Long-term Hepatitis B Surface Antigen Profile and Seroclearance after Severe Acute Flares of Chronic Hepatitis B
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Background/Aims: Hepatitis B surface antigen (HBsAg) seroclearance remains uncommon in chronic hepatitis B (CHB) infection. During acute flares of CHB (AFOCHB), alanine aminotransferase elevation reflects a mounting immune response toward viral clearance. We hypothesized that severe AFOCHB is associated with a greater quantitative HBsAg (qHBsAg) decline and HBsAg seroclearance rate. Methods: A total of 75 patients with severe AFOCHB with alanine aminotransferase 10× the upper limit of normal were matched to a control group by age and sex in a 1:2 ratio. qHBsAg levels were measured at the time of flare and annually (for both cases and controls) until the last follow-up. Results: The median follow-up times for patients with severe AFOCHB and controls were 8.8 and 10.5 years, respectively. The cumulative rate of HBsAg seroclearance was higher in the severe AFOCHB group than in the control group (11.8% vs 5.0%, p=0.04) despite the former group having a trend of a higher baseline median qHBsAg (3,127 IU/mL vs 1,178 IU/mL, p=0.076). Compared with the control group, the severe AFOCHB group had a greater annual qHBsAg reduction (–242.4 IU/mL/yr vs –47.3 IU/mL/yr, p=0.002). Increasing age (p=0.049), lower baseline qHBsAg (p=0.002), and severe AFOCHB (p=0.014) were independently associated with HBsAg seroclearance. However, the cumulative rate of hepatocellular carcinoma was significantly higher in the severe AFOCHB group than in the control group (15.8% vs 1.9%, p<0.001). Conclusions: Severe AFOCHB was associated with a greater incidence of HBsAg seroclearance and qHBsAg decline. However, it was associated with a higher incidence of hepatocellular carcinoma.
Abstract
Background/Aims: Hepatitis B surface antigen (HBsAg) seroclearance remains uncommon in chronic hepatitis B (CHB) infection. During acute flares of CHB (AFOCHB), alanine aminotransferase elevation reflects a mounting immune response toward viral clearance. We hypothesized that severe AFOCHB is associated with a greater quantitative HBsAg (qHBsAg) decline and HBsAg seroclearance rate. Methods: A total of 75 patients with severe AFOCHB with alanine aminotransferase 10× the upper limit of normal were matched to a control group by age and sex in a 1:2 ratio. qHBsAg levels were measured at the time of flare and annually (for both cases and controls) until the last follow-up. Results: The median follow-up times for patients with severe AFOCHB and controls were 8.8 and 10.5 years, respectively. The cumulative rate of HBsAg seroclearance was higher in the severe AFOCHB group than in the control group (11.8% vs 5.0%, p=0.04) despite the former group having a trend of a higher baseline median qHBsAg (3,127 IU/mL vs 1,178 IU/mL, p=0.076). Compared with the control group, the severe AFOCHB group had a greater annual qHBsAg reduction (–242.4 IU/mL/yr vs –47.3 IU/mL/yr, p=0.002). Increasing age (p=0.049), lower baseline qHBsAg (p=0.002), and severe AFOCHB (p=0.014) were independently associated with HBsAg seroclearance. However, the cumulative rate of hepatocellular carcinoma was significantly higher in the severe AFOCHB group than in the control group (15.8% vs 1.9%, p<0.001). Conclusions: Severe AFOCHB was associated with a greater incidence of HBsAg seroclearance and qHBsAg decline. However, it was associated with a higher incidence of hepatocellular carcinoma.
참고문헌 (21)
- Fattovich G, "Natural history of hepatitis B", J Hepatol, 39(Suppl 1), pp.S50~S58 (2003)
- Dienstag JL, "Hepatitis B virus infection", N Engl J Med, 359, pp.1486~1500 (2008)
- Tran TT, "Immune tolerant hepatitis B: a clinical dilemma", Gastroenterol Hepatol(N Y), 7, pp.511~516 (2011)
- Zoulim F, "Kinetics of intrahepatic covalently closed circular DNA and serum hepatitis B surface antigen during antiviral therapy for chronic hepatitis B : lessons from experimental and clinical studies", Clin Gastroenterol Hepatol, 11, pp.1011~1013 (2013)
- European Association for the Study of the Liver, "EASL 2017Clinical Practice Guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
- Yuen MF, "HBsAg seroclearance in chronic hepatitis B in Asian patients : replicative level and risk of hepatocellular carcinoma", Gastroenterology, 135, pp.1192~1199 (2008)
- Yeo YH, "Incidence, factors, and patient-level data for spontaneous HBsAg seroclearance : a cohort study of 11, 264 patients", Clin Transl Gastroenterol, 11, pp.e00196~ (2020)
- Yeo YH, "Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection : a systematic review and meta-analysis", Gastroenterology, 156, pp.635~646 (2019)
- Fung J, "Long-term outcomes and predictive scores for hepatocellular carcinoma and hepatitis B surface antigen seroclearance after hepatitis B eantigen seroclearance", Hepatology, 68, pp.462~472 (2018)
- Chan HL, "Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response", Clin Gastroenterol Hepatol, 5, pp.1462~1468 (2007)
- Ramachandran J, "Serum HBsAg quantification in treatment-naïve Indian patients with chronic hepatitis B", Indian J Gastroenterol, 33, pp.131~135 (2014)
- Thompson AJ, "Serum hepatitis B surface antigen and hepatitis B e antigen titers : disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers", Hepatology, 51, pp.1933~1944 (2010)
- Jaroszewicz J, "Hepatitis B surface antigen(HBsAg)levels in the natural history of hepatitis B virus(HBV)-infection : a European perspective", J Hepatol, 52, pp.514~522 (2010)
- Nagaoka S, "Hepatic flares promote rapid decline of serum hepatitis B surface antigen(HBsAg)in patients with HBsAg seroclearance : a long-term follow-up study", Hepatol Res, 46, pp.E89~E99 (2016)
- Kim GA, "HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B : clinical outcomes and durability", Gut, 63, pp.1325~1332 (2014)
- Terrault NA, "AASLD guidelines for treatment of chronic hepatitis B", Hepatology, 63, pp.261~283 (2016)
- Wursthorn K, "Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen(HBsAg)in the serum", J Clin Virol, 50, pp.292~296 (2011)
- Seto WK, "A large case-control study on the predictability of hepatitis B surface antigen levels three years before hepatitis B surface antigen seroclearance", Hepatology, 56, pp.812~819 (2012)
- Sterling RK, "Development of a simple noninvasive index to predict significant fibrosis in patients with HIV", HCV coinfection, 2006, pp.43, 1317~1325
- Yang N, "Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients", J Med Virol, 90, pp.1240~1245 (2018)
- van Bömmel F, "Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients : results of the Stop-NUC trial", J Hepatol, 73, pp.S118~S119 (2020)
