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Background
Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.
Case Presentation
We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.
Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.
The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.
Conclusions
This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.
Background
Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.
Case Presentation
We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.
Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.
The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.
Conclusions
This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.
Background
Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.
Case Presentation
We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.
Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.
The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.
Conclusions
This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.