Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: a nationwide multicenter study by the Japanese Red Cross Liver Study Group

• DOI: 10.1007/s00535-018-1455-1
• Publication Date: 2018-04-19T15:35:00Z
• Authors: Keiji Tsuji; Masayuki Kurosaki; Jun Itakura; Nami Mori; Shintaro Takaki; Chitomi Hasebe; Takehiro Akahane; Kouji Joko; Hitoshi Yagisawa; Jirou Takezawa; Ryou Nakata; Atsunori Kusakabe; Yuji Kojima; Hiroyuki Kimura; Takashi Tamada; Haruhiko Kobashi; Akeri Mitsuda; Masahiko Kondou; Chikara Ogawa; Yasushi Uchida; Tetsuro Sohda; Ryouichi Narita; Namiki Izumi
• Keywords: Adult; Aged, 80 and over; Liver Cirrhosis; Male; 0301 basic medicine; Fluorenes; 0303 health sciences; Carcinoma, Hepatocellular; Liver Neoplasms; Hepacivirus; Hepatitis C, Chronic; Middle Aged; Antiviral Agents; Polymorphism, Single Nucleotide; Red Cross; 3. Good health; 03 medical and health sciences; Japan; Humans; Benzimidazoles; Drug Therapy, Combination; Female; Prospective Studies; Aged

We aimed to describe the real-world efficacy and safety of combination therapy with ledipasvir and sofosbuvir (LDV/SOF) for chronic hepatitis C virus (HCV) genotype 1 (GT1) infection.This retrospective analysis of a prospective, nationwide, multicenter registry included GT1-infected patients treated with LDV/SOF for 12 weeks. We assessed the rate of sustained virological response at 12 weeks post-treatment (SVR12), incidence of adverse events, and serum markers of hepatocellular carcinoma (HCC).Among the 1461 patients included (mean age, 69 years; 29.5% aged > 75 years; cirrhosis, 23.8%; history of treatment for HCC, 10.9%), the overall SVR12 rate was 98.4% (1438/1461). Factors associated with treatment failure were cirrhosis (odds ratio, 4.19; p = 0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p = 0.0004). The SVR12 rate in patients with cirrhosis and NS5A RASs was 93.0% compared to 100% in patients without cirrhosis or NS5A RASs. In patients with SVR, the levels of alpha-fetoprotein (AFP), AFP-L3, and Mac-2 binding protein glycosylation isomer (M2BPGi) decreased from baseline to end of treatment (from 13.4 ± 37.6 to 6.0 ± 10.6 ng/mL, p < 0.0001; from 2.2 ± 4.9 to 1.5 ± 6.3%, p < 0.005; and from 3.6 ± 3.7 to 2.0 ± 3.5 cut-off index, p < 0.0001; respectively). Adverse events were rare and not associated with age. No decrease in estimated glomerular filtration rate was observed in patients with baseline chronic kidney disease stage 3.LDV/SOF therapy is highly effective and safe in elderly Japanese patients with HCV GT1, even in the presence of cirrhosis or NS5A RASs. Patients with SVR may have a lower risk of HCC.