Successful prolonged treatment with sofosbuvir/velpatasvir for a hepatitis C patient with decompensated cirrhosis and treatment failure after 12-week therapy.

There is no established rescue therapy for hepatitis C patients with decompensated cirrhosis who experience treatment failure on 12-week sofosbuvir (SOF)/velpatasvir (VEL) therapy that is the only approved regimen for decompensated cirrhosis in Japan. We experienced a patient with decompensated cirrhosis who showed virologic relapse at post-treatment week 7 following 12-week SOF/VEL therapy. She had resistance-associated substitutions (RASs) against VEL before therapy but did not achieve new RASs against VEL or SOF after therapy. We considered rescue therapy following strong demand from her and her family. The drug adherence of therapy was 100%, and the treatment was well tolerated. Because we prioritized the safety and drug adherence of the regimen, we performed prolonged 24-week SOF/VEL therapy without ribavirin at her own expense with the approval of the ethics board in the hospital where the first author belongs. Fortunately, a sustained virologic response 24 was achieved without any adverse events. Hepatocellular carcinoma that had developed after 12-week SOF/VEL therapy recurred and was treated near the end of rescue therapy, but hepatic functional reserve improved. Although this was a single case report and was assumed to be very rare, the same regimen might be effective for treatment failure with 12-week SOF/VEL therapy.

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.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Immune thrombocytopenic purpura in patients with hepatitis C virus infection.

BACKGROUND/AIMS: Immune thrombocytopenic purpura could occur as an extrahepatic manifestation of hepatitis C virus infection. The aim of this study was to clinically analyze hepatitis C virus-positive cases with immune thrombocytopenic purpura and to examine the relationship between hepatitis C virus and immune thrombocytopenic purpura. METHODOLOGY: Eight hepatitis C virus-positive patients with immune thrombocytopenic purpura were compared with 67 cases with chronic hepatitis C without immune thrombocytopenic purpura. We examined various clinical and hematological parameters including platelet and platelet-associated immunoglobulin G. RESULTS: Two men and 6 women with hepatitis C virus infection (age 58.0 +/- 11.8) were diagnosed with immune thrombocytopenic purpura. Platelet counts (x10(4)/mm3) were significantly lower in these 8 patients (2.9 +/- 2.1) than in chronic hepatitis C patients without immune thrombocytopenic purpura (16.7 +/- 0.3) (P<0.001). Hepatitis C virus infection predated immune thrombocytopenic purpura in 6 patients and none of the patients with immune thrombocytopenic purpura was infected with hepatitis C virus after the diagnosis. Three of the 6 patients with chronic hepatitis C, which predated immune thrombocytopenic purpura, were treated with interferon and 2 developed immune thrombocytopenic purpura after the treatment. None of them eradicated hepatitis C virus by interferon. CONCLUSIONS: The fact that hepatitis C virus infection predated immune thrombocytopenic purpura in 6 of 8 patients suggests that hepatitis C virus could potentially induce immune thrombocytopenic purpura and interferon itself might induce immune thrombocytopenic purpura.