Only treating patients with cirrhosis with DAAs will have limited impact on HCV epidemic in England

Targeting new hepatitis C virus (HCV) direct-acting antivirals (DAAs) at patients with cirrhosis will substantially reduce short-term incidence of end-stage liver disease (ESLD) and liver cancer (HCC) in England, according to a model published in the Journal of Viral Hepatitis. However, this strategy would have no meaningful impact on incidence of new HCV infections among people who inject drugs (PWID), the main HCV risk group. Effective use of new HCV therapies as prevention would require the treatment of patients with only mild liver disease.

“These analyses suggest that targeting new DAAs to people with cirrhosis will result in a rapid reduction in incident cases of ESLD/HCC within 2 – 3 years, to around half of that currently predicted in 2020, but with little impact on HCV incidence among PWID,” comment the authors.

Moreover, only targeting patients with cirrhosis would not be sufficient to prevent a medium-term increase in severe liver-related disease. “Due to lower SVR [sustained virologic response] rates in those with cirrhosis, continued post-SVR progression (albeit at a low rates) and rising numbers developing cirrhosis, treating those at moderate disease stage is also required to prevent a rebound in incident cases of ESLD/HCC,” explain the investigators.



Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 


Thickening and scarring of connective tissue. Often refers to fibrosis of the liver. See also ‘cirrhosis’, which is more severe scarring.


Short for people who inject drugs.

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

direct-acting antiviral (DAA)

Modern drugs for the treatment of hepatitis C, which work directly against the hepatitis C virus. They stop the virus from reproducing by blocking certain steps in its lifecycle.

The implications of the investigators’ models are clear: targeting patients with cirrhosis alone will not be enough to achieve either a sustained reduction in the incidence of serious HCV-related liver disease or reductions in HCV incidence among the main risk group.

“With a budget of £190 million for new DAAs announced in June 2015 and current focus on treating those with cirrhosis, only the short-term goal of reducing ESLD/HCC over the next five years can be achieved,” they write. “Reductions in HCV transmission…will require a change in strategy to treat substantial numbers of active PWID, most of whom have relatively mild disease.”

HCV-related liver disease is a growing public health problem in the UK. New diagnoses of serious liver disease related to HCV have increased from 574 per year in 1998 to 2652 per year in 2014; reported deaths due to such complication have risen more than fourfold since 1996. It has been estimated that by 2030, HCV will be the underlying cause of up to 1500 cases of ESLD each year.

However, new HCV treatments have the potential to transform the course of the epidemic. In both clinical trials and “real world” settings, combinations of DAAs have achieved SVR rates of 90% or more.

These new therapies are expensive, a single course of therapy costing at least £30,000. In 2015 the NHS in England allocated £190 million for their use, prioritising patients with cirrhosis.

Investigators wanted to determine the potential impact of targeted use of DAAs on the England’s HCV epidemic.

They therefore designed two models.

The first estimated the impact of treating various stages of HCV-related liver disease – cirrhosis, moderate fibrosis, mild fibrosis. A second model was used to determine the impact of DAA use on incidence and prevalence of chronic HCV among PWID, the main HCV risk group in England.

In the first model, treatment of 3500 patients with cirrhosis each year from 2015 was predicted to reduce the incidence of ESLD/HCC from 1110 cases per year in 2015 to 630 cases per year by 2020. Over ten years, 6350 cases of ESLD/HCC were predicted with the use of DAAs, compared to 12,510  with use of older interferon-based therapies.

However, a risk of continued disease progression and a diminishing pool of patients with cirrhosis would mean that eligibility for treatment would have to be expanded to patients with mild fibrosis to sustain these reductions.

Treating an additional 5000 patients with moderate fibrosis per year from 2016 was sufficient to prevent incident cases of ESLD/HCC rebounding to above 600 cases per year, with by a slow decline in disease progression from 2025. This strategy would prevent an additional 660 cases of serious liver disease – on top of that achieved by treating patients with cirrhosis – over ten years.

Further scale-up to encompass patients with mild fibrosis had limited additional benefit, preventing only 16 additional cases of ESLD/HCC by 2025.

The prevention model assumed that 34% of PWID in England are chronically infected with HCV and that 4.8% of this population is newly infected with the virus each year.

Treating only patients with cirrhosis had very limited impact on both prevalence and incidence. Only 7474 PWID would be treated over 15 years, reducing prevalence modestly to 32% and incidence to 4.4% by 2030.

Treating an additional 2500 PWID with moderate HCV-related liver fibrosis would reduce prevalence to 24% and incidence to 2.8%. However, the model showed that the biggest impact on the epidemic would be achieved if treatment strategies were extended to include patients with mild fibrosis, which would reduce prevalence to 11% and incidence to 1.4%.

“With the arrival of new DAA treatments, the outlook is extremely good for HCV-infected patients, with the risk of severe HCV-related liver disease being markedly reduced,” conclude the authors. “Focusing solely on cirrhotics is not a tenable long-term strategy if continued reductions in incident cases are to be achieved. NHS England is currently rolling out new DAAs for those with cirrhosis, but treatment of other groups will need to follow quickly.”


Harris RJ et al. New treatments for hepatitis C virus (HCV): scope for preventing liver disease and HCV transmission in England. Journal of Viral Hepatitis, online edition. DOI: 10.1111/jvd.12529 (2016).