Clinical Review

CKD and HCV: Do We Know What We’re Doing?

How are the newest HCV drugs best used in patients with chronic kidney disease—especially when CKD reaches stage 4 or 5? Can these agents make it possible to forego interferon use in these vulnerable patients?

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Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.1 The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.2 Genotypes 2 and 3 account for most of the rest.3

While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.

Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.4 Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen®, when blood transfusions were common) are more likely to be HCV-positive.

Unfortunately, patients often convert to HCV while on hemodialysis.4 This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.

With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m2. The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak) suggest that no dosing modifications are necessary in the moderately impaired kidney population.

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