Peroral cholangioscopy of nivolumab-related (induced) ulcerative cholangitis in a patient with non-small cell lung cancer

Kuraoka, Naosuke; Hara, Kazuo; Terai, Shuji; Yatabe, Yasushi; Horio, Yoshitsugu

doi:10.1055/a-0640-2392

Cited by 27 publications

(21 citation statements)

References 4 publications

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“…In these cases, no increase in IgG4 was found. [75][76][77][78][79] The presence of non-specific anti-tissue antibodies was described in 30% to 50% of the patients but at a low titre (1:80), while IgG levels were usually normal. 66,67 It should be pointed out that the immune-mediated hepatitis induced by ICI is an entity that is entirely different from autoimmune hepatitis (AIH).…”

Section: Diagnosis Of Liver Toxicity Patient Characteristicsmentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

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Section: Diagnosis Of Liver Toxicity Patient Characteristicsmentioning

confidence: 99%

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

et al. 2020

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“…The histopathological findings of liver biopsy showed steatosis in two of five patients. In contrast, regarding PD‐1 inhibitor‐associated cholangitis, 12 cases had been reported, 8 received nivolumab, and 4 received pembrolizumab . The median cycles to development of cholangitis was four courses (range 1–12 cycles).…”

Section: Discussionmentioning

confidence: 99%

Non‐alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor

Sawada

Hayashi

Nakajima

et al. 2019

J of Gastro and Hepatol

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Background and Aim Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced‐stage malignancies. During ICI treatment, drug‐induced liver injury (DILI) occasionally occurs. In particular, hepatic immune‐related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI‐associated DILI remain unknown. In the present study, we identified a risk factor for ICI‐associated DILI. Methods We retrospectively analyzed 135 patients treated with anti‐programmed cell death‐1 (PD‐1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade ≥ 2 hepatotoxic AEs during anti‐PD‐1 therapy, and PD‐1 inhibitor‐associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW‐J) 2004 scale. The risk factors for PD‐1 inhibitor‐associated DILI were identified by Cox hazard analysis. Results Thirty‐six patients developed grade ≥ 2 hepatic AEs during anti‐PD‐1 therapy. Among them, eight patients were diagnosed with PD‐1 inhibitor‐associated DILI based on the DDW‐J 2004 scale. Cox hazard analysis revealed that non‐alcoholic fatty liver disease (NAFLD) was a risk factor for PD‐1 inhibitor‐associated DILI. In addition, we revealed that the outcomes of patients with the DDW‐J 2004 score = 3 were improved without steroid treatment. Conclusions NAFLD is a potential risk factor for PD‐1 inhibitor‐associated DILI based on the DDW‐J 2004 scale. The DDW‐J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD‐1 inhibitor‐associated DILI.

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“…Anti‐PD‐1 antibody‐related cholangitis was mainly reported in NSCLC patients receiving nivolumab (Table ) . Nivolumab‐related cholangitis was characterized by (1) extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) increase in the biliary enzymes ALP and GGT relative to the hepatic enzymes AST and ALT; (4) absence of the serum immunological markers ANA, AMA, anti‐smooth muscle antibody, and IgG4; (5) CD8 + T cell infiltration in the portal area by liver biopsy; and (6) a moderate‐to‐poor response to steroid therapy .…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab‐induced secondary sclerosing cholangitis in a non‐small cell lung cancer patient

Matsumoto

Watanabe

Kobayashi

et al. 2020

Respirology Case Reports

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A 50-year-old woman with stage IV lung adenocarcinoma received seven cycles of pembrolizumab as third-line chemotherapy. Following the failure of pembrolizumab, she commenced fourth-line chemotherapy of docetaxel and ramucirumab. The patient complained of epigastric pain and a computed tomography (CT) scan revealed oedema-like thickening of the gallbladder wall, dilation of the bile ducts from the common to the intrahepatic bile ducts, and thickening of the common bile duct wall without any visible obstructions. Accumulation of fluorodeoxyglucose (FDG) in the gallbladder wall and bile duct was also detected with positron emission tomography (PET)-CT. A biopsy of the extrahepatic bile duct showed non-specific inflammation. Antibiotic treatment was not effective and pathogens were not detected. The patient was diagnosed with secondary sclerosing cholangitis (SSC) by pembrolizumab. She received 80 mg/day of prednisolone (PSL); however, SSC recurred with tapering of PSL. SSC then improved with steroid pulse therapy and subsequently 50 mg/day azathioprine and 80 mg/day PSL.

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Peroral cholangioscopy of nivolumab-related (induced) ulcerative cholangitis in a patient with non-small cell lung cancer

Cited by 27 publications

References 4 publications

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors

Non‐alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor

Pembrolizumab‐induced secondary sclerosing cholangitis in a non‐small cell lung cancer patient

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