scholarly journals Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC)

2021 ◽  
Vol 11 ◽  
Author(s):  
Pin Zhao ◽  
Samiullah Malik ◽  
Shaojun Xing
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Hcv Infection ◽  
Specific Gene ◽  
Epigenetic Alterations ◽  
Chronic Hcv Infection ◽  
Mechanisms Of Carcinogenesis ◽  
Chronic Hcv ◽  
Insight Into

Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.

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 Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

2011 ◽  
Vol 3 (3) ◽  
pp. 704-712 ◽  
Author(s):  
EIMAN ALEEM ◽  
AYMAN ELSHAYEB ◽  
NIHAL ELHABACHI ◽  
AMAL REFAAT MANSOUR ◽  
AHMED GOWILY ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Igfbp 3

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.

scholarly journals Elevated serum activity of MBL and ficolin-2 as biomarkers for progression to hepatocellular carcinoma in chronic HCV infection

Virology ◽  
2019 ◽  
Vol 530 ◽  
pp. 99-106 ◽  
Author(s):  
Paywast J. Jalal ◽  
Barnabas J. King ◽  
Amanj Saeed ◽  
Yemisi Adedeji ◽  
Christopher P. Mason ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Elevated Serum ◽  
Hcv Infection ◽  
Serum Activity ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

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.

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 Transcriptional Suppression of miR-181c by Hepatitis C Virus Enhances Homeobox A1 Expression

2014 ◽  
Vol 88 (14) ◽  
pp. 7929-7940 ◽  
Author(s):  
Anupam Mukherjee ◽  
Shubham Shrivastava ◽  
Joydip Bhanja Chowdhury ◽  
Ranjit Ray ◽  
Ratna B. Ray
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Therapeutic Intervention ◽  
Growth Promotion ◽  
Hcv Infection ◽  
Exogenous Expression ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Hepatocyte Growth

ABSTRACTHepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). The molecular events leading to HCC following chronic HCV infection remain poorly defined. MicroRNAs (miRNAs) have been implicated in the control of many biological processes, and their deregulation is associated with different viral infections. In this study, we observed that HCV infection of hepatocytes transcriptionally downregulates miR-181c expression by modulating CCAAT/enhancer binding protein β (C/EBP-β). Reduced expression of the pri-miR-181c transcript was noted following HCV infection.In silicoprediction suggests that homeobox A1 (HOXA1) is a direct target of miR-181c. HOXA1 is a member of the homeodomain-containing transcription factor family and possesses pivotal roles in normal growth, development, and differentiation of mammalian tissues. Our results demonstrated that HOXA1 expression is enhanced in HCV-infected hepatocytes. Exogenous expression of the miR-181c mimic inhibits HOXA1 and its downstream molecules STAT3 and STAT5, which are involved in cell growth regulation. Interestingly, overexpression of miR-181c inhibited HCV replication by direct binding with E1 and NS5A sequences. Furthermore, accumulation of HCV genotype 2a RNA with miR-181c was observed in an RNA-induced silencing complex in Huh7.5 cells. Our results provide new mechanistic insights into the role of miR-181c in HCV-hepatocyte interactions, and miR-181c may act as a target for therapeutic intervention.IMPORTANCEChronic HCV infection is one of the major causes of end-stage liver disease, including hepatocellular carcinoma. An understanding of the molecular mechanisms of HCV-mediated hepatocyte growth promotion is necessary for therapeutic intervention against HCC. In this study, we have provided evidence of HCV-mediated transcriptional downregulation of miR-181c. HCV-infected liver biopsy specimens also displayed lower expression levels of miR-181c. We have further demonstrated that inhibition of miR-181c upregulates homeobox A1 (HOXA1), which is important for hepatocyte growth promotion. Exogenous expression of miR-181c inhibited HCV replication by directly binding with HCV E1 and NS5A sequences. Taken together, our results provided new mechanistic insights for an understanding of the role of miR-181c in HCV-hepatocyte interactions and revealed miR-181c as a potential target for therapeutic intervention.

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