Editorial: impact of the introduction of direct-acting antiviral drugs on hepatocarcinogenesis-a prospective serial follow-up MRI study. Author’s reply

Abstract Background and Aim: Direct-acting antiviral drugs (DAAs) have a very high efficacy in patients with hepatitis C virus (HCV) infection, but they have not been extensively used in patients with haemoglobinophaties. To evaluate the safety and efficacy of DAA regimens in this subset we used the ITHACA-SITE dataset, which includes patients with haemoglobinophaties and chronic HCV liver disease treated in Italy. Patients and methods: Between March 2015 and June 2016, 121 patients included in the ITHACA-SITE dataset started DAA regimens. Cirrhosis was defined by FibroScan®showing≥12 kPa performed within 6 months before the treatment. Regimen choice and use of ribavirin were based on viral genotype and stage of disease, according to guidelines. Negative HCV RNA at week 12 of post-treatment follow up was considered as Sustained Virological Response (SVR). Results: The mean age of 121 patients was 42 years, 75 (62%) were males, 101 (83.5%) had β-thalassemia major, 9(7.5%) had β-thalassemia intermedia and 10 (8.3%) had sickle cell disease. Sixty-six patients (54%) had the diagnosis of chronic hepatitis and 55 (46%) hadthe diagnosis of cirrhosis. The prevalence of HCV genotypes (G) was: G1a 6 (5%), G1b 70 (57.8%), G2 31 (25.6%), G3 6 (5%), G4 8 (6.6%). Fifty-six patients (46.3%) were Peg-interferon (P) and Ribavirin (R) naïve and 65 (53.7%) were P/R experienced, 20 patients (16.5%) had diabetes and 29 (24%) had heart disease. By June 2016 63 patients (52%) had concluded the treatment and 33 (27.3%) had concluded the post-treatment follow-up. By ITT, the rate of response at the end of treatment (ETR) was 100% (63/63) and 94% (31/33) of patients achieved a SVR. No patients stopped treatment because of adverse events. No interference with chelation therapy was observed. Conclusions: Use of DAAs regimens in practice is safe and effective in patients with haemoglobinophaties and cirrhosis or chronic hepatitis due to HCV. The therapy is indicated also in patients with co-morbidity. The lifetime utility of HCV eradication in terms of reduction of events and overall survival needs evaluation in long-term observational cohorts. Disclosures Piga: Novartis: Research Funding; Apopharma: Honoraria. Di Marco:Gilead: Research Funding. Forni:Novartis, Celgene: Research Funding.

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Remdesivir and Ledipasvir among the FDA-Approved Antiviral Drugs Have Potential to Inhibit SARS-CoV-2 Replication

Cells ◽

10.3390/cells10051052 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1052

Author(s):

Rameez Hassan Pirzada ◽

Muhammad Haseeb ◽

Maria Batool ◽

MoonSuk Kim ◽

Sangdun Choi

Keyword(s):

Antiviral Drugs ◽

Effective Concentration ◽

Nonstructural Proteins ◽

Rna Dependent Rna Polymerase ◽

Direct Acting Antiviral ◽

Rapid Spread ◽

Half Maximal Effective Concentration ◽

Dynamics Simulations ◽

Direct Acting ◽

Transcription And Replication

The rapid spread of the virus, the surge in the number of deaths, and the unavailability of specific SARS-CoV-2 drugs thus far necessitate the identification of drugs with anti-COVID-19 activity. SARS-CoV-2 enters the host cell and assembles a multisubunit RNA-dependent RNA polymerase (RdRp) complex of viral nonstructural proteins that plays a substantial role in the transcription and replication of the viral genome. Therefore, RdRp is among the most suitable targets in RNA viruses. Our aim was to investigate the FDA approved antiviral drugs having potential to inhibit the viral replication. The methodology adopted was virtual screening and docking of FDA-approved antiviral drugs into the RdRp protein. Top hits were selected and subjected to molecular dynamics simulations to understand the dynamics of RdRp in complex with these drugs. The antiviral activity of the drugs against SARS-CoV-2 was assessed in Vero E6 cells. Notably, both remdesivir (half-maximal effective concentration (EC50) 6.6 μM, 50% cytotoxicity concentration (CC50) > 100 µM, selectivity index (SI) = 15) and ledipasvir (EC50 34.6 μM, CC50 > 100 µM, SI > 2.9) exerted antiviral action. This study highlights the use of direct-acting antiviral drugs, alone or in combination, for better treatments of COVID-19.

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Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000002204 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Ceren Atasoy Tahtasakal ◽

Ahsen Oncul ◽

Dilek Yildiz Sevgi ◽

Duygu Demirbas ◽

Alper Gunduz ◽

...

Keyword(s):

Antiviral Treatment ◽

Direct Acting Antiviral ◽

Direct Acting

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Hepatitis C Virus Infection and Renal Disorders

Journal of Renal and Hepatic Disorders ◽

10.15586/jrenhep.2019.43 ◽

2019 ◽

Vol 3 (1) ◽

pp. 1-14

Author(s):

Maurizio Salvadori ◽

Aris Tsalouchos

Keyword(s):

Hepatitis C Virus ◽

Renal Transplantation ◽

Hepatitis C ◽

Sustained Virologic Response ◽

Virologic Response ◽

Antiviral Drugs ◽

Renal Diseases ◽

Renal Disorders ◽

Direct Acting Antiviral ◽

Direct Acting

Hepatitis C virus (HCV) infection is frequently associated with extrahepatic disorders, among which renal diseases are frequent. This article highlights the most frequent HCV-associated renal disorders, the impact of HCV infection on chronic renal disease and renal transplantation, and the role of current direct-acting antiviral therapies. HCV is associated with membranoproliferative glomerulonephritis, acceleration of end-stage renal diseases in patients with glomerulopathies, and a higher risk of death in patients affected by chronic kidney disease. Before the introduction of direct-acting antiviral drugs as treatment modality, renal transplantation was a challenging clinical problem because the drugs available until 2011 obtained a poor sustained virologic response, had several side effects, and caused acute rejection when used after transplantation. The knowledge of the viral structure and its replication allowed the discovery of new classes of direct-acting antiviral drugs that revolutionized this scenario. These new drugs are comparatively more effective and safer. Accumulating evidence suggests that it is possible to cure HCV-related glomerulonephritis, and obtain a sustained virologic response in patients with renal failure, or on dialysis, before commencing transplantation. Finally, it became possible to transplant HCV-positive kidneys into HCV-positive or HCV-negative recipients.

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Direct-acting antiviral drugs for chronic hepatitis C and risk of major vascular events: a systematic review

Internal and Emergency Medicine ◽

10.1007/s11739-018-1828-8 ◽

2018 ◽

Vol 13 (5) ◽

pp. 775-790 ◽

Cited By ~ 1

Author(s):

Eleonora Tamborini Permunian ◽

Lorenzo Gervaso ◽

Victor Gerdes ◽

Lorenzo Moja ◽

Luigina Guasti ◽

...

Keyword(s):

Systematic Review ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Antiviral Drugs ◽

Vascular Events ◽

Direct Acting Antiviral ◽

Direct Acting

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Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy

Clinical Infectious Diseases ◽

10.1093/cid/ciz693 ◽

2019 ◽

Vol 70 (12) ◽

pp. 2695-2702 ◽

Cited By ~ 14

Author(s):

Matthew J Akiyama ◽

Daniel Lipsey ◽

Moonseong Heo ◽

Linda Agyemang ◽

Brianna L Norton ◽

...

Keyword(s):

Hepatitis C ◽

People Who Inject Drugs ◽

Controlled Trial ◽

Extension Study ◽

Agonist Therapy ◽

Opioid Agonist ◽

Direct Acting Antiviral ◽

Opioid Agonist Therapy ◽

Direct Acting

Abstract Background Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. Methods PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. Results Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25–3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5–21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). Conclusions HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

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Hepatic resection for two giant hepatocellular carcinoma after oral direct-acting antiviral therapy: Is there a relationship?

Journal of Solid Tumors ◽

10.5430/jst.v8n2p32 ◽

2018 ◽

Vol 8 (2) ◽

pp. 32 ◽

Cited By ~ 1

Author(s):

Mohamed Abdel Wahab ◽

Ahmed Shehta ◽

Mahmoud Ali

Keyword(s):

Hepatocellular Carcinoma ◽

Antiviral Drugs ◽

Hcv Infection ◽

Dramatic Improvement ◽

Direct Acting Antiviral ◽

Increased Risk ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

The Relationship

Introduction: Direct-acting antiviral drugs have been recently introduced for management of chronic hepatitis C virus (HCV) patients. Those medications have achieved a dramatic improvement of sustained virologic response (SVR) reaching almost 90%. However, reports regarding the increased risk of occurrence or recurrence of hepatocellular carcinoma (HCC) in chronic HCV patients who achieved SVR after direct-acting antiviral drugs are controversial.Methods: We report two cases of giant HCCs complicating chronic HCV infection after direct-acting antiviral drugs-based therapies and were managed by major hepatic resection.Results: Two male patients with chronic HCV infection received several regimens oral direct acting antiviral drugs with a SVR for 3 and 6 months, respectively. They complained of progressive right hypochondrial pain and abdominal enlargement. Two large HCCs were diagnosed (16.2 cm * 17.6 cm * 16.9 cm, and 18 cm * 13 cm * 16.5 cm in dimensions) with markedly elevated serum alpha feto-protein (36,000 and 7,000 ng/ml, respectively). Due to the presence of adequate residual liver volume, the decision was to proceed for surgical resection. Central hepatectomy and extended right hemi-hepatectomy were performed, respectively. Patients had smooth postoperative course and were discharged after 10 and 9 days, respectively.Conclusion: The relationship between direct-acting antiviral drugs and HCC is controversial. Those cases add support to the accumulating literature suggesting the relationship of HCC development in chronic HCV patients receiving direct-acting antiviral drugs. Further prospective studies with adequate long term follow up are needed to prove or disprove this relationship.

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Is treatment of hepatitis C with controlled generic direct acting antiviral drugs effective? An Egyptian experience

Journal of Hepatology ◽

10.1016/s0168-8278(18)30769-4 ◽

2018 ◽

Vol 68 ◽

pp. S276 ◽

Cited By ~ 1

Author(s):

G. Soliman ◽

M.S. Negm ◽

M. Elzalabany ◽

A.A. Malik ◽

A. Khattab ◽

...

Keyword(s):

Hepatitis C ◽

Antiviral Drugs ◽

Direct Acting Antiviral ◽

Direct Acting

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Direct-acting antiviral drugs and hepatitis C virus: A therapeutic revolution?

Cancer ◽

10.1002/cncr.29648 ◽

2015 ◽

Vol 121 (23) ◽

pp. 4268-4269 ◽

Cited By ~ 4

Author(s):

Alain Braillon

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Drugs ◽

Direct Acting Antiviral ◽

Direct Acting

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APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation

Hepatology International ◽

10.1007/s12072-019-09988-7 ◽

2019 ◽

Vol 13 (6) ◽

pp. 649-661 ◽

Cited By ~ 15

Author(s):

Tatsuo Kanda ◽

George K. K. Lau ◽

Lai Wei ◽

Mitsuhiko Moriyama ◽

Ming-Lung Yu ◽

...

Keyword(s):

Hbv Dna ◽

Hbv Reactivation ◽

Close Attention ◽

Short Term ◽

Direct Acting Antiviral ◽

B Virus ◽

Direct Acting ◽

Very High

Abstract In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.

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