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Aim of the work To determine the frequency of anti-mutated citrullinated vimentin (anti-MCV) antibodies in chronic hepatitis C virus (HCV) patients and its relation to HCV associated arthritis. Patients and methods The study included 60 HCV patients and 30 age and sex matched control. Patients were subgrouped according to the presence and absence of associated arthritis. Laboratory investigations were performed and anti-MCV antibodies were measured. Results The age of the patients ranged between 29 and 75 years (mean 57.65 ± 8.49 years) and they were 38 males (63.3%) and 22 females (36.7%) M:F 1.7:1. 32 (53.3%) patients had arthritis while the remaining 28 (46.7%) did not. There was a significantly higher anti-MCV antibody level in the patients (median 250 ug/L; range 175–375 ug/L) compared to the control (p < 0.001). There was no significant difference in the anti-MCV antibodies between HCV patients with and without arthritis (p = 0.15). The HCV patients without arthritis had a significantly higher level of anti-MCV antibody (median 200 ug/L, range 175–375 ug/L) than the control (median 30 ug/L, range 5–15 ug/L) (p < 0.001) and the area under the curve (AUC) was 0.85 (95% CI 0.69–1, p = 0.004). When the cut-off value for anti-MCV antibody was set at 57.5 ug/L, clinical sensitivity was 80% and specificity was 80% between those without arthritis and the control. There was no significant correlation between anti-MCV antibody with various studied parameters in the HCV patients. Conclusion Anti-MCV antibody is significantly increased in HCV patient and has no role in diagnosing HCV-associated arthritis. [ABSTRACT FROM AUTHOR]

The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25-53 years) with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet) and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100%) achieved sustained virological response, including two with cirrhosis and two with HCV RNA .6,000,000 IU/mL. The treatment was well tolerated: none of the patients presented with a serious adverse event requiring hospital admission and none had anemia or any significant changes in blood count. One patient had a short period of diarrhea, which was resolved with antibiotic treatment. The combination of reduced-dose SOF and full-dose DCV, daily, was a safe and effective treatment in our group of hemodialyzed patients infected with HCV genotype 3. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. Due to the asymptomatic nature of the infection, many acute cases of HCV infection are left undiagnosed, so screening individuals at risk is an important public health priority. New medications offer sustained virologic response rates of over 95%, fewer adverse reactions, and shorter durations of therapy. This article reviews the new treatment guidelines for the evaluation and management of patients with HCV infection. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the dynamical behavior of the fractionalorder model within Caputo derivative of HCV infection. Stability analysis of the equilibrium points is according to the basic reproduction number R0. The numerical simulations are also presented to illustrate the results. [ABSTRACT FROM AUTHOR]

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HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored. [ABSTRACT FROM AUTHOR]

Objective: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir (Zoval) among Pakistani population with the rapid virologic response (RVR2/4 weeks) with HCV infections. Methods: This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir (Zoval) 400 mg plus ribavirin (with or without peg interferon) for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics. Results: A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 ± 11.41 years. Out of 573 patients 535 (93.3%) were treatment naive, 26 (4.5%) were relapser, 7 (1.2%) were non-responders and 5 (1.0%) were partial responders. A rapid virologic response was reported in 563(98.2%) of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated. Conclusion: Sofosbuvir (Zoval) is effective and well tolerated in combination with ribavirin in HCV infected patients. [ABSTRACT FROM AUTHOR]

Background and Aim Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. Methods A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. Results In 2014, an estimated 230 470 individuals (range: 180 490-243 990) were living with HCV, among whom 75% were diagnosed ( n = 172 720; range: 156 720-188 770), 20% had ever received treatment ( n = 45 000; range: 39 280-50 720), and 11% had been cured ( n = 24 750; range: 21 520-27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage ≥F3 doubled during the last decade, increasing from 9% ( n = 18 580) in 2004 to 19% ( n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. Conclusions The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies. [ABSTRACT FROM AUTHOR]

Background:unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct acting antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir, simeprevir and fixed combination medicines containing ledipasvir plus sofosbuvir and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. The aim of this study was to assess of ledipasvir plus sofosbuvir as treatment of HCV infection in patients with advanced liver disease including cirrhotic patients with child B and C. Patients and methods:in this prospective study, seventy five HCV PCR positive patients were classified into three groups according to child score. Each group included twenty five patients. All patients received ledipasvir plus sofosbuvir for six months. For all patients thorough medical history, clinical examination, kidney function tests, liver function tests, complete blood count, pelvi-abdominal ultrasound, HCVantibodies, hepatitis C viral RNA, quantitative, HbsAg, alpha fetoprotein as baseline screening. HCV PCR done for all patients at end of treatment and three months later to detect sustained virological response (SVR12). Patients with combined HCV and HBV infection, hepatic or extrahepatic malignancies and late child C were excluded. Results: showed that no statistical significant difference were detected in patients of group A as regard liver function tests before and after treatment and SVR12 achieved by 96%. Patients of group B showed significant statistical difference as regard liver function tests before and after treatment with SVR12 achieved by 88%. In patients of group C there were significant statistical difference in liver function tests with SVR12 achieved by 80%. Also there were clinical improvement in patients of group B and C after end of treatment. Conclusion:it could be concluded that there will be a dramatic improvement in HCV therapy followed the introduction of oral medicines that directly inhibiting the replication cycle of HCV. The combination pill contains a fixed-dose of ledipasvir 90 mg and sofosbuvir 400 mg, two direct-acting antiviral agents against HCV. Ledipasvir is an inhibitor of the NS5A protein, which is required for HCV replication. Sofosbuvir inhibits the HCV NS5B RNA-dependent RNA polymerase, which is also required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form a pharmacologically active triphosphate that can incorporate into the HCV RNA. Ledipasvir plus sofosbuvir can be used safely in treatment of compensated and decompensated post hepatitis C liver cirrhosis. SVR12 can be achieved by 96% in patients with early cirrhosis (child A), 88% in patients with child B cirrhosis and 80% in patients with child C with subsequent improvement in liver functions. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population. [ABSTRACT FROM AUTHOR]

HCV infection is significantly more prevalent in the population of psychiatric patients, drug addicts and people tending to undertake risky sexual behaviors than in the general population. This article presents a spectrum of psychopathological symptoms and psychological dysfunctions, an outline of current theories on the neuropathology and psychiatric aspects of HCV infection treatment. The unspecific character of the psychopathological symptoms in the HCV infection makes the process of thorough diagnostics and adequate treatment difficult, thus the specific and characteristic features have been emphasized. The aim of this review is to shed light not only on the basic information concerning CNS pathology but also on the conclusions emerging from the studies of different authors, of various methodology, in diverse study groups and also to investigate current topics of research. The results of neuroimaging studies have been presented as well. Attention has also been dedicated separately to specific issues, like psychiatric aspects of co-infection with HCV and HIV viruses, the chronic fatigue in the course of HCV infection, the influence of substance use disorders and difficulties encountered during treatment with interferon. Undiagnosed psychiatric disorders, not only inevitably decrease the already rather low quality of life but also cause non-adherence with recommendations and medications regimes, contributing to a worse treatment outcome. Finally, the above disorders, when left untreated, result in higher rates of risk-taking behaviors among the infected, thus imposing a danger not only to patients themselves but also to the healthy population. [ABSTRACT FROM AUTHOR]

Summary Objectives About 2% of the world population is infected with hepatitis C virus (HCV), a leading cause of hepatic cirrhosis and hepatocellular carcinoma. The Niemann–Pick C1-like 1 cholesterol absorption receptor (NPC1L1) was recently identified to be an important factor for HCV entry into host cells. Whether genetic variations of the NPC1L1 gene are associated with HCV infection is unknown. Methods In this study, five single nucleotide polymorphisms (SNPs) of the NPC1L1 gene were analyzed in 261 HCV-infected individuals and 265 general controls from Yunnan Province, China. Results No significant differences were identified in genotypes or alleles of the SNPs between the two groups. After constructing haplotypes based on the five SNPs, a significant difference between HCV-infected individuals and general controls was shown for two haplotypes. Haplotype GCCTT appeared to be a protective factor and haplotype GCCCT was a risk factor for HCV-infected individuals. Genotypes of four SNPs correlated with biochemical characteristics of HCV-infected persons. Genotypes of SNPs rs799444 and rs2070607 were correlated with total bilirubin. Genotype TT of rs917098 was a risk factor for the gamma-glutamyltransferase level. Furthermore, HCV-infected individuals carrying genotype GG of rs41279633 showed statistically higher gamma-glutamyltransferase levels than HCV-infected persons with GT and TT. Conclusion The results of this study identified the association between genetic susceptibility of the NPC1L1 gene and HCV infection, as well as biochemical characteristics of HCV-infected persons in Yunnan, China. [ABSTRACT FROM AUTHOR]

Background. HCV infection and transfusional iron overload in Thalassemic patients may result in liver disease. HCV treatment in Thalassemia has raised safety concerns.Aim. Estimate effectiveness and tolerability of interferon-based therapy in HCV-infected Thalassemic patients.Material and methods. Over a 12-year period, consecutive patients with β Thalassemia major (TM) and chronic hepatitis C received treatment. Liver biopsy, HCV-RNA and genotyping were performed beforehand. Sustained virological response (SVR) was defined as negative HCV-RNA 6 months post-treatment. Forty eight patients (26 M-22 F, mean age 39.8) were enrolled. Twenty nine patients were treated with conventional interferon alpha (IFNa) for 48 weeks (group A). Nineteen patients (10 naïve-9 previously IFNa experienced) received pegylated interferon (PEG-IFN) (group B).Results. HCV-1 was found in 44%, HCV-2 in 14%, HCV-3 in 23% and HCV-4 in 19%. Group A: ten patients (38.5%) achieved SVR, 2 (7.5%) relapsed and 17 (54%) were non responders. Group B: five (28%) achieved SVR, 8 (44%) relapsed and 6 (28%) never responded. High HCV-RNA levels, genotype 1 and advanced liver fibrosis were independently associated with no response. Four patients (3 treated with IFNα, 1 with PEG-IFN) had to discontinue treatment due to complications.Conclusions. The response rate of IFN monotherapy in multi-transfused, HCV-infected Thalassemic patients is not inferior to that in non-multi-transfused patients. IFNa administration is well-tolerated and should be recommended as initial treatment schedule in this setting.

Objectives: To evaluate the level of knowledge of, to investigate the attitudes toward, and to determine the emphasis given to the national prevalence of HBV/HCV infections among healthcare professionals. Materials and Methods: A total of 206 healthcare professionals (mean (SD) age: 37.0 (6.3) years; 86.9% – females) including medical laboratory technicians (N = 54) and nurses (N = 152) employed in the Antalya Training and Research Hospital, Antalya, Turkey. Laboratory (N = 53), operating room (N = 41) and in-patient clinic (N = 112) staff were included in this descriptive study. A 33-questionnaire composed of questions related to their level of knowledge and attitudes toward HBV/HCV infections, the sources of their knowledge of HBV/HCV infections and the emphasis given to the national and global importance of the diseases was administered via a face–to-face interview method with each subject; participation was volunteer based. Results: The participants working in the in-patient clinic (18.0 (3.2)) had the highest mean (SD) knowledge level compared to the laboratory (16.4 (3.1), p < 0.05) and operating room (17.0 (2.8), p < 0.05) staff. The participants from the in-patient clinic (44.6%) had a more advanced level of knowledge compared to the participants working in the laboratory (27.8%, p < 0.05) and the operating room (30.0%, p < 0.05). Most of the subjects (60.7%) had education concerning HBV/HCV infections in the past. There was no signifi cant difference between the hospital units in terms of the attitudes of healthcare workers (HCWs) toward HBV/HCV infections and the level of education concerning them. Conclusions: Our fi ndings revealed a moderate level of knowledge in most HCWs, regardless of their exposure to risk. While the highest knowledge scores and vaccination rates were noted among the in-patient clinic staff, there was no signifi cant difference between the hospital units in terms of the attitudes of HCWs towards a patient or a colleague with an HBV/HCV infection.

Highlights from the article: Successful direct-acting antiviral therapy in HIV/HCV co-infected patients fails to restore circulating mucosal-associated invariant T cells Little is known about MAITs frequency or function in HIV/HCV co-infected patients and their fate after HCV elimination by direct-acting antiviral (DAA) therapy. All patients were initially treated with peg-IFN-based anti-HCV treatment: nine of 15 patients (60%) achieved a sustained virologic response (SVR), 6/15 patients (40%) failed to clear HCV infection (nonresponders [NR]). In line with data obtained by Hengst et al. in HCV monoinfected patients, we hereby describe a profoundly depleted circulating MAIT compartment in cART-treated HIV/HCV co-infected patients that is not restored by successful anti-HCV treatment and HCV virus eradication.

Objectives: Hepatitis C virus (HCV) is the major cause of post-transfusion hepatitis infection (PTH). Patients with thalassemia major are at high risk of hepatitis C due to the blood transfusion from donors infected by HCV. The aim of this study was to detect the prevalence of anti-HCV antibodies and risk factors in multitransfused thalassemic patients in Isfahan-Iran to establish more preventive strategies. Methods: This study was conducted to assess the patients with beta-thalassemia in Isfahan hospitals during 1996-2011 for HCV infection. A structured interview questionnaire was developed by the trained researcher to collect the demographic and risk factors. Statistical analysis was done by Chi-square test, Mann-Withney and multiple logistic regressions using SPSS software, version 15. Results: 466 patients with major thalassemia participated in this study. The mean age of patients was 17.46 ± 8.3. Two hundred and seventy (58.3%) and 193 (41.7%) of participants were male and female, respectively. The prevalence of HCV was estimated 8% among thalassemia patients. History of surgery, history of dental procedure, number of units transfused per month, number of transfusion per month and duration of transfusion had significant association with HCV seropositivity in univariate analysis. There were no statistical significant risk factors for HCV seropositivity in multiple logistic regression models. Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

We evaluated the performance of a hepatitis C virus (HCV) antigen/antibody combination test [Murex HCV Antigen/Antibody Combination Test (Murex Ag/Ab test)] by comparing it with the current third-generation HCV antibody enzyme immunoassay (anti-HCV). A total of 403 serum samples were consecutively collected from four patient groups: healthy controls (n=100); HCV-infected patients (HCV group, n=102); Human immunodeficiency virus (HIV)/HCV-infected patients (HIV/HCV group, n=100); and patients with uremia (uremia group, n=101). Performances were evaluated for the Murex Ag/Ab, anti-HCV, and HCV RNA in the HIV/HCV and uremia patient groups. In the HCV group, all 102 samples showed concordant positive and negative results for anti-HCV, Murex Ag/Ab, and HCV RNA tests. In the HIV/HCV group, all 100 samples were positive for both anti-HCV and Murex Ag/Ab tests, whereas 88 patients (88%) were HCV RNA positive. In the uremia group, 14 (69.0%) of the 23 anti-HCV-positive patients were HCV RNA positive, whereas 14 (77.8%) of the 18 Murex Ag/Ab–positive patients were HCV RNA positive. None of anti-HCV-negative or Murex Ag/Ab–negative patients were HCV RNA positive. Based on the HCV RNA assay, the sensitivities for both anti-HCV and Murex Ag/Ab assays were 100%, whereas the specificities of these two assays were 89.7% and 95.4%, respectively. With good sensitivity and specificity, the Murex Ag/Ab assay could be a useful alternative diagnostic tool, especially in immunocompromised populations, such as patients with uremia or those infected with HIV.

A case is reported of a female patient with apical hypertrophic cardiomyopathy with negative chest T waves associated with HCV infection.

We review various existing models of hepatitis C virus (HCV) infection and show that there are inconsistencies between the models and known behaviour of the infection. A new model for HCV infection is proposed, based on various dynamical processes that occur during the infection that are described in the literature. This new model is analysed, and three steady state branches of solutions are found when there is no stem cell generation of hepatocytes. Unusually, the branch of infected solutions that connects the uninfected branch and the pure infection branch can be found analytically and always includes a limit point, subject to a few conditions on the parameters. When the action of stem cells is included, the bifurcation between the pure infection and infected branches unfolds, leaving a single branch of infected solutions. It is shown that this model can generate various viral load profiles that have been described in the literature, which is confirmed by fitting the model to four viral load datasets. Suggestions for possible changes in treatment are made based on the model.

Introduction. Patients with primary antibody deficiency (PAD) can complicate with liver disease. This study was performed in order to study the prevalence and causes of hepatobiliary diseases in Iranian patients with PAD.Material and methods. Sixty-two patients with PAD were followed-up and signs and symptoms of liver disease were recorded. All patients were screened for hepatitis C virus (HCV-RNA) and those patients with any sign of liver disease or gastrointestinal complaints were tested for Cryptosporidium parvum.Results. Clinical evidences of liver disease, including hepatomegaly, were documented in 22 patients (35.5%). Eight patients (13%) had clinical and/or laboratory criteria of chronic liver disease. Only one patient was HCV-RNA positive; he had stigmata of chronic liver disease and pathologic evidence of chronic active hepatitis with cirrhosis. Cryptosporidium parvum test was positive for one patient with hyper-IgM syndrome. In liver biopsy of patients with liver involvement, one had histological findings related to sclerosing cholangitis, and five had mild to moderate chronic active hepatitis with unknown reason.Conclusions. Chronic active hepatitis is the most common pathologic feature of liver injury in Iranian patients with PAD. Liver disease in PAD usually accompanies with other organ involvements and could increase the mortality of PAD. Whether this high rate of liver disease with unknown origin (75%) is the result of an unidentified hepatotropic virus or other mechanisms such as autoimmunity, is currently difficult to understand.

Viral infections contribute greatly to the high global burden of chronic kidney disease (CKD) especially in parts of the world where the prevalence of glomerulonephritis is high. These infections pose special challenges in the management of patients throughout the spectrum of chronic kidney disease. Hepatitis C virus infection in patients with chronic kidney disease could be coincidental or be responsible for the CKD. The observance of universal principle against transmission of blood borne infections remain the single most effective tool to stop the tide of increasing HCV infections in CKD patients. Combination therapy using nucleoside analogue, ribavarin and interferons offers the only real chance of treating HCV infected patients.

Introduction: Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy., Methods: This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs)., Results: The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI., Conclusions: Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI., (Copyright © 2022 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. Frequency of HCV infection was studied in 785 referred patients to a private Laboratory, Tehran, Iran from April 2003 until March 2006 by PCR method. Analyzed results revealed infection rate was 40.27%, 35.51% and 33.09% in the first, second and third year, respectively. Frequency rate of the infection shows a fluctuated shape during months of three years. Maximum rate of the HCV infection was in May of the first and in June of the second and third year, respectively. It shows decrease and increase within rest months in each year. HCV infection rate was higher in 31 to 40 years old group of patients. Analysis of the data revealed higher HCV infection in men than women had. It was concluded that HCV frequency pattern underlines specific attention to suspected patients during high rate time.

Background:  Chronic inflammation, as defined by persistent immune activation, is associated with adverse clinical outcomes. People who inject drugs (PWID) have evidence of persistent immune activation. Here, in a cohort of PWID with or without hepatitis C virus (HCV) infection, we sought to dissect out the contribution of chronic HCV infection (common in PWID) from the effects of injection drug use itself.Methods:  Four groups of study volunteers were recruited: group 1 comprised active PWID; group 2, individuals who ceased injecting drugs 1-2 months before recruitment; group 3, individuals who ceased injecting drugs 3-4 months before recruitment; and group 4, healthy volunteers. Soluble and cell-associated markers of immune activation were quantified.Results:  HCV-viremic PWID have elevated levels of immune activation when compared to healthy volunteers. Cessation of injection drug use results in a decline in immune activation in the absence of HCV viremia, while HCV-viremic individuals who previously were PWID continue to harbor elevated levels of immune activation, as defined by increased levels of soluble CD14 and tumor necrosis factor α and by the presence of CD38+HLA-DR+ CD4+ and CD8+ T cells.Conclusions:  Immune activation, a well-defined surrogate of poor clinical outcome that is elevated in PWID, can regress to normal levels in former injection drug users who are HCV aviremic. Therefore, enhanced harm-reduction efforts should incorporate aggressive treatment of HCV infection.Clinical Trials Registration:  NCT01831284. [ABSTRACT FROM AUTHOR]

Aims To evaluate whether CB2 variants are associated with the presence of immune-mediated disorders (IMDs) in patients with chronic HCV infection. Methods One hundred and sixty-eight anti-HCV/HCV-RNA-positive patients were enrolled, 81 with signs of IMDs and 87 without. In the IMDs group, 22 (27.2%) showed ANA positivity (titers ≥1:160), 3 (3.7%) SMA positivity (titers ≥1:160), 24 (29.6%) had cryoglobulinemia, 25 (30.9%) autoimmune thyroiditis, 4 (4.9%) psoriasis, 2 (2.5%) B-cell non-Hodgkin lymphoma and 1 (1.2%) autoimmune hemolytic anemia. All patients were screened for the CNR2 rs35761398 single nucleotide polymorphism using a TaqMan Assay. Results Compared with the 87 patients without IMDs, the 81 with IMDs were more frequently females (65% vs. 45%, p = 0.01), but no significant difference was found in the initial demographic, epidemiological, serological, biochemical or virological data. Instead, the prevalence of patients with the CB2-63 RR variant was significantly higher in the IMD than in the non-IMD group (49.4% vs. 24.1%, p = 0.001). A logistic regression analysis including the CB2-63 receptor (RR vs. QR or QQ), age and sex identified the CB2-63 RR as the only independent predictor of IMDs ( p = 0.005). Conclusions The data suggest a significant, previously unknown, independent association between the CB2-63 RR variant and IMDs in anti-HCV-positive patients. The study was approved by the Ethics Committee of the Azienda Ospedaliera Universitaria of the Second University of Naples (n° 214/2012). [ABSTRACT FROM AUTHOR]

As part of an ongoing effort in NS5A inhibition at Merck we now describe our efforts for introducing substitution around the tetracyclic indole core of MK-8742. Fluoro substitution on the core combined with the fluoro substitutions on the proline ring improved the potency against GT1a Y93H significantly. However, no improvement on GT2b potency was achieved. Limiting the fluoro substitution to C-1 of the tetracyclic indole core had a positive impact on the potency against the resistance associated variants, such as GT1a Y93H and GT2b, and the PK profile as well. Compounds, such as 62 , with reduced potency shifts between wild type GT1a to GT2b, GT1a Y93H, and GT1a L31V were identified. [ABSTRACT FROM AUTHOR]

This review summarizes the crucial epidemiological data concerning the hepatitis virus C (HCV) infection forming the basis of screening strategies in countries throughout the world. Analysis of the situation in the Czech Republic shows why the currently applied strategy is founded in the knowledge of risk of HCV exposure. The role of primary care physicians and specialists in the screening for HCV infections is discussed in detail. [ABSTRACT FROM AUTHOR]

Cryoglobulinaemia should be taken into consideration as a cause of vertigo. It is the timing of shrewd. An 82-year old man, suffering from peripheral vertigo is evaluated thoroughly. After a long, detailed evaluation the result is cryoglobulinaemia related vertigo. The presence in the serum of one or more immunoglobulins, which precipitate at a temperature below 37-Celsius degrees and redissolve on reheating is called cryoglobulinaemia. Cryoglobulinaemia seems to be responsible for audiovestibular damage probably through an immunologic mechanism. ln recent years the audio vestibular manifestations of immun-mediated diseases have been the issue of numerous reports. But there were a few reports about cryoglobulinaemia- related audiovestibular disturbances. The aim of this article is to remind the vestibular manifestations of cryoglobulinaemia; a kind of systemic vasculitis. [ABSTRACT FROM AUTHOR]

Background The advent of new HCV drugs has generated widespread economic concerns, particularly within the Italian setting, characterized by continuous linear cuts and spending review actions. The overall trade-off between investments and savings needs an in depth analysis. Aims The study aimed to estimate the budget impact of the introduction of the novel drugs approved during the year 2015, compared with the historical situation based on the different treatment options available prior to 2015. Methods A three-year budget impact model was developed, taking into consideration the Lombardy Region (Northern Italy) Health Service perspective. The degree of liver fibrosis, genotypes, presence of only HCV or HIV/HCV co-infections, presence or absence of sustained virological response, and direct healthcare total costs were the variables of the model. Results With the introduction of the novel regimens, a higher number of HCV patients achieved a sustained virological response (+20%). Further analysis showed that an investment in innovative technologies would have given the Regional System significant economic savings within the 36-month period (−6.64%/−7.15%). Conclusions Treating HCV-infected persons in the Lombardy Region with the new drugs would reduce healthcare expenditure on this specific disease, in each forecast implemented, thus reducing the economic burden of the pathology. [ABSTRACT FROM AUTHOR]

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 majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100-fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi-species) pre-existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment-induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA-experienced patients. J. Med. Virol. 88:1659-1671, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) has a growing incidence and studies regarding the risk factors or pathogenesis for this type of carcinoma benefit special interest. This study evaluates the correlations between p53 protein expression and clinical and laboratory factors in patients with HCC. Methods: The study group included 76 patients diagnosed with HCC, either by biopsy or after surgical resection (with curative intent). Immunohistochemistry for p53 protein assessment was performed in all patients. Correlations between the protein 53 expression and age, tumour size, viral infection, liver cirrhosis were performed using the chi-square test (Pearson's chi-square) together with the contingency coefficient Kendall's coefficient in the tau-b form. Results: In the study group, 51 patients were male (67%) and 25 female (33%). Cirrhosis due to hepatitis virus B or C infection (in a proportion of 63% of the study group) was not significantly associated with the presence of HCC. Altered expression of p53 protein was observed in 69 patients (91%). The relationship between p53 protein expression and patient sex (p=0.067), age (p=0.531), tumour size (p=0.270), presence of hepatitis B and C viral infections (p=0.7), and of liver cirrhosis (p=0.511) was not statistically significant. Conclusion: The p53 protein expression was not significantly associated with the demographic characteristics of the patients, tumour size, presence of viral B and C infections or liver cirrhosis. [ABSTRACT FROM AUTHOR]

A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology. [ABSTRACT FROM AUTHOR]

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti-hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti-HCV activity was determined in infected Huh7.5 cells using quantitative real-time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti-HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 μM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck’s effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure. [ABSTRACT FROM AUTHOR]

Herein we describe our research efforts around the aryl and heteroaryl substitutions at the aminal carbon of the tetracyclic indole-based HCV NS5A inhibitor MK-8742. A series of potent NS5A inhibitors are described, such as compounds 45 – 47 , 54 , 56 , and 65 , which showed improved potency against clinically relevant and resistance associated HCV variants. The improved potency profiles of these compounds demonstrated an SAR that can improve the potency against GT2b, GT1a Y93H, and GT1a L31V altogether, which was unprecedented in our previous efforts in NS5A inhibition. [ABSTRACT FROM AUTHOR]

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%). Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma worldwide. 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 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. [ABSTRACT FROM AUTHOR]