Evolving Clinical and Virological Perspectives on Hepatitis B And C: A Critical Review

The hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the leading causes of chronic liver diseases worldwide. The two viruses, with or without complications such as cirrhosis and liver cancer, are responsible for a large part of the illness and death globally, directly or indirectly. Despite the fact that the scientific world has made huge advances in their diagnosis and treatment, HBV and HCV continue to pose a formidable challenge to health of communities around the world. The current paper seeks to comprehensively and comparatively describe the clinical and virological aspects of HBV and HCV including their epidemiology, pathogenesis, transmission, diagnosis, and therapy. Being a DNA virus, HBV can exist in the form of covalently closed circular DNA (cccDNA) which the cell nucleus can keep as a reservoir, and this persistence makes it possible that restoring a patient completely free of virus may not be achieved, and long-term treatment with antiviral drugs will be necessary in order to maintain a low level of viral load. On the other hand, HCV is an RNA virus and since does not have a stable intracellular reservoir it can be almost completely eradicated in most of cases by the use of direct-acting antivirals (DAAs). Such major differences have resulted the two viruses being targeted for very different prevention and treatment approaches. For instance, there is a highly effective vaccine against HBV while there is not yet a vaccine against HCV.This paper also discusses the major problems in disease control today such as underdiagnosis, restriction of treatment availability, and difficulties in the global elimination of viral hepatitis. By reviewing state-of-the-art knowledge and drawing attention to the main differences between HBV and HCV, the present work demonstrates that there is a great need for specific interventions, better healthcare services, and ongoing research to meet the target of eliminating viral hepatitis as a public health threat.

Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Viral Hepatitis, Chronic Hepatitis, cccDNA,

1. American Association for the Study of Liver Diseases. (n.d.). How to approach elevated liver enzymes. https://www.aasld.org/liver-fellow-network/core-series/back-basics/how-approach-elevated-liver-enzymes [Google Scholar] [Crossref]

2. American Society for Microbiology. (2016). Role of serologic and molecular diagnostic assays in identification of hepatitis viruses. Journal of Clinical Microbiology, 54(7), 1695–1696. https://doi.org/10.1128/jcm.02407-15 [Google Scholar] [Crossref]

3. Hepatitis B Foundation. (n.d.). Hepatitis B virus testing and interpreting test results. https://hepatitisb.org.au/hepatitis-b-virus-testing-and-interpreting-test-results/ [Google Scholar] [Crossref]

4. Bailey, J. R., Barnes, E., & Cox, A. L. (2019). Approaches, progress, and challenges to hepatitis C vaccine development. Gastroenterology, 156(2), 418–430. https://doi.org/10.1053/j.gastro.2018.08.060 [Google Scholar] [Crossref]

5. Bertoletti, A., & Ferrari, C. (2021). Adaptive immunity in HBV infection. Journal of Hepatology, 74(5), 1217–1230. https://doi.org/10.1016/j.jhep.2021.01.024 [Google Scholar] [Crossref]

6. Centers for Disease Control and Prevention. (n.d.-a). Clinical overview of hepatitis C. https://www.cdc.gov/hepatitis-c/hcp/clinical-overview/index.html [Google Scholar] [Crossref]

7. Centers for Disease Control and Prevention. (n.d.-b). Clinical overview of viral hepatitis. https://www.cdc.gov/hepatitis/hcp/clinical-overview/index.html [Google Scholar] [Crossref]

8. Centers for Disease Control and Prevention. (n.d.-c). Global viral hepatitis. https://www.cdc.gov/hepatitis/global/index.html [Google Scholar] [Crossref]

9. Centers for Disease Control and Prevention. (n.d.-d). Hepatitis B prevention and control. https://www.cdc.gov/hepatitis-b/prevention/index.html [Google Scholar] [Crossref]

10. Centers for Disease Control and Prevention. (n.d.-e). Viral hepatitis basics. https://www.cdc.gov/hepatitis/about/index.html [Google Scholar] [Crossref]

11. Cleveland Clinic. (n.d.). Liver function tests: Types, purpose & results interpretation. https://my.clevelandclinic.org/health/diagnostics/17662-liver-function-tests [Google Scholar] [Crossref]

12. Pawlotsky, J. M. (2019). Transmission routes of hepatitis C virus infection. Annals of Hepatology, 16(6), 806–820. https://doi.org/10.1016/j.aohep.2019.05.007 [Google Scholar] [Crossref]

13. Zhang, Z., & Zoulim, F. (2020). Hepatitis B virus: Modes of transmission, immune pathogenesis, and therapeutic vaccine research. Exploration of Digestive Diseases, 1, 36–48. https://doi.org/10.37349/edd.2020.00004 [Google Scholar] [Crossref]

14. Smith, D. B., et al. (2018). Evolutionary analysis of hepatitis C virus. Frontiers in Microbiology, 9, 854. https://doi.org/10.3389/fmicb.2018.00854 [Google Scholar] [Crossref]

15. Hepatitis B Foundation. (n.d.-a). Hepatitis B vaccination. https://www.hepb.org/prevention-and-diagnosis/vaccination/ [Google Scholar] [Crossref]

16. Hepatitis B Foundation. (n.d.-b). Treatment options. https://www.hepb.org/treatment-and-management/treatment/ [Google Scholar] [Crossref]

17. Hepatitis B Foundation. (n.d.-c). What's the difference: Hepatitis B vs hepatitis C? https://www.hepb.org/blog/whats-the-difference-hepatitis-b-vs-hepatitis-c/ [Google Scholar] [Crossref]

18. HIV.gov. (n.d.). Hepatitis B & C. https://www.hiv.gov/hiv-basics/staying-in-hiv-care/other-related-health-issues/hepatitis-b-and-c [Google Scholar] [Crossref]

19. Ioannou, G. N., Feld, J. J., & Locke, E. (2020). Long-term liver-related outcomes after sustained virologic response in chronic hepatitis C. Clinical Gastroenterology and Hepatology, 18(11), 2424–2433.e2. https://doi.org/10.1016/j.cgh.2020.02.038 [Google Scholar] [Crossref]

20. Lazarus, J. V., Picchio, C. A., Nayagam, S., Ratzan, S., & Thursz, M. (2022). Strengthening viral hepatitis elimination through quality of care framework. Journal of Hepatology, 77(4), 1199–1208. https://doi.org/10.1016/j.jhep.2022.06.015 [Google Scholar] [Crossref]

21. Liang, X. (2006). Hepatitis B virus infection: Epidemiology and vaccination. Epidemiologic Reviews, 28(1), 112–125. https://doi.org/10.1093/epirev/mxj009 [Google Scholar] [Crossref]

22. Mak, L. Y., et al. (2020). Occult hepatitis B infection and hepatocellular carcinoma. Journal of Hepatology, 73(4), 952–964. https://doi.org/10.1016/j.jhep.2020.05.042 [Google Scholar] [Crossref]

23. Mayo Clinic. (n.d.-a). Hepatitis B – Diagnosis and treatment. https://www.mayoclinic.org/diseases-conditions/hepatitis-b/diagnosis-treatment/drc-20366821 [Google Scholar] [Crossref]

24. Mayo Clinic. (n.d.-b). Hepatitis B – Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/hepatitis-b/symptoms-causes/syc-20366802 [Google Scholar] [Crossref]

25. Mayo Clinic. (n.d.-c). Hepatitis C – Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/hepatitis-c/symptoms-causes/syc-20354278 [Google Scholar] [Crossref]

26. Mayo Clinic Laboratories. (n.d.). Hepatitis C virus RNA detection and quantification by RT-PCR. https://www.mayocliniclabs.com/test-catalog/overview/97291 [Google Scholar] [Crossref]

27. Smith, J. A. (2023). Hepatitis C virus: History and current knowledge. Infectious Disease Reports, 15(3), 249–262. https://doi.org/10.3390/idr15030025 [Google Scholar] [Crossref]

28. Kumar, S. (2017). Epidemiology and clinical features of hepatitis B. International Journal of Vaccines & Vaccination, 5(1), 00103. https://doi.org/10.15406/ijvv.2017.05.00103 [Google Scholar] [Crossref]

29. Medical News Today. (2021, June 29). Difference between hepatitis B and C. https://www.medicalnewstoday.com/articles/323455 [Google Scholar] [Crossref]

30. Michigan Department of Health and Human Services. (n.d.). Hepatitis B serologic testing guidance. https://www.michigan.gov/mdhhs/-/media/Project/Websites/mdhhs/Adult-and-Childrens-Services/Children-and-Families/Heath-and-Safety/Communicable-Disease/HBsAg_Guidance_Document.pdf [Google Scholar] [Crossref]

31. Ghany, M. G. (2012). Laboratory diagnostics for hepatitis C virus infection. Clinical Infectious Diseases, 55(Suppl. 1), S43–S48. https://doi.org/10.1093/cid/cis368 [Google Scholar] [Crossref]

32. Alter, M. J. (2005). Hepatitis C virus diagnosis and testing. International Journal of Medical Sciences, 2(1), 21–25. https://doi.org/10.7150/ijms.2.21 [Google Scholar] [Crossref]

33. Shepard, C. W. (2010). Global epidemiology of hepatitis C virus infection. Journal of Viral Hepatitis, 17(Suppl. 1), 4–15. https://doi.org/10.1111/j.1365-2893.2010.01366.x [Google Scholar] [Crossref]

34. Dienstag, J. L. (2015). Antiviral therapy for hepatitis B. World Journal of Hepatology, 7(8), 1030–1040. https://doi.org/10.4254/wjh.v7.i8.1030 [Google Scholar] [Crossref]

35. Terrault, N. A. (2015). Diagnosis of hepatitis B. Annals of Translational Medicine, 3(Suppl. 1), S3. https://doi.org/10.3978/j.issn.2305-5839.2015.09.20 [Google Scholar] [Crossref]

36. Yuen, M. F. (2022). Current trends in antiviral therapy for hepatitis B. Viruses, 14(2), 234. https://doi.org/10.3390/v14020234 [Google Scholar] [Crossref]

37. Revill, P. A., et al. (2019). A global strategy to cure hepatitis B. The Lancet Gastroenterology & Hepatology, 4(7), 545–558. https://doi.org/10.1016/S2468-1253(19)30119-0 [Google Scholar] [Crossref]

38. Song, J. E. (2016). Diagnosis of hepatitis B. Annals of Translational Medicine, 4(21), 421. https://doi.org/10.21037/atm.2016.10.60 [Google Scholar] [Crossref]

39. StatPearls Publishing. (n.d.-a). Hepatitis B. https://www.ncbi.nlm.nih.gov/books/NBK555945/ [Google Scholar] [Crossref]

40. StatPearls Publishing. (n.d.-b). Liver function tests. https://www.ncbi.nlm.nih.gov/books/NBK482489/ [Google Scholar] [Crossref]

41. U.S. Department of Health & Human Services. (n.d.). Hepatitis B basics. https://www.hhs.gov/hepatitis/learn-about-viral-hepatitis/hepatitis-b-basics/index.html [Google Scholar] [Crossref]

42. University of Washington. (n.d.-a). When to initiate HBV treatment. https://www.hepatitisb.uw.edu/go/hbv-initial-treatment/core-concept/all [Google Scholar] [Crossref]

43. University of Washington. (n.d.-b). Hepatitis C diagnostic testing. https://www.hepatitisc.uw.edu/go/screening-diagnosis/diagnostic-testing/core-concept/all [Google Scholar] [Crossref]

44. Urban, S., Neumann-Haefelin, C., & Lampertico, P. (2021). Hepatitis D virus in 2021. Gut, 70(9), 1782–1794. https://doi.org/10.1136/gutjnl-2020-323888 [Google Scholar] [Crossref]

45. Viral Hepatitis and Liver Disease. (n.d.-a). HBV treatment goals. https://www.hepatitis.va.gov/hbv/treatment/medications.asp [Google Scholar] [Crossref]

46. Viral Hepatitis and Liver Disease. (n.d.-b). Laboratory tests and hepatitis C. https://www.hepatitis.va.gov/hcv/screening-diagnosis/laboratory-tests.asp [Google Scholar] [Crossref]

47. World Health Organization. (n.d.-a). Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b [Google Scholar] [Crossref]

48. World Health Organization. (n.d.-b). Vaccination against hepatitis B and C. https://www.who.int/thailand/news/feature-stories/detail/how-to-vaccinate-and-protect-against-hepatitis-b-and-c [Google Scholar] [Crossref]

49. World Health Organization. (n.d.-c). Serological markers of hepatitis B virus. https://cdn.who.int/media/docs/default-source/hq-hiv-hepatitis-and-stis-library/training-modules/hepatitis-b/hepatitis-b-serological-markers-ppt-notes.pdf [Google Scholar] [Crossref]