Interpretation of liver stiffness measurement‐based approach for the monitoring of hepatitis B patients with antiviral therapy: A 2‐year prospective study

Abstract

Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen-positive treatment-naive patients receiving telbivudine-based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (-2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6-49.5) kPa at baseline to 6.1 (2.2-37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (-0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0-2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52-week liver stiffness from baseline was independently associated with 104-week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52-week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104-week fibrosis regression in treated patients with chronic hepatitis B.

Ultrasound-Based Liver Stiffness Surveillance in Patients Treated for Chronic Hepatitis B or C

“…Biochemical responses were also revealed to be in parallel with the liver stiffness decline over time [38]. However, only one study has analyzed the two-phased liver stiffness declines or the rapid-to-slow rates of liver stiffness kinetics (typically declines) through liver stiffness surveillance at shorter time intervals by including patients with CHB [7]. Among the noninvasive liver fibrosis evaluation approaches or indices, elastography-based liver stiffness measurements in particular were affected at an early stage by hepatic necroinflammatory activity [32].…”

“…The activity typically remained relatively stable over the later phase. After ALT normalization, liver stiffness continued to decline gradually, reflecting the ongoing occurrence of fibrosis reversal over time [7,8]. Therefore, lower cutoff values than those acquired at the treatment baseline have been recommended for surveillance by dichotomizing the fibrosis stages in patients with CHC using elastography on and off treatments [32,34,42].…”

“…Except in the study [50], employing the absolute value of follow-up liver stiffness (<7.2 kPa on FibroScan) as the outcome, participants with lower baseline liver stiffness were more likely to achieve favorable outcome than those with higher liver stiffness values. In addition, time elapsed and biochemical response typically superseded the baseline hepatitis B virus DNA, viral genotypes, serology, and several host factors, in their correlation with a decline in liver stiffness [7]. The liver stiffness surveillance of the CHB cohort was not grouped by virologic response because of the uniform virologic response to antiviral treatment with nucleoside or nucleotide analogs.…”

“…With the advent of direct-acting antivirals (DAAs) for CHC, recent studies have demonstrated that DAA therapy can improve hepatic reserve and delay progression in patients with CHC with decompensated cirrhosis [4]. Furthermore, most patients with CHB or CHC-even those without a treatment response-benefit from antiviral treatment, evidenced by a marked early resolution in hepatic necroinflammation [5,6] and a fibrosis reversal over time [7,8].…”

“…Recent studies have further revealed that liver stiffness measurement is a promising solution to modeling liver disease progression and regression on a continuous noncategorical scale as changes in liver stiffness per year or liver stiffness progression or regression rate to refine liver stiffness measurement-based prognostics [7,[20][21][22][23]. Regarding the heterogeneous surveillance intervals in reports using liver stiffness measurements, the durations were significantly shorter either during treatment or between the end of treatment (EOT) and follow-up in patients with CHB and CHC than those reported in histological studies with follow-up periods of up to 10 years [24,25].…”