Hepatitis C – New drugs and treatment prospects

Zajac, M; Muszalska, Izabela; Sobczak, Agnieszka; Dadej, Adrianna; Tomczak, Szymon; Jelińska, Anna

doi:10.1016/j.ejmech.2019.01.025

Cited by 65 publications

(57 citation statements)

References 88 publications

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“…However, little information is available to estimate the contribution of the increased fat mass to the decrease in plasma levels often observed during pregnancy . All DAAs, except sofosbuvir, show a high degree of plasma protein binding . Particularly for these highly protein bound drugs, an increase in the unbound fraction may be expected due to decreased plasma levels of the main drug‐binding plasma proteins albumin and α1‐acid glycoprotein during pregnancy.…”

Section: Effect Of Pregnancy On Maternal Exposure To Direct‐acting Anmentioning

confidence: 99%

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Freriksen

Seyen²,

Judd

et al. 2019

Aliment Pharmacol Ther

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Summary Background With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct‐acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. Aim To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation Methods A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. Results Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy‐induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. Conclusions Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.

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Section: Effect Of Pregnancy On Maternal Exposure To Direct‐acting Anmentioning

confidence: 99%

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Freriksen

Seyen²,

Judd

et al. 2019

Aliment Pharmacol Ther

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“…The first two direct-acting antivirals (DAAs)-the protease inhibitors telaprevir and boceprevir-enhanced viral clearance rate by 70% compared to the pIFNa and RBV treatment, but still induced significant side effects [8][9]. Then, new FDA-approved DAAs were developed, including the protease inhibitors glecaprevir, grazoprevir and simeprevir, the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitors daclatasvir and elbasvir [10].…”

Section: Introductionmentioning

confidence: 99%

Structurally distinct cyclosporin and sanglifehrin analogs CRV431 and NV556 suppress established HCV infection in humanized-liver mice

et al. 2020

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We previously reported that the non-immunosuppressive cyclophilin inhibitors (CypIs)cyclosporin A analog CRV431 and sanglifehrin analog NV556-efficiently inhibit HCV replication in vitro. In this study, we asked whether they can also reduce HCV replication in vivo. We found that a single oral administration of CRV431 and NV556 to HCV-infected humanized-liver mice drastically reduced HCV blood levels. The antiviral effect was observed when CRV431 or NV556 were each individually administered with HCV, 3, 6 weeks or even 3 months post-infection when viral replication is robust. These results were confirmed in chimeric mice implanted with human hepatocytes isolated from three distinct donors. Remarkably, no viral rebound was observed 5 months after a single dose administration of 50 mg/kg of CRV431 or NV556 four weeks post-HCV infection, indicating the possibility of suppression of an established viral infection. Since we recently demonstrated that both CRV431 and NV556 also inhibit the development of liver fibrosis and hepatocellular carcinoma in nonviral-induced non-alcoholic steatohepatitis mouse models, our present data suggest that the two entirely structurally different CypIs-CRV431 and NV556-derived from unrelated natural products, represent attractive partners to current direct-acting agent (DAA) regimens for the treatment of hepatitis C and liver diseases.

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“…The prevalence of steatosis in the present cohort (27%) is at the lower end of the spectrum compared to past reports on HIV-HCV coinfection (23-75%) [1] and is related to BMI, obesity, and dyslipidemia, but not to diabetes and hypertension-two components of the metabolic syndrome. The prevalence of steatosis may be lower in this cohort because of the high proportion of black participants (81%) who have been observed to have a lower rate of steatosis compared to that in white and Hispanic individuals [44]. This discrepancy may also be due to the small sample size of the cohort.…”

Section: Discussionmentioning

confidence: 77%

The Prevalence and Impact of Hepatic Steatosis on Response to Direct-Acting Antiviral Therapy in HIV–HCV Coinfection

Johnson

Sterling

2020

Biology

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(1) Background: Direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection is associated with high sustained virologic response (SVR) and overcomes negative predictive factors, including steatosis, in patients without human immunodeficiency virus (HIV) coinfection. The impact of steatosis on SVR in patients with HIV–HCV coinfection is unknown. (2) Methods: A retrospective analysis of patients treated with direct-acting antivirals was performed. Demographic, laboratory and direct-acting antiviral regimen data were prospectively collected. Metabolic syndrome and its components—diabetes mellitus, hypertension, dyslipidemia and obesity—were assessed. Hepatic steatosis (≥5%) was defined by liver biopsy or controlled attenuation parameter (CAP) measurement during vibration-controlled transient elastography (VCTE). (3) Results: A total of 151 HIV–HCV-coinfected patients on combined antiretroviral therapy and direct-acting antiviral therapy were included in this analysis. Prevalence of steatosis by liver biopsy (n = 34) or CAP (≥263 db/m) during VCTE (n = 92) was 27% and was independently associated with obesity (OR 3.11; 95% CI 1.43–6.82; p = 0.004) and the metabolic syndrome (OR 1.08; 95% CI 1.01–0.15; p = 0.01). The overall SVR rate (n = 148) was 95% and was not impacted by the presence of steatosis (p = 0.42). (4) Conclusions: Hepatic steatosis is common in HIV–HCV coinfection, correlates with obesity and the metabolic syndrome and does not impact SVR.

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Hepatitis C – New drugs and treatment prospects

Cited by 65 publications

References 88 publications

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Structurally distinct cyclosporin and sanglifehrin analogs CRV431 and NV556 suppress established HCV infection in humanized-liver mice

The Prevalence and Impact of Hepatic Steatosis on Response to Direct-Acting Antiviral Therapy in HIV–HCV Coinfection

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