Prevalence And Clinical Characteristics Of Antibiotics Associated Drug Induced Liver Injury
Jin Hwa Park1#, Susie Hong2#, Dae Won Jun2^, Jai Hoon Yoon2, Kang Nyeong Lee2, Hang Lak Lee2, Oh Young Lee2, Byung Chul Yoon2, Ho Soon Choi2
1Department of Internal Medicine, Hanyang University School of Medicine , , South Korea
Contributions: Conception and design: DW Jun Administrative support: OY Lee, BC Yoon, HS Choi Provision of study materials or patients: DW Jun, JH Park Collection and assembly of data: JH Park, S Hong Data analysis and interpretation: JH Park, S Hong, JH Yoon, KN Lee, HL Lee Manuscript writing: All authors Final approval of manuscript: All authors.
#These authors contributed equally to this work.
^ORCID: 0000-0002-2875-6139
Correspondence to:
Background: The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI.
Methods: This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set.
The Prevalence of antibiotics associated with DILI was 214%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.
Submitted Jul 05, 2020. Accepted for publication Jan 25, 2021.
Medicinal Herbs And The Liver
Some medicinal herbs contain substances that can damage the liver. The liver is a prime target for damage because it processes everything that enters the mouth and is swallowed.
Pyrrolizidine alkaloids: Hundreds of herbs contain pyrrolizidine alkaloids, which may damage the liver. These herbs include borage, comfrey, and certain Chinese herbs, such as zi cao , kuan dong hua , qian li guang , and pei lan . Some herbs used to make teas contain pyrrolizidine alkaloids. Sometimes milk, honey, and cereals are contaminated with pyrrolizidine alkaloids, which are then consumed unknowingly.
Pyrrolizidine alkaloids can damage the liver gradually if small amounts are consumed for a long time. Damage can occur more quickly if a large amount is consumed. The hepatic veins may become clogged, blocking blood flow out of the liver.
), liver failure Liver Failure Liver failure is severe deterioration in liver function. Liver failure is caused by a disorder or substance that damages the liver. Most people have jaundice , feel tired… read more , and even death may result.
Other herbs: Liver damage may also result from herbs such as Atractylis gummifera, Camellia sinensis , celandine , chaparral, Garcinia cambogia , green tea extract , germander, jin bu huan, kava, ma huang , mistletoe, pennyroyal oil , and syo-saiko-to .
Signs And Symptoms Of Hepatotoxic Reactions
Most cases of antibiotic-induced hepatotoxicity are idiosyncratic .2,4,16 It is thought to occur either via an immunological reaction, including concomitant liver inflammation associated with viral or bacterial infection of liver or inflammatory disease,17 in response to hepatotoxic metabolites,18 or, as more recently suggested, when the drug synergizes with lipopolysaccharide-induced inflammatory cytokine signalling to cause acute hepatocyte death.17,19 Symptoms are similar to those of other liver diseases, and include jaundice, malaise, abdominal pain, unexplained nausea and anorexia.2 Because antibiotic-induced hepatotoxicity mimics other liver diseases, diagnosis is necessarily one of elimination and is usually based on a high degree of clinical suspicion following exclusion of competing aetiologies, such as viral hepatitis or biliary disease.18 Clues suggestive of drug allergy include rash, fever or eosinophilia, duration of exposure of 15 weeks and an often rapid response following re-administration of the antibiotic.2,18,20
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How Does Kratom Affect The Liver
The active ingredients of kratom are a group of around 12 alkaloids. Each of these alkaloids needs to be metabolized by the liver before we can eliminate them from the body .
This is the same for just about any medication or supplement.
What makes kratom different is the sheer volume of alkaloids it provides which places extra strain on the liver to be able to process all of them effectively.
People with healthy livers are unlikely to have any trouble metabolizing kratom and will therefore not experience any liver injury.
However, people with a genetic defect, preexisting liver damage, sensitivities to kratom, or those who are taking known liver-toxic medications or substances are at the highest risk of experiencing liver damage after using kratom.
The most abundant alkaloid in kratom is called mitragynine. This compound primarily requires the CYP2D6 liver enzyme for metabolism, as well as some help from CYP3A4 and CYP2C9 .
Therefore, if users have any issues with this particular pathway or are using medications that also affect these enzymes, the risk of liver damage is higher.
What Side Effects Are Related To Antibiotics
- Allergic reactions: Every year, there are more than 140,000 emergency department visits for reactions to antibiotics. Almost four out of five emergency department visits for antibiotic-related side effects are due to an allergic reaction. These reactions can range from mild rashes and itching to serious blistering skin reactions, swelling of the face and throat, and breathing problems. Minimizing unnecessary antibiotic use is the best way to reduce the risk of side effects from antibiotics. You should tell your doctor about any past drug reactions or allergies.
- C. difficile: C. difficile is a type of bacteria that causes diarrhea linked to at least 14,000 American deaths each year. When you take antibiotics, good bacteria that protect against infection are destroyed for several months. During this time, you can get sick from C. difficile. The bacteria can be picked up from contaminated surfaces or spread from the healthcare environment. People, especially older adults, are most at risk who take antibiotics and also get medical care. Take antibiotics exactly and only as prescribed.
- Antibiotic resistance: The use of antibiotics may increase the risk of bacteria becoming resistant to them. Antibiotic-resistant infections can be very serious and difficult to treat.
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Factors That Raise Your Risk Of Dili
A few risk factors that increase a persons chance of experiencing drug-induced liver injury include 3, 6:
- Drinking alcohol.
- Taking medication or drugs in excess.
- Combining drugs and/or alcohol.
When your doctor prescribes you a medication that is known to cause liver damage, you will want to make sure to tell him or her what other medications youre on in the case of possible drug interactions.
How Do Benzodiazepines Affect The Liver
One method of measuring liver function is serum enzyme elevations. When the liver is struggling to process chemicals or beginning to fail, this will be indicated by higher levels of specific enzymes in the blood.
Benzodiazepine treatment and even benzodiazepine abuse are rarely associated with elevated levels of liver enzymes. However, some benzodiazepines have been linked to rare instances of liver damage.
Other benzodiazepines have not been reported in any instances of liver injury by themselves. However, most of them are metabolized by the liver in some way. Exceptions are:
- Lorazepam
- Oxazepam
- Temazepam
These drugs work well for people who have liver damage or failure, so they have trouble metabolizing several drugs, including benzodiazepines. They may also be important as a method of treatment for people who abuse alcohol and need to manage withdrawal symptoms with medication but cannot metabolize other benzodiazepines safely. This includes Valium, which is the main benzodiazepine prescribed off-label for alcohol use disorder treatment.
However, this enzyme alone does not predict whether the liver is damaged or close to failure. It is, instead, one of several enzymes that must be measured. In the study, GGT was the only enzyme found to be elevated in the group that abused benzodiazepines, and no other signs of damage were recorded.
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Risk Factor Of Antibiotics Associated With Dili In Outpatients
The ratio of male patients was slightly higher than female patients. The average age was 50.5±17.2 in flomoxef associated with DILI group. Antibiotics were mostly prescribed for preventing infection after operation among outpatients, which accounted for the largest proportion , followed by urinary tract infection , upper respiratory infection , ostitis media and cellulitis . Figure 3 shows the purposes of prescribed patients. In addition, hypertension accounted for 14% of the underlying diseases found in outpatients with elevated liver enzyme level associated with the prescribed flomoxef, followed by diabetes , cancer and hyperlipidemia .
Figure 3
Common Meds That Cause Liver Damage
Your liver is one of the bodys most crucial organs. Unfortunately, many drugs can put extra strain on it. Find out which ones do and how to minimize harm.
Day in and day out, week after week and year after year, as you eat, drink and take medications or supplements, theres an unsung hero working hard to filter and process all of these substances, store the nutrients and get rid of the waste: your liver. That adds up to lots of chances that something passing through might harm this vital organ. Numerous medications, for example, have been shown to increase the risk of liver damage that goes for herbal medicines too, as well as dietary supplements.
There is increasing evidence that complementary and alternative medicines such as supplements and herbs can cause liver damage. These include kava, Comfrey, mistletoe and others, says Lauren Aleksunes, PharmD, PhD, associate professor of pharmacology and toxicology at the Ernest Mario School of Pharmacy at Rutgers University, and resident scientist at the Environmental and Occupational Health Sciences Institute. Just because they can be purchased without a prescription does not mean they are safe.
Research on people who used herbal and dietary supplements found that liver damage rose 20% from 2004 and 2013. For more information on supplements and liver damage, read: 15 Supplement Ingredients to Always Avoid.
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Liver Damage From Other Causes
Because no test can confirm the diagnosis, doctors also check for other causes of liver damage. Blood tests to check for hepatitis Overview of Hepatitis Hepatitis is inflammation of the liver. Hepatitis is common throughout the world. Hepatitis can be Acute read more , autoimmune disorders, and other causes are done. Pressing on the upper abdomen to determine the size of the liver and doing imaging tests, such as ultrasonography Ultrasonography Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography , magnetic resonance imaging , endoscopic retrograde cholangiopancreatography… read more or computed tomography Computed Tomography Imaging tests of the liver, gallbladder, and biliary tract include ultrasonography, radionuclide scanning, computed tomography , magnetic resonance imaging , endoscopic retrograde cholangiopancreatography… read more , can also help doctors identify other causes of liver damage.
Are There Any Antibiotics That Cause Liver Injury
The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion.
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How Is Antibiotic Resistance A Threat To Public Health
As WHO ramps up its fight against antibiotic resistance, a new multi-country survey shows people are confused about this major threat to public health and do not understand how to prevent it from growing. Antibiotic resistance happens when bacteria change and become resistant to the antibiotics used to treat the infections they cause.
Acetaminophen As A Recreational Drug
Recent studies suggest that acetaminophen isnt addictive and people dont take it to get high. It is, however, an active ingredient in many painkillers, such as Vicodin or Percocet, which are abused for their highs. It is the acetaminophen contained in these drugs that is often the most damaging.
Overdose from acetaminophen causes about 60,000 people each year to go to the hospital, several hundred of which die from associated liver failure.
Acetaminophen is most commonly misused as a recreational drug in conjunction with other drugs. On its own, acetaminophen is widely accepted to be a safe drug and is easily accessible.
People who abuse painkillers, such as Tylenol 3, are often in search of a calm and relaxed high.
More potent forms of acetaminophen, however, such as Tylenol 3, can only be obtained through a doctors prescription, as it also contains a significant amount of codeine, another painkilling drug. Acetaminophen alone is not particularly habit-forming, but the codeine in Tylenol 3 can lead to dependency.
The codeine in Tylenol 3 can cause feelings of euphoria, which leads some people to misuse the drug. Tylenol 3 has also been shown to enhance the effects of other drugs, such as narcotics, alcohol, general anesthetics, tranquilizers, sedative-hypnotics, and other central nervous system depressants. Combining acetaminophen with any of these drugs increases the risk of experiencing the adverse side effects of each drug.
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Antibiotics: Single Largest Class Of Drugs Causing Liver Injury
- Date:
- American Gastroenterological Association
- Summary:
- Antibiotics are the single largest class of agents that cause idiosyncratic drug-induced liver injury, reports a new study in Gastroenterology. DILI is the most common cause of death from acute liver failure and accounts for approximately 13 percent of cases of acute liver failure in the US. It is caused by a wide variety of prescription and nonprescription medications, nutritional supplements and herbals.
Antibiotics are the single largest class of agents that cause idiosyncratic drug-induced liver injury , reports a new study in Gastroenterology, an official journal of the American Gastroenterological Association Institute. DILI is the most common cause of death from acute liver failure and accounts for approximately 13 percent of cases of acute liver failure in the U.S.
It is caused by a wide variety of prescription and nonprescription medications, nutritional supplements and herbals.
“DILI is a serious health problem that impacts patients, physicians, government regulators and the pharmaceutical industry,” said Naga P. Chalasani, MD, of the Indiana University School of Medicine and lead author of the study. “Further efforts are needed in defining its pathogenesis and developing means for the early detection, accurate diagnosis, prevention and treatment of DILI.”
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How Does Metronidazole Affects The Liver Performance
How does metronidazole affects the liver performance?& if it does then what is the remedy? i have heard that Antibiotics such as Metronidazole has bad effects on liver but if effects are there and liver is not working properly ..and if its not producing digestive enzymes properly then what is the remedy to this problem?
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Antibiotics And Chronic Liver Diseases
Chronic hepatitis patients sometimes need to use antibiotics for unrelated infections and various surgical and dental procedures. Many are not sure about the possible harmful effects some antibiotics may cause their liver so I will try to provide a general guide here.
The liver has very complicated functions and one of the most important is the detoxification of drugs such as antibiotics and its metabolites. Some antibiotics can cause allergic reactions while others can cause direct damage to their liver, which can be quite severe in patients with chronic liver disease. For patients with a pre-existing liver disorder, the detoxification function of the liver is already compromised and substances that would normally be metabolized could actually accumulate in the liver or in the bloodstream. Antibiotics that accumulate in this manner could become toxic to the body and its functions can change drastically from its original purpose.
The following is a list of the most common antibiotics groups being used today. Each is ordered according to their potential harmful effects on the liver, the top group being the most potentially harmful and the last group being the least.
1. Tetracycline family
2. Erythromycin family
3. Chloramphenicolum family.
4. Penicillin family.
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New Zealand Case Reports
The Centre for Adverse Reactions Monitoring has received a total of 360 reports of liver injury associated with the use of non-tuberculosis antibiotics since January 2000. Most reports were in adults aged over 50 years , with 13 reports in patients aged less than 20 years. Seven reports involved a fatality.
The majority of CARM reports of liver injury were associated with -lactam penicillins . Amoxicillin/clavulanic acid, flucloxacillin and erythromycin were the antibiotics most often implicated in the development of liver injury in New Zealand.
Figure 1: Classes of non-tuberculosis antibiotics associated with liver injury in New Zealand
Key Messages
- Antibiotics are a common cause of drug-induced liver injury.
- Most cases of antibiotic-induced liver injury are idiosyncratic, unpredictable and largely dose-independent.
- In New Zealand, the antibiotics most often implicated with liver injury are amoxicillin/clavulanic acid, flucloxacillin and erythromycin.
- Withdrawal of the causative antibiotic is the most effective treatment.
References
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How Can I Lower My Dogs Liver Enzymes Naturally
Green vegetables contain not only valuable vitamins and minerals but they also contain natural cleansers and antioxidants that help to purify the blood and the liver. Giving your pet green vegetables such as green beans, squash or asparagus, along with some carrots can provide fresh enzymes and extra nutrition.
People At An Increased Risk Of Side Effects
Statins should be taken with caution if you’re at an increased risk of developing a rare side effect called myopathy, which is where the tissues of your muscles become damaged and painful. Severe myopathy can lead to kidney damage.
Things that can increase this risk include:
- being over 70 years old
- having a history of liver disease
- regularly drinking large quantities of alcohol
- having a history of muscle-related side effects when taking a statin or fibrate
- having a family history of myopathy or rhabdomyolysis
If one or more of these apply to you, you may need to be frequently monitored to check for complications. A lower dose of statin may also be recommended.
If you have an underactive thyroid , treatment may be delayed until this problem is treated. This is because having an underactive thyroid can lead to an increased cholesterol level, and treating hypothyroidism may cause your cholesterol level to decrease, without the need for statins. Statins are also more likely to cause muscle damage in people with an underactive thyroid.
Read more about the side effects of statins.
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