HCV: new frontiers and controversies was the final session I attended, abstracts 179 to 181. It built on the earlier workshop, HCV in the interferon-free era, blogged by Jane. In the pathogenesis of acute infection, Ashwin Balagopal described a doubling time of 7.5 hours with 21 days to reach a viraemia of over 6 logs. HCV infects a minority of hepatocytes at 20-45% with about 100 copies of HCV RNA per hepatocytes. 1-3 trillion copies of RNA are made daily and rapidly cleared to maintain set point. 20-25% of people clear infection, usually within the first six months, and prior clearance of an earlier infection makes this more likely (as does being female, non-African and HIV negative). In reminding us of ELITE controllers, he raised the vaccine option.
IL28B is now known as interferon lambda 3 which can mutate to IFN L4 to which HCV binds differently. Evidence of immune response is also seen in that neutralising antibodies from people who have cleared HCV previously have an effect in a further clearance of infection.
Greg Dore first defined terminology in his HCV treatment as prevention talk. There are three approaches: eradication as in small pox, elimination in which the incidence is zero but on-going work is required (measles and polio) and epidemic control where incidence decreases over time.
The dilemma in HCV treatment is whether to focus on the liver disease burden in older people (defined as over 35) or on HCV infection prevention in younger people. He presented data which indicated that 75% of people aged 15 to 19 years had ever injected, this rate falling to 25% over the age of 35.
In discussing treatment as prevention in Australia in the 10% co-infected with HIV and HCV, he reported on the CEASE study: approximately 80% of co-infected people have been diagnosed, around 80% of those are linked to / retained in care but only about two thirds are / have received treatment. Of the treated fraction, HIV RNA is suppressed in over 60%.
He spoke of the harm reduction approach for PWID, noting that only 41% of countries have NSP programs and only 30% have opiate substitution programs. HCV incidence in Australia was around 25% per annum in the 1990s falling to about 5% per annum in the 2000s. The target groups for treatment as prevention are PWID, prisoners (12% of injectors are jailed annually with an incident HCV infection rate of 10% per annum), HIV positive MSM and pregnant women.
He outlined the STOP C study of early and deferred treatment with sofosbuvir and GS5816 for 12 weeks planned for two medium to maximum security prisons in New South Wales.
In abstract 181, HCV therapeutics: It's the virus stupid, Mark Sulkowski described the HCV life cycle and where the directly acting molecules fit. He also spoke of the class cross resistance seen (in the low number of people who fail treatment) to date with telapravir and daclatatasvir and of the benefit in preventing failure in adding ribaviron.
He define Perfectovir, introduced by Greg Dore in the preceding talk, as achieving SVR in > 90%, working for all genotypes, administered as a once daily pill and with no side effects. He also thanked all the people who were in clinical trials which did not show benefit.
Marion Peters had given a superb talk in the HCV workshop on HCV cirrhosis with early decompensation in which she demonstrated the usefulness of the Childs Pugh score as well as the MELD during treatment for assessing decompensation. She had reminded us that the natural history of ESLD is that 5-7% of people decompensate annually. In this the last talk of the conference, she was given the title of HCV therapeutics: big sticks with big stickers. In noting that SVR produced a 70% reduction in HCC and a 50% reduction in all cause mortality (renal and bone disease, cryoglobulinaemia, lymphoproliferative disease, CVD and cognitive impairment) as well as reducing portal hypertension.
Cost effectiveness of staging determined treatment as opposed to treating all patients yielded a best result for immediate treatment of anyone with a Fibroscan score of > F1. The cost of treating T2DM, HIV, HER2 positive breast cancer and HCV with IFN RBV and a PI were about the same but the difference is that the costs with HCV treatment are all up front, not spread out over time. A time delay in treatment (until people reached Medicaid age in the USA) meant two thirds had at least one other chronic disease which could complicate treatment.
91 countries across the world to date have made deals of various sorts with pharma to access treatments for their populations. The obvious inequities were discussed in question time.
Marion Peters ended her talk saying that the problem is the patient load of HCV infection worldwide and that in its management of HCV, Australia could be considered the greatest country in the world.