Tackling HCV-3 in Asia: Breakthroughs for Efficient and
Cost-effective Treatment Strategies
Naba Saeed
Citation Information :
Saeed N. Tackling HCV-3 in Asia: Breakthroughs for Efficient and Cost-effective Treatment Strategies. Euroasian J Hepatogastroenterol 2016; 6 (1):35-42.
Hepatitis C virus (HCV) is known to cause chronic hepatitis C, and its sequelae of cirrhosis and
hepatocellular carcinoma. Hepatitis C genotype 3 (HCV-3) in particular is notorious for causing
accelerated liver fibrosis, cardiovascular, and metabolic effects, thus increasing morbidity and mortality.
It is the commonest variant in Asian countries like India and Pakistan. It is also one of the hardest-totreat
genotypes, especially among treatment-experienced and cirrhotic patients. Due to limited health
care affordability and accessibility in these areas, many patients remain untreated.
Until recently, the established therapy for HCV had been a combination of pegylated
interferon + ribavirin. However, it was only effective in about half of patients and had severe adverse
effects; hence a more efficacious option needed to be found. Recent advances have led to the
development of sofosbuvir, an NS5B inhibitor that is fast becoming the standard of care, in combination
with other novel drugs. It was initially marketed at $1,000 per pill, a cost that was too high for most. Thus,
it has not been utilized as a global therapy as yet. Formulation of effective interferon-free regimens is
a huge milestone, and awareness needs to be raised regarding these new highly effective options in
both the physician and the patient population.
This article discusses the newest drugs and combinations that have been developed in the fight
against HCV-3, as a treatment outline for HCV-3-dominant areas. It also highlights recent breakthroughs
in cost reductions of these drugs and the effort to make them globally accessible.
Deinstang JL, McHutchinson JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 2006 Jan;130(1):231-264
Hepatitis C. Available from: http://www.euro.who. int/en/what-we-do/health-topics/ communicable-diseases/hepatitis
Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005 Oct;42(4): 962-973
Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015 Jan;61(1):77-87
Steatosis and insulin resistance in response to treatment of chronic hepatitis C. J Viral Hepat 2012 Jan;19 (Suppl 1):42-47
Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation. J Infect Dis 2008 Jan 15;197(2):283-291
Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 2003 Jul;38(1):75-85
The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004 Mar;40(3):484-490
Associations of chronic hepatitis C with metabolic and cardiac outcomes. Aliment Pharmacol Ther 2013 Mar;37(6): 647-652
Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression. Gastroenterology 2003 Dec;125(6):1695-1704
Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology 2008 Feb;134(2):416-423
Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C J Hepatol 2009 Oct;51(4), 655-666
A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. Clin Gastroenterol Hepatol 2011 Jun;9(6):509-516
Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009 Apr;49(4):1335-1374
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001 Sep 22;358(9286):958-965
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002 Sep 26;347(13): 975-982
Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005 Jun 23;352(25):2609-2617
Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin. J Hepatol 2011 May;54(5):866-871
EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011 Aug;55(2):245-264
The pattern of pegylated interferonalpha2b and ribavirin treatment failure in cirrhotic patients depends on hepatitis C virus genotype. Antivir Ther 2009;14(4): 577-584
Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006 Sep;55(9):1350-1359
Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009 Apr;49(4):1335-1374. Tackling HCV-3 in Asia: Breakthroughs for Efficient and Cost-effective Treatment Strategies Euroasian Journal of Hepato-Gastroenterology, January-June 2016;6(1):35-42 41 EJOHG 23. Keating GM. Sofosbuvir: a review of its use in patients with chronic hepatitis C. Drugs 2014 Jul;74(10):1127-1146
Sovaldi (sofosbovir): EU summary of product characteristics. 2014. [Accessed 2014 Mar 31]. Available from: http://www.ema.europa.eu/
Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription of antiviral ribonucleosides. PLoS Pathog 2012;8(11):e1003030
Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013 May 16;368(20):1867-1877
Recommendations for testing, managing and treating hepatitis C. Available from: http://www.hcvguidelines.org/full-report
New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology 2014 May;146(5):1176-1192
Sofosbuvir in combination with peg-IFN and ribavirin for 12 weeks provides High SVR rates in HCV infected genotype 2 or 3 treatment experienced Patients with and without compensated cirrhosis: results from the LONESTAR-2 study. Hepatology 2013 Nov 26;58(Suppl 6):Abstract LB-4
Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2013 Jan 3;368(1):34-44
Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013 Aug 15;369(7):678-679
Sofosbuvir and Ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014 May 22;370(21):1993-2001
Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013 May 16;368(20):1867-1877
Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with theNS5A inhibitor BMS-790052. J Virol 2011 Jul;85(14):7312-7320
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014 Jan 16;370(3):211-221
All oral 12 week combination treatment with Daclatasvir (DVC) and Sofosbuvir (SOF) in patients infected with HCV genotype (GT) 3: ALLY-3 Phase 3 study. Hepatology 2014;60:(Suppl 6):Abstract LB-3
Profile of Alisporivir and its potential in the treatment of hepatitis C. Drug Des Dev Ther 2013;7:105-115
Review article: HCV genotype 3 – the new treatment challenge. Aliment Pharmacol Ther 2014 Apr;39(7):686-698
The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance. Antimicrob Agents Chemother 2014 Jun;58(6):3327-3334
Safety and efficacy of treatment with the interferon-free, ribavirin-free combination of sofosbuvir + GS-5816 for 12 weeks in treatmentnaive patients with genotype 1-6 HCV infection. J Hepatol 2014 Apr;60(1):S46
Once daily sofosbuvir with GS-5816 for 8 weeks with or without ribavirin in patients with HCV genotype 3 without cirrhosis result in high rates of SVR12: the ELECTRON-2 study. Hepatology 2014 Oct;60(Suppl 4):A79
Safety and efficacy of treatment with sofosbuvir + GS5816 ± ribavirin for 8 or 12 weeks in treatment naive patients with genotype 1-6 HCV infection. Hepatology 2014 Oct;60(Suppl 4):A80
Lack of a clinically important pharmacokinetic interaction between norgestimate/ethinyl estradiol and sofosbuvir (SOF) or ledipasvir (LDV) in HCV-uninfected female subjects [abstract no. 469]. Hepatology 2013;58(Suppl 4):433A
Lack of a clinically significant pharmacokinetic drug-drug interaction between sofosbuvir and GS-5816 in healthy volunteers [abstract no. 465]. Hepatology 2013;58(Suppl 4):431A
No clinically significant pharmacokinetic drug-drug interactions between sofosbuvir (GS-7977) and the immunosuppressants, cyclosporine A or tacrolimus in healthy volunteers [abstract no. 1869]. Hepatology 2012;56(Suppl 4):1063A-1064A
Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2013 Jan 3;368(1):34-44
No resistance detected in four phase 3 clinical studies in HCV genotype 1-6 of sofosbuvir/ribavirin with or without peginterferon [abstract no. 1843]. Hepatology 2013;58(Suppl 4):1091A-1092A
Resistance analysis of treatment-naïve HCV genotype 1-6 infected patients treated with sofosbuvir in combination with GS-5816 for 12 weeks. Hepatology 2014 Oct;60(Suppl 4):A1942
Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open label study. Gastroenterology 2015 Jan;148(1):100-107
A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology 2013 May;57(5):1752-1762.