Presence Of Hepatitis C Virus Infection Research Articles

Hepatitis C virus infection increases risk of peripheral arterial disease in end‐stage renal disease patients receiving maintenance hemodialysis therapy

AbstractBoth hepatitis C virus (HCV) infection and end‐stage renal disease are associated with an increased risk of developing peripheral arterial disease (PAD). Our objective was to explore the relationship between HCV infection and PAD in hemodialysis patients, using brachial‐ankle pulse wave velocity (baPWV) as the assessment method. Since 2016, we have actively been recruiting patients undergoing regular hemodialysis three times a week. All baPWV assessments for our patients were performed before the implementation of direct‐acting antiviral treatment. Furthermore, none of the uremic patients with HCV infection had received interferon‐based treatment in the past. An elevated baPWV measurement surpassing 2100 cm/s is indicative of an increased susceptibility to potential PAD. Our analysis utilized multivariate linear and logistic regression analysis. Individuals with HCV infection exhibited higher baPWV levels compared with those without HCV infection (2006.0 ± 687.4 vs. 1809.3 ± 466.1 cm/s, p = .039). The presence of HCV infection (β = 199.56, 95% CI: 10.56–388.56, p = .039) demonstrated a significantly positive correlation with baPWV levels. In the multivariate logistic regression analysis, HCV infection (OR = 2.67, 95% CI: 1.07–6.68, p = .036) significantly associated with baPWV >2100 cm/s. Furthermore, individuals with a higher viral load (HCV RNA ≥60 × 103 IU/mL) (OR = 4.45, 95% CI: 1.12–17.68, p = .034) demonstrated a significant association with baPWV ≥2100 cm/s when compared with non‐HCV infection patients. Additionally, patients with genotype I exhibited a significant association with baPWV ≥2100 cm/s (OR = 8.13, 95% CI: 2.04–32.42, p = .003) in comparison to non‐HCV patients. The presence of HCV infection has been demonstrated to markedly increase baPWV levels. Particularly, HCV infection with higher viral load and genotype I is significantly linked to an elevated risk of PAD. It emphasizes the importance of HCV elimination in the specific population.

The Extent of Insulin Resistance in Patients That Cleared Viral Hepatitis C Infection and the Role of Pre-Existent Type 2 Diabetes Mellitus: A Meta-Analysis

A high risk of developing insulin resistance (IR) and, eventually, type 2 diabetes mellitus (T2DM) is associated with chronic hepatitis C virus (HCV). Multiple mechanisms can account for the development of IR in chronic HCV patients, steatosis or fatty liver that can lead to metabolic syndrome, and the inflammatory process associated with the presence of HCV infection. In this article, we analyze the reported values of homoeostasis model assessment (HOMA-IR) before and after successful direct-acting agents (DAAs) treatment in the literature (23 studies) at certain intervals, respectively 12, 24, and 52 weeks depending on the presence of T2DM among patients. The meta-analysis showed improvement of IR in most cases except for three studies that presented a minimal increase in HOMA-IR value for the non-T2DM group at the 12- and 24-week check-ups possibly hinting at a prediabetes group. All other studies showed an important decrease in HOMA-IR post-DAA treatment specifically for the T2DM group. The most significant change in HOMA-IR values was noticed after 24 weeks in all categories. Our meta-analysis showed that clearance of HCV leads to improvement of IR, especially in the case of patients with T2DM.

Coinfection of Helicobacter pylori and Hepatitis C Virus in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BackgroundThe relationship between Helicobacter pylori (H. pylori) and hepatocellular carcinoma (HCC) was firstly proposed in 1994 after Ward et al demonstrated the role of Helicobacter hepaticus in the development of HCC in mice. Studies also investigated the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) coexisting with H. pylori in causing HCC. A causal relationship was never confirmed, and the relationship remains controversial. This meta-analysis aimed to summarize the research on this topic and investigate if a relationship exists between H. pylori infection and the development of HCC and if the presence of HCV and HBV along with H. pylori plays a role in liver carcinogenesis.MethodsFollowing PRISMA guidelines, we performed a systematic review of all relevant studies published in the literature using the keywords “Helicobacter pylori” and “hepatocellular carcinoma” on major literature databases, including PubMed, EMBASE, Web of Science, and Cochrane controlled trials register. A total of 656 research studies were identified between 1994 and 2020. Of those, 26 qualified under our selection criteria. Patients who were positive for HCC were classified as cases and those who did not have HCC were classified as controls. The H. pylori status and HCV status, if available, were identified for both groups. Statistical analysis was carried out by a biostatistician according to the Cochrane reviewer’s handbook.ResultsOut of the 26 studies included in the final analysis, 13 were retrospective case-control studies, 11 were cross-sectional studies, and two were prospective case-control and cohort studies. Overall, the prevalence of H. pylori infection was 64.78% (561 of 866) amongst HCC cases and 47.92% (1,718 of 3,585) in the non-HCC control group. The summary odds ratio (OR) for the association of H. pylori infection with the risk for HCC (using the random-effects model, which accounted for the heterogeneity across the 26 studies) was determined to be 4.75 (95% confidence interval (CI): 3.06 - 7.37, I2 = 63%). We also performed a subgroup analysis to determine the odds of developing HCC in the presence of H. pylori and HCV coinfection. The summary OR of it was 12.76 (95% CI: 4.13 - 39.41, I2 = 78%). The summary OR for the risk of developing HCC in the presence of HCV infection without H. pylori infection was 2.21 (95% CI: 0.70 - 6.94, I2 = 79%). Whereas, the odds of developing HCC in the presence of only H. pylori infection without HCV was found to be 0.54 (95% CI: 0.11 - 2.63, I2 = 80%). There was inconsistency in the data presented in some studies regarding HCV infection status. Since data were extracted from different study designs, subgroup analysis by study design was performed which showed no significant difference between the study groups (P = 0.5705).ConclusionThis meta-analysis demonstrates a positive association between H. pylori infection and the development of HCC. There is a significantly higher risk of developing HCC in the presence of HCV infection along with H. pylori. Further prospective cohort studies are needed to prove the causal relationship, especially in cases of HBV and HCV coinfection, and cirrhotic patients.

New markers of oxidative stress in lichen planus and the influence of hepatitis C virus infection – a pilot study

Abstract Introduction. Lichen planus (LP) is a mucocutaneous T-cell mediated disorder of unknown etiology. There is growing evidence that oxidative stress is an important player in the pathogenesis of LP. Therefore, we have investigated oxidative stress markers in LP and the influence of hepatitis C virus (HCV) infection, a frequently associated condition, on oxidative stress in LP patients. Method. We have determined the serum levels of 4- hydroxynonenal (4-HNE) and symmetric dimethylarginine (SDMA), as markers of oxidative stress, and total antioxidant capacity (TAC), as a marker of the antioxidant defence, in 4 groups: group A – HCV positive patients with LP (n=12), group B – HCV positive patients without LP (n=12), group C – HCV negative patients with LP (n=31) and group D – control group (n=26). Results. In LP patients, we have identified an increased level of lipid peroxidation (4-HNE – group A – 8.41±1.11 μg/mL, group B - 7.97±2.17 μg/mL, group C – 7.81±1.96 μg/mL and group D – 6.15±1.17 μg/mL) and alterations in arginine methylation (SDMA – group A – 1.10±0.24 μmol/L, group B – 1.03±0.16 μmol/L, group C – 0.84±0.19 μmol/L and group D – 0.50±0.06 μmol/L) associated with a diminished antioxidant defence (TAC – group A – 234.50±49.96, μmol/L group B – 255.83±41.41 μmol/L, group C – 269.83±43.33 μmol/L and group D – 316.46 ±29.33 μmol/L), processes augmented by the association with HCV infection. Conclusion. There is an imbalance between oxidants and antioxidants in patients with LP, an imbalance that is augmented by the presence of HCV infection. SDMA could be regarded as a novel biomarker of oxidative stress among these patients. To the best of our knowledge this is the first study to investigate the influence of HCV infection on oxidative stress in LP patients.

Features of the immune status in chronic hepatitis C in patients with lymphopriliferative diseases

Tumor transformation of immunocompetent cells in patients with chronic lymphoproliferative diseases (CLPD) leads to the formation of secondary immune deficiency, which increases the prevalence of infectious complications. Whether the presence of hepatitis C virus (HCV) and the formation of chronic hepatitis (HCV) further weaken the immunoreactivity of the patient, remains poorly understood. The purpose of this work was to reveal the patterns of HCG formation in patients with CLPD with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. Another aim of the study was to disclose the patterns of HCG formation in patients with CLP with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. The comparative assessment of immunological and biochemical parameters was carried out in 110 patients with HCV (85 – chronic lymphocytic leukemia, 25 – non- Hodgkin lymphoma), with the presence of hepatitis C virus markers (n=20) and 90 patients negative for HCV. To identify intergroup differences, the method of nonparametric statistics was used: the Mann-Whitney criterion. Results. It was found that the group of HCV-infected patients is represented by younger persons compared to uninfected patients (median age – 44 years vs. 60 years, p=0.004). Analyzing the state of the immune system, we have revealed that regardless of the presence of chronic hepatitis C, all patients had a defect in both cellular and humoral immunity. The degree of immune deficiency did not have a direct dependence on viral liver damage. Moreover, in the presence of HCV infection, there was an increase in the microbicidal activity of neutrophils, as well as an increase in the expression of CD95+ on lymphoid cells. Cytokine levels during HCV contamination fluctuated in different directions. There was an increase in the level of ALT in the group of patients with HCV. Findings. The formation of immune deficiency in patients with CLPD is largely associated with the presence of oncopathology and practically does not depend on the presence of chronic hepatitis C.

Liver Health Literacy and Health Status Among Adults With Hepatitis C: Implications for the Nursing Profession as Part of the 2030 Global Elimination Goal.

To explore the prevalence of hepatitis C virus (HCV) infection as well as the levels of liver health literacy and association with the health status of people with HCV through the nurse-led community health development goal of global elimination. A community-based, cross-sectional study was conducted between July 2018 and June 2019 in coastal Western Yunlin County, Taiwan. This study was conducted at five townships, and serum HCVantibody (anti-HCV) screening was used for the identification of potentially infected people by a collaborating local hospital. Of the 1,963 adults from rural areas enrolled in this study, 321 (16.4%) were anti-HCV positive, 237 (73.8%) reported that they were unaware of their HCV positivity, and none of them were provided information on direct-acting antiviral agent therapy. The levels of anti-HCV positivity were higher among female patients (p < .05), elderly people (p < .001), those with a low education level (p < .001), and those from the Sihu Township within Yunlin County (p < .001). Participants with anti-HCV positivity tended to have lower intakes of vegetables (p < .01) and fruit (p < .05), a greater number of comorbidities (p < .05), as well as a greater incidence of abnormal liver (p < .001) and renal function (p < .001) compared to those with anti-HCV negativity. Multivariable linear regression analysis showed that the presence of HCV infection and a greater number of metabolic syndrome components were associated with poor liver and renal function. These findings showed a high prevalence of HCV infection among adults living in rural areas, who had low literacy levels on hepatitis, unhealthy lifestyles, and abnormal liver and renal function. Clinicians and primary healthcare providers should initiate efforts to increase the levels of liver health literacy by increasing the accessibility to infection confirmation tests and reducing the number of barriers to the reception of antiviral treatment.

Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6-Mercaptopurine in Children With Acute Lymphoblastic Leukemia.

The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.

Hepatitis C and Oral Lichen Planus: Evaluation of their Correlation and Risk Factors in a Longitudinal Clinical Study.

The aim of this study is to evaluate the correlation between hepatitis C virus (HCV) infection and oral lichen planus (OLP), and further examine the relationship between age, sex, systemic diseases and drugs with the presence of HCV infection or OLP. A longitudinal clinical study was carried out from March 2010 to December 2013 with 51 individuals, of whom 33 had been presented with HCV (HCV-positive group) and 18 had OLP (OLP-positive group), in Passo Fundo, RS, Brazil. Hepatitis C virus-positive individuals who presented lesions compatible with OLP were subjected to an intraoral biopsy for histopathological diagnosis, while OLP-positive individuals underwent anti-HCV serological test for diagnosis of HCV infection. Data on age, sex, systemic diseases and drugs used were recorded for later analysis. The data were analyzed using descriptive statistics of frequency and by Pearson's Chi-square test, with a 5% significance level (p < 0.05). Out of the 33 HCV-positive individuals, only one was clinically and pathologically positive for OLP, demonstrating a significant relationship between the presence of HCV infection and the manifestation of OLP (Chi-square test -46.852, p = 7.65 × 10(-12)). None of the individuals in OLP-positive group had HCV infection. The most common systemic diseases were hypertension and diabetes, and the most commonly used drugs were antihypertensives. However, there was no significant relationship between these factors and the presence of OLP or HCV infection (p > 0.05). There was a significant relationship between HCV infection and manifestation of OLP. Age, sex, systemic diseases and drugs were not identified as risk factors for the development of these diseases. The OLP could serve as an indicative of HCV infection in asymptomatic patients, thus enabling early diagnosis and treatment of hepatitis and hence, a better prognosis.

Hepatitis C virus-HIV-coinfected patients and liver transplantation.

To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.

Prognostic impact of hepatitis C virus infection in patients with diffuse large B-cell lymphoma treated with immunochemotherapy in the context of a novel prognostic index

ObjectivePatients with hepatitis C virus (HCV) infection have been associated with development of diffuse large B-cell lymphoma (DLBCL), yet its impact on several clinical aspects, including phenotypic characteristics and treatment-related toxicities as well as survival outcome after rituximab-based immunochemotherapy, remains controversial. MethodsTo elucidate the characteristics of HCV-positive DLBCL in the context of a new prognostic model, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), we retrospectively analyzed DLBCL patients diagnosed and treated with immunochemotherapy at our institute during the last decade. ResultsIn all, HCV infection was identified in 22 (17.7%) of 124 DLBCL patients. Except for being more likely to present with an advanced stage of disease, patients with HCV infection were phenotypically indistinguishable from HCV-negative cases. Multivariate analysis showed 3 factors independently predicted a dismal overall survival (OS) outcome: lower albumin level (<3g/dL vs. ≥3g/dL, p<0.001; HR=13.21, 95% CI=2.69–64.98, p=0.001), presence of HCV infection (vs. HCV-negative; HR=9.75, 95% CI=1.97–48.34, p=0.005), and poor NCCN-IPI risk (high-intermediate or high vs. low-intermediate or low; HR=5.56, 95% CI=1.17–26.55, p=0.031). ConclusionsOur study has demonstrated that HCV infection status and low serum albumin level add important prognostic values to the newly proposed NCCN-IPI model for patients with DLBCL.

Hepatitis C Virus Core Protein Suppresses Mitophagy by Interacting with Parkin in the Context of Mitochondrial Depolarization

Hepatitis C virus (HCV) causes mitochondrial injury and oxidative stress, and impaired mitochondria are selectively eliminated through autophagy-dependent degradation (mitophagy). We investigated whether HCV affects mitophagy in terms of mitochondrial quality control. The effect of HCV on mitophagy was examined using HCV-Japanese fulminant hepatitis-1-infected cells and the uncoupling reagent carbonyl cyanide m-chlorophenylhydrazone as a mitophagy inducer. In addition, liver cells from transgenic mice expressing the HCV polyprotein and human hepatocyte chimeric mice were examined for mitophagy. Translocation of the E3 ubiquitin ligase Parkin to the mitochondria was impaired without a reduction of pentaerythritol tetranitrate-induced kinase 1 activity in the presence of HCV infection both invitro and invivo. Coimmunoprecipitation assays revealed that Parkin associated with the HCV core protein. Furthermore, a Yeast Two-Hybrid assay identified a specific interaction between the HCV core protein and an N-terminal Parkin fragment. Silencing Parkin suppressed HCV core protein expression, suggesting a functional role for the interaction between the HCV core protein and Parkin in HCV propagation. The suppressed Parkin translocation to the mitochondria inhibited mitochondrial ubiquitination, decreased the number of mitochondria sequestered in isolation membranes, and reduced autophagic degradation activity. Through a direct interaction with Parkin, the HCV core protein suppressed mitophagy by inhibiting Parkin translocation to the mitochondria. This inhibition may amplify and sustain HCV-induced mitochondrial injury.

Prevalence, genotype distribution, and risk factors for hepatitis C infection among HIV-infected individuals in Slovenia: a 1986-2013 update.

Since the introduction of highly active antiretroviral therapy, chronic hepatitis C has become one of the leading causes of non-AIDS-related morbidity and mortality in patients with HIV infection. Two previous Slovenian nationwide studies published in 2002 and 2009 showed a very low prevalence of hepatitis C virus (HCV) infection among Slovenian HIV-infected individuals (14.5% and 10.7%, respectively). The presence of HCV infection was tested in 579/639 (90.6%) patients that were confirmed as HIV-positive in Slovenia by the end of 2013. Among them, 7.6% (44/579) of HIV-infected individuals were anti-HCV-positive, and 33/44 (75%) anti-HCV-positive patients were also HCV RNA-positive. HCV genotype 1 was most prevalent among HIV-infected patients (68%), followed by genotype 3 (20%), genotype 4 (8%), and genotype 2 (4%). Anti-HCV positivity was significantly higher in those that acquired HIV by the parenteral route (91.8%) than in those that acquired HIV by the sexual route (2.8%). Slovenia remains among the countries with the lowest prevalence of HCV infection in HIV-infected individuals. Because the burden of HIV among men who have sex with men in Slovenia is disproportionately high and increasing rapidly, the current favorable situation could change quickly and should be therefore monitored regularly.

Antioxidant enzymes gene polymorphisms and hepatocellular carcinoma in hepatitis C virus-infected Egyptian patients

Oxidative stress is an imbalance between production and elimination of reactive metabolites of oxygen and nitrogen, in favor of their production leading to potential damage. During oxidative stress, biologically important molecules and cells can be damaged, and this can be significant in the pathogenesis of many diseases. Reactive oxygen species (ROS) and ROS-induced cytokines are known to trigger the apoptosis of some hepatocytes and therefore contribute to inflammation, regeneration, fibrogenesis, and carcinogenesis. The enzymes generally considered to be the frontline defense against ROS are catalase (CAT), the mitochondrial manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX). Our aim in this work is to assess the possible association of the antioxidant enzyme polymorphisms of CAT (c.C-262T, rs1001179), MnSOD (p.Val16Ala, rs4880), and GPX1 (p.Pro 198 Leu, rs1050450) with the development of hepatocellular carcinoma (HCC) in a sample of hepatitis C virus (HCV)-infected Egyptian patients. Genetic polymorphisms were estimated in 40 HCC patients on top of HCV infection, 20 cirrhotic patients on top of HCV infection, and 20 healthy control individuals. Genetic polymorphisms of CAT (c.C-262T), MnSOD (p.Val16Ala), and GPX1 (p.Pro 198 Leu) were studied using PCR-RFLP technique. With regard to CAT enzyme polymorphism, the frequency of the CC was significantly higher in HCC and cirrhosis patients compared to the healthy control group (p = 0.000). The frequency of the C allele in the three studied groups did not show statistically significant difference (p = 0.081). Patients bearing CT + TT genotypes had 0.107-fold and 0.205-fold reduced risk of development of liver cirrhosis and HCC [p = 0.001, 95 % CI (0.025–0.459); p = 0.010, 95 % CI (0.058–0.721)], respectively, compared to those bearing CC genotype. With regard to the MnSOD, the Ala/Ala genotype was significantly higher in the HCC group and cirrhosis group than in control individuals (p = 0.001). Similar results were found regarding the frequency of the Ala allele in the three studied groups (p = 0.128). Patients bearing Ala/Ala genotype that had 2.8-fold and 1.8-fold increased the risk of development of liver cirrhosis and HCC [p = 0.001, 95 % CI (1.753–4.530); p = 0.001, 95 % CI (1.415–2.471)], respectively, compared to those bearing Val/Val + Val/Ala genotypes. With regard to GPX1 gene, the frequency of Pro/Leu genotype was significantly higher in the HCC and cirrhotic group compared to control group (p = 0.000). There was a significant increase in Leu allelic frequency in HCC and cirrhotic patients than in control group (p = 0.006). The presence of Leu allele increased the risk of development of liver cirrhosis and, consequently, HCC by 3.7-fold [p = 0.018, 95 % CI (1.205–11.78)] and 4.9-fold [p = 0.001, 95 % CI (1.742–13.86)], respectively, compared to Pro allele. The presence of CC of CAT (c.C-262T), Ala/Ala of MnSOD (p.Val16Ala) genes, and Leu allele of GPX1 (Pro 198 Leu) gene is considered as risk factors for development of liver cirrhosis and HCC in the presence of HCV infection.

Hepatitis C virus infection in end-stage renal disease and kidney transplantation.

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.

Investigation of Hepatitis B and Hepatitis C Virus Infections by Serological and Molecular Methods in Hemodialysis Patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are significant causes of morbidity and mortality in hemodialysis patients, since those patients are highly susceptible to infections due to immune suppression. The aims of this study were to investigate the presence of HBV and HCV infections in chronic hemodialysis patients by serological and molecular methods, and to determine the rate of occult HBV infection and the viral genotypes. A total of 201 patients who were under hemodialysis due to end-stage renal disease, were retrospectively evaluated. The study involved the patients at three different centers in Antalya, Turkey during 2006. HBV and HCV markers in the patients' sera were screened by ELISA method, viral nucleic acids were investigated by real-time polymerase chain reaction (PCR) in patients' plasma and viral genotypes were determined by DNA sequence analysis. Detection of at least one of the HBV markers HBsAg, anti-HBc total, and HBV DNA, was accepted as HBV infection, and detection of anti-HCV and/or HCV RNA was accepted as HCV infection. HBsAg positive patients with negative HBV DNA were considered as occult HBV infection. Of the patients 80 (40%) were female, 121 (60%) were male and the mean age was 51.16 ± 16.28 (range 17-93) years. In our study, sole anti-HBs positivity due to HBV vaccination, was detected in 89 (44.3%) patients. One hundred (50%) patients were found positive in terms of HBV infection and 40 (20%) were positive for HCV infection, while 24 (12%) patients had HBV and HCV co-infections. Eighty-five (42.3%) patients had no HBV and HCV infection. Among the 5 (2.5%) patients who were HBsAg positive, four were also HBV DNA positive. Occult HBV infection was detected in 1 (0.5%) patient. Anti-HCV and HCV RNA were found positive in 37 (18.4%) and in 24 (12%) patients, respectively. Among the HCV-RNA positive patients, 3 (12.5%) were anti-HCV negative. ALT and AST levels were found normal in all of the HBV DNA positive patients, and 62.5% (15/24) of HCV RNA positive patients. All of the HBV isolates were identified as genotype D and HCV isolates as genotype 1b. No statistically significant correlation was detected between the HBV infection and patients' age, duration of hemodialysis and elevation of serum transaminase levels (p> 0.05). On the other hand, HCV infection was seen to increase with age (p= 0.047). HCV infection showed a statistically significant increase with the duration of hemodialysis. HCV infection risk was increased in patients who were under hemodialysis for ≥ 25 months (p< 0.001, OR: 0224, 95% CI= 0089-0562). There was also a statistically significant correlation between the presence of HCV infection (anti-HCV and/or HCV RNA positive) and high levels of serum transaminases (p< 0.001). However, in two of the three cases who were anti-HCV negative and HCV RNA positive, serum transaminase levels were normal while the viral loads were high. Therefore to follow-up HCV infection in the hemodialysis patients, anti-HCV and serum transaminase levels may not be sufficient alone and these patients should be evaluated periodically for HCV RNA. In addition, the detection of occult HBV infection in one of the study patients, indicated that HBV DNA should also be investigated at regular intervals in the hemodialysis patients.

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

Background:Hepatitis C virus (HCV) infection as a worldwide health problem is associated with cirrhosis and hepatocellular carcinoma. With current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals. In HCV infection, an inappropriate ratio of cytokines may affect the benefit of antiviral therapy. Given the polymorphisms in regulatory regions of cytokines genes may influence cytokines production.Objectives:We aimed to investigate both the frequency of genotypes and alleles of interferon gamma (IFN-γ) gene at +874A/T, +2109A/G, and -183G/T loci in HCV-infected patients and their associations with response to therapy.Patients and Methods:A total of 158 patients were included and treated with PEG-IFN plus ribavirin. The presence of HCV infection in patients was confirmed by reverse transcription polymerase chain reaction, and genomic DNA was extracted from peripheral leukocytes using salting out method. IFN-γ gene polymorphisms were identified by polymerase chain reaction using sequence specific primers and restriction fragment length polymorphism analysis on genomic DNA.Results:Of 158 patients, 110 (69.5%) subjects achieved SVR and 48 (30.5%) subjects did not respond to therapy. The frequency of AA genotype (P = 0.001; OR: 11.2; CI: 2.26-63.21) and A allele (P = 0.01; OR: 3.23; CI: 1.23 8.56) of IFN-γ gene at +2109 locus were significantly different between the responder and non-responder subjects infected with genotype 1. Regardless of HCV genotype, the frequency of AG genotype was also higher in responder group than those who did not respond to therapy (P = 0.041; OR: 05.05; CI: 1.05-33.25)). In case of IFN-γ gene at +874 locus, there was no difference in genotypes and alleles frequencies between the responder and non-responder subjects infected with HCV genotypes 1 and 3. Haplotype analysis showed no association between haplotypes and response to therapy. All participants had G/T genotype at -183 locus.Conclusions:Our findings indicate that heterogeneity at +2109 locus of IFN-γ gene but not at +874 locus could interfere with successful therapy in patients infected with HCV genotype 1.

Impact of hepatitis C infection on renal transplant patients: a single-center experience in Libya.

The objective of this study was to assess the effect of hepatitis C virus (HCV) infection on graft and patient survival in a cohort of Libyan renal transplant recipients. Medical records of 241 renal transplant (RT) patients who have been followed-up at the Benghazi Nephrology Center up to February 2010 were reviewed. Based on the presence or absence of anti-HCV antibodies and HCV-RNA in the serum, patients were divided into two groups: HCV-positives and HCV-negatives. Anti-HCV antibodies were detected by the enzyme-linked immunosorbent assay technique and HCV-RNA by the polymerase chain reaction. Of the 241 RT patients, 162 were male and 79 were female. One hundred and ten patients (45.6%) were HCV-positives and 131 (54.4%) were HCV-negatives. Acute graft rejection was significantly higher among HCV-negative than HCV-positive patients (42 patients versus 28 patients, respectively; P<0.001). Conversely, chronic graft rejection was higher among HCV-positives than that among HCV-negative patients (35 patients versus 24 patients, respectively; P<0.05), and this difference became more significant after a 12-month period of transplantation (P<0.01). Seventeen patients died during the follow-up: Seven HCV-positives (6.3%) and 10 HCV-negatives (7.6%), and there was no significant difference in the death rate following RT between the two groups (P=0.08). Among the seven deaths of HCV-positives, liver disease-related complications were the main cause of death in three (42.8%) HCV-positive patients compared with none in the HCV-negative patients. The presence of HCV infection influenced chronic graft survival in RT patients and a higher proportion of HCV-infected patients had hepatic dysfunctions after RT. An increase in fatal liver complications was noted in HCV-positive patients with RT. In addition to pre-RT-specific therapy of HCV infection, all measures should be taken to prevent HCV infection pre- and post-RT. HCV-infected RT recipients need close monitoring for graft and liver function to prolong allograft and patient survival.

The prevalence of hepatitis C virus (HCV) infection in HIV‐positive individuals in the UK – trends in HCV testing and the impact of HCV on HIV treatment outcomes

We examined the prevalence of hepatitis C virus (HCV) infection among HIV-positive individuals in the UK, trends in HCV testing and the impact of HCV on HIV treatment outcomes. Trends over time in HCV prevalence were calculated using each patient's most recent HCV status at the end of each calendar year. Logistic regression was used to identify factors associated with having a HCV antibody test, and Cox regression was used to determine whether HCV status was associated with the time to experiencing an immunological response to highly active antiretroviral treatment (HAART), time to virological response and viral rebound. Of the 31,765 HIV-positive individuals seen for care between January 1996 and September 2007, 20,365 (64.1%) individuals were tested for HCV, and 1807 (8.9%) had detectable HCV antibody. The proportion of patients in follow-up ever tested for HCV increased over time, from 782/8505 (9.2%) in 1996 to 14,280/17,872 (79.9%) in 2007. Nine thousand six hundred and sixty-nine individuals started HAART for the first time in or after January 2000, of whom, 396 (4.1%) were HCV positive. Presence of HCV infection did not affect initial virological response, virological rebound or immunological response. The cumulative prevalence of HCV in the UK CHIC Study is 8.9%. Despite UK guidelines, over 20% of HIV-positive individuals have not had their HCV status determined by 2007. HCV infection had no impact on HIV virological outcomes or immunological response to HIV treatment. The long-term impact on morbidity and mortality remain to be determined.

The prevalence of HCV antibodies in skin disease patients in Saudi Arabia

Background/aim Hepatitis C virus (HCV) infection is a worldwide health issue with about 3% of the world’s population having HCV. In Saudi Arabia, prevalence ranges from 1.0% to 5.87%. Cutaneous diseases can indicate the presence of HCV infection. Objectives The research project aims to identify prospectively the prevalence of HCV infection in 200 patients with various types of skin disorders and 50 healthy blood donors, and to quantify this association through clinical and laboratory investigations. Methods Two hundred patients with cutaneous manifestations who presented at the Dermatology outpatient clinics of King Khalid University Hospital (KKUH) and King Abdulaziz University Hospital (KAUH), Riyadh, and 50 healthy blood donors were prospectively studied. Patients were examined by a team of dermatologists and clinical data were collected through a standard questionnaire. Ten milliliters of venous blood were collected from fully consented, 8–10 h fasting patients and serum was analyzed for AST, ALT, double infection with HBsAg, anti-HCV antibodies, and screened for HCV-RNA-PCR. Results Patients from the study ( n = 200) consisted of 25 (12.5%) males and 175 (87.5%) females, with a mean age of 42.9 ± 15.06 years. Clinical examinations revealed that (35%) had urticaria, followed by pruritus (28%), lichen planus (25.5%), prurigo (10%), and palpable purpura (1.5%). The main serum levels of ALT and AST were within the normal reference ranges. Twenty-four patients (12%) tested positive for anti-HCV antibodies, with 15 (62.5%) being positive for the presence of HCV-RNA by PCR and 9 (37.5%) resulting negative for the viral RNA. Of the 24 anti-HCV positive patients, pruritus 12 (50%), urticaria 5 (20.8%), lichen planus 5(20.8%), and palpable purpura 2(8.3%). Five (2.5%) patients were positive for HBsAg, with 3 (60%) having pruritus and 2 (40%) presenting with urticaria. Of the 50 healthy blood donors, only one (2%) tested positive for the presence of anti-HCV antibodies, and all the donors tested negative for HBsAg. Conclusion Results clearly indicate the prevalence of anti-HCV antibodies in 24 out of 200 patients (12%) with skin manifestations seen at the dermatology outpatient clinics and documented with HCV-RNA-PCR positivity of 15/24 (62.5%). A p-value of <0.05 was considered significant, therefore, it is suggested that patients presenting with urticaria, pruritus and LP be investigated to exclude the possibility of HCV infection.

Apparently Nonspecific Enzyme Elevations After Portal Vein Delivery of Recombinant Adeno-Associated Virus Serotype 2 Vector in Hepatitis C Virus-Infected Chimpanzees

Hepatic gene transfer is envisioned as a substitute for protein replacement therapies, many of which are derived from blood products. Thus, the target populations may have a high prevalence of blood-borne pathogens, such as hepatitis C virus (HCV). We sought to determine whether the safety of recombinant adeno-associated virus serotype 2 (rAAV2) would be altered by preexisting HCV infection. Doses of approximately 1 x 10(13) vector genomes of an rAAV2-chimpanzee alpha(1)-antitrypsin (rAAV2-cAAT) vector were injected into the portal vein of each of three HCV genome-positive (HCV+) chimpanzees and three HCV-negative (HCV-) controls. Acute safety studies were performed up to 90 days after vector administration, along with analyses of the peripheral blood and liver tissue for rAAV2-cAAT genomes. Vector genome copy numbers in blood and liver tissue were similar in both groups. All animals demonstrated increases in liver and muscle enzyme levels after the pretreatment liver biopsy (5 days before vector injection) and after the vector injection. However, HCV+ animals demonstrated a substantially greater rise in aspartate aminotransferase, alanine aminotransferase, and creatinine phosphokinase values than HCV- animals. Histopathology demonstrated abnormal lipid accumulation (steatosis) in the hepatocytes of HCV+ animals, both before and after vector injection. These data indicate an increased susceptibility to subclinical liver toxicity from portal vein injection of rAAV2 in the presence of HCV infection.