Background: Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (oLT) remains a serious problem in the clinical management of post-oLT patients. Recently, two case reports have described successful prevention of HCV liver graft reinfection with intravenous silibinin (SIL) monotherapy in two carriers of genotype 3a and 1a/4 HCV. Based on these findings, we decided to offer such a therapy to a 65 year old woman on the oLT list.Case Presentation: A 65 year old patient with HCV 2a cirrhosis, a previous relapse to PegIFn and Rbv therapy, was listed for oLT due to hepatocellular carcinoma. She started SIL monotherapy 24 hours before oLT. After an initial HCV-RnA decline following surgery, a progressive HCV RnA increase was observed. For this reason, SIL was stopped after 15 days of monotherapy.Conclusions: SIL has multiple anti-HCV mechanisms of action, most of them have been characterized in vitro only. Our case report shows that the antiviral effect of SIL might be HCV genotype dependent, as recently suggested by a study, showing no effect of SIL on the HCV-2a subgenomic replicon model. our case reinforces the need for controlled studies to assess the efficacy of silibinin therapy in HCV infected patients before it can be broadly used in all clinical settings.

BACKGROUND: The aim of this study was to evaluate the effectiveness of monotherapy with interferon alpha-2b and combination therapy with interferon alpha-2b plus ribavirin on chronic hepatitis C infection in thalassaemic patients.METHODS: In parallel group randomized, double blind, controlled trial, 32 thalassaemic patients with chronic hepatitis C infection completed the study. In a random fashion, one group was treated with three million units of interferon alpha- 2b three times a week plus ribavirin (800-1200 mg daily) . The second group received interferon alpha-2b alone.Treatment duration was 24-48 weeks. Primary efficacy variables were HCV RNA after treatment and sustained viral response (SVR) six months after treatment.RESULTS: The mean age of patients was 22± 7.4 years; 19 (59.4%) were male and 13 (40.6) were female. At the end of treatment, no statistically significant differences were found between the groups in HCV RNA and AST. The proportion of patients with SVR six months after treatment was significantly greater in the monotherapy group (90.9%) than in the combination therapy group (44.4%; p=0.049) . A significant difference in mean of ALT was also obtained at the end of treatment between monotherapy and combination therapy groups (30.4± 19.2 and 60.1± 48.9, respectively; p=0.02) .Response rates were not associated with genotype and severity of hepatitis C infection in both groups.CONCLUSIONS: These results suggest that monotherapy may be considered as the first-line therapy in patients with thalassemia.

Background: Hepatitis infection represents one of the important causes of morbidity and mortality in developing countries, however there is not any effective vaccine against hepatitis C which is one of the significant problems in vaccine project.Objectives: The aim of the present study is to evaluate the role of HCV core protein in inducing IFn-Gamma secretion and TCL activities as a vaccine in Balb/C mice.Material and Methods: our previous cloned plasmid (HCV Core gene into peTDuet-1) applied for protein expression in bacteria. The expressed and purified recombinant protein together with Freund’s adjuvant was injected to 15 Balb/c mice. The total IgG and IgG2a of immunized mice sera were evaluated after a week. Two weeks after booster injection, we studied the proliferation and IFnγ secretion of spleens, inguinal and popliteal lymph nodes lymphocytes by eLISA and eLISPoT.Results: The FSFC (Frequency of spot forming cells) of secreting cells of immunized mice with HCV/Core protein and sera IgG2a were considerably higher than the control groups.Conclusion: The core protein together with proper adjuvant can be a candidate vaccine against of HCV infection.

Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4-the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12–24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.

Background: Hepatitis C virus (HCV) was found to have a major role in human liver disease by its ability to face the host-cell defenses and the immune system. Heterogeneity of HCV was the key for its adaptation to its host and represented a significant hurdle for the development of both effective vaccines as well as for novel therapeutic interventions.Objectives: Due to the heterogeneity of HCV virus because of both high replication and high mutation rate in vivo, this study was conducted to analyze different isolates of Egyptian patients of genotype 4, of the most mutant regions of the virus (E1 and E2) as they played an important role in viral persistence by escaping from the immune system of the host body.Patients and Methods: This study was conducted through PCR amplification of E1 and E2 regions, sequencing and phylogenetic analysis, calculating synonyms and non-synonyms substitutions, finding the possible glycosylation sites and different epitope domains.Results: The present work figured out that the heterogeneity of the quasispecies of our local strains 4a was high showing up 15% diversity. This study also showed four glycosylation sites that play an important role in the entry of the virus and protein folding. Besides, different epitpoes were identified in different regions of the E1 and E2 domains, a finding which would help in determining the neutralizing and non- neutralizing antibodies.Conclusions: This study would help in understanding the driving forces of genetic diversity and would be fundamental for representing potential candidate targets for antibodies and the development of vaccine trials.

Background: In many regions of southern Italy, hepatitis C virus (HCV) infection represents a major health problem (with a prevalence rate between 6% and 13%). HCV is associated with different kinds of neoplasms such as non-Hodgkin lymphomas (NHL), and with auto-immune diseases (cryoglobulinemia), which develop after the virus has caused immune system alterations.Objectives: To provide updated information on trends in mortality in a major metropolitan area of southern Italy from NHL, multiple myeloma and Hodgkin disease we analyzed cancer mortality data from 1988 to 2009.Materials and Methods: Mortality data were extracted from National death certificates by age groups, gender, residence and cause of death by the Italian national institute of statistics (ISTAT). Age-standardized mortality rates (SMR) were computed applying the direct method and using the world standard population. To quantify the recent direction of temporal trends in older populations over time, truncated age-adjusted mortality rates were calculated for people aged 65 years and older. Cancer mortality trends were described using their estimated annual percent change (EAPC) and related 95% Confidence Interval (CI).Results: Statistically significant increasing EAPC was found among women for NHL (+2.0% / year), while statistically significant decrease was found among men and women for HD (-3.5% / year, -3.4% / year, respectively). No statistically significant EAPC was found for multiple myeloma.Conclusions: The association between viral hepatitis and NHL in the area of interest might provide some degree of explanation to this finding. Our data confirm that due to epidemic infection of HCV in the area of Naples, a high mortality for NHL persists, moreover the adoption of standard therapeutic protocols administered in full accordance with an evidence-based approach and current guidelines explain reduced mortality from Hodgkin lymphomas.

Hepatitis C Virus and Diabetes Both diabetes and hepatitis C virus (HCV) infection are severe health problems worldwide, especially in the developing countries (1, 2). A range of extrahepatic (EH) manifestations such as arthralgias, thyroiditis and diabetes are linked with HCV infections (3-5). Studies have shown that patients infected with hepatitis C virus (HCV) have more glucose intolerance than the general population.

Dear EditorPakistan is a low socio economic country having more than 10 million people infected with hepatitis C Virus (HCV) with a major genotype of 3a (GT 3a) (1). Due to high rate of resistance to standard Interferon plus Ribavirin therapy, it is highly needed to identify new marker for response prediction to therapy. Interleukin 10 (IL-10) is a key member of Cytokine, which regulates Th1/Th2 Cytokine balance, a major part of immune system against infection (2).

Introduction: Hepatitis C virus (HCV) infection and type 2 Diabetes Mellitus (T2DM) are among the severe threats to health care systems worldwide. Here, we investigated the association of HCV genotypes and cirrhosis with T2DM among HCV-positive patients. Methods: This descriptive-analytical study was performed from Jan 2017 to Jan 2018 at Sina Clinical-Educational infectious diseases ward, the reference center of infectious diseases in northwest Iran. All serology HCV– positive patients attending this center were included in the study. Forty-eight patients were included, 19 of which had a positive history of diabetes. Blood samples from patients were used for complete blood count, liver function tests, fasting blood sugar, HbA1C, HCV antibodies, and HCV genotype. Then the characteristics among patients with and without T2DM were compared. A P-value of less than 0. 05 was considered statistically significant. Results: No significant difference in demographic variables were observed between patients with and without T2DM. Of 48 patients with HCV infection, 29 patients (39. 58%) had T2DM. The hepatitis C infection duration among diabetic and non-diabetic patients was 9. 03 ± 0. 76 years and 8. 53 ± 1. 01 years, respectively (P = 0. 04). Of 8 patients with cirrhosis, six patients (75%) had diabetes. The relative risk for diabetic patients with HCV infection to develop cirrhosis was 4. 57 (95% CI [1. 02-20. 36], P = 0. 04). The most prevalent genotype was HCV type 1 among both diabetic and non-diabetic groups. No significant association was observed in logistic regression analysis between the HCV genotypes and T2DM (P = 1. 000). Conclusion: In the current study, we showed that patients with HCV infection are at a higher risk of developing T2DM, and T2DM showed to be a risk factor for the developing cirrhosis among patients with HCV infection.

Background: Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-a/ b), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon- b in macrophages.Objectives: The aim of this study was to assess the role of LRRFIP1 in induction of IFN- b and inhibition of HCV infection in hepatocytes.Materials and Methods: Induction of IFN-β by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed.Results: LRRFIP1 increased the expression of IFN-b in hepatocytes with or without HCV infection. Induction of IFN- b by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1.Conclusions: LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs.