Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

Rotundo, Laura; Pyrsopoulos, Nikolaos

doi:10.4254/wjh.v12.i4.125

Cited by 96 publications

(72 citation statements)

References 88 publications

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“…Sales of APAP-containing products, which are not restricted to pharmacies in many countries, are increasing worldwide 4 . Adverse effects of APAP are well known; for example, intentional overdose, unintentional overdose 5,6 and chronic use have resulted in APAP being the leading cause of acute liver failure in children 7 and adults 5,8 in the Western world. Of note, APAP is widely used by pregnant women, as the FDA and EMA have long considered APAP-containing products to be of minimal risk when used as directed during pregnancy 9,10 .As scientists, medical experts and public health professionals, we are concerned about increasing rates of neurological, urogenital and reproductive disorders.…”

mentioning

confidence: 99%

Paracetamol use during pregnancy — a call for precautionary action

Bauer¹,

Swan

Kriebel³

et al. 2021

Nat Rev Endocrinol

120

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Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.

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mentioning

confidence: 99%

Paracetamol use during pregnancy — a call for precautionary action

Bauer¹,

Swan

Kriebel³

et al. 2021

Nat Rev Endocrinol

120

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“…Acute liver failure is a fatal complication of acetaminophen toxicity. It is defined by the presence of hepatic encephalopathy, jaundice, and coagulopathy in individuals without any history of cirrhosis occurring for less than 26 weeks [11]. The main reasons behind fulminant hepatic failure and death following acetaminophen intoxication are delay in seeking medical attention, delay in recognition of poison or delay in institution of appropriate therapy, and the existence of preexisting comorbidities [3,4].…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen Intoxication with Fulminant Hepatic Failure Salvaged by Plasmapheresis

Karunathilake¹,

Ranasinghe²,

Azher³

et al. 2021

IJCCR

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Introduction Acetaminophen-induced liver injury is the most common cause of acute liver failure, where multiple ingestions or a delay in the presentation may lead to a poor prognosis. N-acetylcysteine (NAC) is the conventional antidote used to treat acute acetaminophen toxicity, and plasmapheresis can be used as an adjunct, though there are no systematic studies to prove its effectivity. Case Presentation An 18-year-old girl was admitted with reduced responsiveness for one day with a few episodes of diarrhea. On admission, she was febrile and had a GCS of 10/15, otherwise normal neurology. She had marked right hypochodrial tenderness, deep icterus, and a pulse of 120 beats per minute, with a blood pressure of 80/50 mmHg; fluid resuscitation with inotropic support was done. Initial investigations revealed severe metabolic acidosis, hemoglobin of 9.5 g/dL, white blood cell count 13,500/mm3, and platelet 119,000 per µL. The prothrombin time (PT) international normalized ratio (INR) was 4.7, and the activated partial thromboplastin time (APTT) was 38.6. The alanine aminotransferase (ALT) level was 8118 U/L, and aspartate aminotransferase (AST) was 3883 U/L with a total bilirubin of 107 µmol/L. The diagnosis of acute liver failure following acetaminophen intoxication was made and managed with intravenous NAC, pantoprazole cover, intravenous ceftriaxone, metronidazole, thiamine, and vitamin K. Fresh frozen plasma and platelets were given for severe coagulopathy. She was started with plasmapheresis at the intensive care unit (ICU), where she had a significant improvement, though she developed hospital-acquired pneumonia, which was successfully managed. Subsequently, her liver functions returned to the baseline, and she was discharged after a psychiatric assessment. Conclusion A high degree of suspicion needs to be adopted to diagnose acetaminophen-induced acute liver failure when a patient presents with hepatic encephalopathy, and plasmapheresis can be considered a life-saving measure adjunct to the NAC.

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“…Paracetamol has been widely used since 1950( 22 ). The increasing use of this drug has resulted in certain adverse events, including an increased mortality rate due to liver toxicity originating from excessive dose uptake ( 23 ).…”

Section: Discussionmentioning

confidence: 99%