Prevention of Progression to Cirrhosis in Hepatitis C With Fibrosis

Effectiveness and Cost Effectiveness of Sequential Therapy With New Direct-acting Anti-virals

R. Faria; B. Woods; S. Griffin; S. Palmer; M. Sculpher; S. D. Ryder


Aliment Pharmacol Ther. 2016;44(8):866-876. 

In This Article

Abstract and Introduction


Background The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments.

Aim To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis.

Methods A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years.

Results Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir–ledipasvir while peginterferon continues to have a role in other genotypes.

Conclusions The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices.


The new direct-acting anti-virals (DAAs) represent a step-change in the treatment prospects of the 185 million people around the world with chronic hepatitis C.[1] Simeprevir (SMV), sofosbuvir (SOF), sofosbuvir–ledipasvir (SOF–LED), daclatasvir (DCV) and ombitasvir–paritaprevir–ritonavir with or without dasabuvir (2D/3D) offer high cure rates and fewer adverse effects than standard interferon-based treatments.[2] However, their high prices raise issues regarding their affordability to health care systems and patients.[3]

From an economic perspective, the new DAAs are cost-effective if their health benefits exceed the opportunity cost. The opportunity cost is the health benefit forgone by other patients if interventions are no longer funded to release the resources to fund the new DAAs. Health benefits associated with extension of survival and/or improved health-related quality of life can be summarised as quality-adjusted life years (QALYs). In the UK, the National Institute for Health and Care Excellence (NICE) has appraised each new DAA and has recommended some as cost-effective options.[4–8] When deciding on the cost-effectiveness of new treatments, NICE compares their incremental cost-effectiveness ratio (ICER) to a cost-effectiveness threshold of £20 000–£30 000 per QALY.[9] The ICER describes the additional cost per QALY gained with the new treatment. The cost-effectiveness threshold represents the opportunity cost of programmes that could be displaced by the introduction of new, more costly, interventions.[9] Hence, treatments with ICERs below the threshold are cost-effective because their health benefits exceed their health opportunity costs. Recent empirical evidence suggests that opportunity costs of additional expenditure are as much as 1 QALY per £13 000 additional costs, although the discrepancy between this evidence and NICE's thresholds may partly reflect additional factors that the Institute considers relevant to its decisions for some products.[10]

The health benefits and opportunity costs of the new DAAs can only be assessed accurately if the clinical pathway is appropriately modelled and all the alternative ways in which treatments can be used are compared. In the case of chronic hepatitis C, this means including not only all of the new DAAs but also the older interferon-based treatments and the possibility of treatment at later disease stages. It also means including sequential therapy, whereby patients who fail therapy are retreated, as seen in clinical practice. The cost-effectiveness analyses used to inform NICE appraisals,[4–8] as well as other published cost-effectiveness studies,[11–19] have not done this. Patients were assumed not to be re-treated if they failed therapy and did not have the possibility of treatment at more severe disease stages. Furthermore, due to the timing of the NICE appraisals relative to the licensing of the DAAs, these new treatments have not all been directly compared.

This study addresses these evidence gaps by comparing the health benefits and opportunity costs of all relevant treatment pathways, from the least intensive option of do nothing and treat when patients develop cirrhosis ('watchful waiting'), to treatment with established or new treatments in up to three lines of sequential therapy. The objectives are to establish whether patients who are at high risk of progression to cirrhosis on the basis of having hepatic fibrosis at a significant stage (METAVIR F3) should be treated before progressing to cirrhosis, and to assess how many lines of treatment and which of these treatments should the patients receive.