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

Abstract

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).

Faecal cytokine profiling as a marker of intestinal inflammation in acutely decompensated cirrhosis

“…There may be a need to therapeutically rebalance these dichotomously acting cytokines in the gut mucosa, and equally, targeting these cytokines in the systemic circulation may not be the way forward. 69 For example, patients with alcoholic hepatitis and underlying cirrhosis who were treated with systemic TNFa inhibitors experienced a higher rate of adverse events, including serious infections and overall mortality. 70 Faecal IL-8 and IL-10 were not found to be elevated in the AD group compared with the SC or HC group in contrast to what was observed in matched plasma samples.…”

The Impact of Biologics for the Management of Inflammatory Bowel Disease on Liver Enzymes

“…12 Overall, hepatocellular injury with autoantibodies is thought to account for up to 92% of DILIs associated with anti-TNF-α. 17 The autoimmune phenotype is associated with a longer median latency and a greater peak ALT compared with cases without autoimmune features. 12 This form of liver disease may require drug discontinuation and steroid initiation.…”

“…In a review of 34 cases of DILI due to TNF‐α inhibitor therapy, 67% tested positive for antinuclear and/or anti‐smooth muscle antibodies, and of those with autoimmune features who underwent liver biopsy, 88% had clear features of autoimmune hepatitis on biopsy 12 . Overall, hepatocellular injury with autoantibodies is thought to account for up to 92% of DILIs associated with anti‐TNF‐α 17 . The autoimmune phenotype is associated with a longer median latency and a greater peak ALT compared with cases without autoimmune features 12 .…”

“…This form of liver disease may require drug discontinuation and steroid initiation. In a study of patients with autoimmune liver injury caused by infliximab, 64% to 80% of patients did not improve with drug withdrawal alone and required steroids 17 …”

Drug‐Induced Liver Injury by Checkpoint Inhibitors: Benefit of a Causality Assessment Tool

“…As recently reported in this journal, hepatoxicity during therapy with immune checkpoint inhibitors (ICIs) is a diagnostic challenge with major clinical implications. (1) Other causes of liver injury, such as increasing hepatic tumor burden or drug-induced liver injury (DILI) caused by comedication, need to be excluded. To address this issue, we used an in vitro test based on blood monocyte-derived hepatocytelike (MH) cells (2,3) to support causality assessment in 6 patients with acute liver injury after ICI.…”