Top

Current Hepatology Reports

Published in:

12-02-2024 | Hepatitis B

Should Indications for Antiviral Therapy for Hepatitis B Be Broadened to Include Immune-Tolerant Patients, Inactive Carriers, or Patients in the “Gray Zone”?

Authors: Yen-Chun Liu, Wen-Juei Jeng

Published in: Current Hepatology Reports | Issue 1/2024

Abstract

Purpose of Review

Current antiviral therapy effectively suppresses hepatitis B virus (HBV) replication and improves the prognosis. It cannot cure HBV infection. Current clinical guidelines do not advocate universal treatment for all with chronic hepatitis B. However, recent studies are deliberating the expansion of treatment eligibility criteria to encompass those in immune-tolerant, inactive carrier, and gray zone statuses. This review examines the updated information regarding this issue.

Recent Findings

For immune-tolerant patients and patients in the gray zone, treatment eligibility might be considered for those with active or significant fibrosis/inflammation, especially those that remain in the immune-tolerant phase older than 30–40. Current evidence does not suggest that antiviral treatment would be beneficial for true inactive carriers.

Summary

Evidence-based management is crucial in current antiviral therapy. Appropriate monitoring and evaluation help identify individuals who would benefit from antiviral treatment. Expanding indications may hinge on new evidence or curative therapies with finite durations if available.

World Health Organization. Global hepatitis report. Geneva, Switzerland: World Health Organization; 2019.

Global health sector strategy on viral hepatitis 2016–2021. Towards ending viral hepatitis. 2016. [press release]. 2016.

Ko C, Chakraborty A, Chou WM, Hasreiter J, Wettengel JM, Stadler D, et al. Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels. J Hepatol. 2018;69(6):1231–41. https://doi.org/10.1016/j.jhep.2018.08.012.CrossRefPubMedPubMedCentral

Ghany MG, Lok AS. Functional cure of hepatitis B requires silencing covalently closed circular and integrated hepatitis B virus DNA. J Clin Invest. 2022;132(18). https://doi.org/10.1172/JCI163175.

Bertoletti A, Ferrari C. Adaptive immunity in HBV infection. J Hepatol. 2016;64(1 Suppl):S71–83. https://doi.org/10.1016/j.jhep.2016.01.026.CrossRefPubMed

Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70(3):361–70. https://doi.org/10.1016/j.jhep.2018.10.014.CrossRefPubMed

Cornberg M, Lok AS, Terrault NA, Zoulim F. Guidance for design and endpoints of clinical trials in chronic hepatitis B - report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference. J Hepatol. 2020;72(3):539–57. https://doi.org/10.1016/j.jhep.2019.11.003.CrossRefPubMed

Chu CM, Hung SJ, Lin J, Tai DI, Liaw YF. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med. 2004;116(12):829–34. https://doi.org/10.1016/j.amjmed.2003.12.040.CrossRefPubMed

Lee HA, Lee HW, Kim IH, Park SY, Sinn DH, Yu JH, et al. Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase. Aliment Pharmacol Ther. 2020;52(1):196–204. https://doi.org/10.1111/apt.15741.CrossRefPubMed

10.

Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007;46(2):395–401. https://doi.org/10.1002/hep.21724.CrossRefPubMed

11.

Lee HW, Kim EH, Lee J, Kim SU, Park JY, Kim DY, et al. Natural history of untreated HBeAg-positive chronic HBV infection with persistently elevated HBV DNA but normal alanine aminotransferase. Clin Transl Gastroenterol. 2020;11(3):e00140. https://doi.org/10.14309/ctg.0000000000000140.CrossRefPubMedPubMedCentral

12.

Andreani T, Serfaty L, Mohand D, Dernaika S, Wendum D, Chazouilleres O, et al. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol. 2007;5(5):636–41. https://doi.org/10.1016/j.cgh.2007.01.005.CrossRefPubMed

13.

Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009;373(9663):582–92. https://doi.org/10.1016/S0140-6736(09)60207-5.CrossRefPubMed

14.

Chu CM, Liaw YF. Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion. J Viral Hepat. 2007;14(3):147–52. https://doi.org/10.1111/j.1365-2893.2006.00810.x.CrossRefPubMed

15.

• Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology. 2010;51(2):435–44. https://doi.org/10.1002/hep.23348. (This long-term cohort study provides important information of natural history of HBeAg-positive patients.)CrossRefPubMed

16.

• Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35(6):1522–7. https://doi.org/10.1053/jhep.2002.33638. (This long-term cohort study provides important information of natural history after HBeAgseroconversion.)CrossRefPubMed

17.

• Lee WM, King WC, Janssen HLA, Ghany MG, Fontana RJ, Fried M, et al. Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: a prospective cohort study. J Viral Hepat. 2021;28(11):1526–38. https://doi.org/10.1111/jvh.13591. (The prospective study determines the rate and predictors of HBeAg loss in chronic hepatitis B patients in the Western cohort.)CrossRefPubMedPubMedCentral

18.

Tai DI, Lin SM, Sheen IS, Chu CM, Lin DY, Liaw YF. Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time. Hepatology. 2009;49(6):1859–67. https://doi.org/10.1002/hep.22878.CrossRefPubMed

19.

Kumada T, Toyoda H, Yasuda S, Ito T, Tanaka J. Mortality of inactive hepatitis B virus carriers in Japan is similar to that of the general population. Hepatol Res. 2022;52(1):81–92. https://doi.org/10.1111/hepr.13723.CrossRefPubMed

20.

Chu CM, Liaw YF. Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus. Am J Gastroenterol. 2009;104(7):1693–9. https://doi.org/10.1038/ajg.2009.187.CrossRefPubMed

21.

Yeo YH, Tseng TC, Hosaka T, Cunningham C, Fung JYY, Ho HJ, et al. Incidence, factors, and patient-level data for spontaneous HBsAg seroclearance: a cohort study of 11,264 patients. Clin Transl Gastroenterol. 2020;11(9):e00196. https://doi.org/10.14309/ctg.0000000000000196.CrossRefPubMedPubMedCentral

22.

Yeo YH, Ho HJ, Yang HI, Tseng TC, Hosaka T, Trinh HN, et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: a systematic review and meta-analysis. Gastroenterology. 2019;156(3):635-46 e9. https://doi.org/10.1053/j.gastro.2018.10.027.CrossRefPubMed

23.

Zhou K, Contag C, Whitaker E, Terrault N. Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: a systematic review and pooled meta-analyses. Lancet Gastroenterol Hepatol. 2019;4(3):227–38. https://doi.org/10.1016/S2468-1253(18)30308-X.CrossRefPubMedPubMedCentral

24.

Kuang XJ, Jia RR, Huo RR, Yu JJ, Wang JJ, Xiang BD, Li LQ, Peng Z, Zhong JH. Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance. J Viral Hepat. 2018;25(9):1026–37. https://doi.org/10.1111/jvh.12905.CrossRefPubMed

25.

Yip TC, Wong VW, Lai MS, Lai JC, Hui VW, Liang LY, Tse YK, Chan HL, Wong GL. Risk of hepatic decompensation but not hepatocellular carcinoma decreases over time in patients with hepatitis B surface antigen loss. J Hepatol. 2023;78(3):524-533. 1016/j.jhep.2022.11.020

26.

•• Jeng WJ, Papatheodoridis GV, Lok ASF. Hepatitis B. Lancet. 2023;401(10381):1039–52. https://doi.org/10.1016/S0140-6736(22)01468-4. (The updated review provides the comprehensive evidences of HBV.)CrossRefPubMed

27.

Lee SK, Kwon JH, Lee SW, Jang JW, Nam H, Baik KW, et al. Sustained off therapy response after peglyated interferon favours functional cure and no disease progression in chronic hepatitis B. Liver Int. 2021;41(2):288–94. https://doi.org/10.1111/liv.14701.CrossRefPubMed

28.

Sun J, Ding H, Chen G, Wang G, Wei L, Zhang J, et al. Sustained serological and complete responses in HBeAg-positive patients treated with peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China. BMC Gastroenterol. 2019;19(1):65. https://doi.org/10.1186/s12876-019-0981-5.CrossRefPubMedPubMedCentral

29.

Marcellin P, Bonino F, Yurdaydin C, Hadziyannis S, Moucari R, Kapprell HP, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013;7(1):88–97. https://doi.org/10.1007/s12072-012-9343-x.CrossRefPubMed

30.

Hoofnagle JH, Di Bisceglie AM, Waggoner JG, Park Y. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology. 1993;104(4):1116–21. https://doi.org/10.1016/0016-5085(93)90281-g.CrossRefPubMed

31.

Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98. https://doi.org/10.1007/s12072-015-9675-4.CrossRefPubMed

32.

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83. https://doi.org/10.1002/hep.28156.CrossRefPubMed

33.

Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99. https://doi.org/10.1002/hep.29800.CrossRefPubMed

34.

European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98. https://doi.org/10.1016/j.jhep.2017.03.021.CrossRef

35.

Loomba R, Liu J, Yang HI, Lee MH, Lu SN, Wang LY, et al. Synergistic effects of family history of hepatocellular carcinoma and hepatitis B virus infection on risk for incident hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2013;11(12):1636-45 e1-3. https://doi.org/10.1016/j.cgh.2013.04.043.CrossRefPubMedPubMedCentral

36.

Mason WS, Gill US, Litwin S, Zhou Y, Peri S, Pop O, et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant. Gastroenterology. 2016;151(5):986-98 e4. https://doi.org/10.1053/j.gastro.2016.07.012.CrossRefPubMed

37.

Bertoletti A, Kennedy PT. The immune tolerant phase of chronic HBV infection: new perspectives on an old concept. Cell Mol Immunol. 2015;12(3):258–63. https://doi.org/10.1038/cmi.2014.79.CrossRefPubMed

38.

Kennedy PTF, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, et al. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012;143(3):637–45. https://doi.org/10.1053/j.gastro.2012.06.009.CrossRefPubMed

39.

Park JJ, Wong DK, Wahed AS, Lee WM, Feld JJ, Terrault N, et al. Hepatitis B virus–specific and global T-cell dysfunction in chronic hepatitis B. Gastroenterology. 2016;150(3):684-95 e5. https://doi.org/10.1053/j.gastro.2015.11.050.CrossRefPubMed

40.

Nguyen MH, Garcia RT, Trinh HN, Lam KD, Weiss G, Nguyen HA, et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels. Am J Gastroenterol. 2009;104(9):2206–13. https://doi.org/10.1038/ajg.2009.248.CrossRefPubMed

41.

Xie Q, Hu X, Zhang Y, Jiang X, Li X, Li J. Decreasing hepatitis B viral load is associated with a risk of significant liver fibrosis in hepatitis B e antigen positive chronic hepatitis B. J Med Virol. 2014;86(11):1828–37. https://doi.org/10.1002/jmv.24000.CrossRefPubMed

42.

Chen J, Xu CR, Xi M, Hu WW, Tang ZH, Zang GQ. Predictors of liver histological changes and a sustained virological response to peginterferon among chronic hepatitis B e antigen-positive patients with normal or minimally elevated alanine aminotransferase levels. J Viral Hepat. 2017;24(7):573–9. https://doi.org/10.1111/jvh.12679.CrossRefPubMed

43.

Kim GA, Lim YS, Han S, Choi J, Shim JH, Kim KM, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018;67(5):945–52. https://doi.org/10.1136/gutjnl-2017-314904.CrossRefPubMed

44.

Yoo JJ, Park SY, Moon JE, Lee YR, Lee HA, Lee J, et al. Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase. Clin Mol Hepatol. 2023;29(2):482–95. https://doi.org/10.3350/cmh.2022.0322.CrossRefPubMedPubMedCentral

45.

Chan HL, Chan CK, Hui AJ, Chan S, Poordad F, Chang TT, et al. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology. 2014;146(5):1240–8. https://doi.org/10.1053/j.gastro.2014.01.044.CrossRefPubMed

46.

Wu IC, Lai CL, Han SH, Han KH, Gordon SC, Chao YC, et al. Efficacy of entecavir in chronic hepatitis B patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage. Hepatology. 2010;51(4):1185–9. https://doi.org/10.1002/hep.23424.CrossRefPubMed

47.

Jonas MM, Chang MH, Sokal E, Schwarz KB, Kelly D, Kim KM, et al. Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B. Hepatology. 2016;63(2):377–87. https://doi.org/10.1002/hep.28015.CrossRefPubMed

48.

• Rosenthal P, Ling SC, Belle SH, Murray KF, Rodriguez-Baez N, Schwarzenberg SJ, et al. Combination of entecavir/peginterferon alfa-2a in children with hepatitis B e antigen-positive immune tolerant chronic hepatitis B virus infection. Hepatology. 2019;69(6):2326–37. https://doi.org/10.1002/hep.30312. (Randomized controlled trial for immune-tolerant pediatric patients.)CrossRefPubMed

49.

• Feld JJ, Terrault NA, Lin HS, Belle SH, Chung RT, Tsai N, et al. Entecavir and peginterferon alfa-2a in adults with hepatitis B e antigen-positive immune-tolerant chronic hepatitis B virus infection. Hepatology. 2019;69(6):2338–48. https://doi.org/10.1002/hep.30417. (Randomized controlled trial for immune-tolerant adult patients.)CrossRefPubMed

50.

•Fattovich G, Olivari N, Pasino M, D’Onofrio M, Martone E, Donato F. Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years. Gut. 2008;57(1):84-90. https://doi.org/10.1136/gut.2007.128496. (Natural history of CHB patients in a Caucasian cohort.)

51.

Lee HW, Kim SU, Baatarkhuu O, Park JY, Kim DY, Ahn SH, et al. Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals. Sci Rep. 2019;9(1):2508. https://doi.org/10.1038/s41598-019-39043-2.CrossRefPubMedPubMedCentral

52.

Lin HC, Jeng RWJ, Liu J, Lee MH, Batrla-Utermann R, Lu SN, et al. Persistent high HBsAg levels predict lower risk of hepatocellular carcinoma in HBeAg-seropositive chronic hepatitis B patients. J Hepatol. 2021;75:S715.

53.

• Zhou K, Wahed AS, Cooper S, Di Bisceglie AM, Fontana RJ, Ghany MG, et al. Phase transition is infrequent among North American adults with e-antigen-negative chronic hepatitis B and low-level viremia. Am J Gastroenterol. 2019;114(11):1753-63. https://doi.org/10.14309/ajg.0000000000000400. (The multicenter study reveals the prevalence of indeterminate patients, and their phase transition and hepatocellular carcinoma risk.)

54.

Huang DQ, Li X, Le MH, Le AK, Yeo YH, Trinh HN, et al. Natural history and hepatocellular carcinoma risk in untreated chronic hepatitis B patients with indeterminate phase. Clin Gastroenterol Hepatol. 2022;20(8):1803-12 e5. https://doi.org/10.1016/j.cgh.2021.01.019.CrossRefPubMed

55.

Bonacci M, Lens S, Marino Z, Londono MC, Rodriguez-Tajes S, Mas A, et al. Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the gray zone. Aliment Pharmacol Ther. 2018;47(10):1397–408. https://doi.org/10.1111/apt.14613.CrossRefPubMed

56.

Oliveri F, Surace L, Cavallone D, Colombatto P, Ricco G, Salvati N, et al. Long-term outcome of inactive and active, low viraemic HBeAg-negative-hepatitis B virus infection: benign course towards HBsAg clearance. Liver Int. 2017;37(11):1622–31. https://doi.org/10.1111/liv.13416.CrossRefPubMed

57.

• Yapali S, Talaat N, Fontana RJ, Oberhelman K, Lok AS. Outcomes of patients with chronic hepatitis B who do not meet criteria for antiviral treatment at presentation. Clin Gastroenterol Hepatol. 2015;13(1):193-201 e1. https://doi.org/10.1016/j.cgh.2014.07.019. (This study provides important information of phase transition and adverse outcome in treatment-ineligible patients under stringent monitoring.)

58.

•• Lok AS, Perrillo R, Lalama CM, Fried MW, Belle SH, Ghany MG, et al. Low incidence of adverse outcomes in adults with chronic hepatitis B virus infection in the era of antiviral therapy. Hepatology. 2021;73(6):2124–40. https://doi.org/10.1002/hep.31554. (The multiethnic study reveals the low incidence of adverse outcomes in the large cohort of North American adults with predominantly inactive, chronic HBV without cirrhosis.)CrossRefPubMed

59.

Huang DQ, Lee DH, Le MH, Le A, Yeo YH, Trinh HN, et al. Liver complications in untreated treatment-ineligible versus treated treatment-eligible patients with hepatitis B. Dig Dis. 2023;41(1):115–23. https://doi.org/10.1159/000526933.CrossRefPubMed

60.

Huang DQ, Tran A, Yeh ML, Yasuda S, Tsai PC, Huang CF, et al. Antiviral therapy substantially reduces hepatocellular carcinoma risk in chronic hepatitis B patients in the indeterminate phase. Hepatology. 2023.

61.

Tseng TC, Hosaka T, Liu CJ, Suzuki F, Hong CM, Kumada H, et al. Hepatitis B core-related antigen stratifies the risk of liver cancer in HBeAg-negative patients with indeterminate phase. Am J Gastroenterol. 2022;117(5):748–57. https://doi.org/10.14309/ajg.0000000000001691.CrossRefPubMed

62.

Choi GH, Kim GA, Choi J, Han S, Lim YS. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther. 2019;50(2):215–26. https://doi.org/10.1111/apt.15311.CrossRefPubMed

63.

Gan QY, Wang JX, Qian F, Wang YL, Huang Y, Zhang ZL, et al. Clinical and histological features of patients with chronic hepatitis B virus infection in the gray zone. J Viral Hepat. 2023;30(10):803–9. https://doi.org/10.1111/jvh.13873.CrossRefPubMed

64.

Yu HS, Jiang H, Li MK, Yang BL, Smayi A, Chen JN, et al. Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients. World J Gastroenterol. 2023;29(35):5166–77. https://doi.org/10.3748/wjg.v29.i35.5166.CrossRefPubMedPubMedCentral

65.

Jiang SW, Lian X, Hu AR, Lu JL, He ZY, Shi XJ, et al. Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication. World J Gastroenterol. 2023;29(16):2479–94. https://doi.org/10.3748/wjg.v29.i16.2479.CrossRefPubMedPubMedCentral

66.

Wang J, Yan X, Zhu L, Liu J, Qiu Y, Li Y, et al. Significant histological disease of patients with chronic hepatitis B virus infection in the gray zone. Aliment Pharmacol Ther. 2022. https://doi.org/10.1111/apt.17272.CrossRefPubMedPubMedCentral

67.

•• Hsu YC, Chen CY, Chang IW, Chang CY, Wu CY, Lee TY, et al. Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial. Lancet Infect Dis. 2021;21(6):823–33. https://doi.org/10.1016/S1473-3099(20)30692-7. (The RCT provides important information about treatment’s impact on gray zone patients.)CrossRefPubMed

68.

• Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, 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(9865):468–75. https://doi.org/10.1016/S0140-6736(12)61425-1. (The RCT provides important information about treatment’s impact on fibrosis regression.)CrossRefPubMed

69.

• Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52(3):886–93. https://doi.org/10.1002/hep.23785. (The RCT provides important information about treatment’s impact on fibrosis regression.)CrossRefPubMed

70.

•• Jeng WJ, Lok AS. Should treatment indications for chronic hepatitis B be expanded? Clin Gastroenterol Hepatol. 2021;19(10):2006–14. https://doi.org/10.1016/j.cgh.2020.04.091. (The review examines the evidences for and against expansion of treatment to patients in whom treatment is not recommended based on current guidelines.)CrossRefPubMed

71.

Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, Wang LY, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology. 2010;138(5):1747–54. https://doi.org/10.1053/j.gastro.2010.01.042.CrossRefPubMed

72.

Abdo AA, Bzeizi KI, Babatin MA, AlSohaibani F, AlMana H, Alsaad KO, et al. Predictors of significant fibrosis in chronic hepatitis B patients with low viremia. J Clin Gastroenterol. 2014;48(6):e50-6. https://doi.org/10.1097/MCG.0b013e3182a9a2e1.CrossRefPubMed

73.

Zhang C, Li JW, Wu Z, Zhao H, Wang GQ. Significant histologic changes are not rare in treatment-naive hepatitis B patients with normal alanine aminotransferase level: a meta-analysis. J Clin Transl Hepatol. 2021;9(5):615–25. https://doi.org/10.14218/JCTH.2020.00136.CrossRefPubMedPubMedCentral

74.

Paik N, Sinn DH, Lee JH, Oh IS, Kim JH, Kang W, et al. Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low-level viremia. Liver Int. 2018;38(1):68–75. https://doi.org/10.1111/liv.13489.CrossRefPubMed

75.

Cao Z, Liu Y, Ma L, Lu J, Jin Y, Ren S, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha. Hepatology. 2017;66(4):1058–66. https://doi.org/10.1002/hep.29213.CrossRefPubMed

76.

de Niet A, Jansen L, Stelma F, Willemse SB, Kuiken SD, Weijer S, et al. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial. Lancet Gastroenterol Hepatol. 2017;2(8):576–84. https://doi.org/10.1016/S2468-1253(17)30083-3.CrossRefPubMed

77.

Cho JY, Paik YH, Sohn W, Cho HC, Gwak GY, Choi MS, et al. Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease. Gut. 2014;63(12):1943–50. https://doi.org/10.1136/gutjnl-2013-306409.CrossRefPubMed

78.

Kim HS, Baatarkhuu O, Lee HW, Park JY, Kim DY, Ahn SH, et al. Fibrosis-matched outcomes between chronic hepatitis B patients with drug-induced virological response and inactive carriers. Liver Int. 2019;39(1):81–9. https://doi.org/10.1111/liv.13948.CrossRefPubMed

79.

Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B (version 2022). Zhonghua Gan Zang Bing Za Zhi. 2022;30(12):1309-1331. https://doi.org/10.3760/cma.j.cn501113-20221204-00607.

80.

Shin JW, Jung SW, Lee SB, Lee BU, Park BR, Park EJ, Park NH. Medication nonadherence increases hepatocellular carcinoma, cirrhotic complications, and mortality in chronic hepatitis B patients treated with entecavir. Am J Gastroenterol. 2018;113(7):998–1008. https://doi.org/10.1038/s41395-018-0093-9.CrossRefPubMed

81.

Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut. 2002;51(4):597–9. https://doi.org/10.1136/gut.51.4.597.CrossRefPubMedPubMedCentral

82.

Wang HH, Sun SL, Jau RC, Tantoh DM, Hsu SY, Nfor ON, Chen PH, Liu WH, Ko JL, Liaw YP. Risk of HBV infection among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. BMC Public Health. 2021;21(1):1831. https://doi.org/10.1186/s12889-021-11846-x.CrossRefPubMedPubMedCentral

Title: Should Indications for Antiviral Therapy for Hepatitis B Be Broadened to Include Immune-Tolerant Patients, Inactive Carriers, or Patients in the “Gray Zone”?
Authors: Yen-Chun Liu
Wen-Juei Jeng
Publication date: 12-02-2024
Publisher: Springer US
Keywords: Hepatitis B
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Current Hepatology Reports / Issue 1/2024
Electronic ISSN: 2195-9595
DOI: https://doi.org/10.1007/s11901-024-00635-w

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 1/2024

Update on HCC Surveillance in Patient With Hepatitis B Virus Infection With Focus on Biomarkers

Cholestatic Pruritus: Pathophysiology, Current Management Approach, and Emerging Therapies

Hepatic Sarcoidosis: A Review of the Diagnosis and Management

Precision Management of Patients with HBV Infection

TIPS for Refractory Ascites and Hepatic Hydrothorax

Secondary Sclerosing Cholangiopathies

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage