Immune Checkpoint Inhibitors-Induced Hepatitis

Tian, Yun; Abu-Sbeih, Hamzah; Wang, Yinghong

doi:10.1007/978-3-030-02505-2_8

Cited by 31 publications

(23 citation statements)

References 36 publications

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“…45,47 The injury occurs between approximately 1 to 3 months with anti-PD-1/PD-L1 agents, and between about 3 to 9 weeks with anti-CTLA-4 agents after initiation of therapy. 45,48,49 The injury may vary with the type of CPI therapy agents used. A systematic review and meta-analysis of published data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) had higher risk of all-grade and high-grade hepatotoxicity than PD-1 inhibitors.…”

Section: Patterns Of Injury To the Liver Andmentioning

confidence: 99%

Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy

Patil

Zhang

2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immune checkpoint inhibitors (CPIs), including cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitors and the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, are being increasingly used for treating many advanced malignancies. However, CPI therapy is also associated with gastrointestinal and hepatobiliary adverse effects. Objectives.— To review the adverse effects of CPI therapy on the gastrointestinal tract and hepatobiliary system. To describe histopathologic patterns and discuss differential diagnostic considerations in the diagnosis of CPI injuries. Data Sources.— Published peer-reviewed literature in the English language and personal experience in the diagnosis of CPI injuries. Conclusions.— The pathologic manifestations of CPI therapy–induced gastrointestinal and hepatobiliary injury are broad. The patterns of esophageal CPI injury include lymphocytic inflammation and ulcerative esophagitis, while those of gastric injury include chronic active gastritis, lymphocytic gastritis, focal enhancing gastritis, and periglandular inflammation. The duodenal injury may present as duodenitis with villous blunting and granulomas. We also noticed active colitis, microscopic colitis, chronic active colitis, increased apoptosis, ischemic colitis, and nonspecific inflammatory reactive changes in colonic injuries. The reported histologic features of hepatobiliary injuries are panlobular hepatitis, centrilobular necrosis, portal inflammation with bile duct injury, steatosis, nodular regenerative hyperplasia, and secondary sclerosing cholangitis. In summary, we here discuss the pathologic features and differential diagnosis of CPI therapy–induced gastrointestinal and hepatobiliary injury. Recognition of CPI injury is important to determine the proper management that often includes cessation of CPI therapy; and administration of steroids or other immunosuppressive agents, based on severity of injury.

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Section: Patterns Of Injury To the Liver Andmentioning

confidence: 99%

Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy

Patil

Zhang

2020

Archives of Pathology &Amp; Laboratory Medicine

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“…The predominant histological pattern of ICI-induced hepatitis demonstrated pan-lobular hepatitis and bile duct injury including fibrin ring granulomas, central vein endotheliitis, prominent sinusoidal lymphohistiocytic infiltrates, and endothelialitis involving central veins. 55 CTLA-4 blockade can cause elevation of several biochemical indicators in liver tests, including alkaline phosphatase, AST/ALT, and bilirubin. Histology related to anti-CTLA-4 mAbs use showed granulomatous hepatitis with fibrin deposition and central vein endotheliitis.…”

Section: Liver-related Complicationsmentioning

confidence: 99%

“…52 In addition, compared with autoimmune hepatitis and drug-induced liver injury, the number of CD3+ and CD8+ lymphocytes in ICIs treatment-related hepatitis increased, and the number of CD20+ B cells and CD4+ T cells decreased. 55 Moreover, lobular hepatitis with necrosis caused by anti-CTLA-4 mAbs is either spotty or confluent because of the inflammatory infiltration that is generated by CD8 lymphocytes, 56 while anti-PD-(L)1 mAbs can cause both CD4 and CD8 lymphocytes infiltration. Furthermore, autoimmune hepatitis has characteristics of plasma cell infiltration, severe interface hepatitis, piecemeal necrosis, and rosette formation, which immunerelated hepatitis lacks.…”

Section: Liver-related Complicationsmentioning

confidence: 99%

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

Cui¹,

Liu²,

Wang³

et al. 2020

OTT

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“…A liver biopsy should be considered in patients with grade 4 adverse events (Table ) to assist with a differential diagnosis and predicting prognosis. Histological examinations of ICI‐related hepatitis include nonspecific features of panlobular hepatitis indistinguishable from autoimmune hepatitis, bile duct injury including fibrin ring granulomas, central vein endotheliitis, prominent sinusoidal lymphohistiocytic infiltrates, and endotheliitis involving the central vein . It has been reported that CTLA‐4 inhibitor‐induced hepatitis caused granulomatous hepatitis with fibrin deposits, whereas PD‐1/PD‐L1 inhibitor induced hepatitis caused lobular nongranulmatous hepatitis .…”

Section: Immune‐related Hepatotoxicitymentioning

confidence: 99%

“…Histological examinations of ICI-related hepatitis include nonspecific features of panlobular hepatitis indistinguishable from autoimmune hepatitis, bile duct injury including fibrin ring granulomas, central vein endotheliitis, prominent sinusoidal lymphohistiocytic infiltrates, and endotheliitis involving the central vein. 6,7 It has been reported that CTLA-4 inhibitor-induced hepatitis caused granulomatous hepatitis with fibrin deposits, whereas PD-1/PD-L1 inhibitor induced hepatitis caused lobular nongranulmatous hepatitis. 4 A recent study has also revealed that ICI-induced hepatitis showed increased numbers of CD3+ and CD8+ lymphocytes and decreased CD20+ B cells and CD4+ T cells compared with autoimmune hepatitis and drug-induced liver injury.…”

Section: Diagnosismentioning

confidence: 99%

Clinical diagnosis and treatment of immune checkpoint inhibitor‐associated adverse events in the digestive system

Kang

Wang

et al. 2020

Thoracic Cancer

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Immunotherapy for malignant tumors is a hot spot in current research and the treatment of cancer. The activation of programmed cell death receptor‐1 (PD‐1) and cytotoxic T lymphocyte‐associated antigen 4 (CTLA)‐4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune‐checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune‐related adverse events (irAEs). The digestive system, including the gastrointestinal tract and liver which are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune‐related organs, is the most commonly affected system of irAEs. This review explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

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Immune Checkpoint Inhibitors-Induced Hepatitis

Cited by 31 publications

References 36 publications

Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy

Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy

<p>Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma</p>

Clinical diagnosis and treatment of immune checkpoint inhibitor‐associated adverse events in the digestive system

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