AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury

Fontana, Robert J.; Liou, Iris; Reuben, Adrian; Suzuki, Ayako; Fiel, Isabel; Lee, William M.; Navarro, Victor J.

doi:10.1002/hep.32689

Cited by 76 publications

(140 citation statements)

References 217 publications

(543 reference statements)

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“…Indirect hepatotoxicity can manifest as fatty liver, acute hepatitis, or immune-mediated injury [ 13 ]. Recently released practice guidance by the American Association for the Study of Liver Disease (AASLD) suggests that liver biopsy may not be needed for mild or self-remitting cases, though it can be useful in those with prolonged disease or uncertain diagnosis [ 14 ]. Histological eosinophilia and granulomas are associated with lower mortality, whereas hepatic necrosis, fibrosis, and portal venopathy are some findings associated with higher rates of liver failure potentially requiring transplantation [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

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Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature

Mohamed¹,

Jahagirdar²,

Fatima³

et al. 2023

Cureus

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Drug-induced liver injury (DILI) is one of the leading causes of death from acute liver failure (ALF) in the United States, accounting for approximately 13% of ALF cases in the United States. Selective androgen receptor modulators (SARMs) were first developed to increase muscle mass while avoiding the side effects of conventional androgenic steroids. Although not Food and Drug Administration (FDA) approved, they are widely available online and are consumed to enhance athletic performance. We report a 22-year-old, previously healthy male, who presented with a two-week history of worsening jaundice, nausea, fatigue, pruritus, dark urine, and light stools. He reported taking the SARM, RAD-140, for 16 weeks. Examination showed scleral icterus. The liver panel showed alkaline phosphatase (ALP) 5.3 µkat/L, alanine transaminase (ALT) 1.66 µkat/L, aspartate transaminase (AST) 1.18 µkat/L, direct bilirubin 294 µmol/L, total bilirubin 427.5 µmol/L, and international normalized ratio (INR) 0.9. Viral hepatitis and autoimmune panel were unremarkable. Alpha-1 antitrypsin and ceruloplasmin levels were within normal limits. Bile sludge was seen on ultrasound. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed segmental narrowing of the intrahepatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. Liver biopsy showed mixed portal hepatitis, cholestasis, and biliary reactive changes with ceroid-loaded macrophages; a picture consistent with DILI. The patient was treated supportively and discharged with scheduled hepatology follow-up. At the one-month follow-up, his total bilirubin had fallen from a peak of 530 mol/L to 188 mol/L. The diagnosis of DILI can be made based on the timing of exposure and the exclusion of other etiologies. Liver enzymes normalized three to 12 months after product discontinuation. We hope this report will remind primary care physicians of the potential hepatotoxic side effects of muscle-building compounds and encourage them to report suspected DILI to the FDA using the MedWatch system.

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Section: Discussionmentioning

confidence: 99%

“…General supportive therapy with antipyretics, antiemetics, analgesics, and hydration remains the mainstay of treatment [ 14 ]. A prospective longitudinal study of 1257 subjects found that 10% of patients required liver transplantation, 17% had chronic liver injury, while the remainder recovered without any long-term sequelae [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature

Mohamed¹,

Jahagirdar²,

Fatima³

et al. 2023

Cureus

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“…The use of corticosteroids in patients with DILI has significantly reduced recovery time (27)(28)(29). Considering clinical practice guidelines of the American Association for the Study of Liver Disease and the European Association for the Study of Liver Disease for DILI, steroids can be considered as a treatment option for DILI or autoimmune hepatitis-like DILI caused by immune checkpoint inhibitors (1,2). One reason for the good response rate to corticosteroids in this study may be that 66.0% of patients had anti-nuclear antibody positivity, which can be interpreted as an autoimmune feature.…”

Section: Discussionmentioning

confidence: 99%

“…Drug-induced liver injury (DILI) is defined as liver damage caused by prescribed or over-the-counter drugs, herbs, health food, dietary supplements, folk remedies, or other causes resulting in abnormal liver tests or liver dysfunction with the reasonable exclusion of other etiologies (1)(2)(3)(4). DILI is a major cause of acute liver failure in the US (5).…”

Section: Introductionmentioning

confidence: 99%

Intrahepatic infiltration of activated CD8+ T cells and mononuclear phagocyte is associated with idiosyncratic drug-induced liver injury

et al. 2023

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BackgroundIdiosyncratic drug-induced liver injury (DILI) is caused by the interplay among drugs, their metabolites, and the host immune response. The characterization of infiltrated immune cells in the liver may improve the understanding of the pathogenesis of idiosyncratic DILI. This study investigated the phenotypes and clinical implications of liver-infiltrating immune cells in idiosyncratic DILI.MethodsFrom January 2017 to June 2021, 53 patients with idiosyncratic DILI who underwent liver biopsy were prospectively enrolled in this study. Immunohistochemical staining and flow cytometry analyses were performed on the biopsy specimens. Serum levels of CXC chemokine ligand 10 (CXCL10) and soluble CD163 were measured. A multivariate cox proportional hazards model was used to evaluate predictors of DILI resolution within 30 days.ResultsThe numbers of intrahepatic T cells and mononuclear phagocytes were positively correlated with serum levels of total bilirubin, alanine aminotransferase (ALT), and the model of end-stage liver disease score. The frequency of activated CD8+ T cells among liver-infiltrating CD8+ T cells in DILI livers was higher than that in healthy livers. Notably, the percentages of activated intrahepatic CD8+ T cells and mononuclear phagocytes in DILI livers showed a positive correlation with ALT. Additionally, serum CXCL10 level was positively correlated with intrahepatic T cell infiltration and ALT, and soluble CD163 level was positively correlated with intrahepatic mononuclear phagocyte infiltration and ALT. Thirty-six patients (70.6%) were treated with steroids. In multivariate analysis, total bilirubin and steroid use independently influenced DILI resolution within 30 days.ConclusionsActivated CD8+ T cells and mononuclear phagocyte are associated with liver injury caused by drugs. Therefore, we suggest that steroids are a potential treatment option for idiosyncratic DILI.

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“…The survival group showed transient mild liver injury, while the death group showed a continuous aggravation trend, mainly reflected in the progressive increase of AST, ALT and TB. ALT is an important index for reflecting acute liver injury (26). As a risk factor for the prognosis of DQ poisoning, its irreversible change was helpful to judge the severity and prognosis of patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of A Novel Signature for Predicting the Prognosis of Patients with Diquat Poisoning

Wang¹

2022

Preprint

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Diquat (DQ), an effective herbicide, has begun to threaten human health with the surge in the number of poisonings every year. Here, we present a powerful signature to improve the prognostic discrimination for patients with DQ poisoning. In this study, a total of 26 patients with acute DQ poisoning were enrolled. The median survival time in the death group was 43 hours. Undoubtedly, plasma concentration (PC), the blood cells (WBC), neutrophils (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and serum creatinine (Scr) in the death group were significantly higher and negatively correlated with survival time. And COX regression analysis suggested that PC, WBC, NE, ALT and Scr were the risk factors for poisoning death of DQ poisoning. Furthermore, risk factors were further developed as a robust signature (PC&Scr) to predict the prognosis of DQ poisoning. Survival analysis as well as time-dependent ROC analysis showed powerful predictive ability of prognostic signature in patients with DQ poisoning. A nomogram containing risk factors and signature could accurately predict the 2-day survival probability of individual DQ poisoning. The study shows that this signature with a powerful ability to predict DQ poisoning outcomes deserves popularizing in clinical practice.

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AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury

Cited by 76 publications

References 217 publications

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature

Intrahepatic infiltration of activated CD8+ T cells and mononuclear phagocyte is associated with idiosyncratic drug-induced liver injury

Identification of A Novel Signature for Predicting the Prognosis of Patients with Diquat Poisoning

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