Boceprevir and telaprevir‐based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end‐stage liver disease score

Abstract

Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)-NS3/NS4A protease inhibitors (PI)] in association with PEG-IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow-up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty-one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non-response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non-responders to 59.1% in partial non-responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P < 0.001). The model for end-stage liver disease (MELD) score was significantly increased at W12 for telaprevir (P = 0.008) and at W24 for boceprevir (P = 0.027). PI-based triple therapy leads to high rates of virological response even in previously non-responder patients. Renal function after triple therapy is impaired as well as MELD score in all patients. Cautious clinical monitoring should focus not only on haematological and dermatological side effects but also on renal function.

Anti-hepatitis C virus drugs and kidney

“…Nevertheless, in a large cohort (1486 patients), Mauss et al[10] showed a reversible decrease of eGFR in patients taking telaprevir or boceprevir. Similar reports involving telaprevir therapy confirmed this observation and suggested a link with anemia occurrence[75-78]. Recently, Kunze et al[30] described competition between telaprevir and OCT2, which interacts with creatinine tubular transport and is involved in proximal tubular secretion.…”

Liver Apparent Diffusion Coefficient Changes during Telaprevir-Based Therapy for Chronic Hepatitis C

“…The current standard of therapy for these patients is PEG-IFN/ RBV for 48-weeks. Unfortunately, less than 50% of patients respond to this therapy (20). The sustained virologic response (SVR) with telaprevir was reportedly approximately 70%-80% in previous reports (1).…”

“…This combination may cause some side effects, including itching, rash, anemia, nausea, fatigue, diarrhea, vomiting, anal or rectal problems, taste changes, and signs or symptoms of dehydration (2). More recently, renal impairment has been reported with telaprevir (20). In that report, the model for end-stage liver disease (MELD) score was also used to evaluate specific effects of treatment on liver health.…”

Antiviral Therapy in Patients with Hepatitis C Virus-Induced Cirrhosis

“…The IL28B genotype was also identified as a predictor of SVR12, with a higher probability of response among patients with the IL28B CC genotype (OR = 3.54, p = 0.031). However, since other studies have reported a limited impact of the IL28B genotype on response rates [51], further studies are needed to confirm this association more precisely [47]. …”

“…Impairment of renal function was also observed in different cohort studies for both PIs. Indeed, a significant decrease in the glomerular filtration rate was observed after the introduction of the PI but a return to normal values occurred after the end of the PI intake [46,47]. Furthermore, an increase in serum RBV concentration was observed in a group of patients treated with telaprevir [48].…”