Accelerated Decrease in HBsAg Seen Before HBV Clearance

Serum hepatitis B surface antigen (HBsAg) seroclearance is preceded by significant, accelerated decreases in serum HBsAg levels during the 3 years leading up to seroclearance, wrote Dr. Yi-Cheng Chen and colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Moreover, serum HBsAg levels of less than 200 IU/mL are highly predictive of spontaneous seroclearance.

"It is therefore recommended to quantify HBsAg every 2 years in hepatitis B e antigen-negative HBsAg carriers with persistently normal alanine aminotransferase levels to detect who requires yearly HBsAg assay for the anticipated HBsAg seroclearance" (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2011.08.029]).

Dr. Chen of the Liver Research Unit at Chang Gung University, Taipei, Taiwan, studied 46 patients who had undergone spontaneous HBsAg seroclearance, defined as "loss of serum HBsAg documented on two occasions at least 6 months apart and maintained to the last visit."

Prior to clearance, all patients were hepatitis B e antigen (HBeAg)–negative for between 8 and 28 years, and most had persistently normal alanine aminotransferase (PNALT) for a mean of 14.2 years, except seven patients with mild ALT elevation.

Their median age at clearance was 48 years, and 87% were male.

"Considering that sustained remission is a prerequisite of HBsAg seroclearance, a group of 46 HBeAg-negative, noncirrhotic HBV carriers with PNALT for greater than 10 years were selected as [a] control group for comparison," wrote the researchers.

Controls were matched for age, gender, and genotype and all had PNALT for greater than 10 years but remained HBsAg seropositive.

Levels of HBsAg were assessed in saved serum specimens collected at 5 years, 3 years, and 1 year before HBsAg seroclearance (or, for controls, the last examination).

The authors found that median HBsAg levels at all time points were significantly lower in the seroclearance group, compared with controls.

For example, at 5 years before seroclearance, the study group’s median HBsAg level was 154.8 IU/mL, vs. 1,361 IU/mL for controls; at 3 years, the median values were 56.3 IU/mL vs. 1,063.3 IU/mL; and at 1 year prior to HBsAg seroclearance, levels were 1.6 IU/mL vs. 642.6 IU/mL (P less than .0001 for all time points).

Not only were the values much lower in the study group at all time points, but also the rate of change from year to year was significantly greater in the seroclearance group, compared with controls.

Indeed, the authors calculated the estimated annual decline of HBsAg to be 0.53 log10 IU/mL for the study group, significantly higher than 0.09 log10 IU/mL per year in the matched controls (P less than .0001).

Finally, the authors looked at the link between the serum HBsAg levels themselves and achievement of clearance.

"In the study group, HBsAg levels declined to less than 200 and less than 100 IU/mL in 55% and 37% of the patients, respectively, at 5 years prior to HBsAg seroclearance," wrote the authors.

"The proportion of patients reaching these levels of HBsAg increased to 81% and 64% at 3 years; [and to] 100% and 98% at 1 year prior to HBsAg seroclearance."

Taken together, "A greater than 1 log10 IU/mL decline in HBsAg during a 2-year period, combined with a single time point HBsAg level less than or equal to 200 IU/mL, can best predict HBsAg seroclearance in 1 and 3 years," with a positive predictive value for clearance in 1 year of 97%, and the positive predictive value for clearance at 3 years of 100%.

The authors mentioned several limitations. "Matching age, gender, and HBV genotype for this study might mask the potential influence of these factors on HBsAg seroclearance," they wrote.

Additionally, some stored serum specimens were of insufficient volume for analysis.

"Nevertheless, more than 90% of stored serum specimens were available at the 1- and 3-year time points, with 83% being available at the 5-year time point."

The authors stated that the study was supported by grants from the Chang Gung Medical Research Fund and the Prosperous Foundation. One of the researchers disclosed serving as a global advisory board member or being involved with clinical trials sponsored by Roche, Bristol-Myers Squibb, Novartis, and Gilead Sciences.

Serum hepatitis B surface antigen (HBsAg) seroclearance is preceded by significant, accelerated decreases in serum HBsAg levels during the 3 years leading up to seroclearance, wrote Dr. Yi-Cheng Chen and colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Moreover, serum HBsAg levels of less than 200 IU/mL are highly predictive of spontaneous seroclearance.

"It is therefore recommended to quantify HBsAg every 2 years in hepatitis B e antigen-negative HBsAg carriers with persistently normal alanine aminotransferase levels to detect who requires yearly HBsAg assay for the anticipated HBsAg seroclearance" (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2011.08.029]).

Dr. Chen of the Liver Research Unit at Chang Gung University, Taipei, Taiwan, studied 46 patients who had undergone spontaneous HBsAg seroclearance, defined as "loss of serum HBsAg documented on two occasions at least 6 months apart and maintained to the last visit."

Prior to clearance, all patients were hepatitis B e antigen (HBeAg)–negative for between 8 and 28 years, and most had persistently normal alanine aminotransferase (PNALT) for a mean of 14.2 years, except seven patients with mild ALT elevation.

Their median age at clearance was 48 years, and 87% were male.

"Considering that sustained remission is a prerequisite of HBsAg seroclearance, a group of 46 HBeAg-negative, noncirrhotic HBV carriers with PNALT for greater than 10 years were selected as [a] control group for comparison," wrote the researchers.

Controls were matched for age, gender, and genotype and all had PNALT for greater than 10 years but remained HBsAg seropositive.

Levels of HBsAg were assessed in saved serum specimens collected at 5 years, 3 years, and 1 year before HBsAg seroclearance (or, for controls, the last examination).

The authors found that median HBsAg levels at all time points were significantly lower in the seroclearance group, compared with controls.

For example, at 5 years before seroclearance, the study group’s median HBsAg level was 154.8 IU/mL, vs. 1,361 IU/mL for controls; at 3 years, the median values were 56.3 IU/mL vs. 1,063.3 IU/mL; and at 1 year prior to HBsAg seroclearance, levels were 1.6 IU/mL vs. 642.6 IU/mL (P less than .0001 for all time points).

Not only were the values much lower in the study group at all time points, but also the rate of change from year to year was significantly greater in the seroclearance group, compared with controls.

Indeed, the authors calculated the estimated annual decline of HBsAg to be 0.53 log10 IU/mL for the study group, significantly higher than 0.09 log10 IU/mL per year in the matched controls (P less than .0001).

Finally, the authors looked at the link between the serum HBsAg levels themselves and achievement of clearance.

"In the study group, HBsAg levels declined to less than 200 and less than 100 IU/mL in 55% and 37% of the patients, respectively, at 5 years prior to HBsAg seroclearance," wrote the authors.

"The proportion of patients reaching these levels of HBsAg increased to 81% and 64% at 3 years; [and to] 100% and 98% at 1 year prior to HBsAg seroclearance."

Taken together, "A greater than 1 log10 IU/mL decline in HBsAg during a 2-year period, combined with a single time point HBsAg level less than or equal to 200 IU/mL, can best predict HBsAg seroclearance in 1 and 3 years," with a positive predictive value for clearance in 1 year of 97%, and the positive predictive value for clearance at 3 years of 100%.

The authors mentioned several limitations. "Matching age, gender, and HBV genotype for this study might mask the potential influence of these factors on HBsAg seroclearance," they wrote.

Additionally, some stored serum specimens were of insufficient volume for analysis.

"Nevertheless, more than 90% of stored serum specimens were available at the 1- and 3-year time points, with 83% being available at the 5-year time point."

The authors stated that the study was supported by grants from the Chang Gung Medical Research Fund and the Prosperous Foundation. One of the researchers disclosed serving as a global advisory board member or being involved with clinical trials sponsored by Roche, Bristol-Myers Squibb, Novartis, and Gilead Sciences.

Serum hepatitis B surface antigen (HBsAg) seroclearance is preceded by significant, accelerated decreases in serum HBsAg levels during the 3 years leading up to seroclearance, wrote Dr. Yi-Cheng Chen and colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Moreover, serum HBsAg levels of less than 200 IU/mL are highly predictive of spontaneous seroclearance.

"It is therefore recommended to quantify HBsAg every 2 years in hepatitis B e antigen-negative HBsAg carriers with persistently normal alanine aminotransferase levels to detect who requires yearly HBsAg assay for the anticipated HBsAg seroclearance" (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2011.08.029]).

Dr. Chen of the Liver Research Unit at Chang Gung University, Taipei, Taiwan, studied 46 patients who had undergone spontaneous HBsAg seroclearance, defined as "loss of serum HBsAg documented on two occasions at least 6 months apart and maintained to the last visit."

Prior to clearance, all patients were hepatitis B e antigen (HBeAg)–negative for between 8 and 28 years, and most had persistently normal alanine aminotransferase (PNALT) for a mean of 14.2 years, except seven patients with mild ALT elevation.

Their median age at clearance was 48 years, and 87% were male.

"Considering that sustained remission is a prerequisite of HBsAg seroclearance, a group of 46 HBeAg-negative, noncirrhotic HBV carriers with PNALT for greater than 10 years were selected as [a] control group for comparison," wrote the researchers.

Controls were matched for age, gender, and genotype and all had PNALT for greater than 10 years but remained HBsAg seropositive.

Levels of HBsAg were assessed in saved serum specimens collected at 5 years, 3 years, and 1 year before HBsAg seroclearance (or, for controls, the last examination).

The authors found that median HBsAg levels at all time points were significantly lower in the seroclearance group, compared with controls.

For example, at 5 years before seroclearance, the study group’s median HBsAg level was 154.8 IU/mL, vs. 1,361 IU/mL for controls; at 3 years, the median values were 56.3 IU/mL vs. 1,063.3 IU/mL; and at 1 year prior to HBsAg seroclearance, levels were 1.6 IU/mL vs. 642.6 IU/mL (P less than .0001 for all time points).

Not only were the values much lower in the study group at all time points, but also the rate of change from year to year was significantly greater in the seroclearance group, compared with controls.

Indeed, the authors calculated the estimated annual decline of HBsAg to be 0.53 log10 IU/mL for the study group, significantly higher than 0.09 log10 IU/mL per year in the matched controls (P less than .0001).

Finally, the authors looked at the link between the serum HBsAg levels themselves and achievement of clearance.

"In the study group, HBsAg levels declined to less than 200 and less than 100 IU/mL in 55% and 37% of the patients, respectively, at 5 years prior to HBsAg seroclearance," wrote the authors.

"The proportion of patients reaching these levels of HBsAg increased to 81% and 64% at 3 years; [and to] 100% and 98% at 1 year prior to HBsAg seroclearance."

Taken together, "A greater than 1 log10 IU/mL decline in HBsAg during a 2-year period, combined with a single time point HBsAg level less than or equal to 200 IU/mL, can best predict HBsAg seroclearance in 1 and 3 years," with a positive predictive value for clearance in 1 year of 97%, and the positive predictive value for clearance at 3 years of 100%.

The authors mentioned several limitations. "Matching age, gender, and HBV genotype for this study might mask the potential influence of these factors on HBsAg seroclearance," they wrote.

Additionally, some stored serum specimens were of insufficient volume for analysis.

"Nevertheless, more than 90% of stored serum specimens were available at the 1- and 3-year time points, with 83% being available at the 5-year time point."

The authors stated that the study was supported by grants from the Chang Gung Medical Research Fund and the Prosperous Foundation. One of the researchers disclosed serving as a global advisory board member or being involved with clinical trials sponsored by Roche, Bristol-Myers Squibb, Novartis, and Gilead Sciences.