WHEN CHRONIC HEPATITIS B TURNS ACUTE: UNDERSTANDING AND MANAGING FLARES

Florean Hartungi; Robert Christeven

doi:10.54630/jk2.v16i2.616

Florean Hartungi Program Profesi Dokter, Universitas Tanjungpura Pontianak, Kalimantan Barat, Indonesia
Robert Christeven Program Profesi Dokter, Universitas Tanjungpura Pontianak, Kalimantan Barat, Indonesia https://orcid.org/0000-0002-7061-6041

DOI: https://doi.org/10.54630/jk2.v16i2.616

Keywords: chronic hepatitis B, flare, ALT elevation, HBV DNA, antiviral therapy

Abstract

Hepatitis B flare is a sudden exacerbation of chronic hepatitis B, defined by an abrupt ALT rise >5× upper limit of normal. Clinically, it may resemble acute hepatitis B, but low IgM anti-HBc titers and high HBV DNA levels aid differentiation. Flares arise from immune-mediated hepatocyte injury, triggered spontaneously, by immunosuppressive or antiviral therapy, pregnancy, viral superinfection, or viral genotype variations. Presentation ranges from asymptomatic biochemical changes to severe hepatitis, coagulopathy, and acute liver failure. Evaluation requires thorough history, physical examination, laboratory testing, imaging, and sometimes liver biopsy. Management focuses on supportive care and early nucleos(t)ide analogue therapy, as interferon can precipitate hepatic decompensation in severe immune-driven flares. Prognosis depends on baseline liver health; patients without cirrhosis generally recover, while acute-on-chronic liver failure carries high short-term mortality and may necessitate liver transplantation. Prompt recognition and timely antiviral therapy are essential to prevent liver failure, highlighting the importance of individualized strategies for optimal outcomes in hepatitis B flares.

Keyword: chronic hepatitis B, flare

References

1. Quirino, A.; Marascio, N.; Branda, F.; Ciccozzi, A.; Romano, C.; Locci, C.; Azzena, I.; Pascale, N.; Pavia, G.; Matera, G.; et al. Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies. Pathogens 2024, 13, 766. https://doi.org/10.3390/pathogens13090766

2. Sonderup, M.W.; Spearman, C.W. Global Disparities in Hepatitis B Elimination—A Focus on Africa. Viruses 2022, 14, 82. https://doi.org/10.3390/v14010082

3. H Muljono D. Epidemiology of Hepatitis B and C in Republic of Indonesia. Euroasian J Hepatogastroenterol. 2017 Jan-Jun;7(1):55-59. doi: 10.5005/jp-journals-l0018-1212. Epub 2017 May 5. PMID: 29201773; PMCID: PMC5663775.

4. Maurya M, Munshi R. Prognosis of Severe Acute Flares of Chronic Hepatitis B. Explor Res Hypothesis Med. 2022;7(2):102-107. doi: 10.14218/ERHM.2021.00066.

5. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. PMID: 29405329; PMCID: PMC5975958.

6. EASL. Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of hepatology, 2017. 67(2): p. 370-398.

7. Puri P. Acute exacerbation of chronic hepatitis B: The dilemma of differentiation from acute viral hepatitis B. J Clin Exp Hepatol. 2013;3(4):301-312.

8. Chang ML, Liaw YF. Hepatitis B flares in chronic hepatitis B: Pathogenesis, natural course, and management. EASL J Hepatol. 2014;61(6):1407-1417.

9. Tsai WL, Sun WC, Cheng JS. Chronic hepatitis B with spontaneous severe acute exacerbation. Int J Mol Sci. 2015;16(12):28126-28145.

10. Perrillo RP. Acute flares in chronic hepatitis B: The natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120(4):1009-1022.

11. Honkoop P, De Man RA, Niesters HGM, Zondervan PE, Schalm SW. Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology. 2000;32(3):635-639.

12. Coffin CS, Ramji A, Cooper CL, et al. Epidemiologic and clinical features of chronic hepatitis B virus infection in 8 Canadian provinces: a descriptive study by the Canadian HBV Network. CMAJ Open. 2019;7(4):E610-E617.

13. Rowley MW, Patel A, Zhou W, Wong M, Seetharam AB. Immune reconstitution syndrome with initiation of treatment of HBV/HIV co-infection: Activity flare associated with E antigen seroconversion. Ann Hepatol. 2019;18(1):220-224.

14. Singhal A, Kanagala R, Jalil S, et al. Chronic HBV with pregnancy: Reactivation flare causing fulminant hepatic failure. Ann Hepatol. 2011;10(2):233-236.

15. Aslam A, Reyes KJC, Malladi VR, Ishtiaq R, Lau DTY. Management of chronic hepatitis B during pregnancy. Gastroenterol Rep. 2018;6(4):257-262.

16. Chang ML, Cheng JS, Chien RN, Liaw YF. Hepatitis Flares Are Associated With Better Outcomes Than No Flare in Patients With Decompensated Cirrhosis and Chronic Hepatitis B Virus Infection. Clin Gastroenterol Hepatol. 2020;18(9):2064-2072.

17. Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific Clinical Practice Guidelines on the Management of Hepatitis B: A 2015 Update. Vol 10. Springer India; 2016.

18. Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int. 2013;33(SUPPL. 1):164-175.

19. Gani, R. A., Hasan, I., Djumhana, A., et al. 2017. Konsensus nasional penatalaksanaan hepatitis B di Indonesia. Jakarta, Perhimpunan Peneliti Hati Indonesia (PPHI), 1-3.

20. World Health Organisation. Guideline For The Prevention, Care And Treatment Of Persons With Chronic Hepatitis B Infection. 2015;(April):124.

21. Yuen MF, Sablon E, Hui CK, et al. Prognostic factors in severe exacerbation of chronic hepatitis B. Clin Infect Dis. 2003;36(8):979-984.