Brief Report: The Impact of Ledipasvir/Sofosbuvir on HIV-Positive and HIV-Negative Japanese Hemophilia Patients With 1, 4, and Mixed-Genotype HCV

Nagao, Azusa; Hanabusa, Hideji

doi:10.1097/qai.0000000000001271

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…Among the HIV/HCV coinfected Japanese patients with inherited bleeding disorders who received interferon-free DAA therapy, all patients achieved sustained virologic response (SVR12 and 24) regardless of past anti-HCV treatment histories with interferon or the presence of compensated cirrhosis. The high treatment efficacy rate of DAA therapy for patients with inherited bleeding disorders reported here is similar to that documented in previous studies [ 10 , 11 ].…”

Section: Discussionsupporting

confidence: 90%

“…Several studies have reported the high efficacy and safety of direct acting antiviral (DAA) therapy in HIV-1 coinfected patients [ 5 – 9 ]. Although two studies reported the high efficacy and safety of DAA therapy in HIV-1 coinfected hemophiliac patients (by contaminated blood products), the effect of such therapies in hemophiliacs is limited [ 10 , 11 ]. Most of the Japanese hemophiliacs have received various forms of therapies against HIV-1, starting with AZT monotherapy, dual nucleoside reverse-transcriptase inhibitors (NRTIs) therapy, and cART, and some have histories of treatment failures.…”

Section: Introductionmentioning

confidence: 99%

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Interferon-free therapy with direct acting antivirals for HCV/HIV-1 co-infected Japanese patients with inherited bleeding disorders

et al. 2017

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IntroductionAlmost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs.MethodsWe conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1. Patients with HCV genotype 1 (GT1) and GT4 received ledipasvir (90 mg) plus sofosbuvir (400 mg), those with HCV GT2 received sofosbuvir plus weight-based ribavirin, and those with HCV GT3 received daclatasvir (60 mg) plus sofosbuvir. Treatment was continued for 12 weeks in all patients. The primary endpoints were rate of sustained virologic response at 12 weeks after end of therapy (SVR12) and occurrence of adverse events during DAA therapy.ResultsEighteen (67%) patients had had received interferon-based therapy, and 11 (41%) had compensated cirrhosis. HCV genotypes were GT1a 4 (15%), GT1b 16 (59%), GT1 undetermined 2 (7%), GT2a 1 (4%), GT3a 3 (11%) and GT4a 1 (4%). All patients were on combination antiretroviral therapy (cART) and had undetectable HIV-1 viral load (<20 copies/μL) at baseline. All patients achieved SVR12. Serious adverse events were observed in 3 patients: arteritis of the leg, which resolved after completion of DAA therapy, asymptomatic QT prolongation and gastrointestinal hemorrhage. cART failure was noted in one patient due to emergence of raltegravir resistance during ledipasvir/sofosbuvir treatment. Although α-fetoprotein, Mac-2 binding protein glycosylation isomer (M2BPGi), and Fibro Scan (FS) scores decreased in most patients during DAA therapy, M2BPGi (>2.0 cutoff index) and FS scores (>15.0 kPa) were still high in 6 patients at week 36.ConclusionsDAA therapy is effective in all patients. However, adverse events and efficacy of cART should be monitored closely.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Interferon-free therapy with direct acting antivirals for HCV/HIV-1 co-infected Japanese patients with inherited bleeding disorders

et al. 2017

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“…Walsh et al [34] also concluded that SOF/LDV for patients with HCV genotype 1 or 4 infection or SOF+RBV for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders. Nagao and Hanabusa [35] studied 43 patients with haemophilia with genotype 1 or 4 HCV treated with SOF/LDV and showed effectiveness and safeness, but with SVR in patients with cirrhosis being lower than that in the non-cirrhotic group, stressing the need for treatment as early as possible, ideally before the onset of cirrhosis. Papadopoulos et al [31] summarized all available DAA studies in inherited bleeding disorders, showing an overall SVR >95% with SOF/LDV regimens.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection

Guedes

Garrido

Küttner-Magalhães

et al. 2020

GE Port J Gastroenterol

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Introduction: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. Methods: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. Results: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. Conclusions: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

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“…Ten HCV genotype 2 (HIV-positive 40%, cirrhosis 20%, treatment-experienced 30%) patients were treated with SOF plus RBV for 12 weeks with an overall SVR12 of 100%, and six HCV genotype 3 (HIV-positive 50%, cirrhosis 33%, treatment experienced 17%) patients were treated with SOF/RBV for 24 weeks with an overall SVR of 83%. The high efficacy of SOF/LDV therapy was further documented in a study by Nagao and Hanabusa: 43 patients with hemophilia and HCV genotype 1/4 infection (HIV-positive 75%) were treated with SOF/LDV for 12 weeks with an overall SVR12 of 95% [ 49 ]. Furthermore, the efficacy did not differ significantly between the HIV-negative and HIV-positive patients (SVR12: 100% in HIV-negative and 95% in HIV-positive, P=0.12).…”

Section: Managementmentioning

confidence: 99%

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

Papadopoulos¹,

Argiana²,

Deutsch

2017

aog

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Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

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Brief Report: The Impact of Ledipasvir/Sofosbuvir on HIV-Positive and HIV-Negative Japanese Hemophilia Patients With 1, 4, and Mixed-Genotype HCV

Abstract: In this cohort study, LDV/SOF was effective and safe, but the SVR in patients with cirrhosis was lower than that in the noncirrhosis group. Thus, patients with hemophilia with genotype 1/4 HCV should be treated as early as possible before the onset of cirrhosis.

Cited by 18 publications

References 26 publications

Interferon-free therapy with direct acting antivirals for HCV/HIV-1 co-infected Japanese patients with inherited bleeding disorders

Interferon-free therapy with direct acting antivirals for HCV/HIV-1 co-infected Japanese patients with inherited bleeding disorders

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

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