Digestive Diseases and Sciences

, Volume 60, Issue 5, pp 1448–1456 | Cite as

Probability-Based Interpretation of Liver Stiffness Measurement in Untreated Chronic Hepatitis B Patients

  • Vincent Wai-Sun Wong
  • Pietro Lampertico
  • Victor de Lédinghen
  • Pik Eu Chang
  • Seung Up Kim
  • Yongpeng Chen
  • Henry Lik-Yuen Chan
  • Giampaolo Mangia
  • Juliette Foucher
  • Wan Cheng Chow
  • Sang Hoon Ahn
  • Jinlin Hou
Original Article



Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis.


We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores.


Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT.


A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r 2 = 0.018–0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3–4 and F4 by 5 and 17 %, respectively.


ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.


FibroScan Transient elastography Cirrhosis Liver fibrosis Liver biopsy 



Alanine aminotransferase

AUROC curve

Area under the receiver operating characteristic curve


Body mass index


Confidence interval


Hepatitis B e antigen


Hepatitis B virus


Integrated discrimination improvement


Interquartile range


Liver stiffness measurement


Net reclassification improvement



This study was partly funded by the National Science and Technology Major Project to Jinlin Hou (2012ZX10002003) and the Direct Grant from The Chinese University of Hong Kong to Vincent Wong (2013.1.040).

Conflict of interest

Vincent Wong, Victor de Lédinghen, and Henry Chan have served as speakers for Echosens. Henry Chan is a consultant of Inner Mongolia Furui Medical Science Co Ltd.

Supplementary material

10620_2014_3488_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 21 kb)
10620_2014_3488_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (DOCX 19 kb)
10620_2014_3488_MOESM3_ESM.xlsx (10 kb)
Supplementary material 3 (XLSX 9 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Vincent Wai-Sun Wong
    • 1
    • 2
  • Pietro Lampertico
    • 3
  • Victor de Lédinghen
    • 4
    • 5
  • Pik Eu Chang
    • 6
  • Seung Up Kim
    • 7
    • 8
  • Yongpeng Chen
    • 9
  • Henry Lik-Yuen Chan
    • 1
    • 2
  • Giampaolo Mangia
    • 3
  • Juliette Foucher
    • 4
  • Wan Cheng Chow
    • 6
  • Sang Hoon Ahn
    • 7
    • 8
  • Jinlin Hou
    • 9
  1. 1.Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
  2. 2.State Key Laboratory of GastroenterologyThe Chinese University of Hong KongHong KongChina
  3. 3.“A.M. e A. Migliavacca” Center for the Study of Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoUniversità degli Studi di MilanoMilanItaly
  4. 4.Centre d’investigation de la Fibrose HepatiqueHopital Haut-LevequePessacFrance
  5. 5.INSERM U1053Universite BordeauxBordeauxFrance
  6. 6.Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
  7. 7.Department of Internal Medicine, Institute of GastroenterologyYonsei University College of MedicineSeoulSouth Korea
  8. 8.Liver Cirrhosis Research CenterSeoulSouth Korea
  9. 9.Hepatology Unit, Nanfang HospitalSouthern Medical UniversityGuangzhouChina

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