HCV DAAs and Severe Renal Impairment

Posted on June 25, 2015

New report provides vital information needed by clinicians to treat HCV in patients with severe renal impairment with the approved DAAs simeprevir and sofosbuvir.

Available clinical information on the use of sofosbuvir in patients with severe renal impairment is minimal, and there are currently no approved direct acting antiviral (DAA) treatments in this population. A report recently published online in Journal of Hepatology details the clinical experience associated with treating 15 HCV genotype 1 patients with end stage renal disease (ESRD) with simeprevir (150 mg/d) and half dose sofosbuvir (200 mg/d) at the University of Miami, Florida (Bhamidimarri K et al. J Hepatol. 2015 Jun 18. [Epub ahead of print]). ESRD was defined as glomerular filtration rate (GFR) of < 30 mL/min per 1.73m2 or requirement for dialysis. Of the 15 patients followed between January 2014 and January 2015, 12 (80%) were on dialysis (11 hemodialysis, 1 peritoneal) and 3 had a GFR between 8 and 15 mL/min.

  • These patients (ages between 39 and 77 years) were infected with HCV genotype 1 (67% genotype 1a), and had a detectable viral load with a mean HCV RNA of 9.7 million IU/mL
  • Nine patients (60%) were cirrhotic, 3 (20%) had stage 2-3 fibrosis and 3 (20%) stage 0-1 fibrosis (Metavir), all documented by liver biopsy. From the cirrhotic patients, 8 patients (89%) were Child-Pugh A (compensated) and 1 (11%) were Child-Pugh B (decompensated).
  • Six patients (40%) were treatment naïve and 9 (60%) were treatment experienced, all of them with Peg-Interferon and Ribavirin (6 relapsers and 3 null responders) and 4 protease inhibitor (PI) failures
  • All patients received the standard dose of Simeprevir of 150 mg daily. 11 patients (73%) received sofosbuvir 200 mg daily (split from the 400 mg pill) and 4 (27%) were on 400 mg every other day. Anti-HCV therapies were administered at least 1 hour pre-dialysis.

Fourteen patients (93%) were treated for a total of 12 weeks and 1 patient had treatment extended to 24 weeks. No dose adjustments were performed during the length of treatment. None of the patients were on Amiodarone.

  • Twelve patients (80%) became aviremic by week 4 and all patients were aviremic by week 8 and remained so until the end of treatment
  • Sustained virologic response (SVR) at week 4 was 93%
  • SVR at week 12 was 87%
  • SVR at week 12:
    • Genotype 1a (90%) versus genotype 1b (80%)
    • Non-cirrhotics (100%) versus cirrhotics (78%)
    • Sofosbuvir 200mg daily (91%) versus sofosbuvir 400mg every other day (75%)
    • Dialysis group (83%) versus non-dialysis group (100%)

Following completion of treatment, 1 patient with HCV genotype 1a and another with genotype 1b relapsed.

  • Both shared similar characteristics
    • Viremic at week 4 of treatment, compensated cirrhosis, hemodialysis dependent, prior PI failures with mean platelet count of 90 000/μl, mean albumin > 3.7 g/dL, mean baseline HCV RNA of 11 million IU/mL
  • Due to insurance approval, treatment in only one cirrhotic patient (HCV genotype 1a) could be extended to 24 weeks, but he relapsed despite prolonged treatment

No major AE’s were reported during treatment. Minor AE’s included fatigue (20%), rash/itching (13%), anemia (13%), diarrhea and loss of appetite (7%). No patient had to interrupt therapy due to side effects.

The authors make the following conclusions about their observations: “HCV in severe renal impairment is considered a difficult-to-treat group and in whom SVR is associated with improved pre- and post-kidney transplant outcomes. Half-dose Sofosbuvir plus full dose Simeprevir regimen is free of interferon and ribavirin and thus is an attractive option to treat HCV genotype 1 in severe renal impairment/ dialysis patients. The regimen appears to be safe, well tolerated and efficacious resulting in high rates of sustained virologic response. The optimal dose of Sofosbuvir in severe CKD needs to be clarified by future studies and in the absence of any approved HCV treatment for this group, our data provides information for clinicians who currently need to treat such patients with the approved DAA’s.”

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