Immune checkpoint inhibitor-related hepatotoxicity: A review

Remash, Devika; Prince, David; McKenzie, Catriona; Strasser, Simone I.; Kao, Steven; Liu, Ken

doi:10.3748/wjg.v27.i32.5376

Cited by 69 publications

(57 citation statements)

References 86 publications

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“…Compared with rejection, hepatitis occurs at a later stage following immunotherapy initiation (median time, 22 d vs 5-6 wk)[ 5 , 55 ] and rarely leads to fatal outcomes. Beyond this, immune-related hepatitis is more common in patients treated with CTLA-4 inhibitors[ 56 ], whereas allograft rejection is more frequently recorded in liver transplant patients treated with PD-1 inhibitors[ 23 ]. When a definite diagnosis cannot be made by virtue of the information above, graft biopsy should be performed and evaluated based on the Banff schema[ 57 ].…”

Section: How To Balance Graft-protective Immunosuppression and Antitumor Immunopotentiationmentioning

confidence: 99%

Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons

Luo¹,

Teng²,

Fang³

et al. 2022

WJGO

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Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients. In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.

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Section: How To Balance Graft-protective Immunosuppression and Antitumor Immunopotentiationmentioning

confidence: 99%

Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons

Luo¹,

Teng²,

Fang³

et al. 2022

WJGO

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“…For example, acetaminophen is considered the most common cause of DILI in the Western world [ 36 , 37 ], while other medications such as ibuprofen [ 38 ] and antituberculosis drugs [ 30 , 39 , 40 ] may drive complications related to the development of DILI. Moreover, an important clinical problem has been reported due to the surge in immunotherapy-related hepatotoxicity caused by anticancer drugs and autoimmune suppressive drug therapies [ 41 – 43 ]. This of course is expected as immune-related side effects for enhancing the body's immune response to malignancies, which involves unwanted inflammation.…”

Section: An Overview On Drug-induced Liver Injurymentioning

confidence: 99%

Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Ntamo

Ziqubu

Chellan

et al. 2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a key pathological feature implicated in both acute and chronic liver diseases, including drug-induced liver injury (DILI). The latter describes hepatic injury arising as a direct toxic effect of administered drugs or their metabolites. Although still underreported, DILI remains a significant cause of liver failure, especially in developed nations. Currently, it is understood that mitochondrial-generated oxidative stress and abnormalities in phase I/II metabolism, leading to glutathione (GSH) suppression, drive the onset of DILI. N-Acetyl cysteine (NAC) has attracted a lot of interest as a therapeutic agent against DILI because of its strong antioxidant properties, especially in relation to enhancing endogenous GSH content to counteract oxidative stress. Thus, in addition to updating information on the pathophysiological mechanisms implicated in oxidative-induced hepatic injury, the current review critically discusses clinical evidence on the protective effects of NAC against DILI, including the reduction of patient mortality. Besides injury caused by paracetamol, NAC can also improve liver function in relation to other forms of liver injury such as those induced by excessive alcohol intake. The implicated therapeutic mechanisms of NAC extend from enhancing hepatic GSH levels to reducing biomarkers of paracetamol toxicity such as keratin-18 and circulating caspase-cleaved cytokeratin-18. However, there is still lack of evidence confirming the benefits of using NAC in combination with other therapies in patients with DILI.

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“…Of the 108 patients in the PAC group, cautious drug rechallenge was recommended by the clinical pharmacist in 10 cases. These decisions were evidence-based and in accordance with guideline recommendations for specific drugs (e.g., hepatotoxicity related to immune checkpoint inhibitors or antituberculosis drugs) ( Senousy et al, 2010 ; Remash et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of pharmacist active consultation on clinical outcomes and quality of medical care in drug-induced liver injury inpatients in general hospital wards: A retrospective cohort study

Dong

et al. 2022

Front. Pharmacol.

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The utility of pharmacist consultation for drug-induced liver injury (DILI) management has not been explored. This retrospective cohort study evaluated the impact of a pharmacist active consultation (PAC) service on the management and outcome in patients with DILI. Consecutive patients meeting clinical biochemical criteria for DILI were enrolled at a tertiary teaching hospital between 1 January 2020 and 30 April 2022. The Roussel Uclaf Causality Assessment Method was used to assess causality between drug use and liver injury for each suspected DILI patient. Included patients were grouped according to whether they received PAC, and a proportional hazard model with multivariate risk adjustment, inverse probability of treatment weighting (IPTW), and propensity score matching (PSM) was used to assess DILI recovery. In the PSM cohort, the quality of medical care was compared between PAC and no PAC groups. A total of 224 patients with DILI (108 who received PAC and 116 who did not) were included in the analysis. Of these patients, 11 (10%) were classified as highly probable, 58 (54%) as probable, and 39 (36%) as possible DILI in the PAC group, while six patients (5%) were classified as highly probable, 53 (46%) as probable, and 57 (49%) as possible DILI in the no PAC group (p = 0.089). During patient recovery, PAC was associated with a ∼10% increase in the cumulative 180-day recovery rate. The PAC group had a crude hazard ratio (HR) of 1.73 [95% confidence interval (CI): 1.23–2.43, p = 0.001] for DILI 180-day recovery, which remained stable after multivariate risk adjustment (HR = 1.74, 95% CI: 1.21–2.49, p = 0.003), IPTW (HR = 1.72, 95% CI: 1.19–2.47, p = 0.003), and PSM (HR = 1.49, 95% CI: 1.01–2.23, p = 0.046). In the PSM cohort, PAC was more likely to identify suspect drugs (90% vs. 60%, p < 0.001) and lead to timely withdrawal of the medication (89% vs. 57%, p < 0.001). Thus, PAC is associated with a better quality of medical care for patients with DILI and can improve patient outcomes.

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Immune checkpoint inhibitor-related hepatotoxicity: A review

Cited by 69 publications

References 86 publications

Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons

Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons

Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Impact of pharmacist active consultation on clinical outcomes and quality of medical care in drug-induced liver injury inpatients in general hospital wards: A retrospective cohort study

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