Hepatitis C Virus Mono Research Articles

Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study.

Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.

MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus–host interaction.Key messagesHCV and HCV/HIV displayed similar plasma-EV size and concentration.EVs- derived miRNA profile was characterized by NGS.37 SDE miRNAs between HCV and HCV/HIV were observed.SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.

Innate immune response in Plasmodium coinfection with HBV and HCV using complement C3, C4, and CD4+ T cells

Study backgroundComplement, CD4+ T cells, and antibodies are immune materials for protection or are expressed for the detection of pathogens. Complements are activated by the classical or alternative pathway complement to cause cell death.Aim and objectiveThis study was designed to evaluate the innate immune response in Plasmodium coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) using complement C3, C4, and CD4+ T cells to provide information for useful directions in the management of malaria and hepatitis B and C.Materials and methodsThe participants recruited for this study include controls who were neither infected with Plasmodium nor hepatitis B and C (n = 50) and Plasmodium-infected participants (n = 50) and hepatitis C-infected participants (n = 30) and hepatitis B-infected participants (n = 30) and Plasmodium coinfected with hepatitis B participants (n = 30) and Plasmodium coinfected with hepatitis C participants (n = 30) aged 19–65 years. Complement C3, C4, CD4+ T cells HCV and HBV were determined in each of the participant by enzyme-linked immunosorbent assay method. Identification of Plasmodium was carried out using the thick and thin film technique using Giemsa and Leishman staining, while test and controls with elevated and normal total bile acids, respectively, were negative to HIV and acid fast bacilli tests were included.ResultsThe results obtained in this study showed a significant decrease in plasma complement C3 in patients with monoinfection of Plasmodium, HCV, HBV, and Plasmodium patients coinfected with HCV and HBV compared with the control (P < 0.005). There was also a significant decrease in plasma complement C4 in Plasmodium patients coinfected with HCV and HBV compared with the control (P < 0.005). The results obtained in Plasmodium patients coinfected with HBV and HCV, and HBV patients coinfected with HCV showed a significant decrease in CD4+ T cells compared with the results obtained in the control (P < 0.005). There was significantly lower plasma complements C3, C4, and blood CD4+ T cells in Plasmodium monoinfected patients than in HBV or HCV monoinfected patients (P < 0.005). There was also a significantly lower plasma complement C4 and CD4+ T cells in Plasmodium patients coinfected with HBV or HCV than patients who were monoinfected with HCV and HBV (P < 0.005).ConclusionThere was significant alterations in the blood complement C3, C4, and CD4+ T cells in response to Plasmodium, HBV, HCV mono- and coinfection which was more influenced by Plasmodium infection.

Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.

Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy. Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation. Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.

Treatment of patients with HIV or hepatitis C by pharmacist clinicians in a patient-centered medical home.

This report describes an innovative pharmacy practice model assisting in the care of patients living with or at risk of acquiring human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV). In the state of New Mexico, pharmacists can obtain prescribing privileges through a Pharmacist Clinician (PhC) license. The license allows PhCs to assess patients, order laboratory/diagnostic tests, prescribe medication, and bill select insurances. PhCs have developed a practice model for patients living with or at risk of HIV and/or HCV at a Level 3 National Committee for Quality Assurance Patient-Centered Medical Home in Albuquerque, New Mexico. In 2015, 5 PhCs, employed part time, were involved with 8 different clinics: (1) HIV Adherence and Complex Care, (2) HIV Transitions of Care, (3) HCV Mono- and Co-Infection, (4) HIV Pre-Exposure Prophylaxis (PrEP), (5) HIV Primary Care and Cardiovascular Risk Reduction, (6) Young Adult Clinic, (7) Perinatal HIV, and (8) Pediatric HIV. In 2015, PhCs at the clinic billed for 774 direct patient encounters. Pharmacists with the PhC license are able to provide high-quality medical care to patients living with or at risk of HIV and/or HCV infections within an interprofessional medical home model.

Effect of Health Insurance on Hepatitis C Sustained Virologic Response Rates to Sofosbuvir-Based Treatment Regimens in a South Florida Community Hospital.

The high cost of direct-acting antiviral–based regimens raises concerns about the outcome of treatment in uninsured patients with chronic hepatitis C virus (HCV) infection. This study assessed the relationship between health insurance status and sustained virologic response (SVR) rates in a community hospital in South Florida. Sofosbuvir-based therapy was initiated in 82 patients, of which 73% were uninsured and 28 (34%) were HIV coinfection. The overall SVR rate for those tested was 98%. The SVR rates were similar between HCV mono- and HCV/HIV coinfected patients (96% versus 100%, P = .204). Uninsured patients, with access to patient assistance programs, had comparable SVR rates to insured patients (100% versus 95%, P = .131). However, there was a trend toward a higher rate of loss to follow-up in uninsured compared to insured patients (25% versus 9%, P = .116). Strategies specific to adherence to treatment for uninsured patients are needed to reduce rates of loss to follow-up.

The Association of PNPLA3, COX-2 and DHCR7 Polymorphisms with Advanced Liver Fibrosis in Patients with HCV Mono- Infection and HCV/HIV Co-Infection

There is increasing evidence that host genetic variations may influence the natural history of chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of PNPLA3 (rs738409), COX-2 (rs689465) and DHCR7 (rs12785878) and advanced liver fibrosis in Thai patients. A total of 220 patients with HCV mono-infection, 200 patients with HCV/HIV co-infection and 200 healthy controls were enrolled. The SNPs were detected by allelic discrimination using real-time PCR with TaqMan probes. Liver stiffness measurement (LSM) was assessed by transient elastography. Our results showed that the distribution of the studied SNPs were not significantly different between the HCV mono- and co-infected groups. The frequencies AG and GG genotypes of rs689465 and GG genotype of rs12785878 were less commonly found in the HCV mono- and co-infected groups compare with healthy controls (P<0.01). Among patients with HCV infection, older age, HIV co-infection, GG genotype of rs738409 and GG genotype of rs689465 were independently associated with advanced liver fibrosis (LSM≥9.5 kPa) in multivariate analysis. Moreover, the percentage of patients with advanced liver fibrosis increased significantly along with the accumulated numbers of these risk genotypes. In conclusion, PNPLA3 (rs738409) and COX-2 (rs689465) polymorphisms were associated with advanced liver fibrosis in patients with HCV mono- and co-infection, suggesting that these variants might play an important role in progressive liver fibrosis in these patients.

UPLC–MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients

Direct-acting antiviral agents (DAAs) represent the major advance in hepatitis C virus (HCV) infection treatment leading to extremely high eradication rates in HCV mono- and HIV/HCV co-infected patients. In this scenery, availability of Therapeutic Drug Monitoring (TDM) is of interest to assess plasma concentrations to prevent either therapeutic failure due to suboptimal medication adherence and drug–drug interactions or avoid adverse events. Aim of this study was to develop and validate an Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC–MS/MS) method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007), and daclatasvir in human plasma.A simple protein precipitation was applied by adding 200 μL acetonitrile with internal standard 6,7-Dimethyl- 2,3-di(2-pyridyl) quinoxaline to 100 μL plasma sample. Drug separation was performed on analytical C-18 Luna Omega column (50 mm × 2.1 mm I.D.) with particle size of 1.6 μm. The mobile phase consisting of water containing 0.1% formic acid and acetonitrile at flow 0.4 mL/min and a gradient run time of 3.5 min. The injection volume was 10 μL. Anti-HCV drugs were detected in positive electrospray ionization mode. The full scan mass spectral analyses of sofosbuvir, GS-331007, daclatasvir and quinaxoline showed protonated molecule ions and transitions m/z: 530.098 → 243.02, 260.93 → 112.94, 739.4 → 339.27 and 313.03 → 77.99 respectively.The linearity of standard curves was excellent (r2 > 0.99), the absolute recovery of anti-HCV drugs ranged between 95 and 98%, and both imprecision and inaccuracy were <15% according to FDA guidelines. The UPLC–MS/MS method was applied to 16 plasma samples of as many HIV/HCV co-infected patients treated with sofosbuvir and daclatasvir. While sofosbuvir was not detectable in all samples, the median plasma concentrations of daclatasvir and GS-331007 were 223.6 ± 319.56 ng/mL and 537.11 ± 242.09 ng/mL, respectively.In conclusion, we describe an UPLC–MS/MS method allowing the simultaneous quantification of sofosbuvir, GS-331007 and daclatasvir in plasma samples. The method was sensitive, specific, robust, and time-saving.

Comparison of HCV viral load and its genotype distributions in HCV mono- and HIV/HCV co-infected illicit drug users

BackgroundBecause of shared modes of transmission, patients with hepatitis C virus (HCV) infection are often co-infected with other types of hepatitis viruses and/or HIV. We studied HCV viral load and its genotype patterns among HCV mono- and HCV/HIV co-infected Illicit Drug Users in Fars province-Iran.MethodsTotally, 580 HCV seropositive IDUs referred to Prof. Alborzi Clinical Microbiology Research Center, Shiraz, Iran, without receiving any anti-HCV treatment, were enrolled. After their HCV infections were reconfirmed by one step rapid diagnostic test, HCV RNA level and HCV genotypes were determined by Taq-man real-time PCR assays. Their HIV serostatus was determined and seropositive patients were excluded from the group.In addition, 104 HIV/HCV co-infected IDUs referred from Shiraz Behavioral Diseases Consultation Center (SBDC) were assessed for HCV RNA level and HCV genotype patterns, as well.ResultsThe overall estimated HIV prevalence was 6.7% (39/580) among HCV seropositive IDUs. Genotype 1, the most prevalent genotype in both groups, was detected in 69% and 49% of co- and mono-infected IDUs, respectively. Median HCV viral load was significantly higher in HIV/HCV co-infected patients, compared with that among HCV mono-infected counterparts.ConclusionsGiven the higher baseline HCV viral load and GT1 attributed to poorer treatments response, HCV treatment must be more considered among HCV/HIV co-infected IDUs, compared to those mono-infected with HCV.

A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort.

ObjectiveHuman Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment.MethodsViral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data.ResultsHIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels.ConclusionOur study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression.

HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.

BackgroundDecreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.MethodsWe measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.ResultsIn acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.ConclusionsThese data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

OCCULT HEPATITIS B VIRUS INFECTION IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION AND HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma is one of the most common cancers worldwide. Primary known risk factors for HCC are Hepatitis C virus (HCV), Hepatitis B virus (HBV) and alcoholic liver disease. There is little information about occult HBV and its relation to HCC in chronic . We aimed to evaluate the prevalence and the possible clinical impact of occult HBV infection in chronic HCV patients with hepatocellular carcinoma. Patient and methods: A total number of 140 patients with hepatocellular carcinoma were examined, 118 patients were included in this study. They had positive HCV-RNA, negative HBsAg and radiological evidence of Hepatocellular carcinoma, previous antiviral therapy or serological evidence of autoimmune hepatitis and were divided into two groups according to their HBc-Ab status: Group (I) 93 patients positive for HBc-Ab (Occult HBV/HCV dual infection), Group (II) 25 patients negative for HBc-Ab (HCV mono infection). The rest of HCC patients were coinfected with HCV and HBV, 8 patients had HBV infection (+ve HBV sAg and –ve HCV Ab) and 4 patients had negative tests for both HCV and HBV were excluded. Results: A statistically significant increase in serum levels of AST, ALT, bilirubin, Alpha-fetoprotein with more cirrhosis, ascites, liver decompensation (according to Child-Turcott-Pugh score) and more hepatic focal lesions and malignant portal vein thrombosis (through radiological diagnosis) in Group (I) as compared to Group (II), while there was no statistically significant difference among Group (I) and Group (II) as regarding PT% or spleen size. Conclusion: Occult HBV infection is extensively common among HCC chronic hepatitis C infected patients and presence of occult HBV infection is associated with more deterioration of liver status. Key words: Occult HBV, chronic HCV, HCC.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients

Background. Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection.Aim. The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness > 9.5 kPa and FIB–4 values > 3.25. The optimal stiffness cut-off according to FIB–4 > 3.25 was evaluated by ROC analysis.Results. No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness > 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79–0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03).Conclusion. Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women. We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry. Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38-0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36-0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07-0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09-0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57-1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56-3.8, p = 0.45) women. African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.

Sustained virologic response and IL28B single-nucleotide polymorphisms in patients with chronic hepatitis C treated with pegylated interferon alfa and ribavirin.

Hepatitis C virus (HCV) infection is a global health problem which can lead to liver cirrhosis or hepatocellular carcinoma in one-fifth of chronically infected patients. The study group consisted of 123 patients: 90 with HCV mono- and 33 with HIV/HCV co-infection, who were treated with pegylated interferon alfa (Peg-IFN-α) and ribavirin. We analyzed selected pretreatment factors: age, sex, HIV/HCV co-infection, grade of inflammation, necrotic changes and fibrosis in histological analysis of liver bioptates, HCV viral load, HCV genotypes, and single nucleotide polymorphisms (SNPs) of IL28B and tried to find out which of them influence sustained virological response (SVR). The IL28B SNP C/T (rs12979860) was analyzed using Custom(®) SNP Genotyping Assays (Applied Biosystems). Multivariate analysis demonstrated that after adjusting for the other variables three predictors independently influence SVR, namely genotype 3 of HCV, presence of the CC genotype and age >40 years (OR respectively 15.14, 3.62, and 0.36). HCV mono-infected patients were infected with HCV genotype 3 or 4 less frequently (p=0.0001) compared to HIV/HCV co-infected individuals. In patients with HIV/HCV co-infection the CC variant occurred more frequently whereas CT was found less frequently (p=0.001, p=0.0146, respectively). In patients with HIV/HCV co-infection, 3 and 4 genotype of HCV occurred more frequently compared to patients with HCV mono-infection (p=0.0001). These data suggest that age, HCV genotype and IL28B polymorphism are useful for prediction of the response to treatment with Peg-IFN-α and ribavirin. The more frequent occurrence of HCV genotypes 3 or 4 in patients with HIV/HCV co-infection could be associated with the route of transmission.

Microsatellite is an important component of complete Hepatitis C virus genomes

Microsatellites are common and play diverse roles in eukaryotic and prokaryotic genomes. However, to our knowledge, microsatellite distribution remains largely enigmatic in viruses yet is crucial for understanding instability of viral genomes. We have therefore, examined microsatellite distribution in 54 complete genomes of Hepatitis C virus (HCV) from six genotypes, showing microsatellites were an important component of HCV genomes. Our results showed, in all analyzed HCV genomes, genome size and GC content had a weak influence on number, relative abundance and relative density of microsatellites, respectively. For each HCV genome, mono-, di- and trinucleotide repeats were very predominant, whereas other types of repeats rarely occurred. Our results revealed that the occurrence of microsatellites was significantly less than higher prokaryotes and eukaryotes and that all identified microsatellites were very short. The discovery of microsatellites in HCV genomes may become useful for population genetic, evolutionary analysis and strain (isolate) identification.

Correlation of transient elastography with APRI and FIB‐4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection

Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono- or human immunodeficiency virus (HIV)/HCV coinfection. Non-invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono- or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV-positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase-to-platelet ratio index (APRI) and a simple index called FIB-4 were calculated and results were correlated with TE. A total number of 174 patients were included (23% HCV, 36% HIV/HCV coinfected, 33% with cleared HCV and 8% with ongoing HIV but cleared HCV). TE correlated significantly with APRI and FIB-4 (r = 0.60; P < 0.001 and r = 0.54; P < 0.001 respectively). This correlation was pronounced in patients with ongoing HCV infection (r = 0.67; P < 0.001 and r = 0.60; P < 0.001). Prediction of advanced fibrosis resulted in concordance rates >80% with combinations of TE plus APRI and APRI plus FIB-4. HIV/HCV coinfected patients did not present with advanced fibrosis stages when compared with HCV-monoinfected patients. Combinations of two non-invasive markers may significantly reduce the number of liver biopsies in patients with bleeding disorders and advanced liver fibrosis. Furthermore, our data support previous studies that observed a favourable outcome in patients with HIV/HCV and a preserved immune function in times of highly active antiretroviral therapy.