Clinical outcomes and management of patients with chronic hepatitis B and liver stiffness measurement in the grey zone

Liver Int. 2019 Mar;39(3):494-502. doi: 10.1111/liv.14001. Epub 2018 Dec 2.


Background: A significant number of patients have liver stiffness measurements in the grey zone where liver biopsy is recommended.

Aims: To study chronic hepatitis B patients with initial liver stiffness measurements in the grey zone with regards to rates of liver biopsy, repeat liver stiffness measurements and outcomes.

Methods: Consecutive chronic hepatitis B patients who underwent transient elastography from August 2006 to July 2017 were retrospectively studied. Liver-related events were defined as hepatocellular carcinoma or cirrhotic complications. Grey zone was defined as liver stiffness measurements: 6.1-9.0 kPa (normal ALT) or 7.6-12.0 kPa (ALT 1-5 × upper limit of normal) on M-probe and 6.9-10.0 kPa on XL-probe.

Results: Of the 3212 patients analysed, 837 (26%) had initial liver stiffness measurements in grey zone. Only 3.6% of grey zone patients proceeded to liver biopsy within 6 months of transient elastography, of which 33% had METAVIR F3-4 fibrosis. Repeat liver stiffness measurements was performed in 44% of grey zone patients. Liver biopsy and repeat liver stiffness measurements prompted change in management in 47% and 31% of patients respectively. Independent predictors for liver-related events in grey zone patients included increased age, low albumin and low platelet count. Liver-related events rates were increased (9%-17%) in patients with METAVIR > F2 fibrosis on biopsy or repeat liver stiffness measurements which did not improve.

Conclusions: Chronic hepatitis B patients with initial liver stiffness measurements in the grey zone rarely proceed to a clarifying liver biopsy which would reveal advanced fibrosis or cirrhosis in one-third of patients. Both liver biopsy and repeat liver stiffness measurements in grey zone patients have clinical utility in prompting changes in management and providing prognostic information.

Keywords: chronic hepatitis B; grey zone; liver stiffness measurement; liver-related events.

MeSH terms

  • Adult
  • Biopsy
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Disease Progression
  • Elasticity Imaging Techniques*
  • Female
  • Hepatitis B, Chronic / diagnostic imaging*
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver / diagnostic imaging*
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / diagnostic imaging*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Time Factors