On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

Abstract

BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs. AIM To clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir. METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls. RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging ( γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively. CONCLUSION HBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.

Hepatitis B Virus-Related Glomerulonephritis with Positive and Negative Serum HBsAg: Different Clinicopathologic Characteristics of Two Clinical Subtypes

“…Moreover, level of HBcAg can influence the progression of liver disease. 19 , 20 Our data showed that the proportion of positive HBcAg was significantly higher in patients with HBsAg+ HBV-GN, which is similar to liver injury of HBV infection. Moreover, our results showed that the levels of Scr, AST, ALT were much higher in HBsAg+ group when compared with HBsAg- group, which indicated HBsAg+ HBV-GN patients had poor kidney and liver function.…”

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients

“…The relationships between HBcrAg and histological changes differed among studies. [ 14 , 16 ] Chang et al [ 16 ] revealed that higher HBcrAg levels were associated with a higher grade of inflammation in all patients, and HBcrAg negatively correlated with liver fibrosis staging ( r = −0.357, P < 0.001) in HBeAg-positive patients but positively correlated ( r = 0.317, P < 0.001) in HBeAg-negative patients. They also found that a greater reduction in HBcrAg was associated with improvements in inflammation and regression of fibrosis when they analyzed 320 CHB patients (164 of whom were HBeAg-positive) who received 72 weeks of ETV.…”

“…They also found that a greater reduction in HBcrAg was associated with improvements in inflammation and regression of fibrosis when they analyzed 320 CHB patients (164 of whom were HBeAg-positive) who received 72 weeks of ETV. [ 16 ] The study showed that there was a positive correlation between HBcrAg and the grade of inflammation and an inverse correlation between HBcrAg and the stage of fibrosis in HBeAg-positive patients but not in HBeAg-negative patients at baseline nor in all patients at 78 weeks. A decline in HBcrAg only correlated with improvements in inflammation in HBeAg-positive patients, not with the regression of fibrosis in all patients.…”

“…[ 14 , 15 ] The relationships between HBcrAg and grade of inflammation, stage of fibrosis, and their degrees of change before and after antiviral therapy also differed. [ 14 , 16 ] Furthermore, few studies have addressed the associations between HBcrAg and virological or histological variables after antiviral therapy or the relationships between the degrees of change for the markers, especially in HBeAg-negative patients.…”

Peculiarities in the designations of hepatitis B virus genes, their products, and their antigenic specificities: a potential source of misunderstandings

“…There are numerous clinical studies on the therapy of chronic hepatitis B, which tried to use HBcrAg instead of or in addition to HBV DNA for patient monitoring. A correlation of HBcrAg levels with the degree of liver fibrosis [35] and the development of hepatocellular carcinoma [36] was reported for HBeAg-negative patients. HBcrAg may be an acceptable substitute for HBV DNA for identification of patients requiring therapy [37], but monitoring of HBV DNA levels under antiviral therapy cannot adequately be done by HBcrAg in HBeAg-positive patients because nucleoside analogues do not suppress transcription of HBV DNA and the subsequent translation of HBeAg.…”