Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy

Abstract Background In co-infected patients with hepatitis B (HBV) and hepatitis C (HCV), the treatment of HCV with direct-acting antiviral agents (DAA) can cause HBV reactivation. However, there are no clear guidelines on the timing of treatment initiation, especially in the absence of clinical signs of flare. Aims Here we discuss the case of a 34-year-old female with HBV and HCV genotype 3 who had HBV reactivation following HCV treatment, but did not require nucleos(t)ide therapy. Methods She initially presented with chronic inactive hepatitis B and chronic hepatitis C with HBV DNA level of 67.5 IU/mL and HCV RNA level of 3.33 x 106 IU/mL. She completed a 12 week course of sofosbuvir and velpatasvir for HCV and achieved sustained virologic remission, but subsequently developed reactivation of her HBV with HBV DNA peaking at 3.41 x 104 IU/mL twelve weeks post-treatment. She did not develop any signs of hepatitis and a decision was made to monitor her clinically. Results Two years later, she spontaneously went into remission with her HBV DNA levels being <10 IU/mL. Conclusions The significance of this case is to illustrate HBV reactivation following treatment of HCV with DAAs may not necessitate immediate treatment, especially if there are no signs of flare. There have been similar reported cases, but larger prospective studies are required to determine the appropriate clinical context where monitoring may be acceptable instead of immediate treatment. Funding Agencies None

Download Full-text

Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent

Journal of Hepatology ◽

10.1016/j.jhep.2015.04.009 ◽

2015 ◽

Vol 63 (3) ◽

pp. 564-572 ◽

Cited By ~ 102

Author(s):

Xavier Forns ◽

Stuart C. Gordon ◽

Eli Zuckerman ◽

Eric Lawitz ◽

Jose L. Calleja ◽

...

Keyword(s):

Combination Therapy ◽

Antiviral Agent ◽

Genotype 1 ◽

Hcv Genotype ◽

Direct Acting Antiviral ◽

Hcv Genotype 1 ◽

Chronic Hcv ◽

Direct Acting

Download Full-text

A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety

BMC Gastroenterology ◽

10.1186/s12876-019-1013-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Akira Sakamaki ◽

Kenya Kamimura ◽

Naoki Fukui ◽

Haruka Watanabe ◽

Norihiro Sakai ◽

...

Keyword(s):

Chronic Hepatitis ◽

Case Report ◽

Hepatitis C ◽

Combination Therapy ◽

Chronic Hepatitis C ◽

Psychiatric Symptoms ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Innate Anxiety

Download Full-text

HCV Core Antigen as an alternative test to Quantitative HCV RNA for assessment of SVR in Chronic HCV infected patients treated with Direct Acting Antiviral agents

QJM ◽

10.1093/qjmed/hcaa052.025 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

S M Mohamed ◽

N I Musa ◽

R S Ghait ◽

B M Abdelrhiem

Keyword(s):

Antiviral Agents ◽

Virologic Response ◽

Hcv Infection ◽

Core Antigen ◽

Hcv Rna ◽

Viral Kinetics ◽

Direct Acting Antiviral ◽

Hcv Core Antigen ◽

End Of Treatment ◽

Direct Acting

Abstract Background and aims Widespread use of direct-acting antiviral (DAA) agents to treat patients with hepatitis C virus (HCV) infection has reduced the need for monitoring of HCV-RNA levels, because viral kinetics do not predict sustained virologic response (SVR) to these drugs. However, the performance of cheaper tests, such as the assay to quantify HCV core antigen (HCV Ag), has not been determined. This study was aimed at investigating the accuracy of the HCV Ag test in predicting which patients receiving DAAs will achieve SVR at week 12 (SVR12). Methods We performed a prospective study on 90 patients, chronically infected with HCV, receiving DAAs therapy from different NCCVH centers in Cairo during the period from August 2017 to June 2018. We collected blood samples and measured the levels of HCV core Ag and HCV-RNA at baseline and 12 weeks after end of treatment. We compared the ability of these assays to predict which patients would have SVR12. Results The median baseline level of HCV-RNA was 1688529.6 ± 994697.3 IU/ml (range, 312700 IU/ml to 3491100 IU/ml) and HCV Ag was 179.2 ± 83.5 pg/ml (range, 33.5 pg/ml to 315.6 pg/ml). HCV Ag became undetectable in 92.2% 12 weeks after the end of treatment. HCV-RNA became undetectable in 87.8% at the end of treatment (P<.0001). 79 out of 90 patients (87.8%) achieved an SVR12; the test for HCV Ag identified 63.6% of these patients. Conclusions Tests that measure HCV Ag monitor efficacy of DAA therapy for HCV infection as well as assays that measure HCV-RNA, and hence could be recommended for clinical practice.

Download Full-text

FRI-388-Hepatitis C ilnfected liver grafts transplanted into non-infected recipients are safe in the era of highly effective direct-acting antiviral therapy

Journal of Hepatology ◽

10.1016/s0618-8278(19)31127-2 ◽

2019 ◽

Vol 70 (1) ◽

pp. e565-e566

Author(s):

Heather O’dell ◽

Alison Rafferty ◽

Natasha Schneider ◽

Andrew Scanga ◽

J. Kelly Wright ◽

...

Keyword(s):

Hepatitis C ◽

Antiviral Therapy ◽

Direct Acting Antiviral ◽

Highly Effective ◽

Direct Acting

Download Full-text

Analysis of HCV Genotype 2 and 3 Variants in Patients Treated with Combination Therapy of Next Generation HCV Direct-Acting Antiviral Agents ABT-493 and ABT-530

Journal of Hepatology ◽

10.1016/s0168-8278(16)00653-x ◽

2016 ◽

Vol 64 (2) ◽

pp. S409-S410 ◽

Cited By ~ 4

Author(s):

T. Ng ◽

T. Pilot-Matias ◽

R. Tripathi ◽

G. Schnell ◽

T. Reisch ◽

...

Keyword(s):

Combination Therapy ◽

Antiviral Agents ◽

Next Generation ◽

Hcv Genotype ◽

Direct Acting Antiviral ◽

Genotype 2 ◽

Hcv Genotype 2 ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Download Full-text

Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV–HCV Coinfected Patients

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.748014 ◽

2022 ◽

Vol 8 ◽

Author(s):

Gaurav Tripathi ◽

Sheetalnath Rooge ◽

Manisha Yadav ◽

Babu Mathew ◽

Nupur Sharma ◽

...

Keyword(s):

Treatment Response ◽

Linear Regression Analysis ◽

Sustained Viral Response ◽

Tryptophan Metabolism ◽

Plasma Metabolites ◽

Hcv Rna ◽

Multivariate Linear Regression Analysis ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Post Therapy

Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV–HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV–HCV patients.Methods: Non-cirrhotic HIV–HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders).Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = −0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = −0.713) significantly differentiated between nonresponders from responders in HIV–HCV coinfected patients and was able to predict the failure of treatment response.Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV–HCV coinfected patients.

Download Full-text