scholarly journals Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Pil Soo Sung ◽  
Eui-Cheol Shin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
De Novo ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

scholarly journals Sa1525 – Visne Analysis of Hepatitis C Virus-Specific Cd8 T Cells from Direct Acting Antiviral-Treated Chronic Hcv Patients and Hcv Resolvers

2019 ◽  
Vol 156 (6) ◽  
pp. S-1232
Author(s):  
Jihad Aljabban ◽  
Pierre Tonnerre ◽  
Dan Kvistad ◽  
Max Robidoux ◽  
Joelle Brown ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cd8 T Cells ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting

scholarly journals Hepatic resection for two giant hepatocellular carcinoma after oral direct-acting antiviral therapy: Is there a relationship?

2018 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Mohamed Abdel Wahab ◽  
Ahmed Shehta ◽  
Mahmoud Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Drugs ◽  
Hcv Infection ◽  
Dramatic Improvement ◽  
Direct Acting Antiviral ◽  
Increased Risk ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Relationship

Introduction: Direct-acting antiviral drugs have been recently introduced for management of chronic hepatitis C virus (HCV) patients. Those medications have achieved a dramatic improvement of sustained virologic response (SVR) reaching almost 90%. However, reports regarding the increased risk of occurrence or recurrence of hepatocellular carcinoma (HCC) in chronic HCV patients who achieved SVR after direct-acting antiviral drugs are controversial.Methods: We report two cases of giant HCCs complicating chronic HCV infection after direct-acting antiviral drugs-based therapies and were managed by major hepatic resection.Results: Two male patients with chronic HCV infection received several regimens oral direct acting antiviral drugs with a SVR for 3 and 6 months, respectively. They complained of progressive right hypochondrial pain and abdominal enlargement. Two large HCCs were diagnosed (16.2 cm * 17.6 cm * 16.9 cm, and 18 cm * 13 cm * 16.5 cm in dimensions) with markedly elevated serum alpha feto-protein (36,000 and 7,000 ng/ml, respectively). Due to the presence of adequate residual liver volume, the decision was to proceed for surgical resection. Central hepatectomy and extended right hemi-hepatectomy were performed, respectively. Patients had smooth postoperative course and were discharged after 10 and 9 days, respectively.Conclusion: The relationship between direct-acting antiviral drugs and HCC is controversial. Those cases add support to the accumulating literature suggesting the relationship of HCC development in chronic HCV patients receiving direct-acting antiviral drugs. Further prospective studies with adequate long term follow up are needed to prove or disprove this relationship.

scholarly journals Hepatocellular carcinoma after direct-acting antiviral therapy for chronic HCV infection: Is it a real risk?

IDCases ◽  
2018 ◽  
Vol 14 ◽  
pp. e00450 ◽  
Author(s):  
Cátia Dias ◽  
Filipa Duarte-Ribeiro ◽  
Sara Pipa ◽  
Ana Rita Barbosa ◽  
Margarida Mota ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Therapy ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Real Risk ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

scholarly journals New Therapies for Hepatitis C Virus

PRILOZI ◽  
2015 ◽  
Vol 36 (2) ◽  
pp. 119-132
Author(s):  
Hari Polenakovik
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Etiologic Agent ◽  
Hcv Infection ◽  
Interferon Α ◽  
Risk Of Death ◽  
Duration Of Therapy ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Abstract Hepatitis C virus (HCV), the major etiologic agent of "non-A, non-B hepatitis" was discovered 26 years ago. Even before its discovery, interferon-α (IFN) was already being used for treatment of this infection. The next two decades saw a series of incremental improvements of the IFN therapies by extending the duration of therapy, using IFN in combination with oral ribavirin, using pegylated IFN with ribavirin, and most recently adding oral compounds that inhibit the HCV replication (directly acting antivirals - DAAs) to that regimen. DAAs target multiple steps in the HCV life cycle and are now used in combination to treat HCV infection without the need of IFN. These IFN-free, oral DAAs regimens are highly efficacious, have minimal toxicity and are given for short duration. Approved DAAs can cure more then 90% of persons with chronic HCV infection, thereby reducing the risk of death from cirrhosis and hepatocellular carcinoma. However, these drugs are very expensive, and currently their exorbitant cost significantly restricts the access to this therapy for many HCV infected patients.

De-novo versus recurrent hepatocellular carcinoma following direct-acting antiviral therapy for hepatitis C virus

2018 ◽  
Vol 30 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Ashraf O. Abdelaziz ◽  
Mohamed M. Nabil ◽  
Ahmed H. Abdelmaksoud ◽  
Hend I. Shousha ◽  
Ahmed A. Cordie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
De Novo ◽  
Direct Acting Antiviral ◽  
Recurrent Hepatocellular Carcinoma ◽  
Direct Acting

Evaluation of Serum Dna Integrity as a Screening and Prognostic Tool in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

2010 ◽  
Vol 25 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Sherien F. El-Shazly ◽  
Manal A. Eid ◽  
Hesham A. El-Sourogy ◽  
Gehan F. Attia ◽  
Sherif A. Ezzat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Healthy Volunteers ◽  
Hcv Infection ◽  
Dna Integrity ◽  
Chronic Hcv Infection ◽  
Total Dna ◽  
Chronic Hcv

Background Hepatocellular carcinoma (HCC) is a common malignancy in Egypt due to the high frequency of hepatitis C virus (HCV) infection among the general population. Circulating free DNA is a potential molecular marker for the diagnosis and prognosis of malignant tumors. DNA released from apoptotic cells usually consists of short uniform fragments while DNA released from cancer cells is longer. The ratio of long DNA fragments to total DNA (DNA integrity) may be a potential marker for early detection of HCC and its progression in HCV patients. Methods Sera from 25 patients with HCV-related HCC, 25 patients with chronic HCV infection, and 15 healthy volunteers were examined for Alu repeats by quantitative real-time PCR (qPCR) using 2 sets of primers of 115 and 247 base pairs. DNA integrity was calculated as the ratio of 247-bp to 115-bp Alu fragments. Results Compared with healthy volunteers and HCV patients, significantly higher DNA integrity was found in HCC patients. DNA integrity was associated with tumor size, TNM stage, vascular invasion, lymph node involvement, and distant metastasis. DNA integrity had a higher sensitivity and specificity in discriminating HCC from HCV patients than total DNA. Patients with high DNA integrity had a significantly shorter overall survival and high DNA integrity was shown to be an independent prognostic factor for survival in HCV-related HCC. Conclusions DNA integrity is a promising molecular biomarker for detecting HCC in patients with chronic HCV infection; it reflects the progression and metastatic potential of the tumor, and high DNA integrity is associated with short overall survival in HCV-related HCC.

scholarly journals Hepatitis C Virus (HCV) Sequence Variation Induces an HCV-Specific T-Cell Phenotype Analogous to Spontaneous Resolution

2009 ◽  
Vol 84 (3) ◽  
pp. 1656-1663 ◽  
Author(s):  
Victoria Kasprowicz ◽  
Yu-Hoi Kang ◽  
Michaela Lucas ◽  
Julian Schulze zur Wiesch ◽  
Thomas Kuntzen ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Hcv Infection ◽  
Cell Phenotype ◽  
Cell Responses ◽  
Cognate Antigen ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV)-specific CD8+ T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127+ T cells is driven by viral variation.

scholarly journals The efficacy and safety of direct-acting antiviral drugs in the management of hepatitis C virus-related arthritis

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Samah M. Alian ◽  
Mohamed Othman Wahba ◽  
Ahmed Fathy Gomaa ◽  
Sahar S. Khalil
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Viral Response ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Group I ◽  
Group Ii ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Post Therapy

Abstract Background Hepatitis C virus (HCV) infection is a worldwide disease. HCV-related arthritis is one of the extrahepatic manifestations of the disease. The treatment of chronic HCV has been revolutionized with the introduction of oral direct-acting antiviral (DAA) drugs. We aim to determine the outcomes of treatment by the combination of sofosbuvir-daclatasvir with or without ribavirin in patients with HCV-related arthritis. Results Post-therapy, all group I patients had sustained viral response. Significant improvement of the outcome parameters was found 12 weeks post-treatment in group I compared to baseline and group II. Complete and partial remission of articular symptoms in group I patients was observed in 80% and 5%, respectively, while 85% of patients in group II showed no remission. Few mild side effects were encountered with therapy. Conclusion The combination of sofosbuvir-daclatasvir with or without ribavirin is an effective and safe therapy for eradication of HCV infection and amelioration of HCV-related arthritis.

Metabolism of Direct-Acting Antiviral Agents (DAAs) in Hepatitis C Therapy: A Systematic Review

2020 ◽  
Vol 21 ◽  
Author(s):  
Ivana Mikolasevic ◽  
Tajana Filipec Kanizaj ◽  
Dorotea Bozic ◽  
Petra Puz ◽  
Sanja Stojsavljevic ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Side Effects ◽  
Drug Interactions ◽  
Hcv Infection ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Background:: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. Objective:: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. Methods:: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. Results:: We present a comprehensive overview of specific direct-acting antivirals metabolism and drug drug interaction issues in different settings. Conclusion:: Despite its complex pharmacokinetics and possibility of drug drug interactions, direct-acting antivirals extremely high efficacy in providing viral clearance is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with a tight control of immunosuppressive therapy.

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