HCV therapies: what have we achieved and remaining challenges?

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:

1. Difficult to treat: cirrhosis, NS5A RAS, GT3
• lower SVR in GT3, cirrhotics and those with NS5A RAS
2. Difficult to treat: renal impairment eGFR <30mL/min or haemodialysis
• Suggested options for GT 1 and 4:
• ombitasvir/paritaprevir/r +/- dasabuvir
• grazoprevir/elbasvir
• Other genotypes:
• use sofosbuvir-based regimens with caution
• close monitoring of renal function
3. Drug-drug interactions:
• especially with HIV ART
• make use of the Liverpool HEP Drug interactions website
4. Events after SVR if therapy is started too late:
• 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
• co-infections
• 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
5. New epidemics and reinfections
6. The cascade of care: comparing HCV with HIV (following the 90:90:90 targets). Increase of treatment rates to reduce prevalence by 90% in 2030.
7. Affordability and reimbursement restrictions
• 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.
8. Treatment-as-prevention and risk behaviour
• 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)

In summary:

Goals of HCV therapy: achievements and challanges.

• Cure HCV infection
• Minimise adverse events
• Provide universal access to therapy
• Prevent HCV transmissions