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 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 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.

IgM and IgA antibodies generated against hepatitis C virus core antigen in patients with acute and chronic HCV infection

1994 ◽  
Vol 39 (9) ◽  
pp. 2022-2031 ◽  
Author(s):  
Shinjiro Sato ◽  
Shigetoshi Fujiyama ◽  
Motohiko Tanaka ◽  
Masafumi Goto ◽  
Yuko Taura ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Core Antigen ◽  
Virus Core ◽  
Iga Antibodies ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

scholarly journals Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection

2001 ◽  
Vol 45 (2) ◽  
pp. 517-524 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Lawrence Feinman ◽  
Leonard Liebes ◽  
Nancy Ostrow ◽  
Victoria Koslowski ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Pharmacokinetic Data ◽  
Serious Adverse Events ◽  
Dosing Schedule ◽  
Diarrhea Virus ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.

scholarly journals Replication of Hepatitis C Virus (HCV) RNA in Mouse Embryonic Fibroblasts: Protein Kinase R (PKR)-Dependent and PKR-Independent Mechanisms for Controlling HCV RNA Replication and Mediating Interferon Activities

2006 ◽  
Vol 80 (15) ◽  
pp. 7364-7374 ◽  
Author(s):  
Kyung-Soo Chang ◽  
Zhaohui Cai ◽  
Chen Zhang ◽  
Ganes C. Sen ◽  
Bryan R. G. Williams ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Replication ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Protein Kinase R ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as determined by cell colony formation efficiency and the detection of HCV proteins and both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was found to replicate more efficiently in the PKR knockout (PKR−/−) MEF than in the wild-type (PKR+/+) MEF. The knockdown expression of PKR by specific small interfering RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by HCV RNA replication, indicating the activation of PKR-independent antiviral pathways. Furthermore, IFN-α/β inhibited HCV RNA replication in PKR−/− MEFs as efficiently as in PKR+/+ MEFs. These findings demonstrate that PKR-independent antiviral pathways play important roles in controlling HCV replication and mediating IFN-induced antiviral effect. Our findings also provide a foundation for the development of transgenic mouse models of HCV replication and set a stage to further define the roles of cellular genes in the establishment of chronic HCV infection and the mediation of intracellular innate antiviral response by using MEFs derived from diverse gene knockout animals.

Lack of monomeric IgM anti-hepatitis C virus (HCV) core antibodies in patients with chronic HCV infection

1996 ◽  
Vol 60 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Francesco Negro ◽  
Hugo Troonen ◽  
Gerd Michel ◽  
Emiliano Giostra ◽  
Monika Albrecht ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

scholarly journals Acute hepatitis C virus infection

2008 ◽  
Vol 13 (21) ◽  
Author(s):  
W L Irving ◽  
D Salmon ◽  
C Boucher ◽  
I M Hoepelman
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Acute Hcv ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
The Individual ◽  
Acute Hcv Infection ◽  
Subsequent Risk

Around 25% of people infected with hepatitis C virus (HCV) are able to clear the infection spontaneously, while the majority become chronically infected, with a subsequent risk for the individual patient of progressive inflammatory liver disease, cirrhosis, hepatocellular carcinoma and liver-related death (Figure 1). Much is known about the epidemiology, pathogenesis, diagnosis and management of chronic HCV infection. In comparison, knowledge about acute HCV infection is patchy. In this article, we will highlight concerns relating to acute HCV infection and suggest that public health bodies responsible for managing the HCV epidemic should redirect at least some of their resources to dealing with these issues.

scholarly journals Chronic hepatitis C virus infection: Is there a correlation between HCV genotypes and the level of viremia?

2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Objective Assessment ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Genotype 4 ◽  
Hcv Genotypes ◽  
Genotype 2 ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

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. .

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