Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle. The target genes were downregulated individually as well as in combinations and their impact on viral replication was evaluated. Individual downregulation of La autoantigen, PSMA7, hVAP-A, and NS5B resulted in inhibition of HCV replication by about 67.2&#x25;, 50.7&#x25;, 39&#x25;, and 52&#x25;, respectively. However, antiviral effect was more pronounced when multiple genes were downregulated simultaneously. Combinations of siRNAs against La autoantigen with NS5B or hVAP-A resulted in greater inhibition in HCV replication. Our findings indicate that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target.

Anirban Mandal

Krishna Kumar Ganta

Binay Chaubey

Combinations of siRNAs against La Autoantigen with NS5B or hVAP-A Have Additive Effect on Inhibition of HCV Replication

Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50&#x25;) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67&#x25;) and 7/12 (58&#x25;) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore.

Fritz Klein

Ruth Neuhaus

Dennis Eurich

J&#xf6;rg Hofmann

Sandra Bayraktar

Johann Pratschke

Marcus Bahra

Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a First Step towards Modern HCV Therapy

Hepatitis C virus (HCV) has emerged as the major pathogen of liver diseases in recent years leading to worldwide blood-transmitted chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Accurate diagnosis for differentiation of hepatitis C from other viruses is thus of pivotal importance for proper treatment. In this work we developed a recombinant multiepitope protein (rMEHCV) for hepatitis C diagnostic purposes based on conserved and immunodominant epitopes from core, NS3, NS4A, NS4B, and NS5 regions of the virus polyprotein of genotypes 1a, 1b, and 3a, the most prevalent genotypes in South America (especially in Brazil). A synthetic gene was designed to encode eight epitopes in tandem separated by a flexible linker and bearing a his-tag at the C-terminal end. The recombinant protein was produced in Escherichia coli and purified in a single affinity chromatographic step with &#x3e;95&#x25; purity. Purified rMEHCV was used to perform an ELISA which showed that the recombinant protein was recognized by IgG and IgM from human serum samples. The structural data obtained by circular dichroism (CD) spectroscopy showed that rMEHCV is a highly thermal stable protein at neutral and alkaline conditions. Together, these results show that rMEHCV should be considered an alternative antigen for hepatitis C diagnosis.

Alexsandro S. Galdino

Jos&#xe9; C. Santos

Marilen Q. Souza

Yanna K. M. N&#xf3;brega

Mary-Ann E. Xavier

Maria S. S. Felipe

Sonia M. Freitas

Fernando A. G. Torres

A Novel Structurally Stable Multiepitope Protein for Detection of HCV

Hepatitis B virus (HBV) is a serious cause of liver disease affecting millions of people throughout the world. When HBV is acquired during pregnancy, prenatal transmission can occur to the fetus. Therefore, this study is aimed at estimating seroprevalence and associated factors of HBV infection among pregnant women attending Antenatal Clinic (ANC) of Arba Minch Hospital, Southern Ethiopia. A facility based cross-sectional study was conducted on 232 pregnant women visiting ANC from February to April, 2015. Data regarding sociodemographic and associated factors were gathered using questionnaire. Serum samples were tested for hepatitis B surface antigen (HBsAg) by Enzyme Linked Immunosorbent Assay. Data was analyzed using SPSS version 20. The overall seroprevalence of HBV infection was 4.3&#x25; (95&#x25; CI: 2.2&#x2013;6.9&#x25;). Multivariate analysis showed that history of abortion (AOR = 7.775; 95&#x25; CI: 1.538&#x2013;39.301) and having multiple sexual partners (AOR = 7.189; 95&#x25; CI: 1.039&#x2013;49.755) were independent predictors of HBsAg seropositivity. In conclusion, the prevalence of HBV infection is intermediate. Therefore, screening HBV infection should be routine part of ANC; health information on having single sexual partner for women of childbearing age and on following aseptic techniques during abortion should be provided to health facilities working on abortion.

Tsegaye Yohanes

Zerihun Zerdo

Nega Chufamo

Seroprevalence and Predictors of Hepatitis B Virus Infection among Pregnant Women Attending Routine Antenatal Care in Arba Minch Hospital, South Ethiopia

Chronic hepatitis C virus infection is associated with significant morbidity and mortality, as a result of progression towards advanced natural course stages including cirrhosis and hepatocellular carcinoma. On the other hand, the SVR following successful therapy is generally associated with resolution of liver disease in patients without cirrhosis. Patients with cirrhosis remain at risk of life-threatening complications despite the fact that hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced. Furthermore, recent data suggest that the risk of HCC and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear HCV compared to untreated patients and nonsustained virological responders. Data derived from studies have demonstrated a strong link between HCV infection and the atherogenic process. Subsequently HCV seems to represent a strong, independent risk factor for coronary heart disease, carotid atherosclerosis, stroke, and, ultimately, CVD related mortality. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus which may influence the life expectancy and the quality of patients&#x2019; life.

Theodoros Voulgaris

Vassilios A. Sevastianos

Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus

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Hepatitis Research and Treatment