Virological and clinical significance of detectable HCV-RNA below limit of quantification at End-of-Treatment in patients treated with direct antiviral agents

Abstract Background Egypt has the highest prevalence rate of HCV in the world. About 14.7% of the Egyptian people have HCV antibodies and 9.8% have an active infection. The death rate due to liver disease about 40,000 each year (near10% of all deaths). It is the second after the cardiac diseases. Aim of Work to assess Doppler haemodynamic changes suggestive of portal hypertension in cirrhotic HCV Egyptian patients after sustained virological response to direct antiviral agents, and their correlation with liver stiffness measurements by Fibroscan. Patients and Methods This prospective cohort study was conducted at Viral Hepatitis Unit at Ain Shams University Hospital and Al-Agouza Police Hospital during the period from May 2018 to July 2019. The study included 50 Egyptian treatment-naïve chronic hepatitis C patients with cirrhosis on Sofosbuvir, Daclatasvir for 12 weeks. Patients were subjected to history and full physical examination, radiology assessment (Abdominal Ultrasound and color Doppler), Upper GI endoscopy and Fibroscan before treatment and 6 months after treatment. Followed up with CBC, AST, ALT, Total bilirubin, Albumin, creatinine and Coagulation profile before and after 12 weeks of treatment And HCV RNA by PCR and HCV CORE Antigen before and then after 12 weeks of treatment. Results Treatment with sofosbuvir plus Daclatasvir for 12weeks resulted in undetectable HCV RNA by PCR in 100% of the patients at the end of treatment. There was a significant improvement in portal hemodynamics 6 months after treatment as well as a significant correlation between Doppler indices and fibroscan. Conclusion: Doppler portal hypertensive parameters, as a marker of portal hypertension, were improved in parallel with the improvement in fibroscan values after viral clearance and its improvement in the current study mandate urgent treatment to avoid possible complications.

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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.

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P0281THE EFFECT OF DIRECT ANTIVIRAL AGENTS ON GLOMERULAR FILTRATION RATE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0281 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Iman Sarhan ◽

Reem Elsharabasy ◽

Fatma Ahmed ◽

Mohamed Hassan

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Antiviral Agents ◽

Post Treatment ◽

P Value ◽

Insignificant Change ◽

End Of Treatment ◽

Direct Antiviral Agents ◽

Kidney Functions

Abstract Background and Aims HCV infects 170 million individuals approximately worldwide. The kidney is a major component of the HCV clinical syndrome. This viral infection imposes itself as a cause of kidney disease, a major risk in hemodialysis units and a significant threat in kidney transplantation. In 2011, direct acting antivirals (DAA) had been developed, which represented a huge boom in the treatment of HCV. Some doubtful data suggest possibility of association between some DAA administration and AKI occurrence, but larger prospective studies are recommended for confirming this suggestion. Method Retrospective cohort study of 118 adult HCV infected patients with normal baseline kidney functions (GFR ≥ 60ml/min) were included. Patients coinfected with HBV and those with impaired kidney functions at beginning of treatment were excluded. Patients were divided into 3 groups according to their DAA-combination treatment regimen. Patients’ eGFR were measured at baseline, at the end of treatment and one year later. Results Our results showed that patients who received Sofosbuvir/Daclatasvir/Ribavirin, their pre-treatment eGFR Mean ± SD. was (86.15±16.37). Post treatment eGFR showed an insignificant change after end of treatment (84.73±17.41) and 1 year after treatment (82.0±18.07) (P-value: 0.998 and 0.220 respectively). Those who received Sofosbuvir/Daclatasvir, their pretreatment eGFR Mean ± SD was (94.60±19.32). Post treatment eGFR showed an insignificant change after end of treatment (89.39±18.39) and 1 year after treatment (89.17±20.27). (P-value: 0.156 and 0.097 respectively). As for patients who received Sofosbuvir/Simeprevir, their pretreatment eGFR Mean ± SD was (92.71±15.11). Post treatment eGFR showed an insignificant change after end of treatment (88.36±16.27) and 1 year after treatment (89.01±15.72). (P-value: 0.620 and 0.676 respectively). Conclusion The new direct antiviral agents (sofosbuvir, daclatasvir and simeprevir) are effective and safe regarding glomerular filtration rate in patients with normal renal function. However, a meticulous monitoring of kidney function is mandatory during the use of these medications to early detect any untoward side effects.

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Evolutive Aspects Of Patients With Cirrhosis After Harvoni Therapy

Journal of Internal Medicine and Emergency Research ◽

10.37191/mapsci-2582-7367-2(2)-025 ◽

2021 ◽

Author(s):

Mircea-Catalin Fortofoiu

Keyword(s):

Antiviral Treatment ◽

Antiviral Agents ◽

Treatment Completion ◽

Fixed Dose ◽

Decompensated Cirrhosis ◽

Hcv Rna ◽

Study Group ◽

Significant Difference ◽

Before And After ◽

Direct Antiviral Agents

Introduction: Cirrhosis, is a final pathway of chronic liver diseases. In recent years, Direct-Acting Antiviral Agents (DAAs) gained a leading role in the treatment of chronic hepatitis of viral etiology. Aim of the study: The proposed aims of this research are to estimate the virological response after 12 weeks after treatment completion and to evaluate the beneficial effects of the treatment on patients with decompensated cirrhosis. Patients and methods: The study was of a descriptive type, longitudinal and retrospective, conducted over a 15 months period, including patients with HCV-related cirrhosis patients. It was established the correlation between liver function, metabolic function, comorbidities and severity of cirrhosis and the level of HCV RNA before and after treatment. It was assessed also the neuroinflammatory activity from the results of Fibromas and the complication after therapy. Results: From January 2018 to April 2019, patients with liver cirrhosis were hospitalized. 48 HCV- related cirrhosis patients have fulfilled the eligibility criteria for antiviral treatment and they have constituted the study group. From all the HCV-infected patients with cirrhosis, 41.66% were women and 58.33% were men, most of them in the interval 60-70 years (37.5%) and 70-80 years (33,33%). 87.5% from the patients had compensated cirrhosis (Child-Pugh A class) and 12.5% had decompensated cirrhosis (Child-Pugh B and C class). 77.08% of the patients had severe neuroinflammatory activity – A3, 10.41% had moderate -A2 activity and 12.5% had lower neuroinflammatory activity-A1. The treatment with direct antiviral agents for the study group consisted in three treatment regimens.60% received a two-drug fixed-dose combination- sofosbuvir (SOF)/ledipasvir (LDV). 10% received SOF/LDV combination with Ribavirin. Only 1 patient with Child-Pugh C decompensated cirrhosis received SOF/LDV combination without Ribavirin. Also, a double combination received 10.48% of the patients- grazoprevir (GZR)/ elbasvir (EBR) 20.83% received quadruple combination ombitasvir (OBV)/ paritaprevir (PTV)/ritonavir(r) and dasabuvir (DSV). After 12 weeks from treatment completion, all the HCV-RNA’s level were undetectable. There were no side effects of the treatment. None of the patients didn’t stop the treatment during the period of treatment. There was a statistically significant difference between the ASAT and ALAT level before and after treatment (p<0.0001). 1 patient with Child-Pugh score C, died and another patient with Child-Pugh score B had an episode of variceal bleeding. Conclusion: Treatment with direct antiviral agents as Harvoni regimen, is a safe therapy and effective for HCV-infection and advanced liver disease. Despite the efficiency of the treatment on HCV-RNA, there were patients with complications due to the cirrhotic status of the subjects. The patients with existing decompensated cirrhosis remain at an elevated risk of numerous other complications.

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Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients

Liver International ◽

10.1111/liv.13932 ◽

2018 ◽

Vol 38 (11) ◽

pp. 1906-1910 ◽

Cited By ~ 9

Author(s):

Benjamin Maasoumy ◽

Peter Buggisch ◽

Stefan Mauss ◽

Klaus H. W. Boeker ◽

Tobias Müller ◽

...

Keyword(s):

Clinical Significance ◽

Hcv Rna ◽

End Of Treatment

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Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x16672392 ◽

2016 ◽

Vol 10 (1) ◽

pp. 68-73 ◽

Cited By ~ 14

Author(s):

Miguel Malespin ◽

Tamara Benyashvili ◽

Susan L. Uprichard ◽

Alan S. Perelson ◽

Harel Dahari ◽

...

Keyword(s):

Antiviral Agents ◽

Sustained Viral Response ◽

Hcv Rna ◽

Genotype 1 ◽

Genotype 3 ◽

Hcv Genotype ◽

End Of Treatment ◽

Genotype 2 ◽

Study Population ◽

Hcv Genotype 1

Background: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. Methods: Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. Results: The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir–simeprevir, 38 sofosbuvir–ribavirin and 6 sofosbuvir–ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, had EOT+ by ART assay and each achieved SVR12&24. Conclusions: A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.

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Role of Direct Antiviral Agents in Treatment of Chronic Hepatitis C Infection in Renal Transplant Recipients

Journal of Transplantation ◽

10.1155/2018/7579689 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Sourabh Sharma ◽

Debabrata Mukherjee ◽

Ranjith K. Nair ◽

Bhaskar Datt ◽

Ananth Rao

Keyword(s):

Renal Transplant ◽

Virological Response ◽

Antiviral Agents ◽

Transaminase Level ◽

Graft Function ◽

Hcv Rna ◽

Rapid Virological Response ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Direct Antiviral Agents

Background. Since the introduction of direct antiviral agents (DAAs), morbidity of HCV has considerably decreased but still no guidelines have been formulated in renal transplant recipients (RTRs). We studied efficacy and tolerability of direct antiviral agents in RTRs.Methods. This prospective observational study was conducted at Army Hospital Research & Referral, Delhi, from June 2016 to May 2017. Forty-five HCV infected RTRs with stable graft function were included.Results. Median time between renal transplantation and the start of anti-HCV therapy was 36 months (1–120 months). The majority (66.7%) were infected with genotype 3. Baseline median HCV RNA level was 542648 IU/ml (1189–55028534 IU/ml). Sofosbuvir-Ribavirin combination (24 weeks) was given to 30 patients including 3 cirrhotics, Ledipasvir-Sofosbuvir combination to 8 patients, and Daclatasvir-Sofosbuvir combination to 7 patients, including 2 cirrhotics. Rapid virological response was observed in 29 patients treated with Sofosbuvir/Ribavirin, all 8 patients on Sofosbuvir/Ledipasvir, and all 7 patients on Sofosbuvir/Daclatasvir. End treatment response and sustained virological response (12 weeks) were achieved in all patients irrespective of genotype or treatment regimen. Decrease in mean HCV RNA level and transaminase level was statistically significant (p<0.01). Ribavirin was significantly associated with anaemia (p=0.032).Conclusions. DAA regimens are well tolerated and highly efficacious. Response to DAA is good irrespective of genotype, drug combination, initial HCV RNA level, age or sex of patient, or graft age. However, Sofosbuvir/Ledipasvir and Sofosbuvir/Daclatasvir combination is preferable.

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Platelet Count Improvement after Chronic Hepatitis C Treatment among Cirrhotic Patients Who Achieved Sustained Virological Response: Realworld Results from 2186 Patients in Egypt

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200917113650 ◽

2020 ◽

Vol 20 ◽

Author(s):

Rehab Badawi ◽

Shaimaa Soliman ◽

Lobna Aboali ◽

Mahmoud Elkadeem ◽

Asem Elfert ◽

...

Keyword(s):

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Platelet Count ◽

Hepatitis C ◽

Sustained Virological Response ◽

Virological Response ◽

Hcv Rna ◽

End Of Treatment ◽

Pugh Class ◽

Direct Acting

Background & Aims: This study aimed to assess the changes in platelet counts of patients with liver cirrhosis due to chronic HCV, who achieved sustained virological response (SVR) after taking direct acting antivirals (DAAs) in a large cohort study in Egypt. Methods: This multicenter observational retrospective study was carried out on 2500 chronic hepatitis C virus (HCV) infected patients who achieved (SVR) after treatment with direct acting antiviral drugs (DAA). HCV infection was confirmed by positive PCR for HCV RNA infection. SVR was defined as a negative PCR test for HCV-RNA 12 weeks after completion of DAA therapy. Platelets count was measured before therapy, during therapy, at the end of treatment, and 12 weeks after the end of the treatment. Results: There were 2186 patients enrolled in the study; 1866 (85.4%) were treatment naïve. There were 1006 (46%) males and 1180 (54%) females. Mean age was 50.82± 11.66 years, 2142 (98 %.0) patients achieved SVR, 2118 (96.9%) patients had Child -Pugh class A cirrhosis, and 68 (3.1%) had Child -Pugh class B liver cirrhosis. A significant increase of the platelets count was detected at the end of treatment in comparison to the pretreatment levels (P<0.001), and after achieving SVR (P <0.001) when compared to the pretreatment values. Conclusion: Improvement of platelets count occurs after HCV therapy with DAAS in patients with liver cirrhosis. These results suggested that HCV eradication may have a role in improvement of platelet count.

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