Treating HCV Infection in Patients Receiving Hemodialysis

December 17, 2013

Atif Zaman, MD, MPH reviewing Liu CH et al. Ann Intern Med 2013 Dec 3.

Until next-generation drugs become approved for this population, adding low-dose ribavirin to standard peginterferon therapy improves sustained virologic response.

Although the next-generation regimens for hepatitis C virus (HCV) are effective, currently, the standard approved regimen for patients receiving hemodialysis is still peginterferon plus low-dose ribavirin (200 mg/day). The addition of low-dose ribavirin was approved by the FDA in August 2011. However, that approval was based on small studies that were very heterogeneous with regard to treatments, HCV genotypes, and endpoints. Therefore, the efficacy and safety of combination therapy compared with monotherapy in this population is unclear.

In the current open-label, randomized, controlled trial, 205 treatment-naive patients with genotype 1 HCV infection receiving hemodialysis were randomized to receive either peginterferon alone (135 µg weekly) or in combination with ribavirin (200 mg daily) for 48 weeks. Outcomes were sustained virologic response (SVR) rate and adverse event–related withdrawal rate.

SVR was significantly higher in the combination group compared with the monotherapy group (64% vs. 33%, respectively; P<0.001). As expected, significant anemia (hemoglobin level <8.5 g/dL) was higher among the patients receiving ribavirin (72% vs. 6%; P<0.001), who also required higher doses of erythropoietin (P=0.006) for a longer duration (P=0.004). Adverse event–related withdrawal rates were similar in the combination and monotherapy groups (7% and 4%).

COMMENT

In this large treatment study, sustained virologic response was higher with combination peginterferon and ribavirin compared with monotherapy in patients with genotype 1 hepatitis C virus infection receiving hemodialysis. Using the very low dose of 200 mg daily of ribavirin not only achieved an SVR rate comparable to that reported in patients who were not receiving hemodialysis, but also kept the discontinuation rate due to adverse events low. While we wait for the safety and efficacy data of the new HCV regimens in patients receiving hemodialysis, peginterferon plus low-dose ribavirin is a viable option.

Editor Disclosures at Time of Publication

CITATION(S):

1. Liu CH et al. Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: A randomized trial. Ann Intern Med 2013 Dec 3; 159:729. (http://dx.doi.org/10.7326/0003-4819-159-11-201312030-00005)

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ASN: HCV Infection Virtually Untreated in Dialysis Patients

By Todd Neale, Senior Staff Writer, MedPage Today
Published: November 12, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
 
PHILADELPHIA -- Hepatitis C virus (HCV) infection is associated with an increase in mortality in patients on hemodialysis, but treatment is rare in that population, researchers found.

In a large, international cohort study of patients on hemodialysis, only one in every 100 of those who were HCV-positive received antiviral treatment, according to David Goodkin, MD, of the Arbor Research Collaborative for Health in Ann Arbor, Mich.

Treatment of HCV infection was associated a 73% lower risk of dying during follow-up, even after accounting for numerous potential confounders (HR 0.27, 95% CI 0.08 to 0.92), he reported at the American Society of Nephrology meeting here.

"We may be doing a disservice to our hemodialysis patients by not treating HCV, particularly those who are awaiting transplantation," Goodkin said.

A randomized trial examining the effect of treating HCV infection in patients on hemodialysis has not been done, and Goodkin said such a trial is unlikely because all previous trials of HCV treatments have excluded patients with renal failure.

But even if such a trial is undertaken, it would be years before conclusions could be drawn, he said.

"In the interim, clinicians are going to go on rounds, 10% of the patients are HCV-positive, and I really hope, at least for the transplant waiting list patients, [clinicians will] think again about whether [the patients] should be treated or not."

The findings came from a data analysis of the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective cohort study of patients at 382 randomly selected hemodialysis clinics in 12 countries.

The current study included information on 47,004 patients participating in the study between 1996 and 2011. Median follow up ranged from 0.94 to 1.76 years.

The overall prevalence of HCV infection -- determined by a diagnosis of HCV infection in the medical record or a positive test for HCV antibodies at baseline or during follow-up -- was 9.6%, indicating that "this is not a trivial problem," according to Goodkin.

Overall, only 47 patients in the study (1.1% of those who were HCV-positive) were receiving antiviral medications. For patients on the kidney transplant waiting list who were HCV-positive, 3.8% were receiving antivirals.

Goodkin acknowledged that it is possible the use of antiviral medications was underestimated, but said that after calling some of the hemodialysis centers, he trusted the figures.

"Even if we were off by a factor of three, it's still almost no one is being treated," he said.

That is particularly important because HCV infection is associated with a 22% increased risk of mortality after adjustment for patient characteristics (HR 1.22, 95% CI 1.11 to 1.33), Goodkin said, noting that the hazards of death associated with congestive heart failure and diabetes are of similar magnitude.

HCV infection has also been shown to be associated with increased allograft loss, new-onset diabetes, serious infections, and death among untreated HCV-positive patients who had undergone a kidney transplant.

Treating HCV infection in patients on hemodialysis does work, Goodkin said, pointing to a systematic review that showed a 40% sustained virological response to interferon in those patients, which is comparable to or better than in the general population.

But antiviral therapy can be difficult for patients, which could account for the low treatment rates in patients on hemodialysis, who already have impaired quality of life, he noted.

Interferon is associated with flu-like symptoms, fatigue, depression, and neurological and cardiovascular complications. And ribavirin carries a risk of severe anemia.

Even so, Goodkin said guidelines from KDIGO (Kidney Disease: Improving Global Outcomes) addressed the issue correctly. Those recommendations state that HCV-positive patients who are awaiting a kidney transplant should receive antiviral treatment, whereas treatment in other patients should be considered on a case-by-case basis.

DOPPS is supported by Amgen, Kyowa Hakko Kirin, Abbott, Sanofi/Genzyme, and Baxter Healthcare without restrictions on publications.

Goodkin reported relationships with Affymax, AMAG, Amgen, Arbor Research Collaborative for Health, Cerevast, ChemoCentryx, FibroGen, Keryx, Seattle Life Sciences, Spectrum, Xenon (stock options), and Koronis (shareholder).

Primary source: American Society of Nephrology
Source reference:
Goodkin D, et al "Treatment of hepatitis C in hemodialysis patients is associated with markedly decreased mortality, but is rarely prescribed" ASN 2011; Abstract FR-OR281.

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