Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection

2020 ◽  
Vol 20 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Ossama A. Ahmed ◽  
Mohamed A Elsebaey ◽  
Mohamed Hassan A. Fouad ◽  
Mahmoud Elkadeem ◽  
Rehab Badawi ◽  
...  

Background & Aims: Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. Methods: This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. Results: 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. Conclusion: Twelve weeks’ regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).

2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .


2009 ◽  
Vol 84 (1) ◽  
pp. 475-481 ◽  
Author(s):  
J. R. Vidal-Castiñeira ◽  
A. López-Vázquez ◽  
R. Díaz-Peña ◽  
R. Alonso-Arias ◽  
J. Martínez-Borra ◽  
...  

ABSTRACT Killer immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells and may play an important role in the innate response against infection with viruses such as hepatitis C virus (HCV). We examined whether the different combinations of KIRs with their HLA class I ligands influenced the response to combined treatment (pegylated alpha interferon and ribavirin) of patients infected by HCV. A total of 186 consecutive patients diagnosed with chronic HCV infection were analyzed. Seventy-seven patients exhibited HCV RNA levels at 6 months posttreatment and were called nonresponders (NR), while 109 cleared viral RNA and were named sustained viral responders (SVR). Patients were typed for HLA-B, HLA-Cw, KIR genes, and HCV genotype. In our study, the frequency of the KIR2DL2 allele was significantly increased in NR (P < 0.001; odds ratio [OR] = 1.95), as was the frequency of the KIR2DL2/KIR2DL2 genotype (P < 0.005; OR = 2.52). In contrast, the frequencies of the KIR2DL3 genotype (P < 0.001) and KIR2DL3/KIR2DL3 genotype (P < 0.05; OR = 0.54) were significantly increased in the SVR. Different combinations of KIR2DL2 and KIR2DL3 alleles with their ligands were analyzed. The frequency of the KIR2DL2/KIR2DL2-HLA-C1C2 genotype was significantly increased in the NR (P < 0.01; OR = 3.15). Additionally, we found a higher frequency of the KIR2DL3/KIR2DL3-HLA-C1C1 genotype in the SVR group (P < 0.05; OR = 0.33). These results were not affected by the HCV genotype. In conclusion, patients who carried the KIR2DL2/KIR2DL2-HLA-C1C2 genotype were less prone to respond to treatment. However, the KIR2DL3/KIR2DL3-HLA-C1C1 genotype clearly correlated with a satisfactory response to treatment, defined by the clearance of HCV RNA.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yousry Esam-Eldin Abo-amer ◽  
Rehab Badawi ◽  
Mohamed El-Abgeegy ◽  
Heba Fadl Elsergany ◽  
Ahmed Abdelhaleem Mohamed ◽  
...  

Background and Aims. Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5–15% of patients treated with DAA‐based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients. Methods. This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000–1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded. Results. SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded. Conclusions. Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.


2007 ◽  
Vol 81 (18) ◽  
pp. 9633-9640 ◽  
Author(s):  
Kyeong-Ok Chang ◽  
David W. George

ABSTRACT Hepatitis C virus (HCV) is a cause of chronic liver disease, with more than 170 million persistently infected individuals worldwide. Although the combination therapy of alpha interferon (IFN-α) and ribavirin is effective for chronic HCV infection, around half of all patients infected with HCV genotype 1 fail to show sustained virologic responses and remain chronically infected. Previously, we demonstrated that bile acids were essential for growth of porcine enteric calicivirus in cell culture in association with down-regulation of IFN responses. Because hepatocytes are exposed to high concentrations of bile acids in the liver, we hypothesized that bile acids have similar effects on HCV replication. We incubated HCV replicon-harboring cells (genotype 1b, Con1) in the presence of various bile acids and monitored the expression of HCV RNA and protein (NS5B). The addition of an individual bile acid (deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, or glycochenodeoxycholic acid) in the medium increased the levels of HCV RNA and proteins up to fivefold at 48 h of incubation. An antagonist of bile acid receptor farnesoid X receptor (FXR), Z-guggulsterone, reduced the bile acid-mediated increase of HCV RNA. When IFN (α or γ) and each bile acid were incubated together, we observed that bile acid significantly reduced the anti-HCV effect of IFN. These results indicated that bile acids are factors in the failure of IFN treatment for certain patients infected with HCV genotype 1. Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway.


2006 ◽  
Vol 196 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Ankur Goyal ◽  
Wolf P. Hofmann ◽  
Eva Hermann ◽  
Stella Traver ◽  
Syed S. Hissar ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256711
Author(s):  
Hiroyuki Kobayashi ◽  
Satoru Joshita ◽  
Yuki Akahane ◽  
Katsuhiko Matsuzaki ◽  
Hiromi Yamada ◽  
...  

Background The World Health Organization has set a goal of hepatitis C virus (HCV) elimination by the year 2030. However, no regions in Japan have succeeded in eradicating HCV. Micro-elimination is an approach to attain hepatitis C eradication in which national eradication goals are applied to specific populations so that viral treatment and control efforts can move forward quickly and efficiently. In order to eradicate HCV from Japan, this study aims to achieve HCV micro-elimination in the town of Nagawa. Methods and design The Nagawa Project is an ongoing, prospective, multiple-institution, observational study running from April 1, 2021, to March 31, 2024. All residents of Nagawa town, excluding those under 20 years of age, not consenting to the study, or unable to undergo health check-ups due to nursing care needs, will be included. If found to be HCV antibody-positive, the participant will be recommended to see a doctor in consideration of MAC-2 binding protein glycosylation isomer values. Then, the participant will undergo serum HCV RNA measurement with the real-time polymerase chain reaction by an attending physician. If the participant is HCV RNA-positive, he or she will be referred to a hepatologist for further evaluation. In the case of a definitive diagnosis of chronic hepatitis C, direct acting antiviral treatment will be initiated. Through this process, HCV will be systematically micro-eliminated from the region. Discussion The Nagawa Project will reveal the prevalence of chronic HCV in addition to the HCV eradication rate in Nagawa town towards achieving HCV micro-elimination. Trial registration This study is performed by Shinshu University School of Medicine and was registered as UMIN 000044114 on May 6, 2021.


2019 ◽  
Vol 49 ◽  
Author(s):  
Irma Salimović- Bešić ◽  
Adna Kahriman ◽  
Suzana Arapčić ◽  
Amela Dedeić- Ljubović

Background: Hepatitis C virus (HCV) genotypes and subtypes exhibit significant geographic variations.Aim: To analyse the distribution of genotypes/subtypes of HCV in a group of patients with chronic hepatitis C from Canton Sarajevo during 2012-2018.Material and methods:The study enrolled 247 human plasma samples of HCV-RNA positive patients with available results of HCV genotyping test.Results: During 2012-2018, the domination of subtypes 1a (34.01%), 1b (28.34%) and genotype 3 (23.89%) was registered. In 2012 and 2013, HCV subtype 1a was the most common (27/63; 42.86% and 17/40; 42.50%, respectively). In 2014, the leading HCV genotype/subtype were 3 and 1b (17/57; 29.82%). In 2015, the dominance of HCV genotype 3 (14/39; 35.90%) continued, while in 2016, the same number of HCV subtypes 1a and 1b (11/30; 36.67%) was recorded. Although in a small number of tested, during 2017, HCV subtype 1b was the most prevalent (7/14; 50.00%), and in 2018, it was replaced by a HCV subtype 1a (3/4; 75.00%). Distribution of HCV genotypes/subtypes by age group of patients varied significantly (p=0.000). The largest number of patients (71/247; 28.74%) belonged to the age category 30-39 years and HCV genotypes/subtypes 1, 3, 4, 1a and 1b were identified. Except in 2017, male gender significantly dominated (p=0.000). In males, HCV subtype 1a (68/170; 40.00%) was the most common, while in women it was HCV subtype 1b (44/77; 57.14%).Conclusion: This six-year retrospective study showed the time variations of the circulating HCV genotypes/subtypes among patients with chronic hepatitis C in Canton Sarajevo. Genotyping of the HCV has an important implications for diagnosis and treatment of the patients.


Author(s):  
Nahed A Makhlouf ◽  
Mohamed O Abdelmalek ◽  
Mohamed Eltaher Ibrahim ◽  
Nagla H Abu-Faddan ◽  
Abeer E Kheila ◽  
...  

Abstract Background Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness. Methods Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase–platelet ratio index (APRI) score were estimated at baseline and at SVR12. Results SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P &lt; .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects. Conclusions Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.


2019 ◽  
Vol 156 (6) ◽  
pp. S-1232
Author(s):  
Jihad Aljabban ◽  
Pierre Tonnerre ◽  
Dan Kvistad ◽  
Max Robidoux ◽  
Joelle Brown ◽  
...  

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