Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives

Abstract

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE), as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.

Keywords: Fibroscan; Fibrosis; Liver stiffness; Longitudinal; Outcome; Transient elastography.

Figure 1

Cumulative incidences of variceal bleeding based on liver stiffness-spleen diameter to platelet ratio score values. A: The incidence of variceal bleeding increased significantly in association with higher liver stiffness-spleen diameter to platelet ratio score (LSPS) values (long-rank test, P < 0.001); B: In particular, among patients with high risk esophageal varices (EV), the incidence of variceal bleeding was significantly higher in patient with LSPS 6.5 (subgroup 2) than those with LSPS < 6.5 (subgroup 1).

Figure 2

Cumulative incidence of hepatocellular carcinoma development based on stratified transient elastography values in patients with chronic hepatitis C (A, n = 866) and those with chronic hepatitis B (B, n = 1130). The cumulative incidences increased significantly in association with higher TE values (log-rank test, all P < 0.001). In particular, the overall incidence of HCC differed significantly among the four groups (C) (both initial and follow-up TE values ≤ 13 kPa (group 1), initial TE value > 13 kPa and follow-up TE value ≤ 13 kPa (group 2), initial TE value ≤ 13 kPa and follow-up TE value > 13 kPa (group 3), and both initial and follow-up TE values > 13 kPa (group 4) according to changing patterns of TE value during follow-up (P < 0.001; Figure 2C). A: Cited from Masuzaki et al[52]; B and C: Cited from Jung et al[53]. HCC: Hepatocellular carcinoma; TE: Transient elastography; LSM: Liver stiffness measurement.

Figure 3

Incidence of liver-related events according to changes in transient elastography values after 6 mo of antiviral therapy. The overall incidence of liver-related events differed significantly among the four groups using TE value cutoffs of 11.6 kPa (A) and 18.2 kPa (B) (both P < 0.0001). Adapted from Kim et al[79]. TE: Transient elastography; LSM: Liver stiffness measurement; LREs: Liver-related events.