Noninvasive markers for staging fibrosis in chronic delta hepatitis.
Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) virus but have not been evaluated in chronic hepatitis D virus (HDV).



To evaluate the utility of serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, aspartate aminotransferase ratio (AAR), age-platelet index (API), AST-to-platelet-ratio-index (APRI) and Hui score] in HDV infection.



Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak = 6) were evaluated and compared between viral infections.



A total of 1003 subjects (HCV = 701, HBV = 240 and HDV = 62) with mean age of 46 ± 11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak ≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4 = 0.70 (0.55-0.84), API = 0.69 (0.55-0.82), APRI = 0.68 (0.54-0.82), Hui score = 0.63 (0.49-0.78), AAR = 0.63 (0.48-0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4 = 0.83 (0.69-0.97), API = 0.80 (0.66-0.95), APRI = 0.75 (0.61-0.89), Hui score = 0.70 (0.49-0.91) and AAR = 0.70 (0.48-0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV.



Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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V
Takyar
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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P
Surana
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
D E
DE
Kleiner
Office of the Director, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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K
Wilkins
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
J H
JH
Hoofnagle
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
T J
TJ
Liang
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
T
T
Heller
Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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C
Koh
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D019701:Hepatitis D, Chronic / Q000097:blood* / Q000175:diagnosis*; D003698:Hepatitis Delta Virus; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000379:methods; D012189:Retrospective Studies
D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase