Biomarkers of liver injury for hepatitis clinical trials: a meta-analysis of longitudinal studies.

Background: Liver biopsy and virological end points are standard references for assessing the effect of viral hepatitis treatments. We aimed to review evidence-based published data of biomarkers that have been validated as non-invasive alternatives to biopsy as end points for HBV and HCV infection trials.

Methods: Studies were included if there were at least two repeated estimates of fibrosis per patient using biomarkers with at least two studies and a control group. Meta-analysis of the percentage of fibrosis progression per year (pFPy) was performed.

Results: Two biomarkers were included, FibroTest and liver stiffness measurement (LSM; FibroScan. A total of 1,413 patients with chronic hepatitis C (11 populations) and 772 with chronic hepatitis B (6 populations) were analysed. In a comparison of HCV patients with controls, the FibroTest pFPy was -18% (95% confidence interval [CI] -23--14; P<0.001) in treated patients and the LSM pFPy was -15% (95% CI -28--1; P=0.01), both with differences according to virological responses. In HBV patients, there was a significant decrease of the pFPy only in patients with baseline advanced fibrosis (mean difference -5% [95% CI -10--0.1]; P=0.02). In patients with advanced fibrosis, stratified by virological response, there were similar differences between pFPy estimated either using FibroTest or biopsy, both in HCV and HBV infections. Repeated LSM in HBV patients had an early variability related to necroinflammatory activity.

Conclusions: In patients with chronic hepatitis C and B, the treatment effect on fibrosis progression rate was similarly estimated using FibroTest or biopsy. The same concordance was observed for FibroScan but with a possible overestimation of the fibrosis regression during the first weeks of treatment.