Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer

Abstract

Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

Antiprogrammed Cell Death‐1 Immunotherapy‐Related Secondary Sclerosing Cholangitis

“…Cholangitic liver diseases have also been reported, although rare. (2) These cases include avelumab (3) and nivolumab (4,5) related cholangitis, which present similar images ( Fig. 1) and patterns of CD8-positive T-cell infiltration into the bile duct ( Fig.…”

“…However, further studies are necessary to establish the optimal management of patients with this immunotherapy-related SSC. (2,4) These findings suggest that the possibility of SSC should be considered when administering immune checkpoint inhibitors to patients.…”

“…2B) as in our case, which resulted in immune-related cholangitis and a cholestatic pattern of liver injury. (1)(2)(3)(4)(5) Inflammation and destruction of the bile duct can result in SSC and lead to chronic cholestasis. (3,4) This study reports on a patient with pembrolizumab-induced SSC.…”

Secondary sclerosing cholangitis with hemobilia induced by pembrolizumab: Case report and review of published work

“…Kawakami et al . reported that nivolumab‐related cholangitis was characterized by: (i) extrahepatic bile duct dilation without obstruction; (ii) diffuse hypertrophy of the extrahepatic bile duct wall; (iii) increase of the biliary enzymes ALP and GGT relative to the hepatic enzymes AST and ALT; (iv) absence of the serum immunological markers ANA, AMA, smooth muscle antibody, and IgG4; (v) the pathological finding of CD8 + T cell infiltration in the portal area by liver biopsy; and (vi) a moderate to poor response to steroid therapy . The present case showed most of these features.…”

“…Among irAEs, cholangitis is rare and its clinicopathological features and management remain unclear. There are some reports about nivolumab‐related cholangitis that describe its imaging and clinicopathological features . Ogawa et al .…”