Probable case of drug reaction with eosinophilia and systemic symptom syndrome due to combination therapy with daclatasvir and asunaprevir

Abstract

A 66-year-old, interferon-ineligible, treatment-naive man who was diagnosed with chronic hepatitis C due to hepatitis C virus genotype 1b began combination therapy with daclatasvir and asunaprevir. On day 14 of treatment, hepatic reserve and renal function deterioration was observed, while his transaminase levels were normal. Both daclatasvir and asunaprevir were discontinued on day 18 of treatment, because the patient complained of dark urine and a rash on his trunk and four limbs. After discontinuing antiviral therapy, the abnormal laboratory finding and clinical manifestations gradually improved, without recurrence. Our case fulfilled the diagnostic criteria of probable drug reaction with eosinophilia and systemic symptom (DRESS) syndrome. Despite the 18-d treatment, sustained virological response 12 was achieved. Based on the clinical course, we concluded that there was a clear cause-and-effect relationship between the treatment and adverse events. To our knowledge, this patient represents the first case of probable DRESS syndrome that includes concomitant deterioration of hepatic reserve and renal function due to combination therapy with daclatasvir and asunaprevir, regardless of normalization of transaminase levels. Our case suggests that we should pay attention not only to the transaminase levels but also to allergic symptoms associated with organ involvement during combination therapy with daclatasvir and asunaprevir.

Keywords: Hepatitis C, Daclatasvir, Renal dysfunction, Asunaprevir, Hepatic reserve deterioration

Core tip: Oral combination therapy with daclatasvir and asunaprevir for chronic hepatitis C demonstrates a relatively favorable safety profile. Although the incidence of hyperbilirubinemia, hypoalbuminemia, and a decreased prothrombin activity have been reported, as well as renal damage, concomitant deterioration of hepatic reserve and renal function without transaminase elevations have not been reported. We observed probable drug reaction with eosinophilia and systemic symptom syndrome, including concomitant deterioration of hepatic reserve and renal function due to the combination therapy, regardless of normalized transaminase levels. Thus, our case highlights the importance of paying attention not only to transaminase levels but also to the allergic symptoms associated with organ involvement during combination therapy.