High Hepatitis C Virus RNA Research Articles

A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study.

Prevention of the vertical transmission of the hepatitis C virus (HCV) presents an obstetric challenge. There are no approved antiviral medications for the treatment or prevention of HCV for pregnant patients. We aimed to create a composite score to accurately identify a population of pregnant patients with HCV who have high potential for vertical transmission. In a retrospective, multicenter cohort study, we identified pregnant patients with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data, including age and race/ethnicity, as well as clinical and laboratory data, including tobacco/alcohol use, infections, liver function tests, the HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count, were collected. Data were analyzed using logistic regression and receiver operating characteristics (ROCs) and internally validated using the forward selection bootstrap method. We identified 157 pregnant patients and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141, or 89.8%) were White. A high HCV RNA titer, high absolute lymphocyte count, and high platelet count were associated with vertical transmission. A high HCV RNA titer had an AUROC of 0.815 with sensitivity, specificity, a positive predictive value, and a negative predictive value of 100.0%, 59.1%, 17.6%, and 100.0%, respectively. A composite score combining the three risk factors had an AUROC of 0.902 (95% CI = 0.840-0.964) but with a risk of overfitting. An HCV RNA titer alone or a composite score combining the risk factors for HCV vertical transmission can potentially identify a population of pregnant patients where the rate of vertical transmission is high, allowing for potential interventions during antepartum care.

Validation and Sensitivity of HCV Core Antigen in Patient with HCV Infection in Diagnosis and Monitoring Post DAA Therapy

Abstract Background Successful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new directacting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays, Aim of the Work to evaluate the clinical utility of hepatitis C virus core antigen in detection of chronic hepatitis C virus at pre-treatment and eradication of HCV post DAAs treatment using core antigen ELISA and detection of its sensitivity and specificity in comparison to HCV RNA, Subjects and Methods This was Cross sectional study, carried out at El Galaa and Kobri Al koba military hospitals on 90 Egyptian individuals, divided into 3 groups: (Group A); included 30 healthy individual with HCV Ab and HCV RNA negative as a control, (Group B); included 30 patients with chronic HCV infection in pre-treatment, (Group C): included 30 patients who have received anti HCV treatment (DAAs) 12 weeks post treatment, Result There were insignificant correlation between laboratory parameters of the patient group with HCV-cAg before treatment, Conclusion Fast and immediate results, lower costs of the technique are some of the main advantages of HCVcAg. Therefore, ELISA for HCV-cAg can replace the high sensitivity HCV RNA molecular assay to confirm the presence of HCV infection and to monitor treatment outcome especially in low-income countries with limited resources,

Outcome of direct-acting antiviral treatment in patients with hepatitis C virus/hepatitis B virus coinfection

BackgroundOral direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection have greatly improved treatment efficacy, with sustained virological response (SVR) rates of > 95% for HCV monoinfected patients. However, hepatitis B virus (HBV)/HCV coinfection is more complex than monoinfection with HBV or HCV alone. We evaluated the SVR rate at 12 weeks post-treatment with DAAs in patients with HCV/HBV and evaluated the rate of HBV reactivation during and 6 months after treatment.ResultsAmong the included patients, 191 (95.5%) achieved SVR. Older age, low platelet count, high serum creatinine, and higher liver stiffness value measured by fibroscan were predictors of failure to achieve SVR. The 16 patients (8%) with HBV reactivation patients had significantly higher ALT and serum creatinine and a high HCV RNA viral load at baseline compared with that of those without HBV reactivation.ConclusionPatients who received DAAs to treat HCV/HBV coinfection showed a high SVR. However, it is important to be aware of the potential risk for HBV reactivation during and after treatment with DAAs.

A composite score for predicting vertical transmission of hepatitis C: a multicenter study

Prevention of vertical transmission of hepatitis C virus (HCV) presents an obstetric challenge. We aimed to create a composite score to accurately isolate a population of pregnant women with HCV who will have a high rate of vertical transmission. In a retrospective, multicenter, cohort study, we identified pregnant women with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data including age and race/ethnicity as well as clinical and laboratory data including tobacco/alcohol history, infectious history, liver function tests, HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count were collected. Data were analyzed by logistic regression and receiver operating characteristic (ROC). We identified 157 pregnant women and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141 or 89.8%) were white, high HCV RNA titer, high absolute lymphocyte count and high platelet count were associated with vertical transmission. A composite score combining the three risk factors ha an AUROC of 0.934 (95% CI= 0.883-0.985), superior to any of the three risk factors individually. The sensitivity, specificity and positive predictive value were 100.0%, 86.4%, and 42.9%, respectively. A composite score combining risk factors HCV vertical transmission can isolate a population of pregnant women where the rate of vertical transmission is high, allowing for potential interventions during antepartum or intrapartum care.

An observational, prospective, multicenter study on the utilization and effectiveness of elbasvir-grazoprevir treatment association for chronic hepatitis C in France (ZEPHYR study).

The efficacy and safety profiles of elbasvir-grazoprevir (EBR/GZR) has been established in more than 10 clinical trials. However, the characteristics of patients treated in routine clinical practice may differ. The present study was therefore designed to assess the real-life effectiveness of EBR/GZR therapy in the general population and among subgroups with a high hepatitis C virus(HCV) prevalence in France. The Zephyr study was designed as a French, multicentre, prospective, observational study on EBR/GZR use and effectiveness in current practice in chronic hepatitis Cpatients. These results are based on data regardingthe adult patients who received at least one dose of EBR/GZR between December 2017 and June 2019 in 67 French hospitals and clinics. Overall, 478 patients were included. The Full Analysis Setcorresponded to the 467 patients who met all the inclusion criteria and none of the exclusion criteria. Gender was balanced and the mean age was 55.7 ± 13.3 years. The patients were mainly treatment-naive (89.5%) and infected with Genotype 1b (70.4%). Among the 75 patients with HCV Gt1a genotype, 56% had HCV RNA ≥ 800,000 IU/ml. F3-F4 fibrosis stage involved 24.2% of our population. Our subgroups were distributed among 110 migrants (23.6%), 58 (15.3%) using opioid agonist treatment, including people who inject drugs, 30 (6.8%) with chronic kidney disease Stages 3-5, 9 (1.9%) with aninherited blood disorder, and 4 (0.9%) coinfected with HIV. The remaining 269 (58.7%) were included in the general population subgroup. Overall, sustained virologic response 12 weeks after the end of treatment reached 98.0% and remained consistent among genotype, HCV RNA values, fibrosis stage, and the subgroup of interest. The rate of Alcohol Use Disorders Identification Test-Consumption​​​and Life Habit questionnaire completion was high at each visit, with data suggesting alcohol consumption decrease and an improvement in quality of life. Using real-world evidence data on a French population representative of HCV patients, we confirmed the results obtained during EBR/GZR development program.

Point-of-care hepatitis C reflex testing and treatment referral in methadone clinic settings in Hong Kong—a pilot study

ObjectivesPeople who inject drugs (PWID) constitute a population group with a high hepatitis C virus (HCV) burden. With the objectives of assessing the HCV prevalence in PWID and determining the proportion requiring treatment who could be linked to care, this study piloted onsite reflex HCV testing at low threshold methadone clinics, with prompt referral of HCV RNA-positive participants for treatment. MethodsThis was a prospective study on methadone clinic attendees in Hong Kong. Questionnaires were completed, finger-prick anti-HCV rapid testing was performed, and positive blood samples were collected for laboratory HCV RNA testing. The proportions of participants along the cascade of HCV care were calculated. ResultsIn 2021–2022, after 14 evening screening sessions at three methadone clinics, 86 of 354 regular attendees (24%) were recruited. The anti-HCV prevalence was 63% (54/86, 95% confidence interval 52–73%), with 78% (42/54) testing positive for HCV RNA and 79% (33/42) successfully referred. Almost all (31/33) referred participants received direct-acting antiviral (DAA) treatment, 94% (29/31) with full treatment compliance; 55% (16/29) of these compliant participants achieved a sustained virological response, while the remainder had not received post-treatment testing. ConclusionsThe use of a simplified testing algorithm in the setting of substitution treatment services, incorporating reflex HCV testing, could be an effective strategy for contributing towards the micro-elimination of HCV in PWID.

Risk Factors for Treatment Failure with Oral Antivirals in HCV

Introduction: Chronic hepatitis C virus (HCV) infection is one of the major cause of cirrhosis of liver and leads to significant morbidity and mortality. In past, HCV therapy was limited to subcutaneous peg interferon plus oral ribavirin, a regimen that was generally poorly tolerated and provided low efficacy, with cure rates below 40% for HCV genotypes 1 and 4, and below 75% for HCV genotypes 2 or 3. The availability of oral direct-acting antiviral (DAA) as treatment for chronic hepatitis C has revolutionized the field. Although current HCV therapies rarely fail to achieve viral eradication, a subset of patients experience treatment failure. Aim: To study the risk factors associated with treatment failure with oral antiviral drugs in patients of Chronic hepatitis C. Materials & Methods: It was a retrorospective study done at Medical Gastroenterology Department, PGIMS, Rohtak in which six years data i.e.from 01.01.2015 to 31.12.2020, pertainining to Eighty Six (86) chronic hepatitis C patients who had treatment failure i.e. SVR failure on oral antiviral drugs was analyzed. Observations: Out of the total 86 patients, there was clear cut male predominance i.e. 54 (62.79 %) with rural background (villages) i.e.73 (84.88%). The age distribution in these 86 patients varied between 10-80 yrs of age and characterstically peak was seen in 31-40 yrs age group i.e.25 patients (29.06 %). The majority of patients had high baseline HCV viral load (> 4 lakhs I.U. /ml) i.e. 52 patients (60.46%). Out of total 86 patients, , 50 patients (58.13%) were cirrhotic, 34 patients (39.53 %) were smokers, 33 patients (38.37%) were alcoholic, 26 patients (30.23 %) had past history of surgical intervention, 9 patients (10.46 %) were diabetic, 9 patients (10.46 %) had got tattoo, 8 patients (9.30%) had history of previous blood transfusion and 13 patients (15.11%) gave history of use of alternative medications. Results: The direct risk factors associated with development of failed SVR in HCV patients are high baseline HCV RNA viral load, cirrhosis, rural background and indirect risk factors are smoking, alcohol and Diabetes Mellitus but large scale studies in future are required to confirm the same.

Development of Near-Infrared Nucleic Acid Mimics of Fluorescent Proteins for In Vivo Imaging of Viral RNA with Turn-On Fluorescence.

GFP-like fluorescent proteins and their molecular mimics have revolutionized bioimaging research, but their emissions are largely limited in the visible to far-red region, hampering the in vivo applications in intact animals. Herein, we structurally modulate GFP-like chromophores using a donor-acceptor-acceptor (D-A-A') molecular configuration to discover a set of novel fluorogenic derivatives with infrared-shifted spectra. These chromophores can be fluorescently elicited by their specific interaction with G-quadruplex (G4), a unique noncanonical nucleic acid secondary structure, via inhibition of the chromophores' twisted-intramolecular charge transfer. This feature allows us to create, for the first time, FP mimics with tunable emission in the near-infrared (NIR) region (Emmax = 664-705 nm), namely, infrared G-quadruplex mimics of FPs (igMFP). Compared with their FP counterparts, igMFPs exhibit remarkably higher quantum yields, larger Stokes shift, and better photostability. In a proof-of-concept application using pathogen-related G4s as the target, we exploited igMFPs to directly visualize native hepatitis C virus (HCV) RNA genome in living cells via their in situ formation by the chromophore-bound viral G4 structure in the HCV core gene. Furthermore, igMFPs are capable of high contrast HCV RNA imaging in living mice bearing a HCV RNA-presenting mini-organ, providing the first application of FP mimics in whole-animal imaging.

Thiol-disulphide balance and total oxidant-antioxidant status in patients with chronic hepatitis C.

To assess the dynamic thiol/disulphide homeostasis (DTDH) and total oxidant/antioxidant status in patients with hepatitis C virus (HCV) infection and to evaluate their association with HCV-RNA levels. Levels of serum total thiol (TT), native thiol (NT), disulphide (DS), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) as oxidative stress markers were determined in 162 individuals, including 74 patients with HCV infection and 88 non-HCV controls. HCV genotypes and HCV-RNA levels of the patients were recorded. The NT, TT and TAS levels and NT/TT ratio were significantly lower in the HCV group compared with the control group. On the contrary, DS, TOS and OSI levels and DS/NT and DS/TT ratios were significantly higher. Patients with high HCV RNA levels (> 650000IU/mL) had higher DS levels than patients with low HCV-RNA levels (<650000IU/mL). Genotype 1 was observed in 68.9% of patients with HCV. Levels of oxidative stress parameters were similar between genotype 1 and other genotypes (2, 3 and 5). No significant correlations were found between oxidative stress markers and albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin and HCV-RNA levels in patients with HCV infection. A negative correlation was found only between OSI and albumin. Our results suggest that DTDH shifts towards the DS direction because of thiol oxidation in HCV-infected patients. Furthermore, DS levels were significantly higher in patients with high HCV-RNA levels compared with patients with low HCV-RNA levels.

Microelimination of Chronic Hepatitis C by Universal Screening Plus Direct-Acting Antivirals for Incarcerated Persons in Taiwan.

BackgroundIncarcerated persons are a special population with higher hepatitis C virus (HCV) prevalence and should be prioritized for microelimination. In this study, we investigate the seroprevalence and evaluate the effectiveness and safety of direct-acting antiviral (DAA) therapy in custodial settings.MethodsIncarcerated persons in Yunlin Prison were recruited to receive anti-HCV antibody screening. Patients with positive HCV ribonucleic acid (RNA) were treated with glecaprevir/pibrentasvir (GLE/PIB) in our special chronic hepatitis C (CHC) clinic in prison. The primary endpoint was sustained virologic response at week 12 off therapy (SVR12).ResultsA total of 1402 incarcerated persons were invited to anti-HCV screening and 824 (58.7%) accepted. The prevalence of anti-HCV positivity was 33.5% (276 of 824), and the viremic rate (detectable HCV RNA) was 69.2% (191 of 276). According to fibrosis index based on 4 factors, patients with F3 stage were 6 (3.1%), but none met the criteria of F4 stage. However, 6 (3.1%) had liver cirrhosis with splenomegaly, confirmed by findings of ultrasonography. The median log10 HCV RNA level at baseline was 6.235 (2.394–7.403). Genotype (GT) 6 was predominant (39.3%), followed by GT 1a (22.0%) and 1b (14.1%). Mixed GT HCV infection accounted for 3.6% of total infections. In total, 165 patients received GLE/PIB therapy. The overall SVR12 rates were 100%.ConclusionsDirect-acting antiviral therapy is highly effective and safe for incarcerated patients in Taiwan. Our special prison-based CHC clinic, linking universal screening to medical care, can serve as a model for microelimination of HCV in custodial settings.

2382 Successful Hepatitis C Virus Antibody-Positive Donor Liver Transplantation in Acute Sickle Cell Intrahepatic Cholestasis: A Case Report

INTRODUCTION: Sickle cell hepatopathy (SCH) is the umbrella term referring to liver dysfunction in sickle cell disease (SCD) patients. We report a case of acute intrahepatic cholestasis (ASCIH) with underlying cirrhosis managed with hepatitis C virus (HCV) antibody-positive donor liver transplantation (LT). CASE DESCRIPTION/METHODS: A 29-year-old African American male with known medical history of SCD (Hb SS) and cirrhosis presented to the medical intensive liver unit with vaso-occlusive pain crises and jaundice. Patient was afebrile with benign exam. Labs were consistent with obstructive jaundice (total serum bilirubin of 57 mg/dL, direct serum bilirubin of 30 mg/dL), and elevated liver enzymes (alkaline phosphatase 306 U/L, aspartate transaminase 227 U/L and alanine transaminase 54 U/L). He had significant leukocytosis 38.6 k/uL, low hemoglobin 6.3 g/dL and thrombocytopenia 39 k/uL. Sodium level was 149 mg/dl and INR was 2.3. Computed tomography scan showed changes consistent with cirrhosis but no evidence of ductal dilatation. He developed encephalopathy after 24 hours of presentation, acute kidney injury (serum creatinine 3.57 mg/dl) and respiratory failure requiring endotracheal intubation. He was diagnosed with acute liver failure secondary to ASCIH after a non-revealing extensive workup for acute liver failure. Exchange transfusion was started without improvement in hepatic function or mental status. His MELD-Na (Model for End-Stage Liver Disease-Sodium) score was 43 and thus patient was listed for urgent LT. He received an HCV positive donor liver after 9 days of hospitalization. Explanted liver biopsy showed widespread sinusoidal dilatation with innumerable clusters of sickled red blood cells, scattered pigmented histiocytes, and cholestasis. Following transplant, exchange transfusion was resumed and immunosuppression treatment started with mycophenolate, tacrolimus and steroid taper. Glecaprevir/Pibrentasvir started for high HCV RNA titer. He was discharged after 23 days with total bilirubin of 4.2 mg/dL and normalization of his liver enzymes. He was doing well during his 4 months follow up. DISCUSSION: We present a rare case of acute sickle cell intrahepatic cholestasis treated with successful LT. This represents the 1st case of a positive HCV donor LT and the 20th LT case in SCD. ASCIH is the most severe, often fatal, form of SCH. Our goal with this case is to increase the awareness of this important condition and emphasize the role of liver transplantation as a potential treatment.

Integrated, Co-located, Telemedicine-based Treatment Approaches for Hepatitis C Virus Management in Opioid Use Disorder Patients on Methadone.

Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Sixty-two HCV RNA-positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.

Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study.

This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).

High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease

Associations between chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD) remain controversial. Here we aimed to clarify the association between HCV viral load, genotype, and CKD in 13,805 participants aged 30-65 years enrolled in the REVEAL-HCV Study, a community-based prospective study conducted in 1991-1992. CKD was defined by consecutive proteinuria oran estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2. Chronic HCV infection was defined by detectable HCV viral load. Logistic regression models were used to estimate prevalence odds ratio of CKD for chronic HCV infection after adjusting for other risk factors. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio (95% confidence interval) for CKD was significantly increased to 1.91 (1.27-2.88) for chronically HCV-infected participants. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio of CKD was 1.21 (0.54-2.70), 1.40 (0.66-3.00) and 3.44 (1.92-6.14) for chronically HCV-infected participants with low to high tertiles of serum HCV RNA, respectively. The adjusted prevalence odds ratios of CKD were 0.54 (0.17-1.75) for participants with low HCV RNA and genotype 1, 1.80 (0.84-3.87) for those with low HCV RNA and genotype 2, 2.62 (1.11-6.17) for those with high HCV RNA and genotype 1 and 4.99 (2.25-11.06) for those with high HCV RNA and genotype 2, compared with non-chronically HCV-infected participants. Thus, chronic HCV infection is associated with an increased risk of CKD. High HCV viral load and HCV genotype 2 are strong CKD predictors.

Retrospective analysis of post-transplant liver biopsies – From diagnosis to therapy – Can we guide further? Experience from a tertiary care center in India

Background and Aim: Post-transplant liver biopsies form a critical part of management of complications arising post-transplant. The objective of this study was to analyze the Indian experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLT) with special emphasis on cases presenting with intrahepatic cholestasis (IHC). Type, incidence, and timing of major complications were analyzed. All cases with IHC were retrospectively analyzed with clinical inputs to look for cryptic clues in subclassifying such cases. Materials and Methods: Forty-five post-transplant liver biopsies from 39 OLT patients were retrospectively analyzed from May 2015 to May 2016. All biopsies were stained with hematoxylin and eosin and Masson's Trichrome, and other stains were performed as required. Results: The number of liver biopsies performed for each patient ranged from 1 to 3. The timing of these biopsies varied from 5 days to >4 years post-transplant. Of the 39 patients who underwent post-transplant liver biopsies, most common etiology of a liver transplant was hepatitis C virus (HCV)-related chronic liver disease in 66.6% cases. The common complications post-transplant were acute cellular rejection (ACR) (33.3%), biliary stricture (13.3%), HCV recurrence (11.1%), plasma cell hepatitis (4.4%), chronic hepatitis (4.4%), IHC (22.2%), and others. On analysis of post transplant biopsy cases with IHC, we found that patients with high baseline HCV RNA levels had recurrences presenting only with prominent IHC without fibrosis and ballooning of hepatocytes. These changes might represent early stages of fibrosing cholestatic hepatitis (FCH). Conclusions: This study evaluated the types, incidence, and timing of major complications occurring after OLT. ACR remains major complication following transplant. The presence of IHC on biopsy, especially in HCV-positive patients, should prompt anti-HCV therapy even if other features of FCH were not found.

High hepatitis C virus (HCV) prevalence among men who have sex with men (MSM) in Vietnam and associated risk factors: 2010 Vietnam Integrated Behavioural and Biologic Cross-Sectional Survey

BackgroundHepatitis C virus (HCV) is an increasing health issue among key populations such as men who have sex with men (MSM). We sought to assess the burden of and risk...

Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection.

BackgroundThis study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis.MethodsParticipants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis.ResultsAmong 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels.ConclusionsDuring acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0482-x) contains supplementary material, which is available to authorized users.

Persistence of Hepatitis C Virus Traces after Spontaneous Resolution of Hepatitis C.

Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was rarely investigated. The current study aimed to assess incidence and robustness of HCV persistence after self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus by conventional tests. Applying high sensitivity HCV RNA detection approaches, we analyzed plasma and peripheral blood mononuclear cells (PBMC) from individuals with previous hepatitis C infection. Parallel plasma and PBMC from 24 such non-viraemic individuals followed for 0.3–14.4 (mean 6.4) years were examined. Additional samples from 9 of them were obtained 4.5–7.2 (mean 5.9) years later. RNA was extracted from 250 μl plasma and, if HCV negative, from ~5 ml after ultracentrifugation, and from ex vivo stimulated PBMC. PBMC with evidence of HCV replication from 4 individuals were treated with HCV protease inhibitor, telaprevir. HCV RNA was detected in 14/24 (58.3%) plasma and 11/23 (47.8%) PBMC obtained during the first collection. HCV RNA replicative strand was evident in 7/11 (63.6%) PBMC. Overall, 17/24 (70.8%) individuals carried HCV RNA at mean follow-up of 5.9 years. Samples collected 4.5–7.2 years later revealed HCV in 4/9 (44.4%) plasma and 5/9 (55.5%) PBMC, while 4 (80%) of these 5 PBMC demonstrated virus replicative strand. Overall, 6/9 (66.7%) individuals remained viraemic for up to 20.7 (mean 12.7) years. Telaprevir entirely eliminated HCV replication in the PBMC examined. In conclusion, our results indicate that HCV can persist long after spontaneous resolution of hepatitis C at levels undetectable by current testing. An apparently effective host immune response curtailing hepatitis appears insufficient to completely eliminate the virus. The long-term morbidity of asymptomatic HCV carriage should be examined even in individuals who achieve undetectable HCV by standard testing and their need for treatment should be assessed.

Chronic hepatitis C infection is associated with insulin resistance and lipid profiles

Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.