The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.
The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m2, HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America5 include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.
When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.
REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.
2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.
3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.
4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.
5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.