scholarly journals Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 531 ◽  
Author(s):  
C. Hayes ◽  
Peiyi Zhang ◽  
Yizhou Zhang ◽  
Kazuaki Chayama
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Molecular Mechanisms ◽  
Significant Difference ◽  
Chronic Hepatitis C Virus

Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.

scholarly journals IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection

2013 ◽  
Vol 154 (32) ◽  
pp. 1261-1268 ◽  
Author(s):  
Alajos Pár ◽  
Gabriella Pár ◽  
István Tornai ◽  
Ferenc Szalay ◽  
Dalma Várszegi ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Pegylated Interferon ◽  
Hepatitis C Virus Infection ◽  
Pegylated Interferon Plus Ribavirin ◽  
Chronic Hepatitis C Virus

Introduction: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. Aim: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. Method: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24–72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. Results: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) Conclusions: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients. Orv. Hetil., 2013, 154, 1261–1268.

Effectiveness and Safety of Ombitasvir/Paritaprevir/Ritonavir in Treatment of Chronic Hepatitis C Egyptian Hemodialysis Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Waleed A Abdel-Mohsen ◽  
Ossama A Ahmed ◽  
Nahla M Teama ◽  
Ahmed M ElGhandour ◽  
Sarah M El Sayed
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Hemodialysis Patients ◽  
Renal Functions ◽  
Chronic Hepatitis C Virus ◽  
Regular Hemodialysis

Abstract Background prevalence of hepatitis C virus infection in patients with renal diseases is higher compared to the general population FDA has approved ombitasvir/paritaprevir/ritonavir for the treatment of patients with severe renal disease. Aim of the Work to evaluate the efficacy and safety of Ombitasvir/Paritaprevir/Ritonavir in treatment of chronic Hepatitis C Egyptian Prevelant Hemodialysis patients to compare it with the same treatment result in chronic Hepatitis C Egyptian patients with normal renal functions. Patients and methods Written informed consent was obtained from all patients participating in the study .This case-control study was conducted on one hundred patients with confirmed diagnosis of HCV positive infection at Center of National Committee for Control of Viral Hepatitis [NCCVH] at Ain Shams University Hospital. Patients were divided into two groups Group I (Control Group): 50 Chronic Hepatitis C virus patients with normal renal functions Group II (Case Group) 50 chronic Hepatitis C virus Prevelant Hemodialysis patients on regular hemodialysis. Results 95.1% of Prevelant Hemodialysis patients achieved Sustained Virological Response (SVR) while 100% of patients with normal kidney functions achieved Sustained Virological Response. Most common side effects were Hemoglobin drop, GIT disturbance, Sever fatigue and Itching. Conclusion Ombitasvir, paritaprevir, and ritonavir considered as a safe and effective in treatment in HCV infection in patients on regular hemodialysis.

Response of Ns5a inhibitors resistant patients to Qurevo-Sovaldi-Ribavirin regimen as a retreatment strategy for chronic hepatitis c virus infection

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ahmed A Moanes ◽  
Hesham H Radwan ◽  
Yasser O Abd El Rahman ◽  
Mostafa M Abd El Nabi
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Hcv Treatment ◽  
Number Of Patients ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv

Abstract Background Hepatitis C Virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide, with 3–4 million new infections and 350 000 deaths occurring each year because of HCV-related complications. Aim of the work to determine the efficacy of Qurevo-Sovaldi-Ribavirin regimen as a retreatment strategy in NS5A inhibitors (Sofosbuvir & Daclatasvir) resistant patients infected with chronic hepatitis C virus. Patients and Methods An observational cross-sectional study was carried out on 20 chronic hepatitis C virus infected patients in The centre of HCV treatment at El Quabary specialized centers in Alexandria where large number of patients receiving their HCV treatment. Results all patients (20/20) achieved sustained virological response after 3 months of the last dose of treatment (SVR12). Conclusion the new retreatment strategy composed of the triple therapy Qurevo (Ombitasvir/Paritaprevir/Ritonavir)/Sofosbuvir/Ribavirin is effective in the treatment of chronic HCV infected patients previously treated with Sofosbuvir/Daclatasvir/Ribavirin for 12 weeks without achieving sustained virological response (Ns5a inhibitors resistant chronic HCV patients).

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