Nonacetaminophen Drug-Induced Acute Liver Failure

Thomas, Arul; Lewis, James H.

doi:10.1016/j.cld.2018.01.006

“…Drug induced liver injury (DILI) is the leading cause of ALF (more than 50% of overall cases) with the leading cause being acetaminophen/APAP (mainly from unintentional overdose); According to the latest registry from the US ALF Study Group (US ALF SG), non-APAP drug injury represents 11% of all cases with isoniazid presentingthe most common agent in a US registry, in addition to amoxicillin/clavulanate and nonsteroidal anti-inflammatory drugs [1,3,4].…”

Section: Discussionmentioning

confidence: 99%

“…Risk factors for DILI include older age > 55 year old (to note that some idiosyncratic drug have a specific age range), female sex, African American, pharmacological risk (including daily dosage, degree of lipophilicity andextent of hepatic metabolism), preexisting liver disease and Host Genetic Factors [1,4,5].…”

Section: Discussionmentioning

confidence: 99%

“…The most representative example of this type of liver damage is the acetaminophen (APAP) induced hepatotoxicity considered the most common cause of drug induced acute liver failure occurring in around 40% of patients in US [2,3]. To note that non-APAP drug injury represents 11% of all cases of DILI in the latest registry from the US ALF Study Group [4].…”

Section: Introductionmentioning

confidence: 99%

“…The hepatocellular type is the most common manifestation of idiosyncratic liver injury with a high mortality especially when coupled with jaundice forming the Hy's law. Common causes of drug-induced idiosyncratic acute hepatocellular injury are isoniazid, amoxicillin/clavulanate, nitrofurantoin, and NSAID [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Case Report of Acute Liver Failure Induced By Isotretinoin Medication

Akouch¹,

Bouhairie²,

Nasreddine³

2021

J Gast Hepa Rep

0

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Introduction: Drug induced liver injury or DILI is any injury to the liver by a medication, herb, or dietary supplement. Ranking as the first cause of acute liver failure in the USA and Europe, spectrum of clinical presentation may range from asymptomatic elevated liver function test to ALF. Approximately 20 new cases of DILI per 100,000 persons occur each year worldwide. Classified as intrinsic (with the most common cause being acetaminophen), and idiosyncratic adverse drug reaction (including mostly those related to antibiotics, NSAID drugs, and isoniazid). Isotretinoin is indicated to treat severe inflammatory acne that is refractory to antibiotics or topical agents; Although it has a high margin of safety, adverse effects include transaminasitis, like many retinoids, but unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver failure. We report a case of 31 year old lady on isotretinoin therapy for her acnea since 8 month with poor follow up, presenting with acute liver failure to our emergency department. Case Presentation: 31 year old lady , NKDFA, on isotretinoin for her acne, started 8 month ago at a dose 40mg daily, is brought by her family for decrease level of consciousness and increasing jaundice since around 5 days associated with mild abdominal disconfort. Intubated for GCS of 3, laboratory tests showed prolonged INR and elevated total bilirubin, mainly direct, with elevated transaminase levels, all work up for other etiologies turned negative, and patient was diagnosed with isotretinoin inducing acute liver failure. Discussion: Hepatotoxicity manifesting by liver test abnormalities, occur in up to 15% of patients on isotretinoin. These liver test abnormalities are usually asymptomatic and resolve spontaneously even without discontinuation of therapy in most cases. Severe liver injury due to isotretinoin is exceedingly rare: The acute liver failure was only been described with etretinate and acitretin and not with isotretinoin therapy. Risk factors for DILI include older age, female sex, African American, pharmacological risk (including daily dosage, degree of lipophilicity and extent of hepatic metabolism), preexisting liver disease and Host Genetic Factors. An important association was found between the dose of oral medication and hepatotoxicity in the United States and Sweden, in addition to a positive association between higher drug lipophilicity and DILI in condition to be coupled with high dose ingestion. Our patient meets the criteria for sex and for the pharmacological characteristic of isotretinoin (which is a highly lipophilic drug and was ingested at 40mg daily). DILI may cause cholestatic or hepatocellular liver injury or mixed on the basis of the R value, In addition, studies have showed that DILI in females is more often hepatocellular and may be associated with a more severe course, which can result in the need for liver transplant, or death and all that were compatible with our case. As the disorder is rare, there are no specific biomarkers for diagnosis of idiosyncratic DILI, and diagnosis is made by exclusion. Recent advances in the diagnosis of DILI include the recognition of the importance of the establishment of clinical networks to refine causality assessment estimated by RUCAM score and also the use of expert panels in the diagnosis of DILI [3]. The calculated RUCAM score for our case is equal to 8, indicating probable drug reaction. Concerning acute liver failure, the most widely accepted definition from the American Association for the Study of Liver Diseases (AASLD) is ‘’evidence of coagulation abnormality, usually an international normalized ratio above 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting liver disease and with an illness of less than 26 weeks’ duration’’. Based on all above, the presentation of our patient was typical for an acute liver failure induced by the drug isotretinoin. The only curative treatment of drug induced acute liver failure is liver transplantation. Conclusion: This is probably the first case reporting an acute liver failure induced by isotretinoin therapy. Strict monitoring of liver tests is highly recommended for patients receiving isotretinoin at regular intervals, with close observation and follow up, because, although rare, it may induce an acute liver failure with deleterious results. Future works must include a discovery of an early markers of DILI, for early detection and prevention in the high risk patients.

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“…The hepatocellular type is the most common manifestation of idiosyncratic liver injury with a high mortality especially when coupled with jaundice forming the Hy's law. Common causes of drug-induced idiosyncratic acute hepatocellular injury are isoniazid, amoxicillin/clavulanate, nitrofurantoin, and NSAID [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Case Report of Acute Liver Failure Induced By Isotretinoin Medication

Akouch¹,

Bouhairie²

2021

J Gast Hepa Rep

0

View full text Add to dashboard Cite

Introduction: Drug induced liver injury or DILI is any injury to the liver by a medication, herb, or dietary supplement. Ranking as the first cause of acute liver failure in the USA and Europe, spectrum of clinical presentation may range from asymptomatic elevated liver function test to ALF. Approximately 20 new cases of DILI per 100,000 persons occur each year worldwide. Classified as intrinsic (with the most common cause being acetaminophen), and idiosyncratic adverse drug reaction (including mostly those related to antibiotics, NSAID drugs, and isoniazid). Isotretinoin is indicated to treat severe inflammatory acne that is refractory to antibiotics or topical agents; Although it has a high margin of safety, adverse effects include transaminasitis, like many retinoids, but unlike acitretin and etretinate, isotretinoin has not been clearly implicated in cases of clinically apparent acute liver failure. We report a case of 31 year old lady on isotretinoin therapy for her acnea since 8 month with poor follow up, presenting with acute liver failure to our emergency department. Case Presentation: 31 year old lady , NKDFA, on isotretinoin for her acne, started 8 month ago at a dose 40mg daily, is brought by her family for decrease level of consciousness and increasing jaundice since around 5 days associated with mild abdominal disconfort. Intubated for GCS of 3, laboratory tests showed prolonged INR and elevated total bilirubin, mainly direct, with elevated transaminase levels, all work up for other etiologies turned negative, and patient was diagnosed with isotretinoin inducing acute liver failure. Discussion: Hepatotoxicity manifesting by liver test abnormalities, occur in up to 15% of patients on isotretinoin. These liver test abnormalities are usually asymptomatic and resolve spontaneously even without discontinuation of therapy in most cases. Severe liver injury due to isotretinoin is exceedingly rare: The acute liver failure was only been described with etretinate and acitretin and not with isotretinoin therapy. Risk factors for DILI include older age, female sex, African American, pharmacological risk (including daily dosage, degree of lipophilicity and extent of hepatic metabolism), preexisting liver disease and Host Genetic Factors. An important association was found between the dose of oral medication and hepatotoxicity in the United States and Sweden, in addition to a positive association between higher drug lipophilicity and DILI in condition to be coupled with high dose ingestion. Our patient meets the criteria for sex and for the pharmacological characteristic of isotretinoin (which is a highly lipophilic drug and was ingested at 40mg daily). DILI may cause cholestatic or hepatocellular liver injury or mixed on the basis of the R value, In addition, studies have showed that DILI in females is more often hepatocellular and may be associated with a more severe course, which can result in the need for liver transplant, or death and all that were compatible with our case. As the disorder is rare, there are no specific biomarkers for diagnosis of idiosyncratic DILI, and diagnosis is made by exclusion. Recent advances in the diagnosis of DILI include the recognition of the importance of the establishment of clinical networks to refine causality assessment estimated by RUCAM score and also the use of expert panels in the diagnosis of DILI [3]. The calculated RUCAM score for our case is equal to 8, indicating probable drug reaction. Concerning acute liver failure, the most widely accepted definition from the American Association for the Study of Liver Diseases (AASLD) is ‘’evidence of coagulation abnormality, usually an international normalized ratio above 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting liver disease and with an illness of less than 26 weeks’ duration’’. Based on all above, the presentation of our patient was typical for an acute liver failure induced by the drug isotretinoin. The only curative treatment of drug induced acute liver failure is liver transplantation. Conclusion: This is probably the first case reporting an acute liver failure induced by isotretinoin therapy. Strict monitoring of liver tests is highly recommended for patients receiving isotretinoin at regular intervals, with close observation and follow up, because, although rare, it may induce an acute liver failure with deleterious results. Future works must include a discovery of an early markers of DILI, for early detection and prevention in the high risk patients.

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