Utility of Liver Biopsy in Diagnosis and Management of High-grade Immune Checkpoint Inhibitor Hepatitis in Patients With Cancer

Li, Michael; Sack, Jordan; Bell, Phoenix; Rahma, Osama E.; Srivastava, Amitabh; Grover, Shilpa; Zucker, Stephen D.

doi:10.1001/jamaoncol.2021.4342

Cited by 21 publications

(22 citation statements)

References 3 publications

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“…We acknowledge that other authors concluded in their series that, in ICI-related grade 3 liver injury, performing a liver biopsy was associated with a delay in starting CSs and did not result in a faster resolution of the hepatitis. 48 Importantly, in this report by Li et al, 12 of 107 biopsied patients (11%) did not actually have ICI hepatitis. In these cases, liver biopsy was therefore certainly of great help in avoiding potentially deleterious immunosuppressive therapy in an oncological context.…”

Section: Discussionmentioning

confidence: 62%

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events

Coukos

Vionnet

Obéid

et al. 2022

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs) affecting, among others, the liver and sharing some similarities with classic autoimmune liver diseases (AILD).We aimed to compare clinical, laboratory and histological features of patients with liver-related irAEs and AILD.MethodsWe systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.ResultsTwenty-seven patients with liver irAEs (ICI group) and 14 patients with AILD were identified. We observed three distinct ICI-induced histological liver injury patterns: hepatitic (52%), cholangitic (19%), and mixed (29%). When comparing the ICI and AILD groups, centrilobular injury as well as granuloma formation were more prevalent in the former (p=0.067 and 0.002, respectively). CD4+/CD8+ T cell ratios were heterogeneous between the two groups, without statistically significant difference but with a trend toward increased CD8+ T cells among hepatitic irAEs as compared with AIH. Pattern of liver function test alteration was predictive for the type of irAEs but did not correlate with histological severity.ConclusionsLiver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.

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Section: Discussionmentioning

confidence: 62%

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events

Coukos

Vionnet

Obéid

et al. 2022

J Immunother Cancer

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“…Additionally, we were limited by the absence of liver biopsies and incomplete serologic evaluations to diagnose alternative etiologies of liver injury. However, recent retrospective studies have indicated that liver biopsy does not necessarily influence the outcome or management of patients with grade 3 or 4 hepatotoxicity and that corticosteroids can be initiated in patients with moderate hepatocellular injury while other causes are being investigated ( 29 ). Furthermore, the histology of ILICI has been fairly heterogeneous to date so that liver biopsy may not necessarily impact clinical management.…”

Section: Discussionmentioning

confidence: 99%

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis

et al. 2022

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BackgroundDurvalumab is approved for the treatment of lung cancer, advanced biliary tract cancers, and is also being evaluated in many other solid organ tumors. The aim of our study is to define the incidence, etiology, and outcomes of liver injury in consecutive patients receiving durvalumab-based immunotherapy.Patients and methodsDurvalumab treated patients between 1/2016 – 7/2020 were identified from the electronic medical record. Liver injury was defined as serum AST or ALT ≥ 5x upper limit of normal (ULN), ALP ≥ 2x ULN, bilirubin ≥ 2.5 mg/dl, or INR ≥ 1.5. Potential drug induced liver injury (DILI) cases were adjudicated using expert opinion scoring and confirmed with Roussel Uclaf Causality Assessment Method (RUCAM).ResultsAmongst 112 patients, 58 (52%) had non-small cell lung cancer, the median age was 65 years, and 60% were male. The 21 (19%) liver injury patients were significantly more likely to harbor hepatic metastases (52% vs 17%, p=<0.001), experience tumor progression (67% vs 32%, p=0.01) or die (48% vs 11%, p<0.001) during follow-up compared to the 91 without liver injury. Using multivariate regression analysis, the development of liver injury during treatment as well as baseline hepatic metastases were independently associated with mortality during follow-up. Six of the 21 (29%) liver injury cases were adjudicated as probable DILI with four attributed to durvalumab and two due to other drugs (paclitaxel, pembrolizumab). Durvalumab was permanently discontinued in two DILI patients, three received corticosteroids, and one was successfully rechallenged. Only one patient with DILI developed jaundice, and none required hospitalization. Liver biochemistries normalized in all 6 DILI cases, while they only normalized in 27% of the 15 non-DILI cases (p=0.002). The 6 DILI patients also had a trend towards improved survival compared to those with other causes of liver injuryConclusionLiver injury was observed in 19% of durvalumab-treated patients and is associated with a greater likelihood of tumor progression and death during follow-up. The four durvalumab DILI cases were mild and self-limited, highlighting the importance of causality assessment to determine the cause of liver injury in oncology patients receiving immunotherapy.

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“…Li et al [ 17 ] retrospectively analyzed a cohort of 213 patients who developed grade 3 or higher grade of hepatitis linked to ICIs therapy. The most common pattern of DILI was panlobular hepatitis.…”

Section: Role Of Liver Biopsymentioning

confidence: 99%

“…This study suggested that LB in patients treated with ICIs and developing grade 3 or higher liver injury presented a delay in the initiation of corticosteroid therapy and not associated with a faster resolution of liver inflammation. These authors also stated that LB can provide valuable information in patients who do not improve despite the indication of corticosteroids before another immunosuppressant is prescribed[ 17 ].…”

Section: Role Of Liver Biopsymentioning

confidence: 99%

Checkpoint inhibitor-induced hepatotoxicity: Role of liver biopsy and management approach

Bessone¹,

Bjõrnsson²

2022

WJH

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Immunological checkpoint inhibitors (ICIs) have revolutionized therapy of many different malignanices. Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin, lungs, gastrointestinal and endocrine organs as well as the liver. Liver injury has been reported in 3%-8% of patients with grade III-IV hepatitis in retrospective studies. The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation. The role for liver biopsy (LB) in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management. LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected. Although there are no distinctive histological features, the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs. The natural history of hepatotoxicity of ICI therapy is not well known. Recent studies have demonstrated that 33%-50% of patients improve spontaneously with discontinuation of ICIs. In patients with jaundice and/or coagulopathy corticosteroids are used. The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial. Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens. Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

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Utility of Liver Biopsy in Diagnosis and Management of High-grade Immune Checkpoint Inhibitor Hepatitis in Patients With Cancer

Abstract: The utility of liver biopsy in diagnosis and management of immune checkpoint inhibitor (ICI) hepatitis is uncertain. [1][2][3] We examined the association of histology with management and outcomes of high-grade ICI hepatitis.

Cited by 21 publications

References 3 publications

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events

Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis

Checkpoint inhibitor-induced hepatotoxicity: Role of liver biopsy and management approach

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