FROM GASTROENTEROLOGY

Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.

Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD , at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”

Chronic HCV infection was rarely treated in patients with end-stage renal disease during the interferon era because of its toxicities and low tolerability, the researchers noted. Among the new direct-acting antivirals, sofosbuvir is cleared renally and therefore is not recommended in patients with estimated glomerular filtration rates below 30 mL/min per 1.73 m2. Most other direct-acting antiviral agents are metabolized by the liver, but blood levels of simeprevir and daclatasvir can rise in the setting of severe renal impairment. In contrast, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and did not require dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. Thus, the investigators studied this regimen in 20 adults with treatment-naive noncirrhotic HCV genotype 1 infections and stage 4 (estimated glomerular filtration rate [eGFR] 15-30 mL/min per 1.73 m2) or stage 5 (eGFR less than 15 mL/min per 1.73 m2 or requiring hemodialysis) chronic kidney disease. Patients with genotype 1a infections also received ribavirin at a reduced dose of 200 mg once daily (Gastroenterology. 2016 Mar 11. doi: 10.1053/j.gastro.2016.02.078 ).

All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.

Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.

AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.

ginews@gastro.org

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