Dr Philippe Halfon is Actively Involved in the International Symposium on HIV, Hepatitis Viruses and Emerging Infectious Diseases (ISHEID). Today, he speaks about HCV care and the consequences of PrEP in terms of HCV epidemic.
Philippe Halfon is a clinician in infectious diseases and a researcher; mainly in virology and in oncology.
He is the Head of the Department of infectious diseases and internal medicine the European hospital of Marseille (France) and manages the laboratory Alphabio.
His main research topics concern the resistance of the Hepatitis C (HCV) virus to directly active antiviral drugs, the characterization of latent HIV reservoirs, the characterization of biomarkers in molecular oncology and the pharmaceutical development of anti-cancer molecules targeting the cancerous stem cells.
He agreed to answer some of our questions:
1-What are the essential methods of diagnosis available today to get the pre-therapeutic score of a patient infected by HCV?
To date as we wrote it in the reference book for good practice lead by Pr Morlat, the pre-therapeutic tests must contain:
- HCV viral load;
- HCV genotype and sub-type; to re-check if previously obtained from non-coding 5 ' region, by performing a new genotype in NS5B regions or other coding regions of the virus;
- Renal evaluation in blood and urine samples;
- A thyroid test with a TSH and the search for auto-antibody anti-TPO, anti-thyroglobulin, anti-nuclear, antis-mooth muscles, anti-LKM, anti mitochondria;
- In front of the existence of extra-hepatic clinical complications of VHC, it is advisable to look for a cryoglobulinemia (in the adequate conditions of taking) and to measure the complement (CH50, C3, C4), the anti-nuclear antibodies and anti-cardiolipid antibodies.
- An abdominal ultrasound - and, if suspicion of cirrhosis, an oesophageal endoscopy to rule out esophageal varicose veins;
- the evaluation of the hepatic consequences of chronic infection with HCV must be favored by not invasive methods rather than by liver biopsy: by blood test: three scores are to be used: Fibrometer®, Hepascore and Fibrotest®; or by ultrasonic impulsive elastometry (Fibroscan®) which is a non-invasive technique allowing to measure in a objective and quantitative way the hardness of the liver, correlated itself with the degree of hepatic fibrosis. For the diagnosis of cirrhosis, the Fibroscan® only is enough if the value is superior to 14,5 kPa (positive predictive value close to 90 %).
To note: In France, Fibroscan®, Fibrotest® and Fibrometer® are paid off within the framework of patients care in the context of global health coverage by government (one test a year and by patient -with a part which sometimes stays chargeable to the patient for Fibrotest®). Fibroscan® is also paid off in co-infected HIV-HCV patient's.
2-What are the recommendations for starting anti-HCV drugs in patients according to the stage of fibrosis, the genotype and the existence or not of HIV co-infection?
Thanks to the support of scientific societies and to the support of the government, we have a favored situation in France, which offers us the possibility of treating all the patients with HIV-HCV co-infection whatever their fibrosis is, and for now mono-infected by HCV with a significant fibrosis (said F2 more, F3 and F4), as well as the patients presenting certain extra-hepatic manifestations of VHC (like cryoglobulinemia). Because of the competition between the pharmaceutical firms, the cost of these treatments should gradually fall. It will have for consequence a possibility of being able to treat all the patients infected by VHC and so allow eradication of this disease.
3-How to use the currently available drugs in each situation? Is there a competition between them?
There are indeed recommendations of treatment according to genotypes and sub-types, on one hand, and on the other hand according to the existence of cirrhosis or not. According to these clinical or virological situations, a treatment for 12 or 24 weeks is at present proposed with or not addition of ribavirin.
Various possibilities of therapeutic combinations are recommended to handle genotypes 1 and 4 with combinations associating a nucleoside inhibitor (sofosbuvir) with one anti-NS5A or combinations associating a protease inhibitor, an anti NS5A and a non nucleotidic inhibitor. For the treatment of genotypes 3, sofosbuvir is recommended in combination with daclatasvir for 12 weeks or 24 weeks in case of cirrhosis. Only the treatment of patients with genotype 2 virus is simplified with the use of sofosbuvir with ribavirin during 12 weeks. These therapeutic choices are validated in “RCP” (meeting of multidisciplinary approaches) and are mainly based on clinical criteria but sometimes on criteria of cost with comparable clinical efficiency.
4-What can we wait in terms of virological results?
The objective of the treatment is to cure 100 % of patients whatever the clinical situation is (HIV co-infection, liver transplanted patients, patients with renal insufficiency or on dialysis, decompensated cirrhosis) and the genotype of the patient. This objective will be reached in a near future with the advent of new drugs in development.
The objective of the treatment is to cure 100 % of patients whatever the clinical situation is
5-What can we wait exactly for molecules under development?
Besides the clinical efficiency which was discussed, these treatments will combine more powerful molecules thus generating an absence of resistance, will be combined in a combo (what is already the case with Harvoni®), will be very well tolerated and especially will allow a shorter treatment: less than 8 weeks, even 6 or 4 weeks of treatment!
6-Is the cost of these treatments an obstacle to their more premature use?
Of course because all the governments are confronted to establish a health policy based on the cost of the treatments of hepatitis C and cancers. These treatments strongly unbalanced the budgets of the health care system. In France, the cost of treatments represented in 2014 more than 2 % of the budget of the health insurance to treat approximately 12000 patients.
The healthy competition between pharmaceutical companies is going to allow a notable reduction of the costs and thus a use at a larger scale of these drugs which should allow to treat every patient infected by HCV whatever his stage of fibrosis is and to finally allow HCV eradication….at least in countries with access to these drugs.
7-What can the ISHEID bring to its attendees?
The bridge between HIV and viral hepatitis -and other emergent infections- which ISHED offers must tackle the issue of Prep (HIV Pre Exposure Prophylaxis by Truvada®) - whose efficiency is demonstrated in terms of prevention of HIV transmission- as a risk for an overexposure to HCV and other STDs (sexually transmitted diseases). Indeed, and without any stigmatization for these populations, hepatitis C, just like syphilis and other STDs do not frighten anymore because we "are very easily cured of it" and, consequently, these populations are no longer afraid to be contaminated.
This aspect was little discussed or considered during this political decision in France, and its consequences in terms of increasing the HCV epidemic in MSM (the men who have sex with men) with strong sexual activity and multiple partners, often under the influence of narcotics, were underestimated. There is a role and an opportunity for the ISHEID to spread a message of information and prevention.
There is a role and an opportunity for the ISHEID to spread a message of information and prevention against HCV in the context of PrEP
Key words: HCV, HIV, PrEP, Truvadapre exposure prophylaxis