Emergence of resistance against direct acting antivirals in chronic HCV patients: A real-world study

Background Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. Methods A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. Results A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. Conclusion Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.

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Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan

Scientific Reports ◽

10.1038/s41598-021-93095-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kao-Chi Chang ◽

Shui-Yi Tung ◽

Kuo-Liang Wei ◽

Chen-Heng Shen ◽

Yung-Yu Hsieh ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Real World ◽

Population Analysis ◽

Virologic Response ◽

Efficacy And Safety ◽

Hepatitis C Virus Infection ◽

Direct Acting Antivirals ◽

Evaluable Population ◽

Direct Acting

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

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The Impact Of Direct‐Acting Antivirals On Hepatitis C Viraemia Among People Who Inject Drugs In England; Real‐World Data 2011‐2018

Journal of Viral Hepatitis ◽

10.1111/jvh.13575 ◽

2021 ◽

Author(s):

Megan Bardsley ◽

Ellen Heinsbroek ◽

Ross Harris ◽

Sara Croxford ◽

Claire Edmundson ◽

...

Keyword(s):

Hepatitis C ◽

Real World ◽

People Who Inject Drugs ◽

Direct Acting Antivirals ◽

Real World Data ◽

World Data ◽

Direct Acting ◽

The Impact

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New direct-acting antivirals for patients with chronic HCV infection: can we monitor treatment using an HCV core antigen assay?

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2016.11.010 ◽

2017 ◽

Vol 87 (3) ◽

pp. 243-246 ◽

Cited By ~ 7

Author(s):

R. Alonso ◽

F. Pérez-García ◽

D. Ampuero ◽

E. Reigadas ◽

E. Bouza

Keyword(s):

Hcv Infection ◽

Core Antigen ◽

Direct Acting Antivirals ◽

Hcv Core Antigen ◽

Antigen Assay ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting

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The occurrence of thrombotic thrombocytopenic purpura during treatment of HCV with direct-acting antiviral agents

african journal of gastroenterology and hepatology ◽

10.52378/kxkq8987 ◽

2018 ◽

Vol 1 (1) ◽

pp. 1-9

Author(s):

Amr Hanafy ◽

◽

Waseem Seleem ◽

Salem Mohamed ◽

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Hemolytic Anemia ◽

Peripheral Blood Smear ◽

Hcv Infection ◽

Severe Thrombocytopenia ◽

Direct Acting Antivirals ◽

Thrombocytopenic Purpura ◽

Direct Acting Antiviral ◽

Chronic Hcv ◽

Direct Acting

Background and aim Experts have reported thrombocytopenia linked to chronic liver disease in up to 70% in patients with advanced fibrosis and portal hypertension. Thrombotic thrombocytopenic purpura (TTP) occurrence with HCV infection is a rare and life-threatening event. We aimed to investigate the cause of disturbed conscious level, acute hemolytic anemia, and severe thrombocytopenia in a male patient with chronic HCV and under treatment with direct-acting antivirals. Case report: Development of severe thrombocytopenia, acute hemolytic anemia, neurological symptoms in the form of fits and coma in a 32- year- old man with chronic HCV infection after one week of treatment with direct-acting antivirals (sofosbuvir 400mg PO daily, and daclatasvir 60 mg PO daily). Brain CT was normal, with a negative Coombs test and the presence of schistocytes in the peripheral blood smear. The patient presentation was suggestive of thrombotic thrombocytopenic purpura (TTP). Conclusion: This is a case of TTP after one week of direct-acting antiviral drugs despite the safety profile of these medications. Studying the pathophysiology of TTP after DAAs needs more clarifications.

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Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus Coinfection in a Community Care Setting

Gut and Liver ◽

10.5009/gnl18004 ◽

2018 ◽

Vol 12 (6) ◽

pp. 694-703 ◽

Cited By ~ 9

Author(s):

Vijay Gayam ◽

Muhammad Rajib Hossain ◽

Mazin Khalid ◽

Sandipan Chakaraborty ◽

Osama Mukhtar ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis C ◽

Clinical Efficacy ◽

Real World ◽

Care Setting ◽

Community Care ◽

Direct Acting Antivirals ◽

Immunodeficiency Virus ◽

Direct Acting

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Sustained Virologic Response Rates of Direct Acting Antivirals in HIV Coinfected Hepatitis C Patients and Its Effect on Liver Fibrosis

International Journal of Clinical Case Reports and Reviews ◽

10.31579/2690-4861/036 ◽

2020 ◽

Vol 3 (2) ◽

pp. 01-07

Author(s):

Dora Lebron

Keyword(s):

Hepatitis C ◽

Real World ◽

Sustained Virologic Response ◽

Virologic Response ◽

Hiv Care ◽

Secondary Outcome ◽

Direct Acting Antivirals ◽

Fibrosis Regression ◽

Direct Acting ◽

End Stage

Background: Hepatitis C virus (HCV) is an important cause of chronic hepatitis with necroinflammation and fibrosis resulting in end stage liver disease and hepatocellular carcinoma. Direct acting antivirals (DAAs) are newer agents that directly interfere with the HCV lifecycle and result in high rates of sustained virologic response (SVR). We evaluated if treatment with DAAs in a real-world setting is as successful in HCV/HIV coinfected patients as it is in HCV monoinfected patients, and if some degree of fibrosis regression can be observed after completion of therapy in both groups. Methods: We retrospectively reviewed data from HCV monoinfected and HCV/HIV coinfected patients who received treatment from 2014-2016 at the East Carolina University Infectious Diseases clinic. The primary outcome was to compare completion and sustained virologic response (SVR) rate at either 12 or 24 weeks between HCV monoinfected patients and HCV/HIV coinfected patients. The secondary outcome was to assess regression of fibrosis at either 12 or 24 weeks after completion of therapy, defined as one METAVIR stage improvement in their FibroSure™, a noninvasive biochemical test to estimate the stage of fibrosis. Results: There were 41 patients in each group. Compared to the coinfected group, patient no show rate was higher in the monoinfected group (p=0.0346). In the HCV monoinfected group, 25 (93%) achieved either SVR 12 or 24. Two patients were non-compliant and had detectable viral load on evaluation at week 12. In the HCV/HIV coinfected group, 37 patients achieved SVR (p=0.0039). One patient in the coinfected group did not complete therapy but achieved SVR. In terms of fibrosis, 12/18 (67%) in the monoinfected group demonstrated improvement in at least 1 Metavir stage and 6/18 (33%) had no change. In the coinfected group, 8/16 (50%) patients demonstrated an improvement in FibroSure™ stage, 5/16 (31%) had no change, and 3/16 (19%) had worsening fibrosis according to FibroSure™ stage, (p=0.4867). Conclusions: In this small, real-world cohort, HCV/HIV coinfected patients treated with DAAs had higher completion and SVR rates than HCV monoinfected patients. Treatment failures in the monoinfected group were all linked to non-adherence, whereas, more coinfected patients achieved SVR, likely related to the fact that they were regularly engaged in routine HIV care. Fibrosis regression based on FibroSure™ was observed more in monoinfected patients than those with coinfection. Although not statistically significant, at least 50% of the patients in each group had regression of fibrosis.

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