Immune-related hepatitis with immunotherapy: Are corticosteroids always needed?

Gauci, Marie-Léa; Baroudjian, Barouyr; Zéboulon, C.; Pagès, Cécile; Poté, Nicolas; Roux, Olivier; Bouattour, Mohamed; Lebbe, Célèste

doi:10.1016/j.jhep.2018.03.034

Cited by 81 publications

(82 citation statements)

References 9 publications

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“…190 The need to start steroid therapy in this type of population has also been questioned by other groups. 192 The recommendations on the management approach to suspected ICI-induced liver injury, which rely on clinical experience and the management of AIH, are summarized in Table 5. These recommendations are similar to protocol procedures used in registrational trials and have been incorporated into CPGs for several organisations including the American Society of Clinical Oncology and the European Society of Medical Oncology.…”

Section: Recommendationsmentioning

confidence: 99%

EASL Clinical Practice Guidelines: Drug-induced liver injury

Andrade¹,

Aithal²,

Bjõrnsson³

et al. 2019

Journal of Hepatology

752

394

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Idiosyncratic (unpredictable) drug-induced liver injury is one of the most challenging liver disorders faced by hepatologists, because of the myriad of drugs used in clinical practice, available herbs and dietary supplements with hepatotoxic potential, the ability of the condition to present with a variety of clinical and pathological phenotypes and the current absence of specific biomarkers. This makes the diagnosis of drug-induced liver injury an uncertain process, requiring a high degree of awareness of the condition and the careful exclusion of alternative aetiologies of liver disease. Idiosyncratic hepatotoxicity can be severe, leading to a particularly serious variety of acute liver failure for which no effective therapy has yet been developed. These Clinical Practice Guidelines summarize the available evidence on risk factors, diagnosis, management and risk minimization strategies for drug-induced liver jury.

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Section: Recommendationsmentioning

confidence: 99%

EASL Clinical Practice Guidelines: Drug-induced liver injury

Andrade¹,

Aithal²,

Bjõrnsson³

et al. 2019

Journal of Hepatology

752

394

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“…Thus, Child‐Pugh and MELD scores should always be computed and changes in their values must be taken in due account. Liver toxicity occurs variably after the first infusion according to the drug employed, with a median 9.9 weeks for anti‐CTLA4, 14.1 weeks for anti‐PD‐1 and 2.9 weeks for the combination . Liver biopsy is the gold standard to confirm the diagnosis of liver‐involving irAEs and to assess the degree of liver damage but it is optional in patients with a CTCAE grade 2 hepatitis and is recommended only in patients with CTCAE grade 3‐4 hepatitis .…”

Section: Liver Side Effects During Therapy With Checkpoint Inhibitorsmentioning

confidence: 99%

“…The peculiar mechanism of action of immune checkpoint inhibitors consists in the blockade of inhibitory molecules responsible for maintaining the immunological homeostasis, avoiding untoward rec- Liver toxicity occurs variably after the first infusion according to the drug employed, with a median 9.9 weeks for anti-CTLA4, 14.1 weeks for anti-PD-1 and 2.9 weeks for the combination. 66 Liver biopsy is the gold standard to confirm the diagnosis of liverinvolving irAEs and to assess the degree of liver damage but it is optional in patients with a CTCAE grade 2 hepatitis and is recommended only in patients with CTCAE grade 3-4 hepatitis. 67 Toxicity related to anti-CTLA-4 mAb is associated with the presence of granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis whereas anti-PD-1/PD-L1 toxicity is characterised by lobular hepatitis without granuloma.…”

Section: Liver S Ide Effec Ts During Ther Apy With Check P Oint Inhmentioning

confidence: 99%

Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

Lombardi

Mondelli

2019

Aliment Pharmacol Ther

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Summary Background Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune‐related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved. Aims To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver Methods We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years. Results The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune‐related adverse events involving the liver are a growing concern related to their widespread use. Conclusions Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non‐malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions.

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“…weeks in those receiving no steroids compared to 8.6 weeks in those who received 777 corticosteroids 168 . A suggested algorithm to detect and manage hepatotoxicity due to ICIs in 778 patients with cancer who are considered for ICI therapy in accordance with current practice is 779 shown in FIG.…”

mentioning

confidence: 92%

“…In both China and 166 India, the incidence of DILI caused by traditional medicines is increasing 19,20 . 167 In India and China, anti-tuberculosis drugs have been revealed as the most common and second 168 most common causes of DILI through large case series 17,21 respectively. Indeed, in India, anti- 169 tuberculosis DILI is a leading cause of ALF, which is not surprising given that India is home to 170 22.7% of the world's tuberculosis population 22 , and given the hepatotoxic potential of 3 of the 171 4 first line anti-tuberculosis drugs (isoniazid, rifampicin and pyrazinamide).…”

mentioning

confidence: 99%

Drug-induced liver injury

Aithal

2019

Medicine

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Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when the subject is exposed to toxic doses of some compounds (acetaminophen overdose) or in an unpredictable way with many drugs in common use. Drugs can be harmful to the liver in a susceptible subject on the background of genetic and environmental factors. This accounts for modifications in the hepatic metabolism and excretion of the agent leading to cellular stress, direct cell death, activation of an adaptive immune response and a failure to adapt with progression to overt liver injury. Idiosyncratic DILI is a relative rare liver disorder but can be severe and even fatal, presenting with a variety of phenotypes, which mimic almost every other liver disease. Diagnosis of DILI relies on the exclusion of other etiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need a refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has yet been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune checkpoint inhibitors.

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Immune-related hepatitis with immunotherapy: Are corticosteroids always needed?

Cited by 81 publications

References 9 publications

EASL Clinical Practice Guidelines: Drug-induced liver injury

EASL Clinical Practice Guidelines: Drug-induced liver injury

Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects

Drug-induced liver injury

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