Can noninvasive biomarkers replace liver biopsy for chronic hepatitis B?
Authors: Chih‐Lin Lin, Jia‐Horng Kao
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article entitled "Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis‐4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta‐analysis" by Xiao et al.1 Severity of hepatic fibrosis is one of the important prognostic factors in patients with chronic hepatitis B virus (HBV) infection, even in those with complete viral response to antivirals.2 Although histological examination remains the gold standard to determine the stage of hepatic fibrosis, there exist several limitations of liver biopsy, such as potential complications, sampling error, and intra‐/interobserver variability.3 Therefore, alternative noninvasive fibrosis assessment by using imaging techniques or surrogate biomarkers have been increasingly recognized. In this timely meta‐analysis, the authors systematically reviewed the diagnostic accuracy of two noninvasive biomarkers, aspartate aminotransferase‐to‐platelet ratio index (APRI) and the fibrosis‐4 index (FIB‐4), for HBV‐related hepatic fibrosis. Their findings demonstrated that APRI and FIB‐4 could not only accurately assess the severity of hepatic fibrosis, but also be applicable to monitor the progression of fibrosis. Nevertheless, these biomarkers for assessment of hepatic fibrosis are still not ideal and deserve attention. First, although the meta‐analysis indicated that both APRI and FIB‐4 were useful noninvasive biomarkers to evaluate severity of hepatic fibrosis in chronic hepatitis B patients, little is known about when liver biopsy could be omitted and how many patients could be correctly diagnosed without invasive liver biopsy. In our recent study, FIB‐4 and APRI were compared to evaluate their diagnostic values in identifying significant fibrosis and cirrhosis among 631 chronic hepatitis B patients.6 FIB‐4 had a significantly higher area under receiver operating characteristic (AUROC) curve than APRI to identify significant fibrosis and cirrhosis. Using FIB‐4 outside the 0.87‐3.40 range, significant fibrosis could be excluded in 69.2% and cirrhosis could be diagnosed in 84.4% of patients. Furthermore, 62.1% of patients in the validation set could be identified without performing invasive liver biopsy. However, it was not likely to differentiate fibrosis stage for those patients with FIB‐4 between 0.87 and 3.40. Therefore, ultrasound‐based transient elastography, or even liver biopsy, is still required for these patients to confirm fibrosis stages. Second, the analysis on the discrepant results between biomarkers and liver histology is important. Our previous study showed a discordant rate of 16.1% for FIB‐4 and 25% for APRI for cirrhosis between noninvasive biomarkers and liver biopsy. In addition, serum alanine aminotransferase level >400 U/L was the main reason of FIB‐4 failure.6 Therefore, the performance of these biomarkers in chronic hepatitis B patients is also limited by hepatitis flares, and repeated measurement after remission of hepatitis activity is required. In summary, despite significant advances in developing noninvasive biomarkers that help practicing physicians evaluate hepatic fibrosis in chronic hepatitis B patients, further large, prospective studies remain essential to validate accuracy, particularly for patients with mild hepatic fibrosis. Furthermore, a combination of noninvasive biomarkers and ultrasound‐based transient elastography may establish an algorithm to increase diagnostic accuracy as it does in chronic hepatitis C.7 Liver biopsy is still the gold standard to confirm fibrosis stage in patients with indeterminate noninvasive staging.