Beverley Kok1, Erica L W Lester2, William M Lee3, A James Hanje4, R Todd Stravitz5, Safwat Girgis6, Vaishali Patel5, Joshua R Peck4, Christopher Esber4, Constantine J Karvellas7,8. 1. Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler-Ledcor Building, Edmonton, AB, T6G-2X8, Canada. 2. Department of Surgery, University of Alberta, Edmonton, Canada. 3. Division of Gastroenterology, University of Texas Southwestern, Dallas, USA. 4. Division of Gastroenterology, Ohio State University, Columbus, USA. 5. Division of Gastroenterology, Virginia Commonwealth University, Richmond, USA. 6. Department of Pathology, University of Alberta, Edmonton, Canada. 7. Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler-Ledcor Building, Edmonton, AB, T6G-2X8, Canada. dean.karvellas@ualberta.ca. 8. Department of Critical Care Medicine, University of Alberta, Edmonton, Canada. dean.karvellas@ualberta.ca.
Abstract
BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.
BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.
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