Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review

Kok, Beverley; Lester, Erica L W; Lee, William M.; Hanje, A. James; Stravitz, R. Todd; Girgis, Safwat; Patel, Vaishali; Peck, Joshua R.; Esber, Christopher M.; Karvellas, Constantine

doi:10.1007/s10620-018-5023-6

Cited by 27 publications

(26 citation statements)

References 27 publications

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“…Previous studies have investigated the feasibility of TNF-α inhibitors in the management of liver injury. However, most of these trials failed to achieve a desired result [32][33][34][35] . The overinhibition of TNF-α using blocking agents might contribute to the failure of these trials.…”

Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

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Previous studies have shown that tumor necrosis factor (TNF)-α is a mediator of hepatotoxicity in liver injury. Moreover, TNF-α has also been reported to have a protective effect in liver regeneration, yet the function of TNF-α during liver injury remains controversial. Here, we report that the concentration of TNF-α determines its functions. High concentrations of TNF-α could aggravate LPS-induced liver injury. However, the TNF-α level was unchanged during APAP-induced liver injury, which exerted a protective effect. We expected that the concentration of TNF-α may affect its function. To test this hypothesis, TNF-α −/− rats or hepatocyte cells were treated with different concentrations of TNF-α. We found low TNF-α could reduce the levels of ALT and AST in the plasma of TNF-α −/− rats and promote the proliferation of hepatocyte cells. However, the levels of ALT and AST increased gradually with increasing TNF-α concentration after reaching the lowest value. Moreover, we showed that TNF-α affects the cell proliferation and cell death of hepatocytes by regulating Yap activity. Low TNF-α promoted Yap1 nuclear translocation, triggering the proliferation of hepatocytes. However, high TNF-α triggered the phosphorylation and inactivation of Yap1, preventing its nuclear import and consequently promoting cell death. Collectively, our findings provide novel evidence that the concentration of TNF-α is an important factor affecting its function in liver injury, which may provide a reference for the clinical treatment of liver injury.

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Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

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“…Of the nine cases of TNF‐α inhibitor‐induced ALF, 8 of the described patients were taking infliximab while the other patient was on adalimumab . The latency between initial drug exposure and ALF ranged from 3 days to 1 year.…”

Section: Tumor Necrosis Factor Alpha Inhibitorsmentioning

confidence: 99%

“…The pattern of liver injury was determined in seven cases, of which four were found to have hepatocellular injury, two with cholestatic injury, and one with mixed injury . In three of these nine cases, ANA went from negative before TNF‐α inhibitor initiation to positive during ALF . Liver biopsy was performed in seven cases, which showed clear histologic autoimmune features.…”

Section: Tumor Necrosis Factor Alpha Inhibitorsmentioning

confidence: 99%

“…Infliximab, a monoclonal mouse–human chimeric antibody to TNF‐α is currently used for IBD and RA. Although the overall risk of DILI with TNF‐α inhibitors is low, there have been a disproportionate amount of liver injury reports related to infliximab compared to other drugs of the same class . When AST and ALT elevations develop, this usually occurs after two to five infusions and can be transient and asymptomatic but do not always improve after cessation of infliximab .…”

Section: Tumor Necrosis Factor Alpha Inhibitorsmentioning

confidence: 99%

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Biologic and Checkpoint Inhibitor‐Induced Liver Injury: A Systematic Literature Review

2020

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Biologics are among the most commonly prescribed medications for several chronic inflammatory diseases. Tumor necrosis factor alpha inhibitors, more so than other agents, have been observed to cause drug-induced liver injury. Additionally, because the approval and popularity of checkpoint inhibitors have grown, similar patterns of liver injury have been documented, with a majority of cases describing immune-mediated hepatitis. Although the exact mechanism of injury is unknown, various host and medication characteristics play a role in the outcome of the molecular cascade invoked by biologics. Prognosis is usually favorable with cessation of the offending agent, but cases of acute liver failure requiring liver transplantation have also been observed. Therefore, algorithms have been created to assist clinicians in treating drug-induced autoimmune hepatitis, mostly with corticosteroids. Additionally, case reports have documented successfully rechallenging patients with a different biologic without recurrence of liver injury, but data are limited. Further investigation is warranted regarding the potential for cross-reactivity and mechanism of injury to develop guidelines to aid clinicians in further management of these patients. (Hepatology Communications 2020;4:172-184).

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“…4–7 Anti-TNF alpha-induced liver failure has been reported but with different characteristics when compared with anti-TNF alpha DILI. 8 We describe a case of infliximab-induced VBDS leading to liver failure and an orthotopic liver transplant.…”

Section: Introductionmentioning

confidence: 99%

Now You See It, Now You Do Not: A Case of Infliximab-Induced Vanishing Bile Duct Syndrome

et al. 2019

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Infliximab is a commonly used antitumor necrosis factor alpha agent, especially in patients with inflammatory bowel disease. It has been associated with drug-induced liver injury including immunologic reactions, with rare cases of acute liver failure. We describe a patient with chronic cholestasis and loss of intrahepatic bile ducts after therapy with infliximab for refractory ulcerative colitis consistent with a diagnosis of vanishing bile duct syndrome. About 3 months after the initial infusion, the patient developed subfulminant liver failure and required liver transplantation.

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Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review

Cited by 27 publications

References 27 publications

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

Biologic and Checkpoint Inhibitor‐Induced Liver Injury: A Systematic Literature Review

Now You See It, Now You Do Not: A Case of Infliximab-Induced Vanishing Bile Duct Syndrome

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