Journal List > Korean J Gastroenterol > v.63(5) > 1007238

Kang and Kim: Is HBsAg Loss an Ideal Endpoint of Oral Antiviral Therapy in Chronic Hepatitis B Patients?

Abstract

Article

HBsAg Seroclearance after Nucleoside Analogue Therapy in Patients with Chronic Hepatitis B: Clinical Outcomes and Durability

References

1. Kim GA, Lim YS, An J, et al. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability. Gut. 2013. DOI: doi: 10.1136/gutjnl-2013–305517. [Epub ahead of print].
crossref
2. Liaw YF, Jia JD, Chan HL, et al. Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. Hepatology. 2011; 54:1591–1599.
crossref
3. Marcellin P, Lau GK, Bonino F, et al. Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004; 351:1206–1217.
crossref
4. Lampertico P, Viganò M, Di Costanzo GG, et al. PegBeLiver Study Group. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B. Gut. 2013; 62:290–298.
crossref
5. Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008; 135:459–467.
6. Marcellin P, Bonino F, Lau GK, et al. Peginterferon alfa-2a in HBeAg-negative Chronic Hepatitis B Study Group. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009; 136:2169–2179. e1-e4.
7. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012; 57:167–185.
8. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009; 50:661–662.
crossref
9. Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012; 6:531–561.
crossref
10. The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol. 2012; 18:109–162.
11. Chen DB, Chen YM, Liu J, et al. Durability of efficacy after telbivudine off-treatment in chronic hepatitis B patients. J Clin Virol. 2014; 59:50–54.
crossref
12. Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012; 143:629–636.e1.
crossref
13. Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology. 2000; 32:803–806.
crossref
14. Song MJ, Song DS, Kim HY, et al. Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B. World J Gastroenterol. 2012; 18:6277–6283.
crossref
15. Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology. 2013; 58:1888–1896.
crossref
16. Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology. 1991; 13:627–631.
crossref
17. Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology. 2002; 123:1084–1089.
crossref
18. Kim JH, Lee YS, Lee HJ, et al. HBsAg seroclearance in chronic hepatitis B: implications for hepatocellular carcinoma. J Clin Gastroenterol. 2011; 45:64–68.
19. Loriot MA, Marcellin P, Walker F, et al. Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg. J Hepatol. 1997; 27:251–258.
crossref
20. Yuen MF, Wong DK, Fung J, et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008; 135:1192–1199.
crossref
21. Arase Y, Ikeda K, Suzuki F, et al. Longterm outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B. Am J Med. 2006; 119:71. e9-e16.
crossref
22. Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol. 1998; 93:896–900.
23. Liaw YF, Sung JJ, Chow WC, et al. Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004; 351:1521–1531.
crossref
24. Martinot-Peignoux M, Lapalus M, Asselah T, Marcellin P. HBsAg quantification: useful for monitoring natural history and treatment outcome. Liver Int. 2014; 34(Suppl 1):97–107.
crossref
25. Suh SJ, Bae SI, Kim JH, Kang K, Yeon JE, Byun KS. Clinical implications of the titer of serum hepatitis B surface antigen during the natural history of hepatitis B virus infection. J Med Virol. 2014; 86:117–123.
crossref
26. Chan HL, Wong VW, Tse AM, et al. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol. 2007; 5:1462–1468.
crossref
27. Dong PL, Zhang X, Zhao WM, Ding HG. HBsAg loss is not an ideal indicator for discontinuing treatment of HBeAg-negative chronic hepatitis B: a case report. J Infect Chemother. 2013; 19:1188–1192.
crossref
28. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006; 130:678–686.
crossref
29. Iloeje U, Yang HI, Su J, et al. HBV viral load less than 104 copies/ml is associated with significant risk of hepatocellular carcinoma in chronic hepatitis B patients: an update from the R.E.V.E.A.L.-HBV study. Hepatology. 2007; 46(Suppl 1):640A. abstract 907.
30. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013; 381:468–475.
crossref
31. Chevaliez S, Hézode C, Bahrami S, Grare M, Pawlotsky JM. Longterm hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely. J Hepatol. 2013; 58:676–683.
crossref
32. Seto WK, Liu K, Wong DK, et al. Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatmentexperienced chronic hepatitis B patients after three years of tenofovir treatment. J Hepatol. 2013; 59:709–716.
crossref
33. Ouzan D, Pénaranda G, Joly H, Khiri H, Pironti A, Halfon P. Add-on peginterferon leads to loss of HBsAg in patients with HBeAg-negative chronic hepatitis and HBV DNA fully suppressed by long-term nucleotide analogs. J Clin Virol. 2013; 58:713–717.
crossref
34. Kittner JM, Sprinzl MF, Grambihler A, et al. Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B. J Clin Virol. 2012; 54:93–95.
crossref
35. Zoulim F, Luangsay S, Durantel D. Targeting innate immunity: a new step in the development of combination therapy for chronic hepatitis B. Gastroenterology. 2013; 144:1342–1344.
crossref

Table 1.
Serum HBV DNA Levels after HBsAg Loss
  Arase et al.21 Yuen et al.20 Kim et al.1
Number of cases 231 298 110
HBV DNA cut-off (IU/mL) 80 1.1 15
Time of HBV DNA(+) after HBsAg loss    
 At 1 yr 3 (0.9%) 19 (13.4%) 13.8%b
 At 5 yr 6 (6.1%) 29.6%c
 At >10 yr 1 (3.7%)a  

a Median HBV DNA 7 IU/mL (1.1–396.8 IU/mL)

b cumulative incidence

c cumulative incidence at 4 years.

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