Currently Available Anti-Hepatitis Viruses Drugs

Mohammad K. Parvez1, Milena Mechkarska2

1 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;
2 Department of Life Sciences, Faculty of Science and Technology, The University of the West Indies, St. Augustine, Trinidad and Tobago.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Mohammad K. Parvez, PhD; Associate professor, Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Email: khalid_parvez@yahoo.com
Telephone: +966-14675132
Fax: +966-14677245

Received: May 6, 2020
Revised: May 10, 2020
Accepted: May 11, 2020
Published online: June 21, 2020


The hepatotropic hepatitis viruses (HAV, HBV, HCV, HDV and HEV) cause acute and chronic liver diseases, including cirrhosis and carcinoma in general population. While there are globally accessible vaccines for HAV and HBV, a recently approved HEV vaccine is restricted to China. Currently, there is a wide range of effective nucleoside analog-based antiviral drugs for treating chronic hepatitis B (e.g., Lamivudine, Adefovir, Tenofovir, Emtricitabine, Entecavir, Telbivudine, Famciclovir and Ganciclovir) and hepatitis C (e.g., Ribavirin, Telaprevir, Simeprevir, Paritaprevir, Sofosbuvir, Daclatasvir, Elbasvir, Ombitasvir and Velpatsvir). However, Ribavirin is the only treatment option for chronic hepatitis E in immunocompromised patients. Nonetheless, viral mutants associated drug-resistance or non-response to therapy remains a big challenge in clinical settings. Also, of the several popular herbal products used for hepatitis B and C, some are known to cause severe side-effects and hepatotoxicity.

Key words: Hepatitis viruses; HAV; HBV; HCV; HDV; HEV; Antiviral; Nucleoside analogs

© 2020 The Authors. Published by ACT Publishing Group Ltd. All rights reserved.

Parvez MK, Mechkarska M. Currently Available Anti-Hepatitis Viruses Drugs. Journal of Gastroenterology and Hepatology Research 2020; 9(3): 3155-3157 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/2819


Hepatitis viruses are inherently hepatotropic pathogens that cause acute and chronic liver diseases, including fulminant liver failure, cirrhosis and hepatocellular carcinoma[1,2]. Since the discovery of hepatitis B virus (HBV) in 1965, followed by hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV), we have enormous information on their biology, mode of transmission and mechanisms of pathogenesis, inluding preventive and therapeutic measures[2,3]. Despite globally available vaccines for HAV and HBV, and effective antiviral drugs against HBV, HCV, HDV and HEV, millions of deaths occur of chronic hepatitis annually. Recently, an approved HEV vaccine is marketed in China that however, still waits global access[4]. In addition, new hepatotropic viruses such as hepatitis F virus (HFV), hepatitis G virus (HGV), GB viruses (GBV), transfusion-transmitted virus (TTV) and SEN virus (SENV) have been also identified in chronic liver disease patients[3]. Notably, all hepatitis viruses have RNA genome except HBV that uniquely replicates its DNA via a pregenomic RNA intermediate and therefore, also called pararetrovirus.


Antiviral drugs are diverse and wide spectrum chemotherapeutic agents, classified according to their target viruses, chemical structures and modes of action[5]. Of these, the nucleoside analogs (NAs) are viral polymerase/reverse-transcriptase (Pol/RT) inhibitors that terminate the growing nascent DNA/RNA chain. Historically, in the last two decades, important antivirals have been developed against the retroviruses, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV) and cytomegalovirus (CMV) infections[6]. The anti-HIV NAs are generally direct-acting (DAA) RT-inhibitors, such as Zidovudine, Lamivudine, Adepovir, Entecavir, Tenofovir, Emtricitabine, Abacavir, Stavudine and Didanosine. The non-NA RT-inhibitors include Delavirdine, Efavirenz, Etravirine, Nevirapine and Rilpivirine etc. The anti-HSV NAs are Acyclovir, Valacyclovir, Cidofovir, Famciclovir, Ganciclovir and Valganciclovir[5]. Some other NAs, like Fialuridine, Didanosine and Zalcitabine, including Stavudine can however, cause direct (mitochondrial dysfunction) or indirect (idiosyncratic) hepatotoxicity as well as exacerbation of underlying liver disease[7,8]. Interestingly, majority of the anti-retroviral drugs are also found to act against genetically close hepatitis viruses.


HBV causes acute and chronic hepatitis B in about one-third of world’s population, of which approximately 360 million are at risk for developing liver cirrhosis or carcinoma[9]. Because of genetic similarity, several anti-HIV (e.g. Lamivudine, Adefovir, Tenofovir, Emtricitabine, Entecavir and Telbivudine) and anti-HSV (e.g., Famciclovir and Ganciclovir) NAs are also effective in treating chronic hepatitis B. Basically, almost all approved anti-HBV drugs were first developed against HIV or HSV. Though these drugs are very effective, generally safe and well tolerated, prolonged treatment with Lamivudine, Adepovir, Famciclovir or Entecavir often leads to drug-resistance due to emergence of viral Pol/RT mutants[10]. In addition, chemokines like interferon alpha (pegIFN-α-2a) is also active but are no longer commonly used because of non-response or side-effects in some chronic patients. In addition, there are several herbal formulations or natural products popular as traditional Chines medicine (TCM), such as Zexie, Bo He, Chuan Lian Zi, Gan Cao, Ji Guo Cao, Jue Ming Zi, Long Dan Xie Gan Tang, Chai Hu, Bai Fang and Zhen Chu Cao etc. used for hepatitis B[11,12]. Nonetheless, some of them are reported to cause hepatotoxicity and other serious side-effects[13].


HCV infects over 180 million people worldwide, of which about 70 million chronic cases remain at high risk of developing liver cirrhosis and carcinoma[14]. The anti-HCV drugs include the NA drug Ribavirin and pegIFN-α-2a, generally given in combination for sustained virological response (SVR). In addition, the HCV RT-inhibitors (ending with -asvir or -buvir; e.g., Daclatasvir, Elbasvir, Lepidasvir, Ombitasvir, Velpatsvir, Sofosbuvir, Dasabuvir and Pibrentasvor) and protease-inhibitors (ending with -previr; e.g., Boceprevir, Telaprevir, Simeprevir, Paritaprevir, Grazoprevir and Glecaprevir) are currently available[5, 15]. Combinations of two or more of these drugs (Harvoni, Technive, Viekira Pak, Zepatier, Epclusa and Mavyret) with enhanced activity are also marketed. Nonetheless, non-response or failure of some DAA therapy is also observed due to emergence of HCV mutants in a proportion of chronic patients[16]. Further, TCM like Silymarin when consumed with DAA like, Simeprevir is related to hepatotoxicity in some HCV patients[13,17]. Another widely used anti-HCV natural product Glycyrrhizin is also known to affect drug-metabolizing enzymes and efflux transporters[18].


HDV is a satellite virus of HBV, which is estimated to co-infect about 13% of chronic hepatitis B patients (60 million), worldwide[19]. It is the most severe form of viral hepatitis with the highest risk to developing liver cirrhosis and carcinoma. To date, only pegIFN-α-2a is recommended for HDV infection where poor response rates, intolerance or ineligibility in many patients remains a big challenge[20].


HEV is a genotype-specific water-/foodborne or zoonotic virus that causes acute and chronic hepatitis E with a fatality rate of ~2%, including 20-30% of pregnant women[21,22]. Needlessly so far, there has been no treatment for self-limiting acute hepatitis E. However, with the emergence of chronic infections, especially in patients who have received solid-organ transplants or cancer chemotherapy, Ribavirin and pegIFN-α-2a are the only anti-HEV regimens[23,24]. Though Ribavirin effectively inhibits HEV replication and induce SVR, drug-resistance associated mutations in HEV RNA-dependent RNA polymerase (RdRP) lead to non-response or therapeutic failure in immunocompromised patients[25,26]. Very recently in a couple of case studies, Sofosbuvir co-treatment with Ribavirin has shown improved viral clearance[27,28].


Despite scientific advancement in virus pathobiology and therapeutics, chronic hepatitis B, C and E remain globally important health issues. A wide range of effective NA-based drugs is currently available for treating viral hepatitis. However, viral mutants associated drug-resistance or non-response to therapy remains a big challenge in clinical settings. In addition, some popular herbal anti-hepatitis B and C products are also related to severe side-effects and hepatotoxicity. Therefore, non-NA agents as well as promising bioactive natural products with no side-effects or drug-resistance in clinical trials offer future anti-hepatitis drugs.


1. Kew MC. Hepatitis viruses (other than hepatitis B and C viruses) as causes of hepatocellular carcinoma: an update. J Viral Hepat 2013; 20: 149-157. [PMID: 23383653]; [DOI: 10.1111/jvh.12043]

2. Oon GC. Viral hepatitis- the silent killer. Ann Acad Med Singapore 2012; 41: 279-280. [PMID: 22892603]

3. Parvez MK. Candidate New Hepatitis Viruses: Juggling with Alphabets. J Liver Clin Res 2015; 2: 1009-1010.

4. Parvez MK. Hepatitis E vaccine: time to let the cat out. J Gastroenterol Hepatol Res 2017; 6: 2384-2385. [DOI: 10.17554/j.issn.2224-3992.2017.06.712]

5. Antiviral drugs. Treat Guidel Med Lett 2013; 11: 19-30. [PMID: 23459414]

6. Flexner C. Antiretroviral agents and treatment of HIV infection. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1623-64.

7. Ogedegbe AO, Sulkowski MS. Antiretroviral-associated liver injury. Clin Liver Dis 2003; 7: 475-499. [DOI: 10.1097/01.idc.0000104902.16995.e1]

8. Núnez M. Hepatotoxicity of antiretrovirals: incidence, mechanisms and management. J Hepatol 2006; 44: S132-139. [DOI: 10.1016/j.jhep.2005.11.027]

9. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 2006; 28: 112-125. [PMID: 16754644]; [DOI: 10.1093/epirev/mxj009]

10. Devi, Locarnin S. Hepatitis B antivirals and resistance. Curr Opin Virol 2013; 3: 495-500. [PMID: 24016777]; [DOI: 10.1016/j.coviro.2013.08.006]

11. Wang G, Zhang L, Bonkovsky HL. Chinese medicine for treatment of chronic hepatitis B. Chin J Integ Med 2012; 18: 53-55.

12. Parvez MK, Arbab AH, Al-Dosari MS, Al-Rehaily AJ. Antiviral natural products against chronic hepatitis B: recent developments. Curr Pharm Des 2016; 3: 286-293. [PMID: 26561057]; [DOI: 10.2174/1381612822666151112152733]

13. Parvez MK, Al-Dosari MS. CAM/Drug-induced hepatotoxicity: implications in viral hepatitis. J Gastroenterol Hepatol Res 2016; 5: 1921-1923.

14. Manns MP, Buti M, Gane E, Pawlotsky J-M, Razavi H, Terrault N, Younossi Z. Hepatitis C virus infection. Nat Rev Dis Prim 2017; 3: 1700. [PMID: 28252637]; [DOI: 10.1038/nrdp.2017.6]

15. European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015; 63: 199-236. [PMID: 25911336]; [DOI: 10.1016/j.jhep.2015.03.025]

16. Ceccherini-Silberstein F, Cento V, Di Maio VC, Perno CF, Craxì A. Viral resistance in HCV infection. Curr Opin Virol 2018; 32: 115-127. [PMID: 30439589]; [DOI: 10.1016/j.coviro.2018.10.005]

17. Köck K, Xie Y, Hawke RL, Oberlies NH, Brouwer KL. Interaction of silymarin flavonolignans with organic anion-transporting polypeptides. Drug Metab Dispos 2013; 41: 958-965. [PMID: 23401473]; [DOI: 10.1124/dmd.112.048272]

18. Feng X, Ding L, Qiu F. Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid. Drug Metab Rev 2015; 47: 229-238. [PMID: 25825801]; [DOI: 10.3109/03602532.2015.1029634]

19. Brancaccio G, Gaeta GB. Treatment of chronic hepatitis due to hepatitis B and hepatitis delta virus coinfection. Int J Antimicrob Agents. 2019; 54: 697-701. [PMID: 31541699]; [DOI: 10.1016/j.ijantimicag.2019.09.012]

20. Mentha N, Clément S, Negro F, Alfaiate D. A review on hepatitis D: From virology to new therapies. J Adv Res. 2019; 17: 3-15. [PMID: 31193285]; [DOI: 10.1016/j.jare.2019.03.009].

21. Aggarwal R, Naik S. Epidemiology of hepatitis E: current status. J Gastroenterol Hepatol 2009; 24: 1484-1493. [PMID: 19686410]; [DOI: 10.1111/j.1440-1746.2009.05933.x]

22. Parvez MK. Chronic hepatitis E infection: risks and controls. Intervirology 2013; 56: 213-216. [PMID: 23689166]; [DOI: 10.1159/000349888]

23. Kamar N, Abravanel F, Behrendt P, Hofmann J, Pageaux GP, Barbet C, Moal V, Couzi L, Horvatits T, De Man RA, Cassuto E, Elsharkawy AM, Riezebos-Brilman A, Scemla A, Hillaire S, Donnelly MC, Radenne S, Sayegh J, Garrouste C, Dumortier J, Glowaki F, Matignon M, Coilly A, Figueres L, Mousson C, Minello A, Dharancy S, Rerolle JP, Lebray P, Etienne I, Perrin P, Choi M, Marion O, Izopet J; Hepatitis E Virus Ribavirin Study Group. Ribavirin for hepatitis E virus infection after organ transplantation: a large European retrospective multicenter study. Clin Infect Dis 2019; pii: ciz953. [PMID: 31793638]; [DOI: 10.1093/cid/ciz953]

24. Crum-Cianflone NF. Therapy for Chronic Hepatitis E Virus Infection - Current Recommendations and Future Aspirations. Clin Infect Dis 2019; pii: ciz955. [DOI: 10.1093/cid/ciz955]

25. Todt D, Gisa A, Radonic A, Nitsche A, Behrendt P, Suneetha PV, Pischke S, Bremer B, Brown RJ, Manns MP, Cornberg M, Bock CT, Steinmann E, Wedemeyer H. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. Gut 2016; 65: 1733-1743. [PMID: 27222534]; [DOI: 10.1136/gutjnl-2015-311000]

26. Parvez MK. Hepatitis E. Diagnostic and Therapeutic Challenges. Arch Hepatitis Res 2017; 3: 10-12. [DOI: 10.17352/ahr.000009]

27. Fraga M, Gouttenoire J, Sahli R, Chtioui H, Marcu C, Pascual M, Moradpour D, Vionnet J. Sofosbuvir add-on to ribavirin for chronic hepatitis E in a cirrhotic liver transplant recipient: a case report. BMC Gastroenterol 2019; 19: 76. [PMID: 31126238]; [DOI: 10.1186/s12876-019-0995-z]

28. Wahid B. Successful treatment of HBV, HCV, & HEV, with 12-week long use of tenofovir, sofosbuvir, daclatasvir, and ribavirin: A case report. J Infect Public Health 2020; 13: 149-150. [PMID: 31235341]; [DOI: 10.1016/j.jiph.2019.06.004]


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.