Abstract
Background & Aims : Hepatitis B virus (HBV) can be completely
suppressed after antiviral treatment; however, some patients with
chronic hepatitis B (CHB) still exhibit elevated alanine
aminotransferase (ALT) levels and sustained disease progression. The aim
of this study was to provide novel insights into the mechanism and
potential predictive biomarkers of persistently elevated ALT (PeALT) in
patients with CHB after complete viral inhibition.
Methods : CHB Patients with undetectable HBV DNA at least 12
months after antiviral treatment were enrolled from a prospective,
observational cohort. Correlations between plasma metabolites and the
risk of elevated ALT were examined using multivariate logistic
regression.
Results : Of the 1238 patients with CHB who achieved complete
viral suppression, 40 (3.23%) had PeALT levels during follow-up (median
follow-up: 2.42 years). Additionally, 40 patients with persistently
normal ALT (PnALT) levels were matched 1:1 as controls. Ser-Phe-Ala
(variable importance in projection [VIP] = 4.28), Lys-Ala-Leu-Glu
(VIP = 4.49), 3-methylhippuric acid (VIP = 3.04), 3-methylxanthine (VIP
= 2.62), and 7-methylxanthine (VIP = 3.35) were identified as critical
differential metabolites between the two groups and independently
associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could
be used to discriminate patients with PeALT from those with PnALT.
Furthermore, N -acetyl-l-methionine (NALM) demonstrated
the strongest negative correlation with ALT levels. NALM supplementation
alleviated liver injury and hepatic necrosis induced by carbon
tetrachloride in mice.
Conclusions : Changes in circulating metabolites may contribute
to PeALT levels in patients with CHB who have achieved complete viral
suppression after antiviral treatment.
Abstract word count: 244
Keywords: chronic hepatitis B; alanine aminotransferase;
metabolites; N -acetyl-l-methionine