Hepatitis C Virus Infected Individuals Research Articles

Rate of hepatitis C reinfection after successful direct-acting antivirals treatment among people who inject drugs in Spain: the LIVERate study.

Hepatitis C virus (HCV) reinfection following successful treatment threatens the achievement of HCV elimination. The primary aim of this study is to assess reinfection rate three years after sustained virologic response (SVR) in people who inject drugs (PWID) that are on opioid agonist treatment (OAT) who underwent anti-HCV treatment with interferon-free regimens. Observational, non-interventional, prospective, descriptive study carried out in Spanish tertiary public hospitals between 2017 and 2022. Participants comprised 186 adult HCV infected individuals, 85.5% males with a mean age (Standard Deviation, SD) of 50.1 (5.9). All were enrolled in an OAT program at baseline and had attained SVR 12 weeks after therapy completion with an interferon-free treatment. Baseline data were abstracted from medical chart information collected through the routine clinical practice. The overall rate of HCV reinfection three years after SVR12 among PWID was 1.2 new cases per 100 person-years of follow-up at a median of 15.9 months. In the subgroup analyses, those with injection drug practice and without a stable housing had higher reinfection rates. Although PWID in OAT present a low rate of reinfection by HCV after successful treatment, a closer monitoring in the first year and strengthening inter-consultations with services responsible for monitoring addiction in these patients will be crucial to reduce risky behaviors avoiding HCV reinfection.

Evaluation of Thyroid Hormones in Chronic Hepatitis C Patients on Oral Antiviral Therapy

Background: Hepatitis C virus (HCV) is a major cause of morbidity and mortality. About 71 million people around the world are chronically infected with HCV, however, in Pakistan, approximately 12 million people are suffering from this dreadful virus. In Pakistan, approximately 6.2 % of population is infected with HCV and its treatment rate is approximately 1 %. The aim of this research was to assess thyroid hormones level in chronic HCV patients which were taking the oral-antiviral therapy. Methods: A total of 1650 suspects were screened by immunochromatographic technique. Then ELISA technique were used to confirmed the sample and PCR were also performed. All data were analyzed through Microsoft Excel and SPSS-21. Results: Out of total ICT positive, 117 patients were positive for HCV. Subsequently, all positive samples were exposed to Enzyme linked Immunosorbant assay, out of 117 tested samples 112 (6.7 %) were found positive. However, the final confirmation was done by using Real Time PCR, which showed 109 (6.6 %) patients positive for HCV. Among these 109 HCV patients, the age-wise prevalence of HCV patients was observed maximum 35 (32 %) in age group (55-74 years). Furthermore, these 109 patients were tested for the thyroid dysfunction, before and after anti-viral therapy (Sofosbuvir and Daclatasvir therapy) which was recommended by World Health Organization. Out of 109 HCV positive patients the frequency, 92 (84.6 %) showed euthyroidism, 6 (5.5 %) hypothyroidism and 11 (10 %) hyperthyroidism. Thyroid dysfunction was high (n=17, 15.6 %) in patients with age above 50 years. Six (35.2 %) of thyroid dysfunction patients revealed hypothyroidism and hyperthyroidism was observed in 11 (64.7 %) patients. Mean values of thyroid function test before antiviral therapy were TSH = 3.88 ± 1.0, TT3 = 1.15 ± 0.58, and TT4 = 7.7 ± 01.99 and mean values after three months therapy were TSH = 2.49±1.72, TT3 =1.38 ± 0.69 and TT4 = 8.78 ± 2.29. Conclusion: It is concluded that HCV infected individuals on oral antiviral drugs have an effect on the thyroid gland, therefore, HCV patients should be frequently screened for thyroid disorders before and after treatment to ensure euthyroid status. Keywords: Thyroid hormones, Hepatitis, Oral Anti-viral therapy, Thyroidism

Transient elastography score is elevated during rheumatoid factor-positive chronic hepatitis C virus infection and rheumatoid factor decline is highly variable over the course of direct-acting antiviral therapy.

BackgroundElevated rheumatoid factor (RF) levels and systemic immune activation are highly prevalent during chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) therapy has been associated with normalization of various soluble immune activation parameters. Whether the RF levels relate to soluble immune activation markers during chronic HCV infection, and over what time frame RF levels normalize during and after DAA treatment is unknown and was investigated here.MethodsIn a longitudinal study, plasma and serum was obtained from HCV infected RF positive (RF+) and RF negative (RF-) participants. The levels of RF, HCV RNA and soluble markers of inflammation were determined before (week 0), during (weeks 4, 8 and 12) and after (week 24) treatment with HCV DAA therapy. In a subset of RF+ participants, the analysis was extended to over 70 weeks after therapy initiation. Hepatic and other clinical parameters were determined at baseline (week 0) in all participants.ResultsBefore therapy, transient elastography (TE) score was greater in RF+ compared to RF- HCV infected participants, while the systemic levels of soluble inflammatory markers were comparable. Following DAA therapy initiation, HCV RNA levels became undetectable within 4 weeks in both the RF+ and RF- groups. RF levels declined in the first 6 months in most RF+ persons but most commonly remained positive. The levels of some soluble inflammatory markers declined, mainly within 4 weeks of DAA therapy start, in both the RF+ and RF- groups. The baseline (week 0) TE score correlated with RF levels before, during and after DAA therapy, while plasma IL-18 levels correlated with RF level after DAA therapy.ConclusionDuring chronic HCV infection, TE score is elevated in RF+ HCV infected individuals and factors other than HCV viremia (including liver stiffness or fibrosis and select markers of inflammation) likely contribute to persistence of RF after treatment of HCV with DAA.

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

Introduction:Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings.Methods:In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry.Results:Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55–3.51), HBV (HR 2.47; 95% CI 1.85–3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47–3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01–3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39–5.71), and HCV/HBV co-infection.Discussion/Conclusion:Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.

A protracted war of human beings against virus: Interpreting for the Nobel Prize in Physiology or Medicine in 2020

On 5th October of 2020, the Nobel committee announced in the Karolinska Institute that the 2020 Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice to commend their contribution in the aspect of discovering hepatitis C virus (HCV). Alter and his team acquired C100-3 protein by utilizing recombinant yeast to express viral sequence segments and found the HCV antibody by performing radioimmunoassay. Houghton and his colleagues successfully created the cDNA library from the serum of non-A and non-B hepatitis patients in bacteriophage. Subsequently, the large-scale blind screening method was performed in the serum of patients, acquired clone 81 from the library screening as the clone 5-1-1 involving short sequences to be the probe, and confirmed HCV ultimately. In 1995, Rice and his collaborators completed the full-length HCV genome sequencing from the 3′ terminal sequence using a quantitatively competitive reverse transcription PCR method and verified the full-length sequence has infectivity. This is the first causative agent entirely discovered by molecular biological techniques in human being’s history. Furthermore, Wakita with his team, acquired a full-length HCV genome from acute HCV patients and transformed viral RNA to Hun-7 cell to generate HCV virion in 2005. On this basis, Rice and his team successfully established the cell-cultured system that can effectively generate HCV with infectivity. According to the WHO latest data, there were approximately 71 million chronic HCV cases and nearly 400000 deaths globally in 2016. About 14% of the total HCV infected individuals worldwide lived in China. As a common infectious pathogen globally, HCV infection may cause severe threats and damages to human health, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The high genetic variation is major characteristics of HCV, which has phylogenetically generated more than 7 genotypes and hundreds of subtypes. The various genotypes and subtypes have distinct geographic distribution and different responses on anti-virus treatment. The resistant mutation for the clinical using drugs including Epclusa (Sofosbuvir and Velpatasvir), is occurring. Moreover, the highly chronic progression render HCV as a silent slayer for human health, and plenty of HCV cases were difficult to be timely diagnosed due to its high proportion of asymptomatic. All these indicated that HCV prevention and control are still facing severe challenges.

Reticulon-3 modulates the incorporation of replication competent hepatitis C virus molecules for release inside infectious exosomes.

BackgroundCell released microvesicles specifically, exosomes, play an important role in mediating immunologic escape, treatment resistance, and disease persistence of Hepatitis C virus (HCV) infection. Reports on the molecular compositions of exosomes released by cells under diverse conditions, especially during viral infections, suggest that their cargo contents are not randomly loaded. However, the precise molecular mechanisms directing the selective cargo sorting and loading inside infectious viral exosomes remains elusive.AimTo decipher the role of Reticulon 3 (RTN3) in the selective molecular cargo sorting and loading inside infectious viral exosomes during HCV infection.MethodsWe used Huh7 cells–JFH1 HCV infection and HCV Full-Length (FL) replicon systems. Additionally, we analyzed human liver and serum exosome samples from healthy and treatment naïve HCV infected individuals. Our experiments made use of molecular biology and immunology techniques.ResultsHCV infection (JFH1-Huh7 or HCV-FL replicon cells) was associated with increased RTN3L&S isoforms expression in cells and cell released exosomes. Accordingly, increased expression of RTN3L&S was observed in liver and serum exosome samples of HCV infected individuals compared to healthy controls. RNA-ChIP analysis revealed that RTN3L&S interacted with dsHCV RNA. Lentiviral CRISPR/Cas9 mediated knockdown (KD) of RTN3 and plasmid overexpression (OE) of wild type, C- and N-terminal deletion mutants of RTN3L&S in HCV- infected Huh7 cells differentially impacted the cellular release of infectious viral exosomes. RTN3L&S KD significantly decreased, while RTN3S OE significantly increased the number of Huh7 cell-released infectious exosomes. The C-terminal domain of RTN3 interacted with and modulated the loading of dsHCV RNA inside infectious exosomes. Antiviral treatment of HCV infected Huh7 cells reduced virus-induced RTN3L&S expression and attenuated the release of infectious exosomes.ConclusionRTN3 constitutes a novel regulator and a potential therapeutic target that mediates the specific loading of infectious viral exosomes.

Determination of Ankyrin Repeats Domain (ANK) a of RNASE L Gene in Hepatitis C Patients and its effects on Viral Load

Background: Hepatitis C virus (HCV) is one of the major global causes of death. Different types of gene are involved as Ankyrin repeat domains of RNASE L gene. It performs a significant role in antiviral response, regulated by interferon, and involved in cleavage of RNA. Therefore, aim of this study was to identify Ankyrin repeat domain expression in Hepatitis C positive patients and correlate it with viral load of Hepatitis C. Methods: In this study, a total of 80 HCV positive patient’s whole blood samples were investigated. RNA was extracted from plasma followed by Real Time PCR for quantization of HCV viral load and genotypic analyses. DNA was also extracted from these samples followed by PCR amplification of Ankyrin repeat domain of RNASE L gene. Data was analyzed using SPSS Results: All of the patients (n=80) included in study had HCV infection. Mean age of patients was 50.86 ±14.84 years. Among them, 48(63.8%) were males and 32 (36.1%) were females. Majority of patients were males and belonged to age group 58-73 years age. All HCV infected individuals 36 (45%) had HCV genotype 3 and had viral loads mean range 837404.21 ±1302. Therefore, Ankyrin repeats domain of RNASE L gene expression was high in HCV patients sample with viral load of 17.00±15.1. Conclusion: Ankyrin repeat domain expression was observed in Hepatitis C patients and its significant correlation with viral load of Hepatitis C. Ankyrin repeat domain of RNASE L gene in conjunction with therapeutic intervention are required for establishing better strategies for controlling HCV infection.

Impact of reimbursement limits on patient access to direct-acting antivirals in Italy: analysis of data from national registries.

Hepatitis C virus (HCV) infection is a global epidemic, still highly prevalent in Europe. Given efficacy and safety of HCV therapy by Direct Antiviral Agents (DAA), World Health Organization called for actions to eliminate HCV infection. A limit is represented by access to care, mostly due to the high costs of medicines. In Italy, in 2015, the access to DAA therapy was reimbursed for patients with advanced disease, whereas in 2017 universal access was granted. The aim of this study was to analyse changes in patient recruitment trends treated with DAA with or without limitations to access to therapy. 165,105 patients treated with DAA in Italy from 2015 to December 2018 were analysed. Daily patient treatment rate was obtained by segmented regression of interrupted time series analysis. 74,199 patients with advanced disease (62% with cirrhosis) had access to the therapy during the time period from 2015 to 2017. Following the extension of reimbursement criteria, 90,906 additional patients were treated (43.2% with F0-F1 and 22.9% with F2), with an absolute reduction of 59.9% of patients with advanced disease (cirrhosis decreased to 18.5%). Segmented regression of interrupted time series analysis of daily patient treatment rate showed a progressive reduction of patients with advanced disease, offset by those with initial disease. Notably, elimination of restrictions to therapy did not change the overall treatment rate. This study showed that a no-limit reimbursement policy for DAAs prescriptions to HCV infected individuals in Italy widened the types of treated patients, but the process towards elimination of HCV infection was not significantly changed.

Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV)

BackgroundA large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial.MethodsINTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID.DiscussionThis study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up.Trial registrationClinicalTrials.gov.no. NCT03155906.

Association of HLA‐DQB1*03:01 and DRB1*11:01 with spontaneous clearance of hepatitis C virus in Chinese Li ethnicity, an ethnic group genetically distinct from Chinese Han ethnicity and infected with unique HCV subtype

Specific human leukocyte antigen (HLA) class I and class II alleles have been associated with spontaneous clearance or persistent infection of hepatitis C virus (HCV), which seemed to be restricted by the host's ethnicity and viral genotype. Recently we reported a high prevalence and spontaneous clearance rate of HCV in a cohort of Chinese Li ethnicity who were infected with new variants of HCV genotype 6. In this study, we found that the distribution of HLA class I and class II alleles in HCV infected individuals of Chinese Li ethnicity (n = 143) was distinct from that of Chinese Han ethnicity which was reported in our previous study. HLA-DRB1*11:01 and DQB1*03:01 were more prevalent in Chinese Li subjects who cleared HCV spontaneously than those who were chronically infected (P = .036 and P = .024, respectively), which were consistent with our previous report regarding the Chinese Han population. Multivariate logistic regression analysis showed that DQB1*03:01 (odds ratio = 3.899, P = .017), but not DRB1*11:01, associated with HCV spontaneous clearance, independent of age, sex, and IFNL3 genotype. Because DQB1*03:01 and DRB1*11:01 were tightly linked because of linkage disequilibrium, our results clearly supported the associations of these two alleles with HCV spontaneous clearance in Chinese Li as well as Han ethnicity.

Molecular Detection of Interleukin 28B Gene rs8099917 Polymorphism in chronic HCV Patients from Khartoum State, Sudan

Background: Hepatitis C virus (HCV) infection represents a major health burden According to the world health organization (WHO) there are more than 170 million people infected worldwide and 3-4 million new infections are estimated per year. Recent studies have demonstrated the role of interleukin B 28(IL B 28) polymorphism in predicting the treatment induced and spontaneous clearance from hepatitis C virus (HCV) infection and genome-wide association studies have shown that single nucleotide polymorphism (SNPs) near interleukin 28B gene are good predictors of response to treatment. The present study aimed to isolate and identify IL 28 B gene rs8099917 polymorphism from HCV infected individuals DNA. Methods: This cross-sectional study was performed on 50 blood samples from patients with chronic HCV infection as detected by ELISA kit (RIBA-11 and c-200/c-22 ELISA Company and country). DNA was extracted from the samples and the frequency of the polymorphism was analyzed by using PCR-RFLP method. Results: The analysis of the data for G/T polymorphism showed that GT heterozygous was found in 14(28%) patients (10 males, 4 females), and TT homozygote was detected in 36(72%) patients (26 males, 10 females) and no GG homozygous genotype was detected. Conclusion: In this study investigation of rs8099917 (T/G) Polymorphism in interleukin 28B gene (IL28B) in 50 HCV positive patients from Khartoum State indicated that the TT genotype was the dominant genotype detected.

Quasispecies Changes with Distinctive Point Mutations in the Hepatitis C Virus Internal Ribosome Entry Site (IRES) Derived from PBMCs and Plasma.

The 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome contains the internal ribosome entry site (IRES), a highly conserved RNA structure essential for cap-independent translation of the viral polyprotein. HCV, apart from the liver, is thought to be associated with lymphocyte subpopulations of peripheral blood mononuclear cells (PBMCs), in lymph nodes and brain tissue. In this study, RT-PCR, cloning, and sequence analysis were employed to investigate the quasispecies nature of the 5'UTR following extraction of viral RNA from PBMCs and plasma of HCV infected individuals. The nucleotide variation between IRES-derived sequences from PBMCs and plasma indicated the existence of polymorphic sites within the IRES. HCV isolates had divergent variants with unique mutations particularly at positions 107, 204, and 243 of the IRES. Most of the PBMC-derived sequences contained an A-A-A variant at these positions. The mutations associated with the IRESes suggested the presence of unique quasispecies populations in PBMCs compared with plasma.

Reduced Incidence and Better Liver Disease Outcomes among Chronic HCV Infected Patients Who Consume Cannabis.

Background and Aim The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals. Methods We analyzed hospital discharge records of adults (age ≥ 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to nonusers on 1:1 ratio (4,728:4,728), using a propensity-based matching system, with a stringent algorithm. We then used conditional regression models with generalized estimating equations to measure the adjusted prevalence rate ratio (aPRR) for having liver cirrhosis (and its complications), carcinoma, mortality, discharge disposition, and the adjusted mean ratio (aMR) of total hospital cost and length of stay (LOS) [SAS 9.4]. Results Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis (aPRR: 0.81[0.72-0.91]), unfavorable discharge disposition (0.87[0.78-0.96]), and lower total health care cost ($39,642[36,220-43,387] versus $45,566[$42,244-$49,150]), compared to noncannabis users (NCUs). However, there was no difference among CUs and NCUs on the incidence of liver carcinoma (0.79[0.55-1.13]), in-hospital mortality (0.84[0.60-1.17]), and LOS (5.58[5.10-6.09] versus 5.66[5.25-6.01]). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use (0.62[0.41-0.93]). Conclusions Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.

Development of an in vitro model to study hepatitis C virus effects on hepatocellular lipotoxicity and lipid metabolism

Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). Particularly in patients infected with non-genotype 3 HCV, hepatic steatosis is closely related to factors of the metabolic syndrome such as hyperlipidemia. However, the molecular mechanisms involved in this “metabolic” steatosis in non-3 genotype HCV infections are not well understood. Here, we aimed to develop an in vitro model to study the effect of genotype 1 HCV infection on hepatic lipotoxicity and lipid metabolism. Cellular lipid accumulation was induced in Huh-7 hepatoma cells transfected with HCV genotype 1b replicon (HCV+) by incubation with increasing doses of palmitic acid (C16:0) or oleic acid (C18:1 n-9) complexed to albumin mimicking hyperlipidemic conditions. Mock transfected hepatoma cells (HCV−) were used as controls. Incubation with oleic acid concentrations as high as 0.5 mM did not induce toxic effects in HCV+ or HCV− cells. In contrast, incubation with palmitic acid caused dose-dependently cytotoxic effects which were more pronounced in HCV+ compared to HCV− cells. Further analysis with subtoxic palmitic and oleic acid concentrations revealed a higher uptake of fatty acids and intracellular triglyceride accumulation in HCV+ compared to HCV− cells. Carnitine palmitoyltransferase I (CPT1) expression, indicative of mitochondrial beta-oxidation, was markedly stimulated by lipid exposure in HCV+ but not in HCV− cells. Furthermore, heme oxygenase 1 (HMOX1) expression levels increased in FA stimulated cells, and this increase was significantly higher in HCV+ compared to HCV− cells. In contrast, expression of the key enzymes of hepatic de novo lipogenesis fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD-1) was significantly reduced upon oleate exposure in HCV− but not in HCV+ cells.In summary, our newly developed cell culture model revealed effects of HCV genotype 1b infection on metabolic susceptibility to lipid accumulation and toxicity particularly to saturated lipids. These results may indicate that HCV (genotype 1b) infected individuals with hyperlipidemia may benefit from dietary or pharmacological intervention.

Comparison of IL-28B favorable genotype frequency between healthy and patients infected with HCV

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared. Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test. Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV. Discussion & Conclusion: Our investigation came to the conclusion that a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HCV

Rheumatology to hepatology cross talk: An evidence based update on the treat to target strategy in hepatitis-C related extrahepatic autoimmune syndromes

Hepatitis C virus (HCV) is a universally identified major epidemiological health problem with an estimated reservoir of almost 200 million or 3% of the global population. In the year 2013, the WHO declared viral hepatitis as “a leading cause of death worldwide 1.46 million deaths, a toll higher than that from HIV, tuberculosis or malaria, and on the increase since 1990” with more than 90% of these deaths being related to the sequelae of the infection with either forms of hepatitis viruses (HBV-HCV). HCV is classically a hepatotropic virus with the liver cells providing the primary bed for viral replication with clinical evidences supporting an additionally significant viral lymphotropism. HCV is a linear single stranded RNA retrovirus, member of the genus hepacivirus of the flaviviridae family. It is a small virus comprised of a positive-sense 9.6 Kb single-stranded RNA genome embodied in a double layered glycosylated protein envelope, the viral genome protein is basically made up of structural and non-structural proteins. The viral enzymes- NS2-3 and NS3-4A proteases, NS3 helicase and NS5BRdRp— are essential contributors for HCV replication, the HCV serine protease NS3, and its cofactor NS4A, constitute a complex that directs polyprotein cleavage. HCV infected individuals are capable of producing 10-13 trillion virions/day with the majority coming primarily from viral replication within the hepatocytes with an unpredictable yet significant extrahepatic contributions that may lead to the development and modulation of systemic extrahepatic disease. The use of conventional antiviral therapy PEGylated interferon (Peg-IFN) and ribavirin (RBV) practically contributed to the disease burden with less than a 50% sustained viral response rates. A major challenge for interferon therapy comes from the Hepatitis C viral genome itself. The challenging draw backs to interferon based regimen in patients with autoimmune extrahepatic disease EHD demanded an evidence based revisit to the classic recommendations on the use of conventional antivirals with immunomodulatory drugs in this indication. It wasn’t until spring of 2011 when the FDA approved the first two directly acting antiviral drugs that the hepatologists experienced a revolutionary shift in Hepatitis C virus (HCV) treatment paradigm. Directly acting antiviral drugs (DAAs are drugs that target some of the main molecular components of HCV, including NS3/4A protease (first and second generation protease inhibitors), NS5B polymerase (nucleoside and non-nucleoside analogs) and NS5A protein. The recent era of DAAs established an additional need to modify treatment regimens in extrahepatic disease. In the year 2017 the international study group of HCV extrahepatic disease published evidence based recommendations on the use of antivirals for control of EHD. The treatment armamentarium in chronic HCV viremia with and without extrahepatic disease has experienced a revolution with the establishment of directly acting antiviral drugs. Interferon free directly acting antiviral drug regimens are currently considered as standard of care in patients with extrahepatic disease. Longitudinal studies are further requested to assess the unmet needs including drugs addressing other potential targets in the viral genome and life cycle.

Sofosbuvir/Velpatasvir for the treatment of Hepatitis C Virus infection.

Hepatitis C Virus (HCV) infection is major health problem worldwide, with 150 million infected people according to recent epidemiologic estimations. The introduction of direct-acting antivirals made a revolutionary change in the management of HCV infected patients with surprisingly high rates of antiviral response, improved tolerability and reduced time of treatment. Sofosbuvir, in combination with different partner drugs, has been the molecule that led this incredible change. The last generation of SOF-based regimens, namely Sofosbuvir/Velpatasvir, represents a single tablet, once a day, pangenotypic and pan-fibrotic combination, demonstrated to be safe and effective in almost all type of HCV infected individuals. This review overviews the main clinical data of SOF/VEL registration trials, underlying the key features of this combination in terms of efficacy, safety and Patients Reported Outcomes obtained in more than 1800 HCV chronically infected subjects. (www.actabiomedica.it)

Association of TNF-alpha (−308 A/G) and IFN-gamma (+874 A/T) gene polymorphisms in response to spontaneous and treatment induced viral clearance in HCV infected multitransfused thalassemic patients

BackgroundMultitransfused thalassemic individuals are at high risk of developing transfusion transmitted Hepatitis C virus (HCV) infection. The aim of the study was to correlate the effects of host cytokine single nucleotide polymorphisms of TNF-α (-308 A/G) and IFN-γ (+874 A/T) in spontaneous or IFN induced treatment response in the HCV infected thalassemic individuals. MethodsA total of 427 HCV sero-reactive thalassemic individuals were processed for HCV viral genomic diversity and host gene polymorphisms analysis of TNF-α (-308 A/G) and IFN-γ (+874 A/T). ResultsOut of 427 HCV sero-reactive individuals, 69.09% were found to be HCV RNA positive with genotype 3 as the predominant infecting strain (94.29%). Study highlighted that, A allele was significantly associated with (p < .05) spontaneous clearance of HCV infection and G allele was correlated with viral persistence at TNF-α (−308) gene polymorphism. Whereas in case of IFN-γ (+874) SNPs, A allele was significantly responsible (p < .05) for spontaneous clearance than T allele. Our study also indicated that in relapsed cases, IFN-γ (+874) T allele is more responsible than A allele. Though no significant correlation was found at both TNF-α (−308) and IFN-γ (+874) gene polymorphism among SVR and relapsed thalassemic patients. ConclusionA allele at both TNF-α (−308) and IFN-γ (+874) were strongly associated with spontaneous clearance among this population. But in case of SVR and relapsed cases no significant association was found. This cytokine gene polymorphisms pattern will help clinicians to take an informed decision about therapeutic management of HCV infected thalassemic individuals.

Cytomegalovirus-Driven Adaptive-Like Natural Killer Cell Expansions Are Unaffected by Concurrent Chronic Hepatitis Virus Infections.

Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C+ NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection. In sizeable cohorts of CMV seropositive hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infected patients, we analyzed NK cells for expression of NKG2A, NKG2C, CD57, and inhibitory KIRs to assess the appearance of NK cell expansions characteristic of what has been seen in CMV seropositive healthy individuals. Adaptive-like NK cell expansions observed in viral hepatitis patients were strongly associated with CMV seropositivity. The number of subjects with these expansions did not differ between CMV seropositive viral hepatitis patients and corresponding healthy controls. Hence, we conclude that adaptive-like NK cell expansions observed in HBV, HCV, and/or HDV infected individuals are not caused by the chronic hepatitis infections per se, but rather are a consequence of underlying CMV infection.

A cross sectional study regarding HCV patients’ knowledge about viral transmission and attitudes regarding toothbrush care

Hepatitis C virus (HCV) is transmitted mainly by parenteral route, although, some studies have pointed the potential of transmission by sharing infected instruments, like toothbrushes. The aim of this study was to investigate the knowledge about viral transmission among HCV infected individuals and attitudes regarding toothbrush care. A cross-sectional study was conducted among 112 HCV-infected individuals from Uberlandia City, Minas Gerais State (Southeast Brazil). Data were collected through a questionnaire containing demographic data and other questions (correct responses were given one point, incorrect and uncertain responses were given zero point) about knowledge of HCV transmission (6 items in total; scores lower than 4 points indicated poor knowledge level and scores equal or higher than 4 indicated good knowledge level); attitudes regarding toothbrush care (7 items; scores 0 to 3 indicated inadequate attitudes, and scores higher than 3 indicated adequate attitudes). The statistical analysis included Chi-square test, Exact Fisher’s test and Maximum Likelihood Estimation (p < 0.05 was considered significant). Out of the 112 questionnaires distributed, 85 (response rate: 75.9%) were included. Most individuals were male (60%), Caucasian (69.4%), aged more than 51 years (51.7%), had attended pre-school (35.1%), and had incomes up to $525.2 per month (49.4%). Fifty four percent of individuals showed good Knowledge level of HCV transmission; 43.5% did not identify HCV transmission through toothbrushes and 80% did not believe in HCV transmission by saliva. A significant association were observed between Knowledge level of HCV and age (p= 0.020); and education level (p= 0.000). Forty-five HCV-infected individuals (64.70%) had adequate attitudes regarding toothbrushes care. Significant associations were observed between toothbrush care level and: age (p= 0.005); education level (p= 0.000); and family income (p= 0.038). HCV-infected individuals showed good knowledge level about main aspects of HCV infection and adequate attitudes regarding toothbrush care.