Journal of gastroenterology and hepatology · 2021
Hepatitis B core-related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen-negative chronic hepatitis B patients.
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Kaneko Shun, Kurosaki Masayuki, Inada Kento, Kirino Sakura, Hayakawa Yuka, Yamashita Koji, Osawa Leona, Sekiguchi Shuhei, Higuchi Mayu, Takaura Kenta, Maeyashiki Chiaki, Tamaki Nobuharu, Yasui Yutaka, Itakura Jun, Takahashi Yuka, Tsuchiya Kaoru, Nakanishi Hiroyuki, Izumi Namiki
Аннотация
BACKGROUND AND AIM: The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients.
METHODS: Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1 year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients.
RESULTS: Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (> 6.8 vs 3.7 log U/mL, P < 0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis = 3.5/4.7 log U/mL, P = 0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1 year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1 log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P < 0.01) and even in non-cirrhosis patients.
CONCLUSION: Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.
METHODS: Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1 year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients.
RESULTS: Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (> 6.8 vs 3.7 log U/mL, P < 0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis = 3.5/4.7 log U/mL, P = 0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1 year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1 log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P < 0.01) and even in non-cirrhosis patients.
CONCLUSION: Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.