Tackling hepatitis C - what PHE modelling shows us Helen Harris BSc PhD FFPH LJWG meeting; November 2014

The burden of hepatitis C in England Around 160,000 adults with chronic infection HCV-related end-stage liver disease and deaths have increased steadily over the last 15 years Around 90% of new infections are amongst people who inject drugs (PWID) Around half of people who inject psychoactive drugs are thought to be infected, with around 1 in 7 sharing needles/syringes PHE hepatitis C in the UK – 214 report

Tackling hepatitis C – we know the actions Prevention of new infections Increasing awareness of infection Increasing testing and diagnosis Getting diagnosed individuals into treatment and care Progress NHS/PH Outcomes Action areas Mortality from liver disease Mortality from causes considered preventable Mortality from cancer Mortality from communicable diseases Successful completion of drug treatment Early diagnosis of cancer Inequalities Quality of life for those with long- term conditions Recovery from ill health Prevention of premature mortality Positive experience of care

How do we tackle hep C in PWID? Helping people to quit injecting Safe injecting for those who continue Treat those with chronic infection Other important groups -Past PWID -Those who acquired infection via blood/blood products -Black and minority ethnic (BME) populations who have close links to countries with a high prevalence of HCV infection.

Modelling acknowledgements Thanks to Ross Harris

Natural history model *Journal of Hepatology 2014, 61: 530–537

Modelling the predicted impact of treatment7 Back-calculation model: the basic idea Estimate past incidence and numbers progressing through a natural history model that would give rise to the observed endpoint data Ingredients: Observed end-point data over time HES data on ESLD, HCC; ONS HCC mortality Progression probabilities Reported estimates from cohort studies Result: Predicted history of disease-stage structure Future predictions of disease burden

Estimated number of people living with HCV- related cirrhosis or decompensated cirrhosis/HCC in England: (95% credible intervals are given in parentheses) Hepatitis C in the UK 2014 report How are we doing..? Nearly 10,850 individuals are currently living with HCV- related cirrhosis or HCC in England Modelling predicts that this figure will rise to 13,590 in 2025 if low coverage of current treatments is maintained PHE hepatitis C in the UK – 214 report

Both increased uptake and new therapies are needed *Journal of Hepatology 2014, 61: 530–537

Modelling the predicted impact of treatment Predictions under different treatment scenarios* Levels of treatment Maintaining current levels (3% treated annually*) 100% increase over next 10 years Scale up to complete coverage over next years Types of treatment Standard treatment (peg interferon and ribavirin) 37% SVR for genotype 1 and 70% non-1 Worse for older patients/more advanced disease Improved treatments over next 5 years 90% SVR rate, 60% in cirrhotics *Journal of Hepatology 2014, 61: 530–537

Modelling the predicted impact of treatment11 over next 10 years over next years

Modelling the predicted impact of treatment12 Findings Disease burden is likely to rise in short term Increasing treatment levels will mitigate this, but short-term rises seem inevitable Improved treatment will help to make more immediate impact Currently those at highest risk of severe disease have low probability of achieving SVR Swift action required as the infected population approaches advanced disease stage Modelling indicates greater impact for treating sooner rather than later

Elimination of infection..? Elimination: “Reduction to zero of the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts; continued measures to prevent re-establishment of transmission are required.” * In theory if the right tools were available, all infectious diseases would be eliminated. In reality there are distinct biological features of organisms and technical factors of dealing with them that make their potential for elimination more or less likely

What can be achieved with new therapies? Improved outcomes Improved SVRs, particularly in many previously considered hard-to- treat groups including genotype 1 infections, those with advanced diease, older patients, and those who have failed previous treatment. Fewer hospitalisations/deaths for ESLD/HCC Being able to treat those in advanced disease states is key (previously low SVR rates in cirrhotics) Widespread uptake Greater patient acceptability and easier to roll out in community settings (accessibility) as drugs have fewer side effects, shorter courses and are easier to administer (all-oral, interferon free) Reductions in prevalence Stemming transmission

Challenges… No vaccine. New therapies may be cost effective but are expensive. Hep C treatment services need to be re-structured country-wide so they are accessible to all those who need them. Asymptomatic nature means large numbers are undiagnosed: increased awareness, testing & diagnosis are required. Under existing systems, investment in hep C prevention, diagnosis and treatment services is largely determined locally and money is tight.

Elimination of infection..? Elimination of hepatitis C- related liver disease as a serious public health concern in England..? No, but… Yes, but challenging...

Goal 1: Prevent further rises in ESLD/HCC, leading to falling numbers New therapies must be made available immediately to anyone presenting with HCV-related cirrhosis Modelling work indicates prevalence of HCV-related cirrhosis is approaching 11,000 individuals and rising * Need to rapidly scale up to at least 20% of cirrhotics receiving new treatments annually ** In other words, around 2000 cirrhotic patients per year treated over the next 10 years Note: Numbers approximate – based on achieving more than a doubling in current numbers but not reaching complete coverage; estimates subject to better quantification of SVR rates in cirrhotics * PHE Hepatitis C in the UK report ** Harris et al. Journal of Hepatology 2014, 61: 530–537

Goal 2: Reduce transmission New infections driven primarily by people who inject drugs (PWID) Opiate substitution, needle exchange and harm reduction programs must continue – but not sufficient alone Target to reduce prevalence of chronic infection in this group by a quarter (from ~40% to ~30%) over the next 10 years

Goal 2: requirements Current rates of treatment vary: 5-20 infected PWID per 1000 annually; need to increase to above 20 * Modelling assumes those treated have equal risk of reinfection, retreatment allowed post re-infection but those failing are not retreated Equates to around 2000 active PWID treated per year ** Decreasing barriers to treatment: Easy access to new all-oral interferon-free therapy Available in community settings Acceptance that treating active PWID is worthwhile * Martin HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact. Journal of Viral Hepatitis **Estimates of the Prevalence of Opiate Use and/or Crack Cocaine Use, 2011/12. National Treatment Agency

Conclusion Tackle the problem from either end: reducing incidence and HCV-related morbidity Elimination of hepatitis C- related liver disease as a serious public health concern in England Important targets with measurable outcomes and specific goals Working towards

21 Acknowledgements Ross Harris Michael Sweeting Dani de Angelis Sema Mandal Mary Ramsay Annastella Costella