Hepatitis C: a treatment revolution

Transcription

1 Sunday, 10th July 2016 Michaelmas Cay 2 Room Concurrent 11 Health Innovation Hepatitis C: a treatment revolution Dr. Heather McNamee Hepatitis C a treatment revolution Dr Heather McNamee Medical Director Cairns Doctors VMO Cairns Sexual Health Service with thanks to Dr Darren Russell Declaration of Conflicts of Interest Speaker s fees and/or travel assistance from Gilead, ViiV, Abbvie, MSD, Janssen and BMS 1

2 Hepatitis C : A Game Changer Brief epidemiology of Hep C What we ve done in the past prevention, testing and treatment The new treatments and how to scale-up HCV in Australia ~ chronic infections Incidence Burden of disease 80-90% of infections related to injecting drug use Up to 50% of all people who inject drugs will have chronic HCV infection Prisoner (½ males, ⅔ females) Blood transfusion prior to 1990 Body piercing or tattoo Sexual transmission? HCV - Consequences Leading cause of liver transplantation in Australia HCC attributable to viral hepatitis the most significantly increasing cause of cancer death in Australia Liver cancer mortality 2014 Australian Institute of Health and Welfare 2014, Liver Cancer Mortality L 2

3 HCV Natural History Chronic infection in 75% Usually cleared or not at 3 months ~15% of these develop cirrhosis over 30 years risks include alcohol use, increasing age and HIV and hepatitis B coinfection 1-3% of cirrhosis develop HCC each year Indigenous Australians Incidence x5 higher Goals of Antiviral Therapy The overall goals of treatment are to cure HCV infection To prevent the development of liver disease and death The impact of HCV infection on quality of life and on transmission also needs to be considered 3

4 What have we done previously? Prevention Needle and Syringe Programs Testing Hep C antibody test ; if positive ask for LFTs and Hep C RNA test (around 25% spontaneously clear Hep C) Treatment in the past Pegylated Interferon and Ribavirin for weeks (+ simeprevir for genotype 1) ~70% SVR Era of New Treatment Older treatments were toxic but somewhat effective (interferon adverse effects) Newer treatments have minimal side-effects and are very effective SVR = sustained virological response Undetectable viral load 12 weeks after finishing all treatment = cure HCV DAA Regimens May depend on Cirrhosis/no cirrhosis Works for treatment-naïve/treatmentexperienced Mainly 12 weeks Working towards no on-treatment monitoring Minimal role for ribavirin Virtually no adverse effects Increasingly STRs (single tablet regimens) 4

5 Who should be treated? How to treat everyone? If necessary, prioritise: HIV (and or hepatitis B) coinfected Those with advanced (or advancing) liver disease Active injectors HIV +ve gay men at risk of transmission Getting People Treatment Ready Blood tests FBC, Chem 20, Hep C genotype and quantitative RNA (viral load) +/- INR Fibroscan Decide on a treatment regimen Start treatment! Check for SVR 12 weeks post-treatment 5

6 Getting people ready - Fibroscan Alternatives to Fibroscan Fibroscan is now the gold standard for measuring liver fibrosis ( stiffness ) Has very good accuracy for detecting cirrhosis If not available, other scores based on blood tests are sometimes used E.g. APRI Score AST to Platelet Ratio Index A score >1 has a sensitivity of 76% for cirrhosis Ratio-Index-APRI-Calculator-700.html No need for Fibroscan? If recently infected and otherwise well If known to be cirrhotic (only 6% of Australians currently living with hep C) Low platelet count (or low normal!) Oesophageal varices, ascites, hepatic encephalopathy, etc But these patients should generally be referred to specialist 6

7 SVR Rates for Approved Therapies in HCV GT 1 Patients Co-infected with HIV Years are not to scale 2015 SVR Rate (%) IFN+RBV PEG PEG+RBV BOC+ TVR+ SMV+ SOF+RBV SOF+ PTV/RTV/OBV+ V/SOF 6 mo 12 mo 12 mo PEG+RBV PEG+RBV PEG+RBV 6 mo PEG+RBV DSV+RBV 3 mo 6-12 mo 6-12 mo 6-12 mo PHOTON-1 3 mo 3-6 mo ION-4, Study 1910 TURQUOISE-1 ERADICATE 2015 AAS/IDSA Guidance: HIV/HCV co-infection should receive the same treatment as recommended for HCV mono-infection Dieterich D et al. CROI 2014; P#24; Rodriguez-Torres M et al. IDWeek 2013; P#714; Sulkowski M et al. Lancet Infect Dis 2013;13: ; Sulkowski M et al. Ann Intern Med 2013;159:86 96; Sulkowski M et al Lancet 2014;314:653 61; Sulkowski M et al. AIDS 2014; P#104 LB; Torriani FJ, et al. N Engl J Med 2004;351:438 50; AAS/IDSA/IAS USA. Recommendations for testing, managing, and treating hepatitis C. Accessed January 15, 2015 Who to refer? Those with cirrhosis Will need gastroscopy to check for varices Will need lifelong monitoring for hepatocellular carcinoma (HCC) 6-monthly liver ultrasound scans Those with complex medical needs Those with complex psychosocial needs?? Those under 18 years of age HCV Life Cycle and DAA Targets drug classes and nomenclature Receptor binding and endocytosis Fusion and uncoating Transport and release..previr (+) RNA ER lumen Virion assembly Translation NS3/4 and polyprotein protease processing inhibitors Membranous web ER lumen NS5B RNA polymerase replication inhibitors Nucleoside/nucleotide Nonnucleoside..ASVIR NS5A* inhibitors *Role in HCV life cycle not well defined UVIR Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:

8 HCV Life Cycle and DAA Targets drugs Receptor binding and endocytosis Telaprevir Boceprevir Simeprevir Asunaprevir Paritaprevir Grazoprevir Translation NS3/4 and polyprotein protease processing inhibitors Daclatasvir Ledipasvir Ombitasvir Elbasvir Valpatasvir Fusion and uncoating (+) RNA Membranous web ER lumen NS5A* inhibitors Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6: *Role in HCV life cycle not well defined Transport and release ER lumen Virion assembly NS5B RNA polymerase replication inhibitors Nucleoside/nucleotide Nonnucleoside Sofosbuvir Dasabuvir In consultation with Unfortunately the new hep C drugs need to be prescribed, in consultation with, or following consultation with, a gastroenterologist or ID physician PBAC has been very clear it wants as many Australians treated as possible It is hoped that this consultation requirement will be dropped/modified after July 8

9 Drug-drug interactions Many potential interactions Beware amiodarone!! Check the University of Liverpool website or app New Drugs on the Horizon for Australia December 2016 Zepatier (grazoprevir + elbasvir) 2017 Sofosbuvir + velpatasvir 2018 Gilead triple combo 2019 Merck triple combo Monitoring on treatment No ribavirin 4 weeks FBE, LFTs End-of-treatment (EOT) FBE, LFTs, (?HCV RNA) 12 weeks after completion FBE, LFTs, HCV RNA With ribavirin (causes anaemia) More monitoring is required 9

10 Getting to Hep C free Make your clinic hepatitis C free by treating all of your patients Retesting those at risk of acquisition with LFTs and hep C RNA Yearly? Reaching out to opiate substitution treatment program participants 10

11 Where are we heading? Manage and treat viral hepatitis in primary/community clinics to prevent stigma, suffering and death Primary Health/GPs Aboriginal Medical Services Sexual Health Clinics Opioid Substitution Treatment (OST) programs Prisons Empower community, GPs, allied health Referral to tertiary services less necessary except in special circumstances DAAs a treatment revolution 11