Hepatology International

, Volume 12, Issue 1, pp 44–55 | Cite as

Repeated liver stiffness measurement compared with paired liver biopsy in patients with non-alcoholic fatty liver disease

  • Sivesh K. Kamarajah
  • Wah-Kheong Chan
  • Nik Raihan Nik Mustapha
  • Sanjiv Mahadeva
Original Article



The value of repeated liver stiffness measurement (LSM) in non-alcoholic fatty liver disease (NAFLD) has not been shown before.


A longitudinal study of biopsy-proven NAFLD patients was conducted at the Asian tertiary hospital from November 2012 to January 2017. Patients with paired liver biopsies and LSM were followed prospectively for liver-related and non-liver related complications, and survival.


The data for 113 biopsy-proven NAFLD patients (mean age 51.3 ± 10.6 years, male 50%) were analyzed. At baseline, advanced fibrosis based on histology and LSM was observed in 22 and 46%, respectively. Paired liver biopsy and LSM at 1-year interval was available in 71 and 80% of patients, respectively. High-risk cases (defined as patients with advanced fibrosis at baseline who had no fibrosis improvement, and patients who developed advanced fibrosis on repeat assessment) were seen in 23 and 53% of patients, based on paired liver biopsy and LSM, respectively. Type 2 diabetes mellitus was independently associated with high-risk cases. The median follow-up was 37 months with a total follow-up of 328 person-years. High-risk cases based on paired liver biopsy had significantly higher rates of liver-related complications (p = 0.002) but no difference in other outcomes. High-risk patients based on paired LSM had a significantly higher rate of liver-related complications (p = 0.046), cardiovascular events (p = 0.025) and composite outcomes (p = 0.006).


Repeat LSM can predict liver-related complications, similar to paired liver biopsy, and may be useful in identifying patients who may be at an increased risk of cardiovascular events. Further studies in a larger cohort and with a longer follow-up should be carried out to confirm these observations.


Liver fibrosis Cirrhosis Fibroscan Liver biopsy NAFLD 



The authors would like to thank Madam Talvant Kaur and Ms. Wan Noor Hidayu for their assistance in the research project. (1) Guarantor of the article: CWK. (2) Specific author contributions: CWK was involved in study concept and design. SKK, CWK, NRNM, and SM were involved in acquisition of data. SKK and CWK were involved with analysis and interpretation of data. SKK and CWK were involved with drafting the manuscript. NRNM and SM were involved with critical revision of manuscript for important intellectual content. (3) All authors have approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no competing interest.

Ethical approval

This prospective study was approved by the University of Malaya Medical Centre (UMMC) Medical Ethics Committee (MEC ID no.: 20168124134).

Informed consent

All patients who participated in this study provided written informed consent.

Supplementary material

12072_2018_9843_MOESM1_ESM.docx (32.7 mb)
Supplementary File 1 Representative photos of the scoring using the Non-Alcoholic Steatohepatitis Clinical Research Network Scoring System from this study (DOCX 33512 kb)
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Supplementary File 2 Profile of patients who developed cardiovascular event during the study period (DOCX 34 kb)
12072_2018_9843_MOESM3_ESM.docx (17 kb)
Supplementary Table 1 The characteristics of patients with and without advanced fibrosis based on histology at baseline (DOCX 17 kb)
12072_2018_9843_MOESM4_ESM.docx (13 kb)
Supplementary Table 2 Independent factors associated with presence of advanced fibrosis based on histology at baseline (DOCX 12 kb)
12072_2018_9843_MOESM5_ESM.docx (18 kb)
Supplementary Table 3 The characteristics of patients with and without NASH at baseline (DOCX 17 kb)
12072_2018_9843_MOESM6_ESM.docx (13 kb)
Supplementary Table 4 Independent factors associated with presence of NASH at baseline (DOCX 12 kb)
12072_2018_9843_MOESM7_ESM.docx (19 kb)
Supplementary Table 5 The characteristics of patients with and without advanced fibrosis based on LSM at baseline (DOCX 19 kb)
12072_2018_9843_MOESM8_ESM.docx (13 kb)
Supplementary Table 6 Independent factors associated with presence of advanced fibrosis based on LSM at baseline (DOCX 12 kb)
12072_2018_9843_MOESM9_ESM.docx (23 kb)
Supplementary Table 7 The number of patients with the different fibrosis stages at follow-up, stratified according to baseline fibrosis stage (based on histology) (DOCX 22 kb)
12072_2018_9843_MOESM10_ESM.docx (13 kb)
Supplementary Table 8 Independent factors associated with high risk cases (based on paired histology) (DOCX 12 kb)
12072_2018_9843_MOESM11_ESM.docx (23 kb)
Supplementary Table 9 The number of patients with the different fibrosis stages at follow-up, stratified according to baseline fibrosisstage (based on liver stiffness measurement) (DOCX 22 kb)
12072_2018_9843_MOESM12_ESM.docx (13 kb)
Supplementary Table 10 Independent factors associated with high-risk cases (based on paired LSM) (DOCX 12 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2018

Authors and Affiliations

  • Sivesh K. Kamarajah
    • 1
    • 2
  • Wah-Kheong Chan
    • 1
  • Nik Raihan Nik Mustapha
    • 3
  • Sanjiv Mahadeva
    • 1
  1. 1.Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  2. 2.College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK
  3. 3.Department of PathologyHospital Sultanah BahiyahAlor SetarMalaysia

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