Letter: rates and determinants of significant liver inflammation in chronic hepatitis B virus-infected patients with low ALT levels in the absence of significant fibrosis

We read with great interest the article by Sonneveld et al, in which they investigated the rates and determinants of significant liver inflammation in patients with chronic hepatitis B (CHB) infection with low levels of alanine aminotransferase (ALT), specifically for patients without significant liver fibrosis.¹ They found that an ALT level <2 times the upper limit of normal (ULN) was associated with low (<5%) probability of significant liver inflammation in CHB patients without significant fibrosis.¹ The study is very important. However, several issues deserve discussion.

First, in the study by Sonneveld et al, patients were included from eight global randomised trials and consecutive CHB patients who underwent liver biopsy in two liver clinics.¹ However, whether all CHB patients were treatment-naïve was not provided by the authors as antiviral treatment may impact liver inflammation. In addition, the indications for liver biopsy for all patients were not described, which may create significant selection bias.

Second, liver biopsy samples were scored by different pathologists and scoring systems (METAVIR or histologic activity index scoring systems).¹ Thus, personal bias cannot be ruled out.

Third, Sonneveld et al analysed factors associated with the presence of significant inflammation.¹ However, other factors such as serum gamma-glutamyl transpeptidase (GGT) levels, and platelet counts were not included for the analysis. Serum GGT levels and platelet counts have been identified as independent predictors of significant liver inflammation in CHB patients.^2-5

In addition, the authors concluded that, if fibrosis can be ruled out by non-invasive tests, liver biopsy to determine inflammatory activity should be discouraged.¹ However, data of the non-invasive tests such as liver stiffness measurement, aspartate transaminase-to-platelet ratio index and the fibrosis index based on the four factors (FIB-4) were not provided. The rates of significant liver inflammation in CHB patients without advanced fibrosis (as determined by non-invasive methods) deserve further investigation.

Thus, more prospective studies are needed to confirm rates and determinants of significant liver inflammation in CHB patients with low ALT levels in the absence of significant liver fibrosis.

Funding information

The study was funded by the National Science and Technology Major Project of China (2018ZX10302205), National Natural Science Foundation of China (81672025 and 81702011), Jiangsu Science and Technology Development Plan (BE2017605), Jiangsu Provincial Medical Innovation Team (CXTDA2017005) and Nanjing Medical Science and Technique Development Foundation (QRX17121).