A Multicenter Study Into Causes of Severe Acute Liver Injury

Breu, Anthony C.; Patwardhan, Vilas; Nayor, Jennifer; Ringwala, Jalpan; DeVore, Zachary; Ganatra, Rahul B.; Hathorn, Kelly; Horton, Laura; Iriana, Sentia; Tapper, Elliot B.

doi:10.1016/j.cgh.2018.08.016

Cited by 29 publications

(18 citation statements)

References 4 publications

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“…The most common cause of ALT greater than 1000 IU/L was ischemic hepatitis, which was associated with a high mortality. This is consistent with previous studies in other regions of the world, where ischemic hepatitis accounts for 15–74% of patients with marked elevations of aminotransferases . However, varying concentrations were used to indicate aminotransferase derangement, and the relative frequency of ischemic hepatitis appears to increase with greater ALT and AST elevation .…”

Section: Discussionsupporting

confidence: 90%

“…This is consistent with previous studies in other regions of the world, where ischemic hepatitis accounts for 15-74% of patients with marked elevations of aminotransferases. [8][9][10][11][16][17][18] However, varying concentrations were used to indicate aminotransferase derangement, and the relative frequency of ischemic hepatitis appears to increase with greater ALT and AST elevation. 7 Drugs and toxins were found to be the second most common cause of marked ALT derangement in our study, which is consistent with a previous study in Ireland.…”

Section: Discussionmentioning

confidence: 99%

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Epidemiology and outcomes of marked elevations of alanine aminotransferase >1000 IU/L in an Australian cohort

et al. 2019

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Background and Aim Marked elevations of alanine aminotransferase (ALT) are caused by a limited number of underlying pathologies, including hepatic ischemia, drugs/toxins, viral hepatitis, and—rarely—autoimmune hepatitis. The aim of this study was to determine the relative incidence of pathologies resulting in ALT greater than 1000 IU/L and factors predicting clinical outcomes in an Australian cohort. Methods A retrospective cohort study of all adult patients with ALT levels greater than 1000 IU/L between January 2013 and December 2015 was conducted at a large teaching hospital network in Australia. Multivariable logistic regression analysis was used to determine predictors of etiology and mortality. Results There were 287 patients identified with ALT levels greater than 1000 IU/L. The most common causes were ischemia (44%), drugs/toxins (19%), biliary obstruction (16%), and viral hepatitis (7%). Independent predictors of a diagnosis of ischemic hepatitis included (adjusted odds ratio; 95% confidence interval): hypotension (29.2; 8.2–104.7), chronic obstructive pulmonary disease (COPD) (20.2; 2.8–145.3), coronary artery disease (12.9; 1.7–98.9), congestive cardiac failure (7.8; 1.2–49.2), diabetes mellitus (7.4; 1.6–33.9), metabolic acidosis (6.2; 2.0–19.4), gamma‐glutamyltransferase < 135 IU/L (5.1; 1.5–17.6), and albumin <34 g/L (3.4; 1.1–11.0). Independent risk factors for all‐cause 28‐day mortality included: septic shock (14.7; 4.3–50.7), metabolic acidosis (7.3; 2.5–21.3), history of COPD (5.4; 1.6–17.8), cardiogenic shock (4.3; 1.6–11.7), prothrombin time ≥ 20 s (3.7; 1.5–9.2), and age ≥ 65 years (3.0; 1.3–7.2). Conclusions Ischemic hepatitis was the most common cause of ALT levels greater than 1000 IU/L and was associated with high mortality.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Epidemiology and outcomes of marked elevations of alanine aminotransferase >1000 IU/L in an Australian cohort

et al. 2019

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“…On binding to its receptor on the plasma membranes, caveolae, (a complex of caveolin and its receptor proteins) are invaginated via clathrin-coated pits and vesicles. Following endocytosis, LDL receptor recycles to the coated pits while the cholesterol moiety is transported to lysosomes, where apo-B protein is enzymatically degraded to amino acids while the remaining component-cholesterol esters, are cleaved to cholesterol and free fatty acids [54]. The cholesterol so formed as a result of the enzymatic cleavage is either incorporated into the cell membrane or re-esterified and stored as lipid droplets [54].…”

Section: And Rifampicin Toxicitymentioning

confidence: 99%

Ameliorative potentials of Persea americana leaf extract on toxicants - induced oxidative assault in multiple organs of wistar albino rat

2021

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Background Persea americana (PA) is a popular medicinal plant in folkloric medicines. The present study therefore investigates the ameliorative potentials of its leaves extract on carbon tetrachloride and rifampicin-induced toxicity in the liver, kidney and heart of albino rat. This was aimed at assessing the potentials of the plant in the management of liver, kidney and heart diseases. Methodology Forty (40) rats were randomly divided into eight (8) groups of five animals each. Groups I and II were administered with only distilled water and carbon tetrachloride (CCl4) respectively. Groups III and IV animals received 3.0 ml/kg bw of CCl4 and were treated with the extract at 50 mg/kg bw and 100 mg/kg respectively, while group V received 100 mg/kg bw. of silymarin orally for 14 days. Groups VI animals were administered with rifampicin (250 mg/kg bw.) only, while groups VII and VIII animals received rifampicin and were treated with 50 mg and 100 mg/kg bw of the extract respectively. Activities of creatine kinase, aspartate amino transferase, alanine amino transferase, alkaline phosphatase, superoxide dismutase, catalase as well as levels of urea, uric acid, bilirubin and malonidialdehyde (MDA) were assayed. Lipid profiles and histopathological examination of liver and kidney slices were also performed. Result Treatment with P. americana significantly (p < 0.05) restored all deranged biochemical parameters (creatine kinase, aspartate amino transferase, alanine amino transferase, alkaline phosphatase, urea, uric acid, bilirubin, MDA, lipid profile as well as superoxide dismutase and catalase) in a dose-dependent manner. Normal hepatic and renal histoarchitecture were also restored following treatment with P. americana. Conclusion Amelioration of distorted cardiac, hepatic and renal histoarchitecture as well as restoration of lipid profile, biomarkers of liver and kidney injury and antioxidant enzymes (catalase and superoxide dismutase) affirm the potential usefulness of P. americana in the management of liver, kidney and heart diseases.

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“…Nevertheless, there are clear uses of biomarkers in DILI that are not as limited by prevalence. Estimates of the prevalence of all-cause DILI among patients presenting with evidence of acute liver injury range from 10% to 15% (Galvin et al, 2015;Björnsson et al, 2016;Breu et al, 2018). Thus, it is theoretically possible to develop a useful biomarker to diagnose DILI in general, though it will have to have high sensitivity and specificity (>90%) in order to achieve moderately high PPV and NPV (70-80%).…”

Section: The Problem Of Low Prevalence In Dili Biomarker Developmentmentioning

confidence: 99%

“…As mentioned above and described in detail elsewhere (Senior, 2014;McGill and Jaeschke, 2018), it would be extremely difficult to develop biomarkers of DILI for most individual drugs. However, APAP overdose accounts for approximately half or more of all DILI cases in many Western countries (Lee, 2008;Galvin et al, 2015;Breu et al, 2018). As a result, it is possible to develop diagnostics specifically for APAP overdose, like APAP-CYS.…”

Section: Biomarkers Of Dili Diagnosismentioning

confidence: 99%

Biomarkers of drug-induced liver injury

McGill

Jaeschke

2019

Advances in Pharmacology

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Drug-induced liver injury (DILI) is a major clinical and regulatory challenge. As a result, interest in DILI biomarkers is growing. So far, considerable progress has been made in identification of biomarkers for diagnosis (acetaminophen-cysteine protein adducts), prediction (genetic biomarkers), and prognosis (microRNA-122, high mobility group box 1 protein, keratin-18, glutamate dehydrogenase, mitochondrial DNA). Many of those biomarkers also provide mechanistic insight. The purpose of this chapter is to review major advances in DILI biomarker research over the last decade, and to highlight some of the challenges involved in implementation. Although much work has been done, more liver-specific biomarkers, more DILI-specific biomarkers, and better prognostic biomarkers for survival, are all still needed. Furthermore, more work is needed to define reference intervals and medical decision limits.

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A Multicenter Study Into Causes of Severe Acute Liver Injury

Cited by 29 publications

References 4 publications

Epidemiology and outcomes of marked elevations of alanine aminotransferase >1000 IU/L in an Australian cohort

Epidemiology and outcomes of marked elevations of alanine aminotransferase >1000 IU/L in an Australian cohort

Ameliorative potentials of Persea americana leaf extract on toxicants - induced oxidative assault in multiple organs of wistar albino rat

Biomarkers of drug-induced liver injury

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