Andri Rauch, Bern University Hospital and University of Bern, Switzerland presented on the achievements and remaining challenges of Hepatitis C treatment.
We have all been fortunate to witness the breakthrough in HCV treatment from interferon-based regimens to DAAs:
- Interferon acts by unspecific activation of innate and adaptive immune responses.
- DAAs are specific and highly efficient in inhibition of the HCV life cycle.
The improvements in treatment efficacy in SVR genotype 1 infection:
- by HIV status:
- HCV SVR (cure) in both HIV/HCV co-infected, as well as HCV-monoinfected patients used to range from ~40% clearance in HIV/HCV co-infected patients to ~50% in HCV-monoinfected patients using PegIFN/RBV alone
- Treatment with DAAs are now showing cure rates over 90% (and in some cases even up to 100%) in BOTH the co-infected and monoinfected patient
- by cirrhosis status:
- Cure rates of just over 30% have been observed in patients with cirrhosis who underwent treatment with PegIFN/RBV alone. The numbers were slightly better for patients with no cirrhosis at ~50% SVR on the PegIFN/RBV regimen
- Treatment with DAAs are showing cure rates of ~95% and over.
- by IL28B status:
- SVR in IL28B risk allele were ~30% when PegIFN/RBV was used, compared to ~75% in IL28B protective allele carriers on the same regemine
- Again, different DAA combinations show cure rates very close to 100%
Thus, DAAs achieve high cure rates irrespective of host and viral characteristics.
Changing from complex to simple treatments resulted a few (very welcomed) changes within the past 5 years:
- Single tablet regimens
- Treatment durations of 8; 12 or 24 weeks (depending on HCV genotype, cirrhosis status and past DAA failure)
- No requirement for response-guided decisions
- Minimal monitoring required
Andri discussed the remaining challenges:
- Difficult to treat: cirrhosis, NS5A RAS, GT3
- lower SVR in GT3, cirrhotics and those with NS5A RAS
- Suggested options for GT 1 and 4:
- ombitasvir/paritaprevir/r +/- dasabuvir
- Other genotypes:
- use sofosbuvir-based regimens with caution
- close monitoring of renal function
- especially with HIV ART
- make use of the Liverpool HEP Drug interactions website
- clinical improvement moderate in patients with decompensated cirrhosis with SVR
- SVR does not eliminate risk of HCC
- deferring treatment increases risk of liver-related events:
- persistent metabolic risk factors
- liver toxicity due to drugs alcohol or co-medication
- genetic predisposition to accelerated liver fibrosis
- reversion of liver fibrosis/cirrhosis is frequent but not universal
- Due to cost the DAAs are not readily available in many countries
- The costs of treating all patients with hepatitis C would be equal to at least a tenth of the current annual cost for all medicines.
- Stabilisation in high-risk behaviour combined with an increase in treatment uptake is required to curb the HCV epidemic among HIV-infected MSM.
- If this can be achieved, treatment-as-prevention can reach to HWO elimination targets (90% reduction in new cases by 2013)
Goals of HCV therapy: achievements and challanges.
- Cure HCV infection
- Minimise adverse events
- Provide universal access to therapy
- Prevent HCV transmissions