Hepatitic graft-versus-host disease after hematopoietic stem cell transplantation: clinicopathologic features and prognostic implication.
BACKGROUND
Graft-versus-host disease (GVHD) of the liver after allogeneic hematopoietic stem cell transplantation classically presents with increased bilirubin and alkaline phosphatase (ALP) levels. A hepatitic variant was recently recognized, with more than a 10-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. This study defines the clinicopathologic features and prognostic implications of hepatitic GVHD compared with classic liver GVHD.


METHODS
A total of 38 cases of hepatitic GVHD, 68 cases of classic liver GVHD, and 13 cases of hepatitis B virus (HBV)-related hepatitis after hematopoietic stem cell transplantation were analyzed.


RESULTS
Hepatitic GVHD cases showed significantly higher ALT, AST, and ALP levels compared with classic liver GVHD cases (at onset, mean ALT: 154 vs. 58 U/L, P <0.001; AST: 167 vs. 77 U/L, P <0.001; at peak, ALT: 435 vs. 112 U/L, P <0.001; AST: 587 vs. 150 U/L, P <0.001; ALP: 416 vs. 238 U/L, P =0.001), persisted longer (74 vs. 32 days, P =0.006), and showed more lobular pathologic changes in biopsy (lobular changes: 16/26 vs. 4/19, P =0.007; hepatocyte necrosis: 16/26 vs. 6/19, P =0.008; acidophil bodies: 15/26 vs. 4/19, P =0.014) but less cholestasis (4/26 vs. 8/19, P =0.045). However, cumulative doses of immunosuppressants prescribed, response, and outcome were similar. Compared with hepatitic GVHD, HBV-related hepatitis occurred later (95 vs. 184 days, P =0.049), but clinical and biochemical profiles were similar, requiring liver biopsies for their distinction.


CONCLUSIONS
Hepatitic and classic liver GVHD differed biochemically and pathologically, but these differences showed no obvious impact on outcome. The distinction of hepatitic GVHD from other hepatitis is mandatory.
Ma
Shing Y
SY
Department of Medicine, Queen Mary Hospital, Hong Kong, China.
Au
Wing Y
WY
Ng
Irene O L
IO
Lie
Albert K W
AK
Leung
Anskar Y H
AY
Liang
Raymond
R
Lau
George K K
GK
Kwong
Yok L
YL
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006505:Hepatitis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D006509:Hepatitis B / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin