![]() Both reports by De Martin et al and Gauci et al concluded that a more patient-oriented management is needed and systemic corticosteroid therapy could be eventually avoided. ![]() 35 No significant difference was observed due to the small number of patients. It is worth noting that resolution of ir-hepatitis was achieved in 4.7 weeks (median, range 2.0–20.6) for patients who did not receive any additional steroids (n=6, including one patient who was already under steroid treatment for cerebral metastasis) vs 8.6 weeks (median, range 4.3–55.1) in patients who received corticosteroids (n=4). 35 Hepatotoxicity recovered in all cases but in half of them no steroids were administered and no second-line immunosuppressive treatment was needed for any ir-hepatic AE. In parallel, Gauci et al presented 10 patients with melanoma that experienced ir-hepatitis during their PD-1 and/or CTLA-4 inhibition. 24 Without receiving any corticosteroid therapy, six of these patients (38%) experienced a spontaneous improvement in LFTs and no severe ir-hepatitis was observed after an immunotherapy rechallenge in two of them. First, De Martin et al noticed the benign course of acute liver injury (grade ≥3) induced by immunotherapy in 16 patients with cancer treated with anti-PD-1/PD-L1 and anti-CTLA-4 monoclonal antibodies, in monotherapy or in combination regimens. Interestingly, two recent reports challenge the necessity of corticosteroids in the management of ir-hepatitis. On receiving systemic corticosteroids, most patients with persistent grade 2 or worse ir-hepatitis will resolve their liver toxicity, with no long-term effects on their prognosis. In cases with more severe hepatotoxicity (grade ≥3), methylprednisolone should be immediately initiated at a dose 1–2 mg/kg/day or an equivalent and on resolution of hepatotoxicity to less than grade 2, a slow tapering should follow. 5 6 For instance, in patients with melanoma receiving monotherapy with pembrolizumab, immune-related (ir) hepatitis occurs in 0.8%, including grade 2, 3 or 4 events in 0.1%, 0.5% and 0.1% of cases, respectively, 7 8 while in those treated with the combination of nivolumab 1 mg/kg and ipilimumab 3 mg/kg, ir-hepatitis is listed as a common (≥1/100 to 1 week should be treated with 1 mg/kg/day prednisolone or equivalents, with at least 1 month tapering. 3 4 Its incidence, onset and severity vary widely, depending on the type of underlying malignancy as well as on the class, the dosage, the duration and mainly the way immunotherapy was administered (as a single agent or in combination with other ICPI or chemotherapy). 1 2 In contrast to bowel and endocrine ICPIs-induced toxicities, hepatotoxicity/hepatitis is a less common and far less well-studied adverse event (AE). Alongside the established clinical benefits, immune-checkpoint inhibitors (ICPIs) have also introduced into oncological practice some distinct immune-mediated toxicities which mimic autoimmune conditions and affect multiple organs, including the liver.
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