ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

HCV therapies: what have we achieved and remaining challenges?

Posted by on in HIV Co-infections, hepatitis B, hepatitis C and TB
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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:
  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

 

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Guest Sunday, 16 December 2018