Drug‐Induced Liver Injury in GI Practice

Sandhu, Naemat; Navarro, Victor J.

doi:10.1002/hep4.1503

“… NOTE. Statistical significance was determined by unpaired Student t test or χ 2 test. All significant covariates were included in the multivariate model.…”

Section: Resultsmentioning

confidence: 99%

“…Continuous variables were displayed as mean ± standard deviation. Contingency tables were analyzed with χ 2 tests, and continuous variables were analyzed by unpaired, two-tailed t tests. The occurrence of ALF was modeled as the outcome variable in a Cox proportional hazard survival analysis that examined the risk associated with PPI while controlling for Charlson comorbidity index, APRI, BMI, and sex.…”

Section: Methodsmentioning

confidence: 99%

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Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury

Schneider

¹

,

Elfers

²

,

Ghallab

³

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Proton pump inhibitor or long-term antibiotics intake, which have been linked to intestinal dysbiosis, are associated with increased risk of acute liver failure in the 500,000 participants of the UK BioBank population-based cohort. In mice, APAP intoxication prompts intestinal dysbiosis, barrier impairment, and bacterial translocation. Dysbiotic microbiota of Nlrp6-/mice induces a Ly6C hi phenotype of hepatic monocyte-derived macrophages and amplifies acute liver injury, a phenotype that is transferable to WT mice by fecal microbiota transfer. BACKGROUND & AIMS: Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF. METHODS: To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK Bio-Bank population-based cohort. For functional studies, male Nlrp6-/mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF. RESULTS: Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6-/mice displayed exacerbated APAP-and LPS

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“…This also fit the timeline of weeks to months as opposed to the non-immune pattern which usually takes more than six weeks until onset. [ 7 ]…”

Section: Discussionmentioning

confidence: 99%

Nafcillin-Induced Hepatic Injury: A Case Report and Literature Review

Khatib

¹

,

Sabobeh

²

,

Bock

³

et al. 2021

Cureus

0

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Background: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Western world. While it requires a diagnosis of exclusion, it is exceedingly prevalent in patients taking multiple hepatotoxic agents, the foremost of which are antibiotics, followed by herbal and dietary supplements. Below we will discuss a case of nafcillin-induced liver injury suggested by a thorough work-up and rule-out of other hepatic and biliary pathologies. Case presentation: We report the case of a 66-year-old white male who presented with painless jaundice. Clinical, laboratory and radiographic features demonstrated a cholestatic pattern of liver injury without significant abnormalities in the biliary tract. All workup for viral hepatitis and autoimmune diseases with liver involvement was negative. Liver biopsy showed acute necro-inflammatory changes suggestive of drug-induced liver injury. The patient had received 18 days of IV nafcillin for blood culture positive methicillin-susceptible Staphylococcus aureus (MSSA) four weeks prior to his presentation. He showed clinical and laboratory improvement of his liver functions with supportive care only. Conclusion: Nafcillin is a safe and effective antibiotic for the treatment of methicillin-susceptible Staphylococcal infections. However, physicians and prescribing healthcare professionals should be aware of the rare, but serious side effects, especially one of drug-induced liver injury with emphasis on the need for early cessation of nafcillin if liver function abnormalities develop.

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“…1 Acetaminophen (APAP) poisoning represents the leading cause of ALF in Western countries and remains a condition with poor outcome and high mortality. 2,3 At therapeutic doses, APAP is safely used as an analgesic and antipyretic drug. However, intake of an overdose can lead to ALF.…”

mentioning

confidence: 99%

Intestinal dysbiosis amplifies acetaminophen induced acute liver injury

Elfers

¹

,

Schneider

²

,

Ghallab

³

et al. 2020

Zeitschrift Für Gastroenterologie

0

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Proton pump inhibitor or long-term antibiotics intake, which have been linked to intestinal dysbiosis, are associated with increased risk of acute liver failure in the 500,000 participants of the UK BioBank population-based cohort. In mice, APAP intoxication prompts intestinal dysbiosis, barrier impairment, and bacterial translocation. Dysbiotic microbiota of Nlrp6 -/mice induces a Ly6C hi phenotype of hepatic monocyte-derived macrophages and amplifies acute liver injury, a phenotype that is transferable to WT mice by fecal microbiota transfer.BACKGROUND & AIMS: Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF. METHODS:To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK Bio-Bank population-based cohort. For functional studies, male Nlrp6 -/mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF. RESULTS:Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6 -/mice displayed exacerbated APAP-and LPS-induced liver injury, which was linked to significantly reduced gut and liver tissue microbiota diversity and correlated with increased intestinal permeability at baseline. Fecal microbiota transfer (FMT) from Nlrp6 -/mice into wild-type (WT) mice augmented liver injury on APAP treatment in recipient WT mice, resembling the inflammatory phenotype of Nlrp6 -/mice. Specifically, FMT skewed monocyte polarization in WT mice toward a Ly6C hi inflammatory phenotype, suggesting a critical function of these cells as sensors of gut-derived signals orchestrating the inflammatory response. CONCLUSIONS:Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF.

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Drug‐Induced Liver Injury in GI Practice

Cited by 51 publications

References 106 publications

Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury

Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury

Nafcillin-Induced Hepatic Injury: A Case Report and Literature Review

Intestinal dysbiosis amplifies acetaminophen induced acute liver injury

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