HCV Treatment in 2014: More Bang for your buck! Barbara Leggett Professor of Medicine, University of Queensland QIMR Berghofer Royal Brisbane and Womens Hospital

HCV Future Therapy We are about to have the drugs Now we have to deliver

Future impact of HCV-related liver diseaseFuture impact of HCV-related liver disease Estimated number of people living with HCV-related cirrhosis or decompensated cirrhosis/HCC in England: 1995–2020 (95% credibility intervals are given in parentheses) Health Protection Agency. Hepatitis C in the UK, 2011 Report; Figure 15 18,000 16,000 14,000 12,000 10, Number of people Year 1960 (1490, 2510) 1960 (1490, 2510) 3290 (2520, 4190) 5090 (3600, 6430) 7240 (5600, 9160) 11,630 (9060, 14700) 590 (530, 640) 1020 (950, 1090) 1640 (1560, 1720) 2430 (2310, 2550) 3330 (3150, 3520) 4210 (3910, 4520) Compensated cirrhosis Decompensated cirrhosis and hepatocellular carcinoma

Benefits of SVR Harry Janssen at AASLD 2013 Hepatitis C is the infectious disease with the greatest morbidity and mortality in Canada By 2030, 45% of chronic Hepatitis C patients will have cirrhosis

Date of download: 11/16/2013 Copyright © 2012 American Medical Association. All rights reserved. From: Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis JAMA. 2012;308(24): doi: /jama

For comparison, screening colonoscopy reduces the risk of death from colorectal cancer with a multivariate hazard ratio of 0.32 and it is difficult to show an effect on overall mortality (Nishihara et al NEJM 2013; 369:1095) Obtaining an SVR in a patient with advanced fibrosis is at least analogous to removing high risk colorectal polyps

UK Strategies to Deliver Care Treatment before advanced fibrosis or cirrhosis has higher rate of SVR whatever the treatment regime Treatment before advanced fibrosis or cirrhosis means the patient can be discharged rather than undergoing HCC surveillance with 6 monthly ultrasound indefinitely Risk of transmission eg mother to child is removed Advantages of Early Treatment

Progression of fibrosis over timeis not linearProgression of fibrosis over timeis not linear Boccatto S, et al. J Viral Hepat 2006;13:297–302 Mean time to follow-up = 7.8 ± 1.5 years F1F2F3F4 51/79 patients (65%) showed fibrosis progression during the follow-up period

Resources needed to treat hepatitis C in 2014 P/R for G3 Triple therapy for G1 Need at least back up of experienced hepatologist because of increasing choices and older, sicker patients: treat or wait, choice of therapy, transplant, treatment of HCC and liver failure Need Mental health team esp whilst still using interferon Nursing support essential – at least 1FTE per pts treated per year – nurses largely manage pts on treatment Shared care with GPs works best in rural and remote

Triple Therapy in treatment-experienced patients with cirrhosis: Cupic Risk of death or severe infection or hepatic decompensation was 6.4% during the first 16 weeks of therapy Hezode et al J Hepatol 2013; 59:434

HCV-TARGET Registry Patient registry from 104 academic and community sites Reported 1100 pts initiated before April 2012 Boceprevir (n=262) Telaprevir (n=838) Age56 (20-76)56 (18-75) G1a51.9%51.6% Cirrhosis29.8%45% Mean Pl count Mean albumin4140 Naïve38.9%38.2% Null16%11.3% Abstr 41 AASLD 2013

HCV-TARGET Registry SVR12 results (%) BoceprevirTelaprevir NaiveExperiencedNaiveExperienced Noncirrhotic Cirrhotic Platelets, albumin, G1a and cirrhosis reduced SVR12

HCV-TARGET Registry Adverse Events 16% in both groups discontinued because of adverse events 2 deaths in telaprevir group and none in boceprevir group

New Therapies Will be safer, more efficacious and of shorter duration Early compassionate access programmes will need to be directed to those most in need In 2014, offer P/R to non-cirrhotic G3 and triple therapy to favourable G1 (G1b, non-cirrhotic, IL28B CC) We need to be getting ready to deliver new therapies efficiently when they become generally available

Hepatitis C in Australia 2014 Currently only about 2% of the ~220,000 Australians with chronic Hepatitis C are treated annually Barriers include: –Not diagnosed (20-30%) –Not referred or patient declined –Service not offered locally –On long waiting list –Not suitable for treatment with pegylated interferon (mental health, too advanced liver disease)

1.Centralised networks 2.Outcome measures with some “teeth” 3.Advocacy Strategies to Improve Delivery of Care

Develop hub and spoke model of large centres (~1 per million population) supervised by specialist hepatologists oLarge experienced centres would develop clear guidelines for selection of patients for treatment and protocols for treatment oLarge centres would lead audit and quality control Strategies to Improve Delivery of Care 1. Centralised networks

oOutreach clinics linked to the large centre would take place in local hospitals and community centres oLocal staff would be involved oConsultant from large centre would visit local centre or undertake telehealth oHigh risk cases could have care transferred to large centre Strategies to Improve Delivery of Care 1. Centralised networks

Joint Advisory Group (JAG) criteria for endoscopy centres have been very successful in: Improving quality of endoscopy Improving funding of endoscopy as there are penalties for a health service not meeting criteria If hepatology continues to have no agreed standards that are measured it will be disadvantaged Strategies to Improve Delivery of Care 2. Outcome Measures with some “teeth”

Outcome measures suggested for Hepatitis C treatment: oPrevalence of Hepatitis C in the population serviced by the health district oNumber (proportion) treated per year oNumber documented to have an SVR Funding could be linked to collection of data and attaining satisfactory benchmarks Strategies to Improve Delivery of Care 2. Outcome Measures with some “teeth”

National Hepatitis C Strategy and the Auckland Statement on Viral Hepatitis are very worthwhile but have no “teeth” Liver services are not key performance criteria for Hospital and Health Service Districts Strategies to Improve Delivery of Care 2. Outcome Measures with some “teeth”

When funding is limited, advocacy by patients is extremely important Limited success so far as not many patients take on the lobbyist role Advocacy by professional lobbyists may be less successful and reports by BCG and Deloitte may be seen as professional lobbying Strategies to Improve Delivery of Care 3. Advocacy