Liver stiffness in the hepatitis B virus carrier: A non-invasive marker of liver disease influenced by the pattern of transaminases

Abstract

AIM:To investigate the usefulness of transient elastography by Fibroscan (FS), a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus (HBV) carriers. METHODS: In 297 consecutive HBV carriers, we studied the correlation between liver stiffness (LS), stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B (CHB) patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up. RESULTS: FS values were 12.3 ± 3.3 kPa in acute hepatitis, 10.3 ± 8.8 kPa in chronic hepatitis, 4.3 ± 1.0 kPa in inactive carriers and 4.6 ± 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis ≥ S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value (PPV), 97.3% and 96.3% negative predictive value (NPV) and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage (t = 13.187, P < 0.001), active vs inactive HBV infection (t = 6.437, P < 0.001), alanine aminotransferase (ALT) (t = 4.740, P < 0.001) and HBV-DNA levels (t = -2.046, P = 0.042) were independently associated with FS. Necroinflammation score (t = 2.158, > 10/18 vs ≤ 10/18, P = 0.035) and ALT levels (t = 3.566, P = 0.001) were independently associated with LS in 83 untreated patients without cirrhosis and long-term biochemical remission (t = 4.662, P < 0.001) in 80 treated patients. During FS monitoring (mean followup 19.9 ± 7.1 mo) FS values paralleled those of ALT in patients with hepatitis exacerbation (with 1.2 to 4.4-fold increases in CHB patients) and showed a progressive decrease during antiviral therapy. CONCLUSION: FS is a non-invasive tool to monitor liver disease in chronic HBV carriers, provided that the pattern of biochemical activity is taken into account. In the inactive carrier, it identifies non-HBV-related causes of liver damage and transient reactivations. In CHB patients, it may warrant a more appropriate timing of control liver biopsies.

Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement

“…Some studies with transient elastography (19)(20)(21), SWE (21), and MR elastography (22,23) have concluded that the correlation between liver stiffness values and fibrosis stage is not affected by steatosis or necroinflammation. Other studies have suggested that inflammation, as suggested by elevated transaminase levels (24,25) or diagnosed at liver biopsy (26)(27)(28), affects transient elastography assessment of fibrosis. Similarly, steatosis has been reported to have no effect on acoustic radiation force imaging-based fibrosis assessment (29), whereas in several transient elastography studies, steatosis has been reported to have an effect on noninvasive fibrosis staging (28,30,31).…”

Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

“…For staging fibrosis F≥2, F≥3 and F=4, the summary sensitivity was 0.81, 0.82 and 0.86, respectively, the summary specificity was 0.82, 0.87 and 0.87, respectively, and the corresponding AUROC was 0.88, 0.91 and 0.93, respectively (96). The cut-off values for significant fibrosis (≥F2) ranged from 5.8 to 8.8 kPa, for fibrosis ≥F3 from 7.0 to 13.5 kPa, and for cirrhosis (F4) from 9.0 to 16.9 kPa (97)(98)(99)(100)(101)(102)(103). A recent study showed the utility of TE for the diagnosis of fibrosis in 263 HBV patients with ALT levels <2× upper limit of normal (ULN), particularly in those with at least significant underlying fibrosis.…”

Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B

“…Thus, we searched previous studies which focused on the performance of LSM in patients with CHB and identified four studies (2 from Europe and another 2 from Asia) in the literature. [17][18][19][20] Of these, one European study with Ishak system with six fibrosis grading which is different from four grading of Batts and Ludwig system was excluded 19,21 Although two Asian studies did not show complete cutoff LSM values for each fibrosis stage (missed cutoff value for ‡F2 fibrosis in one study 17 and missed value for ‡F3 in the other study, 20 we selected one of them with larger sample size (n = 161 vs. 88) as reference for comparison between Asian population. 17 Finally, the optimal cutoff LSM values for ‡F2, ‡F3 and F4 fibrosis stage of Chan et al were 6.0, 8.4 and 9.0 kPa respectively 17 and those of Marcellin et al were 7.2, 8.1 and 11.0 kPa respectively.…”