Entecavir Reduced Serum Hepatitis B Core-Related Antigen in Chronic Hepatitis B Patients with Hepatocellular Carcinoma
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Serum hepatitis B core-related antigen (HBcrAg) was shown to predict the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients undergoing treatment. We investigated the longitudinal profile of HBcrAg in entecavir (ETV)-treated CHB patients with subsequent HCC development. We identified HCC cases diagnosed at ≥1 year after ETV initiation. CHB patients without HCC (matched for age, sex, cirrhosis status, baseline hepatitis B virus [HBV] DNA level, and ETV treatment duration) were identified as controls at an HCC:non-HCC ratio of 1:2. Serum samples were retrieved at baseline (ETV initiation) and at 3 and 5 years of ETV therapy for HBcrAg measurement (log IU/mL). In total, 180 patients (60 HCC patients matched with 120 CHB patients without HCC; median age, 56.5 years; 80.6% male; baseline HBV DNA, 5.9 log IU/mL; median follow-up, 6.8 years) were recruited. The median time from ETV initiation to HCC development was 3.2 years. HBcrAg levels were higher in HCC cases than in controls at all three time points: 5.69 log IU/ mL versus 5.02 log IU/mL (p=0.025), 4.23 log IU/mL versus 3.36 log IU/mL (p=0.007), and 3.86 log IU/mL versus 3.36 log IU/mL (p=0.009), respectively. ETV led to similar rates of decline in HBcrAg from baseline to 3 years in both groups (0.34 log IU/mL/year vs 0.39 log IU/mL/year, p=0.774), although the decline from 3 to 5 years was slower in the non- HCC group (0.05 log IU/mL/year) than in the HCC group (0.09 log IU/mL/year, p=0.055). ETV time-dependently reduced HBcrAg in HCC and non-HCC patients. HBcrAg interpretation should consider the antiviral treatment duration.
Abstract
Serum hepatitis B core-related antigen (HBcrAg) was shown to predict the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients undergoing treatment. We investigated the longitudinal profile of HBcrAg in entecavir (ETV)-treated CHB patients with subsequent HCC development. We identified HCC cases diagnosed at ≥1 year after ETV initiation. CHB patients without HCC (matched for age, sex, cirrhosis status, baseline hepatitis B virus [HBV] DNA level, and ETV treatment duration) were identified as controls at an HCC:non-HCC ratio of 1:2. Serum samples were retrieved at baseline (ETV initiation) and at 3 and 5 years of ETV therapy for HBcrAg measurement (log IU/mL). In total, 180 patients (60 HCC patients matched with 120 CHB patients without HCC; median age, 56.5 years; 80.6% male; baseline HBV DNA, 5.9 log IU/mL; median follow-up, 6.8 years) were recruited. The median time from ETV initiation to HCC development was 3.2 years. HBcrAg levels were higher in HCC cases than in controls at all three time points: 5.69 log IU/ mL versus 5.02 log IU/mL (p=0.025), 4.23 log IU/mL versus 3.36 log IU/mL (p=0.007), and 3.86 log IU/mL versus 3.36 log IU/mL (p=0.009), respectively. ETV led to similar rates of decline in HBcrAg from baseline to 3 years in both groups (0.34 log IU/mL/year vs 0.39 log IU/mL/year, p=0.774), although the decline from 3 to 5 years was slower in the non- HCC group (0.05 log IU/mL/year) than in the HCC group (0.09 log IU/mL/year, p=0.055). ETV time-dependently reduced HBcrAg in HCC and non-HCC patients. HBcrAg interpretation should consider the antiviral treatment duration.
참고문헌 (15)
- Varbobitis I, "The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy", Clin Mol Hepatol, 22, pp.319~326 (2016)
- Papatheodoridis GV, "Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s)starting with lamivudine monotherapy : results of the nationwide HEPNET : Greece cohort study", Gut, 60, pp.1109~1116 (2011)
- Papatheodoridis GV, "Risk of hepatocellular carcinoma in chronic hepatitis B : assessment and modification with current antiviral therapy", J Hepatol, 62, pp.956~967 (2015)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- European Association for the Study of the Liver, "EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
- Chen CJ, "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level", JAMA, 295, pp.65~73 (2006)
- Lam YF, "Seven-year treatment outcome of entecavir in a real-world cohort : effects on clinical parameters, HBsAg and HBcrAg levels", Clin Transl Gastroenterol, 8, pp.e125~ (2017)
- Wong DK, "Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection", J Clin Microbiol, 45, pp.3942~3947 (2007)
- Cheung KS, "Relationship between HBsAg, HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy", J Viral Hepat, 24, pp.654~661 (2017)
- Hosaka T, "Impact of hepatitis B corerelated antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues", Aliment Pharmacol Ther, 49, pp.457~471 (2019)
- To WP, "Relationship between hepatitis B core-related antigen and chronic hepatitis B outcome in HBeAg negative patients : a 10-year longitudinal study", J Hepatol, 68, pp.S478~ (2018)
- Lai CL, "Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B", J Hepatol, 66, pp.275~281 (2017)
- Honda M, "Hepatitis B virus(HBV)core-related antigen during nucleos(t)ide analog therapy is related to intra-hepatic HBV replication and development of hepatocellular carcinoma", J Infect Dis, 213, pp.1096~1106 (2016)
- Yuen MF, "Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B", C, specific mutations of enhancer II, precore regions and HBV DNA levels, pp.Gut, 2008[DOI]
- Yuen MF, "HBsAg seroclearance in chronic hepatitis B in the Chinese : virological, histological, and clinical aspects", Hepatology, 39, pp.1694~1701 (2004)