Do directly acting antiviral agents for HCV increase the risk of hepatic decompensation and decline in renal function? Results from ERCHIVES.
Directly acting antiviral agents (DAA) have been associated with hepatic decompensation, especially in patients with pre-treatment cirrhosis, but this risk is not well defined.



To determine the incidence of hepatic decompensation, liver transplantation, death and worsening renal function in patients treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD), sofosbuvir/simeprevir or sofosbuvir/ledipasvir regimen.



We followed ERCHIVES participants treated with the above regimens for up to 12 weeks post-treatment. We excluded those with HIV, HBsAg+ and pre-existing diagnosis of hepatic decompensation and hepatocellular carcinoma.



Of 3728 persons on PrOD, 1578 on sofosbuvir/simeprevir and 10 440 on sofosbuvir/ledipasvir, incidence rates (95% CI) of hepatic decompensation/1000 patient-years were 10.6 (5.89-17.36) for the PrOD, 32.4 (20.74-48.16) for the sofosbuvir/simeprevir and 13.0 (9.74-17.10) for the sofosbuvir/ledipasvir. Among those with baseline cirrhosis, these rates were 36.9 (19.1-64.5), 61.8 (38.2-94.5) and 41.1 (29.9-55.2) respectively, while among those without cirrhosis at baseline, these rates were 2.7 (0.6-8.0), 7.5 (1.5-21.8) and 2.7 (1.2-5.4). Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups [HR (95% CI) per 0.5 unit increase in FIB-4 score: PrOD 1.11 (1.07-1.16); sofosbuvir/simeprevir 1.03 (1.01-1.05); sofosbuvir/ledipasvir 1.02 (1.01-1.03)]. There were no deaths. Proportion of persons with eGFR decrease >30 ml/min/1.73 m2was higher among the PrOD group, but presence of cirrhosis did not appear to affect this.



The incidence of hepatic decompensation in persons treated with PrOD, up to 12 weeks after completion of treatment, was comparable to those treated with sofosbuvir/ledipasvir regimen, and was lower than among those treated with a sofosbuvir/simeprevir regimen. Such risk was predominantly observed in those with pre-treatment cirrhosis.
VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.|Weill Cornell Medical College, Doha, Qatar.|Weill Cornell Medical College, New York, NY, USA.|Hamad Healthcare Quality Institute, Hamad Medical Corporation, Doha, Qatar.
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Butt
VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
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Y
Ren
Hamad Healthcare Quality Institute, Hamad Medical Corporation, Doha, Qatar.
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K
Marks
VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.|University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Shaikh
University of Cincinnati, Cincinnati, OH, USA.
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Sherman
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D000069616:Simeprevir / Q000008:administration & dosage / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects
D000998:Antiviral Agents; D000069616:Simeprevir; D019438:Ritonavir; D000069474:Sofosbuvir