Case Report: Cholestatic liver injury during atezolizumab therapy in EGFR-mutant combined small cell lung cancer with possible underlying primary biliary cholangitis
4 affiliations
- 1Chongqing Three Gorges Medical College Affiliated Fengjie Hospital
- 2Department of Radiation Medicine, School of Basic Medical Sciences, Chongqing Medical University
- 3The First Affiliated Hospital of Army Medical University (Southwest Hospital)
- 4Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University
Abstract
Background: Combined small cell lung cancer (C-SCLC) may coexist with EGFR driver mutations. For extensive-stage disease, PD-L1 inhibitor plus platinum–etoposide is first-line. Immune checkpoint inhibitor (ICI)-associated cholangiopathy is a rare immune-related adverse event hard to distinguish from pre-existing autoimmune biliary disease such as primary biliary cholangitis (PBC) when baseline serology and histology are unavailable.
Case presentation: A 68-year-old male former smoker presented with an incidentally detected right upper lobe mass. CT-guided percutaneous biopsy showed C-SCLC with a small adenocarcinoma component, neuroendocrine marker positivity, and loss of Rb, and next-generation sequencing revealed an EGFR exon 21 L858R mutation (mutant allele frequency 60.78%). The disease was classified as extensive-stage C-SCLC. First-line etoposide, carboplatin, and atezolizumab (four cycles) achieved partial response; alkaline phosphatase rose from mildly elevated baseline (156 U/L) to 532 U/L and gamma-glutamyl transferase from 87 to 317 U/L, with mild transaminase elevation and normal total bilirubin, a cholestatic pattern (CTCAE v5.0 grade 2). AMA-M2 was positive, raising the possibility of a previously unrecognized PBC background. Imaging showed no biliary dilatation, steatosis, or advanced fibrosis, but magnetic resonance cholangiopancreatography, liver biopsy, and pre-treatment autoantibody testing were not performed. Atezolizumab was stopped and ursodeoxycholic acid continued without high-dose corticosteroids. The cholestatic enzymes fell thereafter, but neither an underlying PBC nor a contribution from superimposed ICI-related biliary injury could be established. Consolidative thoracic radiotherapy and concurrent maintenance with furmonertinib and oral etoposide followed. At the last follow-up on July 28, 2026, partial response was maintained.
Conclusion: This patient with EGFR-mutant C-SCLC was managed with SCLC-directed chemo-immunotherapy then maintenance with EGFR tyrosine kinase inhibitor after cholestatic liver injury. AMA-M2 positivity with pre-existing cholestatic abnormalities raises the possibility of an underlying PBC, but without pre-treatment serology, magnetic resonance cholangiopancreatography, or liver biopsy, neither a definite PBC background nor a definite ICI-related cholangiopathy could be established. Cholestatic liver injury during immunotherapy warrants evaluation for autoimmune biliary disease and drug-related biliary injury.
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BibTeX
@article{zhu2026case,
title = {{Case Report: Cholestatic liver injury during atezolizumab therapy in EGFR-mutant combined small cell lung cancer with possible underlying primary biliary cholangitis}},
author = {Yingqiong Zhu and Jin Xiong and Chuan Tan and Benxu Tan and Yusheng Huang and Ganchao Zhao},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1979503},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1979503/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Cholestatic liver injury during atezolizumab therapy in EGFR-mutant combined small cell lung cancer with possible underlying primary biliary cholangitis
AU - Yingqiong Zhu
AU - Jin Xiong
AU - Chuan Tan
AU - Benxu Tan
AU - Yusheng Huang
AU - Ganchao Zhao
PY - 2026
DA - 2026/10/27
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1979503
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1979503/full
AB - Background: Combined small cell lung cancer (C-SCLC) may coexist with EGFR driver mutations. For extensive-stage disease, PD-L1 inhibitor plus platinum–etoposide is first-line. Immune checkpoint inhibitor (ICI)-associated cholangiopathy is a rare immune-related adverse event hard to distinguish from pre-existing autoimmune biliary disease such as primary biliary cholangitis (PBC) when baseline serology and histology are unavailable. Case presentation: A 68-year-old male former smoker presented with an incidentally detected right upper lobe mass. CT-guided percutaneous biopsy showed C-SCLC with a small adenocarcinoma component, neuroendocrine marker positivity, and loss of Rb, and next-generation sequencing revealed an EGFR exon 21 L858R mutation (mutant allele frequency 60.78%). The disease was classified as extensive-stage C-SCLC. First-line etoposide, carboplatin, and atezolizumab (four cycles) achieved partial response; alkaline phosphatase rose from mildly elevated baseline (156 U/L) to 532 U/L and gamma-glutamyl transferase from 87 to 317 U/L, with mild transaminase elevation and normal total bilirubin, a cholestatic pattern (CTCAE v5.0 grade 2). AMA-M2 was positive, raising the possibility of a previously unrecognized PBC background. Imaging showed no biliary dilatation, steatosis, or advanced fibrosis, but magnetic resonance cholangiopancreatography, liver biopsy, and pre-treatment autoantibody testing were not performed. Atezolizumab was stopped and ursodeoxycholic acid continued without high-dose corticosteroids. The cholestatic enzymes fell thereafter, but neither an underlying PBC nor a contribution from superimposed ICI-related biliary injury could be established. Consolidative thoracic radiotherapy and concurrent maintenance with furmonertinib and oral etoposide followed. At the last follow-up on July 28, 2026, partial response was maintained. Conclusion: This patient with EGFR-mutant C-SCLC was managed with SCLC-directed chemo-immunotherapy then maintenance with EGFR tyrosine kinase inhibitor after cholestatic liver injury. AMA-M2 positivity with pre-existing cholestatic abnormalities raises the possibility of an underlying PBC, but without pre-treatment serology, magnetic resonance cholangiopancreatography, or liver biopsy, neither a definite PBC background nor a definite ICI-related cholangiopathy could be established. Cholestatic liver injury during immunotherapy warrants evaluation for autoimmune biliary disease and drug-related biliary injury.
SN - 2234-943X
ER -