Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events

Abstract

BackgroundSustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen.Case summaryRetreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks.ConclusionRetreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.

APASL clinical practice recommendation: how to treat HCV-infected patients with renal impairment?

“…In some patients with HCV infection and severe renal impairment, treatment with DAAs is discontinued due to renal dysfunction [39]. For patients with CKD stages 4/5, hemodialysis should be prepared if renal function worsens and treatment with a DAA combination is initiated.…”

“…HCV infection is usually asymptomatic in patients with end-stage renal disease [ 38 ]; however, it may lead to decompensated liver diseases and HCC. In some patients with HCV infection and severe renal impairment, treatment with DAAs is discontinued due to renal dysfunction [ 39 ]. For patients with CKD stages 4/5, hemodialysis should be prepared if renal function worsens and treatment with a DAA combination is initiated.…”

Hepatitis C: A Pharmacological Therapeutic Update

“…Therefore, this treatment is recommended in naïve patients or patients previously treated with interferon regimens, without cirrhosis or with compensated cirrhosis (Child A) and for 1 and 4 viral genotypes [ 26 ]. According to the C-EDGE TN and C-EDGE TE studies, another recommendation is established, since differences were observed in the sustained virologic response (SVR) rate based on the patient’s baseline viremia, it being adequate when it was less than 800,000 IU/mL [ 31 , 32 , 33 , 34 , 35 , 36 ].…”

“…The main route of elimination of both drugs is biliary excretion. They present a minimal renal clearance, mainly detected in glecaprevir, although it is less than 1% (0.7%) [ 35 ]. “Glecaprevir/pibrentasvir” has been studied in patients with different degrees of kidney failure with and without dialysis and a 56% increase in AUC and was found not to be clinically significant [ 1 , 17 ].…”