Seto WK, Lam YF, Fung J, et al. Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment
ABSTRACT Hepatitis B surface antigen (HBsAg) kinetics during long-term entecavir therapy has not been well investigated.
We described the cumulative serologic, virologic and biochemical outcomes and the occurrence of signature entecavir mutations among 222 Chinese treatment-naïve chronic hepatitis B (CHB) patient receiving entecavir for up to 5 years.
The median rate of HBsAg reduction over 5 years was 0.125 log IU/mL/year. Patients with high baseline HBV DNA levels (≥8 log copies/mL or ≥7.3 log IU/mL), when compared those with baseline HBV DNA <7.3 log IU/mL, had a significantly greater median rate of HBsAg reduction (0.178 and 0.102 log IU/mL/year respectively, p<0.001). The difference in HBsAg decline was most prominent in the first year (0.324 and 0.062 log IU/mL/year respectively, p<0.001). Greater median rates of HBsAg reduction were also found in hepatitis B e antigen (HBeAg)-positive patients when compared to HBeAg-negative patients (0.144 and 0.098 log IU/mL/year, p=0.015), and in patients with high baseline HBsAg levels (≥3 log IU/mL), when compared with patients with low baseline HBsAg <3 log IU/mL (0.131 and 0.045 log IU/mL/year respectively, p=0.001). The 5-year cumulative rate of HBV DNA undetectability (<20 IU/mL) was 97.1%. There were two cases of entecavir resistance, resulting in a 5-year cumulative resistance rate of 1.2%.
In contrast to the profound HBV DNA suppression, long-term entecavir treatment only achieve slow decline in serum HBsAg. Although certain patient subgroups exhibit a more rapid HBsAg reduction, additional therapeutic agents are needed to increase the chance of HBsAg seroclearance in CHB.
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ABSTRACT: The main purpose of therapy for infectious diseases is restoration or protection of the patient's health, but suppression or elimination of infectious agents is also important. In two well-defined situations, reduction of potential infectivity may be the main reason for therapy in hepatitis B virus (HBV) carriers who do not suffer from significant disease: (1) healthcare providers who perform exposure-prone procedures to prevent transmission of HBV to individuals, and (2) pregnant women in the third trimester to prevent transmission to the fetus. This article describes the necessity to recognize highly viremic HBV-infected individuals in these situations, the methods to estimate the risk of transmission, and the therapeutic possibilities to prevent transmission. With today's methods of monitoring HBV DNA, it is possible to reliably estimate the risk of transmission. The drugs entecavir or tenofovir are able to suppress infectivity of HBV carriers to levels acceptable for healthcare providers performing exposure-prone procedures. According to the CDC, 'chronic HBV infection in itself should not preclude the practice or study of medicine, surgery, dentistry, or allied health professions.' Treatment of pregnant women with very high levels of HBV DNA prevents the transmission to the fetus and further if the newborn receives immediate active/passive immunization against HBV. © 2014 S. Karger AG, Basel.Intervirology 01/2014; 57(3-4):202-11. DOI:10.1159/000360949 · 1.77 Impact Factor
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ABSTRACT: Since the discovery of HBsAg in the early 1960s, presence of HBsAg in serum has only served to diagnose hepatitis B. Recent development in the quantitative measurement of serum HBsAg has enabled us to improve our understanding on the management of chronic hepatitis B. The surface antigen (sAg) level is at its highest in immune tolerance phase and decreases to the lowest level in immune control/inactive phase when HBeAg is cleared from the serum. Combination of serum sAg titer less than 1,000 IU/mL and serum HBV DNA less than 2,000 IU/mL can identify true inactive carrier from e antigen (eAg) negative hepatitis with diagnostic accuracy of 95%. During the natural course of chronic hepatitis B, changes or absolute level of sAg less than certain level can predict spontaneous sero-clearance of HBsAg. Although the decline of sAg is very slow in interferon (IFN)/pegylated interferon (PEG-IFN) or oral nucleos(-t)ide treated patients, interferon based therapy results in a greater decrease of sAg level and sAg loss. Lack of any decline in sAg titer during PEG-IFN therapy could identify the group of patients who do not response to IFN/PEG-IFN therapy. With the aid of serum HBV DNA, quantitative measurement of serum HBsAg level can be used to optimize the management of chronic hepatitis B in our daily practice. (Korean J Gastroenterol 2014;63:335-340).The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 06/2014; 63(6):335-40. DOI:10.4166/kjg.2014.63.6.335
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ABSTRACT: OBJECTIVES:The objective of this study was to determine factors associated with hepatitis B surface antigen (HBsAg) seroclearance after hepatitis B e-antigen (HBeAg) seroclearance.METHODS:This is a cohort study of HBeAg-positive patients with HBeAg seroclearance. Factors associated with subsequent HBsAg seroclearance were examined.RESULTS:A total of 775 patients were included. At 1, 5, 10, 15, 20, and 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 0.3, 1.3, 3.0, 8.9, 15.7, and 23.6%, respectively. The rate of HBsAg seroclearance was highest in those who underwent spontaneous HBeAg seroclearance and required no treatment afterward (group 1), compared with those who underwent treatment-induced HBeAg seroclearance (group 2), and those who required antiviral therapy after spontaneous HBeAg seroclearance (group 3). At 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 38.0, 14.9, and 0% in groups 1, 2, and 3, respectively (P<0.001). There was no difference in the rate of HBsAg seroclearance between those who received interferon-based therapy compared with nucleos(t)ide analogs. The median HBV DNA level was similar between those with and without HBsAg seroclearance. The median HBsAg level was significantly lower in those who had HBsAg seroclearance compared with those who did not achieve loss of HBsAg (2.81 vs. 3.52 log IU/ml, respectively, P=0.009). The area under receiver operating characteristic curve for HBsAg at 1 year after HBeAg seroclearance for predicting HBsAg seroclearance was 0.742, with an optimal cutoff of 751 IU/ml.CONCLUSIONS:Spontaneous HBeAg seroclearance without need for subsequent antiviral therapy was associated with the highest rate of subsequent HBsAg seroclearance. Lower HBsAg levels were also associated with higher chance of HBsAg seroclearance.Am J Gastroenterol advance online publication, 23 September 2014; doi:10.1038/ajg.2014.301.The American Journal of Gastroenterology 09/2014; 109(11). DOI:10.1038/ajg.2014.301 · 9.21 Impact Factor