Vanishing bile duct syndrome after drug-induced liver injury

Wasuwanich, Paul; Choudry, Hassan; So, Joshua; Lowry, Sarah; Karnsakul, Wikrom

doi:10.1016/j.clinre.2022.102015

Cited by 8 publications

(5 citation statements)

References 59 publications

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“…This result was compatible with two recent studies of VBDS associated with DILI. 7 , 22 Hyperbilirubinemia has also been identified as an independent risk factor for poor prognosis in PBC. 14 This phenomenon was also in accordance with the histological presence of hepatocellular cholestasis as an independent predictor of the survival of VBDS patients, suggesting that cholestasis is a hallmark of decompensated bile drainage.…”

Section: Discussionmentioning

confidence: 99%

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome

Lv¹,

Yu²,

Han³

et al. 2023

J Clin Transl Hepatol

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Section: Discussionmentioning

confidence: 99%

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome

Lv¹,

Yu²,

Han³

et al. 2023

J Clin Transl Hepatol

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“…Clinical manifestations of DILI can be life-threatening and typically associated with one or more of the clinical findings: acute liver failure with fulminant hepatitis and loss of liver function occurring in individuals with or without pre-existing liver disease; chronic liver injury with hepatic dysfunction leading to end stage liver disease; hepatic decompensation in patients with underlying cirrhosis; vanishing bile duct syndrome – a rare complication of DILI characterized by sever bile duct destruction and loss in the interlobular and portal areas. 12,38 Clinical signs and symptoms are poorly correlated between animals and humans and as such animal models predict only ~50% of human DILI events. The ambiguous symptoms, inconsistent injury timelines and potentially severe outcome of DILI have made regulatory authorities cautious and sporadic elevations of plasma liver enzymes and bilirubin during clinical studies pose a significant challenge to the marketing approval of new therapeutic agents.…”

Section: Dili: An Overview and Model Systems To Study Dilimentioning

confidence: 99%

Translational Relevance of Rodent Models to Predict Human Liver Disease

Mahapatra,

Maronpot

2023

Toxicol Pathol

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Animals models are essential to understand the complex pathobiology of human diseases. George Box’s aphorism based on statistics “All models are wrong, but some are useful” certainly applies to animal models of disease. In this session, the translational relevance of various animal models applicable to human liver disease was explored starting with a historic overview of the rodent cancer bioassay with emphasis on hepatocarcinogenesis from early work at the National Cancer Institute, refinement by the National Toxicology Program and contemporary efforts to identify potential mechanisms and their relevance to human cancer risk. Subsequently, recently elucidated understanding of the molecular drivers and signaling mechanisms of liver pathophysiology and liver cancer, including factors associated with liver regeneration, metabolic hepatocellular zonation, and the role of macrophages and their crosstalk with stellate cells in understanding human liver disease was discussed. Next, our contemporary understanding of the role of nuclear receptors in hepatic homeostasis and drug response highlighting nuclear receptor activation and crosstalk in modulating biological responses associated with liver damage and neoplastic response were discussed. Finally, an overview and translational relevance of different drug-induced liver injury (DILI) rodent model systems focused on pathology and mechanisms with commentary on current relevant Food and Drug Administration (FDA) perspective were summarized with closing remarks.

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“…TMP-SMX hepatotoxicity often causes cholestatic damage, this type of phenotype accounting for approximately 60% in some series [53]. In comparison to other drugs, TMP-SMX has a not negligible proportion of severe events in terms of deaths or liver transplantation [48].…”

Section: Tmp-smxmentioning

confidence: 99%

“…In comparison to other drugs, TMP-SMX has a not negligible proportion of severe events in terms of deaths or liver transplantation [48]. The hepatotoxicity is attributed to the sulfonamide component [53]. In a recent analysis of vanishing bile duct syndrome cases reported in the literature, TMP-SMX represented 19% of total cases [54].…”

Section: Tmp-smxmentioning

confidence: 99%

Drug-induced cholestasis: causative agents and challenges in diagnosis and management

Pinazo-Bandera,

Toro-Ortiz,

Andrade

et al. 2023

Explor Dig Dis

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Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominantly hepatocellular, a non-negligible percentage of patients who present with cholestatic damage. Mixed damage is typically lumped together with cholestatic damage in the literature. Drug-induced cholestasis is often caused by the use of some non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (i.e., amoxicillin-clavulanic acid), statins, and anabolic agents, among others. Drug-associated cholestasis tends to have a more chronic course and mostly affects older population. There is also a genetic predisposition to toxic cholestasis caused by some drugs (amoxicillin-clavulanic acid, statins, etc.). Recently, anatomical alterations of the biliary tract induced by drugs (especially immunotherapy drugs) have been described. Bile duct injury is one of the histopathological findings that have prognostic significance in DILI. A correct differential diagnosis with other causes of cholestasis is mandatory to reach an accurate diagnosis. Ursodexycholic acid, corticosteroids, and replacement therapies have been used as a therapeutic arsenal, although more evidence is needed to establish them as a routine therapeutic management in clinical practice. The breakthrough and validation of biomarkers of cholestasis and bile duct injury is an urgent need for drug development and post-marketing phase.

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Vanishing bile duct syndrome after drug-induced liver injury

Cited by 8 publications

References 59 publications

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome

Translational Relevance of Rodent Models to Predict Human Liver Disease

Drug-induced cholestasis: causative agents and challenges in diagnosis and management

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