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Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation. [ABSTRACT FROM AUTHOR]

Changes of body immunity and inflammatory response in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients were investigated. Eighty HIV/HCV infected patients admitted to Qingdao No. 6 People's Hospital from August 2015 to December 2017 were selected and divided into two groups according to whether they were complicated with HCV infection or not (n=40 per group). The changes of the related humoral immune indexes, the related cellular immune indexes, the related indexes of hepatic function, the related indexes of inflammatory response in the two groups were compared, and the correlations of high-sensitivity C-reactive protein (hs-CRP) level with alanine aminotransferase (ALT) level, immunoglobulin G (IgG) level and cluster of differentiation 4+ (CD4+) level in the observation group were analyzed. The levels of related humoral immune indexes [immunoglobulin G (IgG), IgA and IgM levels], the related cellular immune indexes (CD4+ and CD8+) in the observation group were lower than those in the control group (P<0.05), and the CD4+/CD8+ ratio in the observation group was lower than that in the control group (P<0.05). The levels of indexes of hepatic function [ALT, aspartate aminotransferase (AST) and total bilirubin] in the observation group were significantly higher than those in the control group (P<0.05). The levels of hs-CRP, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in the observation group were significantly higher than those in the control group (P<0.05). There were positive correlations of hs-CRP level with ALT level and IgG level in the observation group (P<0.05). There was a negative correlation between hs-CRP level and CD4+ level in the observation group (P<0.05). The humoral and cellular immune functions of the HIV/HCV co-infected patients are significantly limited, their hepatic function is significantly impaired and the levels of inflammatory cytokines are markedly increased. The level of hs-CRP is positively correlated with hepatic function and humoral immune function and negatively correlated with cellular immune function. [ABSTRACT FROM AUTHOR]

Aim: In present survey, we attempted to inquire the plausible linkage of rs1327474 A/G and HCV chronic infection or the clearance of the virus. Background: IFN-y signaling pathway is an important trigger for activating antiviral immune responses and production of wide variety of molecules with anti-microbial profiles including type 1 cytokines. Any defect or variation in IFNG signaling pathway may result in susceptibility or progression to diverse diseases such as inflammatory and virus associated disorders. Rs1327474 A/G also known as -611 A/G is an important variation which is located in promoter region of Interferon Gamma Receptor-I (IFNGR1) and may have potent risk for HCV susceptibility. Methods: For this purpose, 154 HCV patients and 200 controls were enrolled in the study, and genomic DNA was isolated from PBMCS and IFNGR1 -611 polymorphism was genotyped by polymerase chain reaction- fragments length polymorphism (PCR-RFLP) method. Results: While, AA, AG and GG genotypes frequency included 37.8%, 53.7%, 8.5% in healthy controls, 41.6%, 46.1%, 12.3% were found in chronic HCV patients. Interestingly, allelic percentage was similar in both separated groups within 64.7%, 35.3% and 65.3%, 34.7% were obtained for T and G allele in control and case group respectively. Conclusion: In spite of our exception for the possible role of this variation in an important promoter region of IFGR1 gene, rs1327474 A/G was not associated with HCV chronic infection among an Iranian studied group. Comprehensively, -611A/G cannot be considered as a risk biomarker for susceptibility to chronic HCV disease. [ABSTRACT FROM AUTHOR]

Introduction and aim. Interferon-free regimen has been reported to be highly efficient in treatment of HCV infection, including patients with compensated cirrhosis. We compared the efficacy of Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir and Ribavirin (OBT/PTV/r, with DSV and RBV) therapy in patients with chronic HCV genotype 1b infection and compensated cirrhosis with and without prior treatment experience with pegylated interferon and ribavirin (IFN/RBV). Material and methods. A prospective twocenter study was conducted in Mures County Hospital and Brasov County Hospital, Romania in period November 2015-July 2016. Both treatment naïve and PegIFN/RBV experienced patients with chronic HCV genotype 1b infection received 12 weeks of OBT/ PTV/r, with DSV and RBV. Sustained virologic response 12 weeks after the treatment and eventual discontinuation of therapy due to adverse events were assessed in order to estimate safety and efficiency of therapeutic regimen. Results. Fifty nine patients were included in study, 35 (59.3%) of them were previously treated with IFN/RBV. Forty four (74.5%) patients were previously diagnosed with cirrhosis Child Pugh score 5, while 15 (25.4%) with Child Pugh score 6. All 59 patients achieved a SVR12 of 100% and one patient from treatment naïve cohort discontinued the therapy due to hyperbilirubinemia and encephalopathy. However viral load assessed at 12 weeks after discontinuation of therapy in this patient was undetectable. Conclusion. An all-oral regimen of co-formulated OBT/PTV/r with DSV and RBV results in high rate of sustained virologic response at post-treatment week 12 among HCV GT1b infected patients associated with compensated cirrhosis, regardless of previous treatment experience with PegIFN/RBV. [ABSTRACT FROM AUTHOR]

In this study, we examined the impact of the rs9264942 single-nucleotide polymorphism, previously shown to be associated with human immunodeficiency virus infection status and HLA-C expression, on the hepatitis C virus status in 359 people who inject drugs (PWID). The linkage of rs9264942 alleles to HLA-C antigens assigned to different expression levels was confirmed. Multivariate analysis revealed the age (P = .003) and the rs9264942 genotype (P = .006) to be independent factors for the classification to the PWID groups. Our study showed that the presence of the rs9264942 C/C genotype was associated with persistent seronegativity. [ABSTRACT FROM AUTHOR]

Abstract Background & aims Chronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. Patients & methods In this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930– > G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique. Results Logistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P < 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection. Conclusions Our results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters. Highlights • The SOCS3 polymorphisms may modulate the progression of HCV infection to advanced liver disease. • rs4969170-A allele at SOCS3 perturbs key metabolic parameters in Moroccan patients with chronic hepatitis C. • rs4969170-A allele at SOCS3 promoter region increases SOCS3 mRNA expression. • The SOCS3 polymorphism modulates HCC development by affecting mRNA expression. [ABSTRACT FROM AUTHOR]

Background: Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients.Methods: The Medline was searched for “HCV infection”, “HCV treatment”, “Directly acting antivirals”,“HCV resistance”.Results: Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration.Conclusions: Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. Results: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). Conclusions: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

Introduction. Hepatitis C is a liver inflammation caused by hepatitis C virus. HCV is about 10 times as infectious as HIV. The acute infection rarely causes symptoms and can clear up spontaneously in the first six months in about 20% of those affected. In most cases, however, the infection becomes chronic (up to 80%)6. Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide7. In the past decades, the standard treatment for hepatitis C viral infection was PEG-IFN and ribavirin (RBV). The future for the treatment of chronic hepatitis C infection is represented by DAAs and for Romania, the future is called Exviera+Viekirax. Objective of the study: The main purpose of the survaillance was to determine how these HCV chronic infection patients with F4 liver fibrosis tolerate the new DAAs treatment and how the liver fibrosis will decrease or increase. Matherial and methods: The study enrolled 33 patients from Internal Medicine Center, Fundeni Clinical Institute, during the time period 02.2016 – 08.2016. We evaluated the inflammatory syndrome, the cholestatic syndrome and the evolution of liver fibrosis. Results: We have noticed a significant decrease of inflammatory syndrome, the bilirubin level decreased also, but the stage of liver fibrosis remained the same, at the end of treatment with Eviera+Viekirax. Conclusions: We had a small experience so far, with Exviera+Viekirax regimen. The patients tolerated very well the therapy and the virological response was 100% for all subjects.

Introduction: Drug users are particularly exposed to the risk of HCV infection. At the same time, this is a difficult group to reach out with preventive measures. The aim of the study was recognition of respondents’ needs for intervention to reduce hepatitis C virus infection, including the identification of preferences on the conditions of its implementation and execution. Method: Results are based on outcomes of 25 group interviews with drug users and professionals and 20 individual interviews with drug users. Analysis included systemic investigation to create the frame of analysis based on codes, which emerged from the material. In the second stage of analysis, selective coding was used to combine a priori categories drawn from research interests. Results: Respondents expressed their suggestions regarding the character of the planned intervention and the conditions for its implementation. They turned attention to the potential barriers that may hinder the use of preventive measures. Physical accessibility, providing a sense of security and anonymity, duration and nature of the intervention adjusted to conditions of implementation and repeatability and complexity of activities are key elements that can affect the success of the intervention. Discussion: So far, HCV was not sufficiently present in the preventive interventions addressed to drug users. There is a need to develop a comprehensive, long-term preventive strategy that on the one hand will provide the necessary knowledge, and on the other, change drug users’ attitudes to becoming more health oriented. Conclusions: The planned intervention should take into account the needs of HCV infected and non-infected drug users. The activities should be carried out cyclically.

Hepatitis C virus (HCV)-induced inflammation contributes to progressive liver disease. The chemoattractant protein chemerin is associated with systemic inflammation. We hypothesized that chemerin is a biomarker that predicts the severity of liver disease in HCV patients. Furthermore, we investigated whether serum chemerin levels change during the course of HCV treatment using direct-acting antivirals (DAAs). Therefore, we measured serum concentration of chemerin in a cohort of 82 HCV-infected patients undergoing DAA treatment. Serum chemerin was positively associated with leukocyte count and negatively with markers of hepatic function and the model of end-stage liver disease (MELD) score. Low circulating chemerin levels significantly correlated with advanced liver fibrosis and cirrhosis as measured by the fibrosis-4 (FIB-4) score, the aminotransferase/platelet (AST/PLT) ratio index (APRI) score and the non-alcoholic fatty liver disease (NAFLD) score. Chemerin did not correlate with viral load or viral genotype. Treatment with DAAs did not improve MELD score and leukocyte count within the observation period, up to three months after the end of DAA treatment. Accordingly, chemerin levels remained unchanged during the treatment period. We conclude that low circulating chemerin is a noninvasive biomarker for hepatic dysfunction and advanced liver fibrosis and cirrhosis in HCV infection.

Background: Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. Methods: We selected 110 patients undergoing HCV eradication therapy with LSM compatible with significant liver fibrosis. LSM was evaluated prior to therapy and one year after HCV eradication. Results: LSM showed a median decrease of 35% from baseline values, and 67 (61%) patients showed posttreatment values compatible with lower fibrosis stages. We developed two logistic regression models to determine the probability of liver fibrosis overestimation according to serum transaminase. The probability of overestimation of two or more fibrosis grade is equal to (1) 50% for AST of 99 IU/L (2.2 ULN) and ALT of 90.5 IU/L (2 ULN), (2) 80% for AST of 123.5 IU/L (2.74 ULN) and ALT of 101.5 IU/L (2.25 ULN), and (3) reaches 100% for AST of 211 IU/L (4.7 ULN) and ALT of 140 IU/L (3.1 ULN). Conclusions: This study highlights the impact of serum transaminases on LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in patients with HCV infection.

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions. [ABSTRACT FROM AUTHOR]

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Background. The evolving pattern of HCV genotypes (GTs) and risk factors (RFs) in HCV-infected patients in Mexico is poorly understood. This study aimed to access the temporal trend of HCV GTs and RFs in HCV patients from two care centers.Material and methods. Chronic HCV patients [177 and 153 patients from the Northeast (NE) and Central West (CW) regions, respectively] were selected. Baseline features were demographics, date of birth (DOB), blood transfusion before 1992 (BTb1992), RFs, sexual promiscuity (SP), dental procedure (DP), injection drug use (IDU), viral load (VL), GTs, cirrhosis status and antiviral therapy (AT). Data were analyzed by Chi-square test for trends, unpaired T-test, and logistic regression.Results. HCV GT distribution was: GT1, 67%; GT2, 16%; GT3, 12% and GT4, 1%. RFs were BTb1992, 56%; surgeries, 56%; tattooing, 18% and IDU, 16%. GT1a mostly prevailed in CW than NE patients. GT1b, surgeries, BTb1992 and cirrhosis were more prevalent in older patients (p < 0.05); GT3, male gender IDU, SP, and tattooing showed an upward trend as younger were the patients in both regions (p < 0.05), contrariwise to the prevalence of GT1b. BTb1992 and surgeries were seen in elder women; BTb1992 was an independent RF for GT1. Age ≥ 50 years old, GT1 and exposure to AT (p < 0.05) were associated with cirrhosis. Conclusion. GT1a prevalence in CW Mexico remained stable, whereas GT3 increased and GT1b decreased in younger patients in both regions, along with associated RFs. Further regional molecular epidemiology and RF analyses are required in order to avoid the dissemination of new cases of HCV infection.

Background & Objective: HCV infection may be transmitted from an infected mother to her fetus in a low percentage however, it is the most important route of infancy HCV infection. The chance of HCV transmission in HIV/HCV co-infected mothers is higher than that in HCV mono-infected ones. The aim of this study is to assess HCV infection status in orphan newborns in Shiraz, Iran by quantitative PCR assay and HCV core-Ag Elisa. Materials & Methods: Twenty nine HCV suspected infants, 2-7 months old, were evaluated for HCV and HIV antibodies, HCV core antigen and quantitative genome viral load. Results: Although HCV-Ab was detected in all the studied infants, HCV-RNA was not detected in plasma or Peripheral Blood Mono-Nuclear Cells (PBMCs). HIV 1, 2 Abs were not detected in none of them, either. Conclusion: A few studies have been conducted on the HCV transmission from infected mothers to their infants. According to the present results, assessment of HCV viral load and HCV core-Ag can serve as reliable tests for the prediction or exclusion of HCV infection from mothers to infants.

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.

The paper presents the steps for studying cryoglobulinemia from essential to cryoglobulinemic vasculitis associated with hepatitis C virus. It shows advances in the study of the etiology of cryoglobulinemia, diagnosis, specific features of renal injury, and current approaches to treating HCV infection-related cryoglobulinemic vasculitis with renal involvement, by using 3 clinical cases (with a difference of a few decades during a follow-up).

Introduction: HCV infection is responsible for liver fibrosis. Fibroscan and diffusion MRI have been proposed for non-invasive diagnosis and staging of hepatic fibrosis. Aim of the work: To assess the accuracy of diffusion MRI and/or fibroscan in the diagnosis of liver fibrosis as compared to histopathology. Patients and methods pre-treatment laboratory work up, fibroscan, diffusion MRI of the liver and liver biopsy were done for 52 chronic HCV patients for assessment of liver fibrosis. Results: There was a significant difference between ADC values of F0 vs. F1, F3 and F4 (P = 0.008, 0.033 and 0.015) respectively, however no significant differences were seen in the ADC values between the other different fibrosis stages. As regard the liver stiffness values, there was a significant difference between F1 and F3 (P = 0.001), F1 and F4 (P = 0.024) and between F2 and F3 (P = 0.014).There was no significant difference in the ADC values between (F0, F1, F2) on one hand and (F3, F4) on the other hand (P = 0.387), while there was a highly significant difference in the liver stiffness values between both groups (p

This study evaluated epidemiological factors for HCV infection associated with sharing perforating and cutting instruments among candidates for blood donation (CBD) in the city of Belém, Pará, Brazilian Amazon. Two definitions of HCV infection cases were used: anti-HCV positivity shown by EIA, and HCV-RNA detection by PCR. Infected and uninfected CBD completed a questionnaire about possible risk factors associated with sharing perforating and cutting instruments. The information was evaluated using simple and multiple logistic regressions. Between May and November 2010, 146 (1.1%) persons with anti-HCV antibodies and 106 (0.8%) with HCV-RNA were detected among 13,772 CBD in Belém. Risk factors associated with HCV infection based on the EIA (model 1) and PCR (model 2) results were: use of needles and syringes sterilized at home; shared use of razors at home, sharing of disposable razors in barbershops, beauty salons etc.; and sharing manicure and pedicure material. The models of HCV infection associated with sharing perforating and cutting instruments should be taken into account by local and regional health authorities and by those of other countries with similar cultural practices, in order to provide useful information to guide political and public strategies to control HCV transmission.

Abstract Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Renal anemia is associated with increased cardio vascular morbidity and mortality and decreased quality of life. It may worsen the preexisting heart disease and consequently may accelerate the progression of renal dysfunction in a vicious circle. Renal anemia related mainly to decreased production of erythropoietin (EPO) by the kidney, decreased it's response by bone marrow and disturbed iron status. Aim of the Study: Was to evaluate the relationship between HCV infection and erythrropoietin in patients on regular HD. Patients and Methods: This study included 50 hemodialysis patients (25 patients +ve HCV and 25 -ve HCV), 16 were male and 34 were female, and their ages ranged from 20 to 67 years, with a mean ± SD of 50.5 ± 12.7 years, 15 apparently healthy individuals with normal kidney function and not anemic were included in the study as a control Group. Results: The patients were divided into two groups as the following: Group I consisted of 25 hemodialysis patients were positive for HCV antibody, which was confirmed by PCR, and their ages ranged from 27 to 67 years, with a mean of 47.28 ± 11.91 years. Group II consisted of 25 hemodialysis patients were negative for HCV antibody; their ages ranged from 20 to 65 years, with a mean age of 46.32 ± 11.50 years. In contrast, 15 patients served as age-matched and gender-matched; their ages ranged from 20 to 55 years, with a mean age of 44.13 ± 10.76 years, and were used as controls. Conclusion: Serum levels of erythropoietin correlate with chronic hepatitis C infection, which was associated with an increased number of RBCs and higher values of hemoglobin and hematocrit, which Result in lowering of the necessary erythropoietin dose and iron therapy. [ABSTRACT FROM AUTHOR]

Abstract: Chronic hepatitis C virus (HCV) infection represents a global public health challenge, and new drugs have been authorized for its treatment. In this study, we evaluated both the clinical efficacy and safety of elbasvir‐grazoprevir fixed‐dose combination in HCV patients. We performed a prospective single‐blind study on patients admitted to the Regional Center for HCV Treatment of the University of Catanzaro from March 1, 2017, to December 31, 2017, in patients >30 years old with a history of chronic HCV infection. During the study period, we enrolled 29 HCV patients (18 women and 11 men; age, 62.5 ± 14 years, range 36‐82; HCV‐RNA: 2 384 859 ± 2 487 747 IU/mL, range, 60 400 − 8 930 000 IU/mL genotype 1b). In 28 of 29 patients (96.5%) we documented a rapid and complete remission of HCV infection 4 weeks after the beginning of the treatment, while in 1 patient it was reached in 8 weeks. During the study, we did not record any serious adverse drug reaction or drug interaction and no patients discontinued the treatment. However, 4 patients (13.8%) developed an asymptomatic plasma transaminase increase that appeared at 8 weeks after the beginning of the treatment and disappeared 4 weeks later in 3 patients and 8 weeks later in 1 patient. In conclusion, we documented that in real life the development of plasma transaminase increase in 4 elderly women >70 years old, suggesting that more attention must be focused on this age population. [ABSTRACT FROM AUTHOR]

Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threatening diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy. Nanoparticles (NP) can be effectively targeted to the liver, and therefore it could be used for improving therapy of hepatic virus infections including hepatitis B virus and hepatitis C virus (HCV). Many studies were performed to encapsulate antiviral agents into nano-delivery system to improve their pharmacokinetics parameters to have a better therapeutic efficacy with lower side effects. However, the effect of virus infection on the uptake of NP has not yet been studied in detail. The latter is a crucial area as modulation of endocytic uptake of nanoparticles could impact on reduce potential therapeutic usefulness of antiviral agents loaded into nano-delivery system. In this study, a fluorescently-labelled polymeric nanoparticle was prepared and used to track NP uptake into Huh7.5, human hepatoma cells transfected with replicating HCV genomes, compared with non-transfected cells as a model representing hepatocyte uptake. Confocal microscopy and flow cytometry of virus transfected Huh7.5 cells unexpectedly demonstrated two-fold increase in uptake of NP compared to non-transfected cells. Therefore, virus transfection enhanced NP uptake into Huh7.5 cells and NP could be considered as a promising delivery system for targeted treatment of hepatitis viruses. [ABSTRACT FROM AUTHOR]

Background Data on the prevalence of hepatitis C virus (HCV) infection in Italy are outdated and usually derived from studying residents in small towns. Methods To assess prevalence of and risk factors for HCV infection among Italian residents in 5 metropolitan areas, subjects ≥20 years of age were randomly selected from the list of the general practitioners' registers in 2015. Anti-HCV was tested by a salivary test; HCV-RNA, HCV genotypes, and ALT were determined in positive individuals. Logistic regression analysis evaluated independent risk factors for HCV. Results Of the 4907 enrolled subjects, 112 (2.3%) tested anti-HCV positive. The prevalence of HCV increased with age, from 0.2% in subjects born after the year 1984, to 4.2% in those born before the year 1935 (P < 0.01). The birth-cohort prevalence peaked (7.0%) in elderly. Serum HCV-RNA was detected in 1.7% of the whole population. Nearly 80% of anti-HCV subjects were aware of their status. Age > 70 years, low education level, past use of glass syringes, blood transfusion, intravenous drug use, and cohabitation with an anti-HCV positive subject predicted the HCV positivity. Interpretation In metropolitan areas in Italy, HCV is prevalent in elderly, reflecting a cohort effect determined by modalities of viral transmission no longer operative. The impact of the infection will further diminish in the years to come due to the natural depletion of the reservoir of the virus. This age pattern and the high proportion of subjects aware of their status do not warrant a policy of screening. [ABSTRACT FROM AUTHOR]

Background: Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients.Methods: Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients.Results: Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection.Conclusions: Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Background Hepatocarcinogenicity of aflatoxin B 1 (AFB 1 ) has rarely been studied in populations with hepatitis C virus (HCV) infection and those without hepatitis B virus (HBV) and HCV infection (non-B-non-C). This case-control study nested in a community-based cohort aimed to investigate the HCC risk associated with AFB 1 in HCV-infected and non-B-non-C participants. Methods Baseline serum AFB 1 -albumin adduct levels were measured in 100 HCC cases and 1767 controls seronegative for anti-HCV and HBsAg (non-B-non-C), and another 103 HCC cases and 176 controls who were anti-HCV-seropositive and HBsAg-seronegative. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. Results In 20 years of follow-up, the follow-up time to newly developed HCC was significantly shorter in participants with higher serum AFB 1 -albumin adduct levels in non-B-non-C ( p = 0.0162) and HCV-infected participants ( p < 0.0001). Within 8 years of follow-up, HCV infection and AFB 1 exposure were independent risk factors for HCC. Elevated serum AFB 1 -albumin adduct levels were significantly associated with an increased risk of HCC newly developed within 8 years of follow-up in non-B-non-C participants with habitual alcohol consumption [crude OR (95% CI) for high vs. low/undetectable levels, 4.22 (1.16–15.37)] and HCV-infected participants [3.39 (1.31–8.77)], but not in non-B-non-C participants without alcohol drinking habit. AFB 1 exposure remained an independent risk predictor for HCV-related HCC after adjustment for other HCC predictors (multivariate-adjusted OR [95% CI], 3.65 [1.32–10.10]). Conclusions AFB 1 exposure contributes to the development of HCC in participants with significant risk factors for cirrhosis including alcohol and HCV infection. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) infection is one of the most frequently encountered public health problems in Egypt. It is associated with many autoimmune diseases such as rheumatoid arthritis. Aim of the work To assess the impact of HCV infection in rheumatoid arthritis (RA) Egyptian patients; its relation to disease activity, functional status and ultrasonography findings. Patients and methods The study included 155 RA patients further classified according to the presence of concomitant HCV infection into 2 groups; rheumatoid arthritis (RA) and rheumatoid arthritis/hepatitis C virus (RA/HCV) groups. All patients were subjected to full history taking, thorough clinical examination, laboratory investigations, assessment of disease activity using the disease activity score 28 (DAS28) and assessment of functional status using the modified health assessment questionnaire (MHAQ). Ultrasonography (US) assessment was done using the German US7 score. Results Both DAS28 and MHAQ scores showed significant differences between both the RA and the RA/HCV groups (p < 0.001), with higher mean values observed in the RA/HCV group (5.4 ± 1.1 and 1.05 ± 0.79 respectively). Significantly higher US7 synovitis scores were found in the RA/HCV group compared to the RA group (p = 0.03). US7 synovitis tenosynovitis scores revealed significant correlations with DAS28 and US7 synovitis scores correlated with MHAQ in both groups. Conclusion Concomitant HCV infection in RA patients had an impact on disease activity. RA patients with concomitant HCV infection (RA/HCV) had higher DAS28 and MHAQ scores, with higher US7 synovitis scores compared to RA patients. US7 score is a valuable objective tool for the assessment of RA disease activity. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis C virus [HCV] shares common transmission pathways with human immunodeficiency virus [HIV]. HIV-HCV co-infection is associated with negative impacts on both HIV and HCV when compare with mono-infection. Anti-HCV test is the main screening method for HCV infection. However, in HIV patients, false-negative anti-HCV may occur as a result of impaired immunity, and HCV RNA may be the sole investigation to diagnose HCV infection in those patients. Data regarding prevalences of both seropositive (anti-HCV) and seronegative HCV (anti-HCV- but HCV RNA) infection in HIV individuals in Thailand are limited. The aims of this study are to define the prevalence of seropositive and seronegative HCV infection in Southern Thai HIV patients. Materials and Methods: This is a cross-sectional study in 2 centers in Southern Thailand: Songklanagarind and Songkhla Hospital. Inclusion criteria were known adult HIV patients with available CD4 count within 6 months of enrollment. Exclusion criteria were patients with coexisting autoimmune disease, renal dialysis, immunosuppressive therapy including corticosteroids treatment, and history or clinical condition that cannot exclude acute HCV infection. Plasma samples were obtained from all eligible patients and test for anti-HCV (third-generation enzyme immunoassay) and HCV RNA. Results: A total of 117 HIV patients were enrolled, with mean age of 44 years and 51.3% were male. The median CD4 level was 524 cells/mm3. The major HIV transmission route was heterosexual (83.8%), and intravenous drug use [IVDU] was found 3.42% of patients. Nine patients (7.7%) were positive for anti HCV and, among those, HCV RNA was detectable in 8 patients (6.8%). However, no HCV RNA was detected in all patients with negative anti-HCV. When compared with no HCV co-infection group, lower CD4 count (343 vs. 549 cells/mm3; p = 0.035), more IVDU (33.3% vs. 0.9%, p = 0.001), lower heterosexual as a route of transmission (55.6% vs. 86.1%, p = 0.037), and more elevated aspartate aminotransferase [AST] level (31 vs. 24 U/L, p = 0.019) were observed in seropositive HCV group. Conclusion: The prevalence of seropositive HCV infection in Southern Thai HIV patients was 7.7%. Low CD4 count, IVDU and elevated AST were significantly associated with HCV co-infection. No seronegative HCV infection was detected in our HIV patients. [ABSTRACT FROM AUTHOR]

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014).Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods.Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014).Conclusion: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy. [ABSTRACT FROM AUTHOR]

The key role of T cells in hepatitis C virus (HCV) elimination and the ability of dendritic cells (DCs) to induce antiviral T cell responses suggest that DC vaccines could be a promising approach in the treatment of chronic HCV infection. The aim of our study was to evaluate, whether immunotherapy with DCs is safe and elicits anti-HCV T cell responses. Ten patients with HCV (genotype 1) were vaccinated with monocyte-derived DCs, generated in the presence of IFN-α (IFN-DCs) and pulsed with recombinant HCV Core and NS3 proteins. Treatment schedule included four subcutaneous vaccinations with 1 week interval and six vaccinations with month interval. No serious adverse events or an increase in hepatitis C biochemical activity were registered after vaccination. Using ex vivo assays for the detection of proliferative responses, IFN-γ production and CD8+ degranulation have shown that immunotherapy elicited antigen-specific responses in all patients although individual heterogeneity existed within their types, magnitude, and timing. Core/NS3-specific proliferative response and CD8+ T cell degranulation have already been registered after the first course of vaccination. Of note, Core-specific responses had higher magnitude. The appearance of antigen-specific IFN-γ responses was registered after the second vaccination course. Vaccination did not cause Th2 response and expansion of the CD4+CD25+CD127− regulatory T cells. Generated immune responses failed to provide virus elimination. Nevertheless, there were inverse correlations between viral load and NS3-specific proliferation (RS = 0.62; p = 0.05) and IFN-γ secretion (RS = − 0.82; p = 0.001) at 6-month post-treatment period. Immunotherapy with IFN-DCs was safe and elicited HCV-specific T cell responses which were insufficient to eliminate viruses but could be implicated in the restriction of viral replication. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV pos ) and in HCV-negative (HCV neg ) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system. Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCV pos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCV pos patients, suggesting a functional impairment in the cytokine production in HCV pos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation. Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection. [ABSTRACT FROM AUTHOR]

Primary hepatitis C virus infection might be spontaneously cleared or become chronic. Polymorphisms in immune regulatory genes might influence the outcome. The aim of this study was to determine the frequency of genotypes and alleles of PD-1.3 and PD-1.5 gene loci in HCV infected patients and their association with the disease outcome. In this study 167 patients with chronic hepatic C and 42 individuals whose infection was spontaneously cleared, and a healthy control group comprising of 300 participants were included. The presence of chronic or spontaneously cleared infection amongst the participants was determined in advance by serologic and molecular methods. Genomic DNA was extracted using salting out method. PD-1 gene polymorphisms assay was performed using PCR-RFLP method. The frequency of alleles of PD-1.3 gene locus was significantly higher in the spontaneously cleared HCV infected group (P = 0.03) as well as the healthy control group (P = 0.04) in comparison to the chronic infected participants. In the case of PD-1.5 locus, there was no association between the frequency of inherited genotype or alleles and HCV infection outcome amongst the three groups. Haplotype analysis showed no statistically significant differences in the frequencies of different haplotypes between the three studied groups. Our finding collectively inferred that individuals with A allele at PD-1.3 locus might clear HCV infection more frequently than those with T allele. Instead, polymorphisms at PD-1.5 locus as well as haplotypes emerged from PD-1.3 G/A and PD-1.5 C/T might not be significant in the HCV infection outcome. [ABSTRACT FROM AUTHOR]

Introduction and aim. In recent decades, Italy has become a land of immigration from countries suffering a socio-economic crisis. The aim of this study was to perform an organized screening to identify and offer care to immigrants with HCV infection. Material and methods. The screening, performed from 2012 to 2015, involved 1,727 immigrants in the Campania and Apulia regions in southern Italy. Results. Screening was accepted by 1,727 (85%) out of 2,032 immigrants interviewed; 70 (4.1%) of the 1,727 were anti-HCV-positive, all unaware of their serological condition, 31 (44.3%) of whom were HCV-RNA-positive and 39 negative. The 31 HCV-RNA-positive immigrants were further investigated at a third-level clinic of infectious diseases. The HCV viral load was 2.6 x 107 ± 7.7 x107 IU/mL, and 35.5% showed HCV-genotype 1a or 1b, 23.8% genotype 2 and 22.6% genotype 3. Two immigrants had liver cirrhosis and, in accordance with the Italian Healthcare Authority guidelines, received an interferon-free regimen and achieved a sustained virological response (SVR); 18 had chronic hepatitis, 6 of whom with a high risk of progression and received interferonbased therapy, with SVR in 4, whereas 12 at low risk were put on a waiting list for future interferon-free treatment, once licensed. The remaining 11 HCV-RNA-positive immigrants were considered HCV inactive chronic carriers and were included in a long-term observational program. Conclusion. The screening program can be considered successful since it was accepted by 85% of the subjects interviewed and identified 70 anti-HCV-positive immigrants, all unaware of their clinical and virological condition. [ABSTRACT FROM AUTHOR]

Objective: To assess prospectively the maternal and fetal outcome among pregnant women with chronic Hepatitis-C virus (HCV) infection compared to normal control group.Methods: A prospective observational study conducted on 342 pregnant women with HCV who were divided into two groups according to polymerase chain reaction (PCR) result, group 1 (n = 184, HCV-PCR negative) and group 2 (n = 154, HCV-PCR positive) with a third group of normal pregnant women (n = 170). Obstetric outcome was recorded.Results: Patients with positive HCV-PCR have more elevated liver enzymes (p < 0.05) and lower prothrombin INR (p < 0.001) than those with negative HCV-PCR testing. Fewer patients with HCV received previous medical treatment (16/342, 4.6%). More women in the HCV groups delivered by vacuum or cesarean section (p < 0.05), experienced higher rates of antepartum hemorrhage, postpartum hemorrhage, anemia, development of GDM, premature rupture of membranes, repeated hospital admissions, blood transfusions, admission to ICU and maternal mortality (p < 0.001) compared to the control group. Fetuses of women with HCV infections were more prone to IUFD with higher rates of low birth weight, prematurity, low Apgar scores at 5 min, admission to NICU, need for ventilation, and acquisition of HCV (p < 0.001) as well as neonatal mortality (p < 0.05) compared to the control group.Conclusion: Patients with HCV infection even those without viremia suffered poor maternal and fetal outcome. Multidisciplinary management of the affected patients should be implemented to improve their obstetric outcome. [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis C virus infection is a serious clinical, epidemiological, and social problem in Poland and worldwide. This type of infection is often registered as: hospital-acquired infection, infection among health care workers, infection of a newborn transmitted via vertical route. Health care professionals are occupationally exposed to HCV. Objective. Presentation of the problem of risk of acquiring HCV infection among medical staff employed in health care facilities. Material and methods. Epidemiological data were analyzed concerning infections with hepatitis C virus from the aspect of exposure of medical staff employed in health care facilities, based on the published results of scientific studies and statistical data. Results. HCV infection among medical professionals employed in health care facilities is a multi-aspect problem, which should be considered as the problem of: hospital-acquired infections, occupational infections, and vertically transmitted infections. Conclusions. Hepatitis C virus infection is a serious clinical, epidemiological, and social problem in Poland, and concerns approximately 1.9% of the population. This is one of the leading causes of hospital-acquired infections – approximately 33%. Health care workers are occupationally exposed to HCV infection – in Poland this risk is from 0.80-1.42%. Care of a pregnant woman infected with HCV and care of a newborn with vertically transmitted infection creates risk for medical staff. Considering high occupational risk of HCV infection among health care workers it is necessary to carry out a wide range of non-specific prophylaxis, and also observe procedures for prevention of occupational exposures.

Introduction: Egypt has the highest prevalence of Hepatitis C Virus (HCV) in the world, estimated nationally at 14.7%. HCV treatment consumes 20% ($80 million) of Egypt’s annual health budget. Outcomes of cirrhotic patients admitted to the ICU may, in fact, largely depend on differences in the state of the disease, criteria and indications for admission, resource utilization, and intensity of treatment. Aim: The aim of the present study was to evaluate the efficacy of liver specific scoring models in predicting the outcome of critically ill cirrhotic patients in the ICU as it may help in prioritization of high risk patients and preservation of ICU resources. Materials and Methods: Over one year, a total of 777 patients with End Stage Liver Disease (ESLD) due to HCV infection were included in this retrospective non-randomized human study. All statistical analyses were performed by the statistical software SPSS version 22.0 (SPSS, Chicago, IL, USA). Child Turcotte Pugh (CTP) score, MELD score, MELD-Na, MESO, iMELD, Refit MELD and Refit MELD-Na were calculated on ICU admission. Results: ICU admission was mainly due to Gastrointestinal (GI) bleeding and Hepatic Encephalopathy (HE). Overall mortality was 27%. Age and sex showed no statistical difference between survivors and non survivors. Significantly higher mean values were observed for all models among individuals who died compared to survivors. MELD-Na was the most specific compared to the other scores. MELD-Na was highly predictive of mortality at an optimized cut-off value of 20.4 (AURC=0.789±0.03-CI 95%=0.711-0.865) while original MELD was highly predictive of mortality at an optimized cut-off value of 17.4 (AURC=0.678±0.01- CI 95%=0.613-0.682) denoting the importance of adding serum sodium to the original MELD. INR, serum creatinine, bilirubin, white blood cells count and hyponatremia were significantly higher in non survivors compared to survivors, while hypoalbuminemia showed no statistical difference. The advent of Hepatorenal Syndrome (HRS) and Spontaneous Bacterial Peritonitis (SBP) carried worse prognosis. Hyponatremia and number of transfused blood bags were additional independent predictors of mortality. Conclusion: In cirrhosis of liver, due to HCV infection, patients who died during their ICU stay displayed significantly higher values on all prognostic scores at admission. The addition of sodium to MELD score greatly improves the predictive accuracy of mortality. MELD-Na showed the highest predictive value of all scores.

Background: Hepatitis C Virus (HCV) infection is one of the major blood-borne infections worldwide. HCV carriers may develop chronic hepatitis leading to liver cirrhosis and hepatocellular carcinoma (HCC). There is no overall estimate of the infection prevalence in the northeast of Iran. We have performed this research in order to determine accurately the prevalence and risk factors of HCV infection among general population in Mashhad. Methods: During 2009, 1678 people between 1 to 90 yr old with the mean age of 29.1±18.5 yr were selected randomly by multistage sampling from different geographical regions of the city proportionate to sex and age distribution of population in 2006 census. ELISA was used to screen for antibodies and RT-PCR tested the positive samples. Results: HCV infection was detected in 7/1654 cases; overall prevalence of the infection was 0.42% (95%CI: 0.17-0.87%), 0.80% and 0.11% among males and females, respectively (P= 0.051). One HCV-infected subject was also positive for hepatitis B surface antigen (HBsAg), however, no cases showed HIV or HTLV seropositivity. Conclusion: In comparison with similar studies, the prevalence of HCV infection in Mashhad is low.

Introduction. In patients with chronic hepatitis C it is still debated whether previous exposure to the hepatitis B virus, diagnosed from the presence of the anti-HBc antibody, is linked to a greater risk of severe hepatitis. The aim of the study was to evaluate whether the presence of anti-HBc antibodies is associated with cirrhosis in patients with HBsAg-negative chronic hepatitis C.Material and methods. Two hundred twenty-two consecutive HBsAg-negative patients with HCV-related chronic hepatitis were enrolled at their first liver biopsy. Ishak’s scoring system was used to grade necroinflammation and fibrosis and the patients with stage 5 or 6 were considered as having histological cirrhosis.Results. Patients with histological cirrhosis had a higher mean age, AST, ALT, a lower platelet count and prothrombin activity compared to those with milder fibrosis. The presence of anti-HBc was identified in 21 (63.6%) of the 33 patients with fibrosis score 5 or 6 and in 56 (29.6%; p < 0.001) of the 189 with score ≤ 4. Patients with cirrhosis had a significantly higher grading than those without cirrhosis (median = 8, IQR 6-11 vs. Median = 6, IQR = 4-8, respectively, p < 0.001). A multivariate logistic regression analysis showed that age, sex and anti-HBc positivity were independent predictors of histological cirrhosis.Conclusion. Our data support the idea that in patients with chronic hepatitis C the presence in serum of anti-HBc is associated with histological cirrhosis and is therefore a marker of clinical value.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR) and type 2 diabetes (T2D). Chronic HCV patients with IR and T2D appear to have a decreased response to the standard pegylated-interferon-alpha and ribavirin (PEG-IFN/RBV) anti-viral therapy. Insulin and metformin are anti-diabetic drugs regularly used in the clinic. A previous in vitro study has shown a negative effect of insulin on interferon signaling. In the clinic, adding metformin to PEG-IFN/RBV therapy was reported to increase the response rate in chronic HCV patients and it has been suggested this effect derives from an improved anti-viral action of interferon. The goal of this study was to further investigate the molecular insight of insulin and metformin interaction with HCV infection and the anti-viral action of interferon. We used two cell culture models of HCV infection. One is a sub-genomic model that assays viral replication through luciferase reporter gene expression. The other one is a full-length infectious model derived from the JFH1 genotype 2a isolate. We found that both insulin and metformin do not affect HCV infection. Insulin and metformin also do not influence the anti-viral potency of interferon. In addition, there is no direct interaction between these two drugs and interferon signaling. Our results do not confirm the previous laboratory observation that insulin interferes with interferon signaling and suggest that classical nutritional signaling through mTOR may be not involved in HCV replication. If metformin indeed can increase the response rate to interferon therapy in patients, our data indicate that this could be mediated via an indirect mechanisms.