Development of a novel histologic diagnostic algorithm for hepatic graft-versus-host disease

Abstract

The histopathologic diagnosis of hepatic graft-versus-host disease post bone marrow and stem cell transplantation can be challenging, but timely and unambiguous diagnosis is essential for appropriate patient management. To address this diagnostic dilemma, we identified histologic features specific for hepatic graft-versus-host disease and developed a diagnostic algorithm. Two hepatopathologists blindly evaluated 40 liver biopsies from patients with clinically and biologically confirmed graft-versus-host disease, as well as 44 controls, for percent bile duct loss, bile duct damage, intraepithelial lymphocytes, ductular reaction, acidophilic bodies/10 high power fields (HPF), cholestasis, portal and lobular inflammation, and endotheliitis. Compared with controls, graft-versus-host disease cases had significantly more bile duct loss (P<0.0001), bile duct damage (P=0.0002), cholestasis (P<0.0001), and acidophilic bodies/10 HPF (P=0.0006), as well as significantly less ductular reaction (P<0.0001). Significance was maintained with a drug-induced liver injury-only control group. No histologic differences were noted in acute versus chronic graft-versus-host disease, nor cholestatic versus hepatitic types. An algorithm to predict likelihood of graft-versus-host disease was developed, with a three-tiered scoring system: 1-2 not, 3-4 probable, and 5-8 unequivocal graft-versus-host disease. This algorithm had a sensitivity of 93%, specificity of 93%, and accuracy of 92%. We identified histologic features with specificity for hepatic graft-versus-host disease and developed a simple algorithm for pathologists to predict its likelihood, distinguishing this critical diagnosis promptly from mimickers having vastly different treatments and prognoses.

Post-allogeneic Hematopoietic Stem Cell Transplantation Portal Hypertension Not Associated with Liver Cirrhosis, Veno-occlusive Disease, or Graft-versus-host Disease

“…Furthermore, our patient was considered to have no chronic cholestasis because hyperbilirubinemia was not observed. There was no histological evidence of bile duct reduction or apoptosis of the bile duct epithelium, which are characteristic of GVHD in the liver ( 15 ), and the involvement of GVHD was considered negative.…”

“…There was no evidence of congestion or hemorrhage of the liver parenchyma around the central hepatic vein or hepatocyte desquamation or necrosis, which were atypical for VOD ( 14 ). Bile duct reduction and apoptosis of the bile duct epithelium, which are characteristic findings of chronic GVHD of the liver ( 15 ), were not observed. Subsequently, the esophageal varices were treated with ligation and sclerotherapy, and no liver dysfunction was observed six months after the diagnosis.…”

Drug-induced Liver Injury

“…The main histological change in GVHD is bile duct injury, often without ductular reaction and little inflammation, but hepatitic variants also exist 65 . Although this differential diagnosis has not been subjected to rigorous study, recent work has been presented that may eventually prove useful 66 .…”

Loss of NLRP3 Function Alleviates Murine Hepatic Graft-versus-Host Disease

“…Acute graft-versus-host disease (GVHD), which might induce rash, diarrhea, gastrointestinal hemorrhage, and jaundice, impedes the development of allo-HCT due to the high death rate of transplant patients [3,4]. Over 80% of transplant patients develop liver abnormalities and commonly elevated liver chemistry tests, and 10% to 40% develop hepatic GVHD [5,6], which can be fatal.…”