Systematic Review

Cost-effectiveness of Direct-acting Antivirals for Treatment of Hepatitis C Genotypes 2–6

T. He; M. A. Lopez-Olivo; C. Hur; J. Chhatwal


Aliment Pharmacol Ther. 2017;46(8):711-721. 

In This Article

Abstract and Introduction


Background The availability of direct-acting antivirals (DAAs) has dramatically changed the landscape of hepatitis C virus (HCV) therapy; however, the cost and budget requirements for DAA treatment have been widely debated.

Aims To systematically review published studies evaluating the cost-effectiveness of DAAs for HCV genotype 2–6 infections, and synthesise and re-evaluate results with updated drug prices.

Methods We conducted a systematic search of various electronic databases, including Medline, EMBASE, Cochrane library and EconLit for cost-effectiveness studies published from 2011 to 2016. Studies evaluating DAAs for genotypes 2–6 were included. Reported costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were abstracted. We re-estimated ICERs by varying the price of DAAs from $20 000 to $100 000, and estimated the threshold price at which DAA regimens would be deemed cost-effective (ICER≤$100 000/QALY).

Results A total of 92 ICERs for 7 different DAA regimens from 10 published articles were included. Among the abstracted 92 ICERs, 20 were for genotype 2, 40 for genotype 3, 30 for genotype 4, 2 for genotype 5 and none for genotype 6; therefore, only genotypes 2–5 were analysed. At the discounted price of $40 000, 87.0% analyses found DAA regiments to be cost-effective, and 7.6% found to be cost-saving. The median threshold price below which DAAs would be deemed cost-effective was between $144 400 and $225 000, and cost-saving between $17 300 and $25 400.

Conclusions HCV treatment with DAAs is highly cost-effective in patients with HCV genotypes 2–5 at a $100 000/QALY threshold. Timely HCV treatment would be an optimal strategy from both a public health and economic perspective.


Hepatitis C virus (HCV) infection remains a major public health concern, with more than 100 million people chronically infected worldwide.[1] Chronic hepatitis C is associated with significant morbidity, mortality and economic burden. It can progressively lead to cirrhosis, liver failure and hepatocellular carcinoma (HCC) and is the most common indication for liver transplantation in USA and Europe.[2] At least six major HCV genotypes have been identified—genotype 1 accounts for about 46% of all infections worldwide, followed by genotypes 3 (30%) and genotype 2 (9%).[3] Genotypes 1–3 are prevalent worldwide, whereas, genotypes 4 and 5 are found mostly in Africa, and genotype 6 is principally prevalent in Asia.[4]

The treatment of hepatitis C experienced a revolution in the past few years with the availability of DAAs beginning in 2014.[5–7] These drugs have increased the response rates and tolerability of treatment dramatically. Several new orally administered drugs have been approved with a larger spectrum of viral genotypes, shorter duration of treatment and can be prescribed without interferon (IFN), which was administered as an injection and associated with many adverse side effects.[8] Multiple phase 3 trials and real-world studies demonstrated that more than 90% of chronic infected patients can now achieve sustained viral response (SVR) with DAAs, an accepted surrogate for cure.[9–17]

The enthusiasm of highly effective DAAs has been dampened by their price and budget impact of treating a large number of HCV-infected persons. Contrary to the recommendation of unrestricted HCV treatment by leading clinical societies,[18] several payers, both in and outside the USA added restrictions to the use of DAAs by limiting the drug to patients with advanced fibrosis stage or other risk factors.[19,20] The reasons for such restrictions include limited budget to treat the infected population, lack of clarity on the cost-effectiveness of new DAAs in different settings, and a lack of prioritisation in addressing the HCV disease burden among policy makers.[20]

Evidence-based cost-effectiveness analysis (CEA) of HCV treatment with DAAs can inform decisions regarding access to treatment.[21] A number of cost-effectiveness studies have been published recently that project long-term costs, benefits and cost-effectiveness of new DAAs.[21] However, substantial heterogeneity exists in these studies with respect to the price of DAAs, analysis perspective, time horizon and other HCV-related disease characteristics. These differences in assumptions could influence the cost-effectiveness results and conclusions. A prior systematic review synthesised the CEA of DAAs in HCV genotype 1 patients and evaluated the impact of various factors on the cost-effectiveness of DAAs.[22] However such information is not available for other HCV genotypes, which account for 54% of all HCV infections worldwide. Therefore, the objective of our study was to synthesise all available CEA studies in HCV genotypes 2–6, and to re-evaluate cost-effectiveness results for different subgroups and estimate the threshold drug prices below which HCV treatment would be deemed cost-effective and cost-saving.