenic trioxide, as long as the dosage is well controlled, is beneficial rather than harmful to cancer patients, but if the dosage is raised it has fatal side effects. Non-toxic ginseng, if its dosage is recklessly increased, likewise has fatal side effects.
Drug-induced liver injury is also related to individual patient differences. The same drug causes different degrees of damage in different patients. So a drug harmless to patient A may be hepatotoxic to patient B; one cannot rely on experience to judge it harmless. The use of any drug must be cautious. Patients on long-term medication must regularly check liver and kidney function; if liver function is abnormal, they should promptly consult a physician or pharmacist. Patients taking long-term supplements also need regular liver and kidney function checks, and patients with underlying liver disease need to be especially careful.
Even if regular checks show no abnormality in liver function, one cannot let one's guard down. A gallbladder cancer patient I treated had long taken medication, with breaks in between, and regular liver and kidney function rechecks all normal. But last year she developed symptoms of acute liver injury requiring hospitalization for liver-protective treatment. This fulminant liver damage generally occurs in patients with hepatobiliary disease.
There are also patients who, perhaps due to family genetics, are extremely prone to liver damage. A lung cancer patient I treated had two brothers, both of whom developed lung cancer, and both brothers were also very prone to drug-induced liver injury; multiple drugs that are nearly harmless to other patients caused abnormal liver function in them. This type of patient's liver damage may be related to family genetics.
Most acute liver injury patients develop symptoms of acute hepatitis: abnormal liver function, impaired digestive function, jaundice, and so on. Generally, acute liver injury requires 1–2 months of hospitalization. Liver damage discovered in time can basically be cured, but some patients lack medical common sense; after developing symptoms of liver damage they fail to pay attention and delay, which can lead to severe liver failure and death.
The liver is the only organ in the human body that can regenerate. After surgical removal of 75% of liver tissue, mice recover their original state in just 3 weeks, dogs need 8 weeks, and humans need four months. An adult liver weighs about 1,500 g; as long as more than 300 g of liver tissue is healthy, liver function can be basically normal. Although liver cancer is called the king of cancers, it can be radically cured by surgical resection.
So drug-induced liver injury is not an irreversible disease either; once it occurs, seeking medical attention promptly basically resolves it well. But preventing drug-induced liver injury is more meaningful than treating it after it occurs. Patients with already abnormal liver function or with already diseased livers must be especially careful when taking internal medications for their cancer. General patients also need regular rechecks to detect problems in time.
Patients who stubbornly take medicine every day and who, without a doctor's guidance, self-administer various drugs of unclear side effects, are a high-risk group for drug-induced liver injury. I advise most cancer patients taking Chinese and Western anticancer drugs to follow the principle of "withdrawing gradually" (xuxu er tui), gradually reducing the dosage and shortening the course. After passing the danger period, when taking recurrence-prevention treatment, it is best to have longer drug-free intervals.