Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy

Abstract

AIMTo investigate the utility of hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODSThis retrospective study included treatment-naïve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, one-year and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTSA total of 211 patients were enrolled. The median treatment time was 5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients (cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSIONBaseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy

“…The enrolled patients began ETV therapy between December 2007 and January 2015, and the last follow-up ended between December 2012 and November 2017. The subjects were included only if they were over 20 years old, ETV was the only anti-HBV therapy administered without interruption, and the indications followed the treatment guideline [5]. All subjects required an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and ECOG scores ≤1 over the study period.…”

“…Serum HBsAg and HBV DNA level measurements followed the methods as previously described [5]. The upper limit of normal for ALT was 50 U/mL in males and 35 U/mL in females at NCKUH.…”

“…In the in-depth analysis, when the difference was statistically significant among the three subgroups, we then conducted post hoc analysis, including Dunn’s test after the Kruskal–Wallis test, Scheffe’s test after one-way ANOVA, and Bonferroni adjustment after Chi-Squared test or Fisher’s exact test. Our previous study indicated that the trajectory of HBsAg was similar one year after ETV therapy among the groups with different statuses of HBeAg and LC [5]. Hence, we distinguished the baseline HBsAg, which was determined ahead of ETV therapy, from the outcome variables, i.e., the subsequent annual HBsAg levels after ETV initiation.…”

“…Nucleos(t)ide analogs, such as entecavir (ETV), potently suppress HBV DNA and, thus, prevent disease progression and reduce HCC development [1,2,5]. Aside from HBV DNA and alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg) or chemokines can help monitor the effects of NA on HBV and immunity [5,6,7]. Serum HBsAg was shown to predict disease progression and the risk of HCC in patients with low HBV loads [8,9].…”

“…Serum HBsAg was shown to predict disease progression and the risk of HCC in patients with low HBV loads [8,9]. In addition, quantitative HBsAg levels could predict HBsAg loss in hepatitis B e antigen (HBeAg)-positive patients whose HBsAg was diminished markedly during the first year of NA treatment and could predict an enduring off-NA response in HBeAg-negative patients with low HBsAg levels (<100 IU/mL) following consolidation therapy [5,7]. Additionally, interferon-γ-inducible protein of 10 kDa (IP-10), a pleiotropic chemokine derived from different immune and tissue cells, contributes to liver injury in HBV transgenic mice and is also an independent biomarker of post-liver transplantation hepatic fibrosis in hepatitis C virus (HCV) infection [10,11].…”