Hepatitis C Virus Infection Research Articles

Modeling the impact of a supervised consumption site on HIV and HCV transmission among people who inject drugs in three counties in California, USA

Supervised consumption sites (SCS) have been shown to reduce receptive syringe sharing among people who inject drugs (PWID) in the United States and elsewhere, which can prevent HIV and hepatitis C virus (HCV) transmission. PWID are at risk of disease transmission and may benefit from SCS, however legislation has yet to support their implementation. This study aims to determine the potential impact of SCS implementation on HIV and HCV incidence among PWID in three California counties. A dynamic HIV and HCV joint transmission model among PWID (sexual and injecting transmission of HIV, injecting transmission of HCV) was calibrated to epidemiological data for three counties: San Francisco, Los Angeles, and San Diego. The model incorporated HIV and HCV disease stages and HIV and HCV treatment. Based on United States data, we assumed access to SCS reduced receptive syringe sharing by a relative risk of 0.17 (95 % CI: 0.04-1.03). This model examined scaling-up SCS coverage from 0 % to 20 % of the PWID population within the respective counties and assessed its impact on HIV and HCV incidence rates after 10 years. By increasing SCS from 0 % to 20 % coverage among PWID, 21.8 % (95 % CI: -1.2-32.9 %) of new HIV infections and 28.3 % (95 % CI: -2.0-34.5 %) of new HCV infections among PWID in San Francisco County, 17.7 % (95 % CI: -1.0-30.8 %) of new HIV infections and 29.8 % (95 % CI: -2.1-36.1 %) of new HCV infections in Los Angeles County, and 32.1 % (95 % CI: -2.8-41.5 %) of new HIV infections and 24.3 % (95 % CI: -1.6-29.0 %) of new HCV infections in San Diego County could be prevented over ten years. Our models suggest that SCS is an important intervention to enable HCV elimination and could help end the HIV epidemic among PWID in California. It could also have additional benefits such facilitating pathways into drug treatment programs and preventing fatal overdose.

Knowledge of, and attitude towards, the treatment of hepatitis C in people who inject drugs

BackgroundDirect acting antivirals (DAAs) as a curative treatment of hepatitis C have been available for several years and have replaced interferon-containing therapies. However, treatment rates of people who inject drugs (PWID) are declining in Germany, putting the elimination of hepatitis C by 2030 at risk. This study aimed at elucidating the knowledge of, and attitude towards, hepatitis C treatment in a clinical sample of PWID.MethodsParticipants were recruited between February 2019 and October 2020 at two opioid agonist therapy (OAT) clinics and two in-patient drug detoxification wards. Based on the European Addiction Severity Index (Europ-ASI), a standardized interview focusing on: sociodemographic data, drug history, risky behavior, infection with hepatitis C virus (HCV) and HIV, and previous experience with HCV treatment was carried out. In addition, participants filled in a questionnaire evaluating 13 statements relating to HCV treatment (right/wrong) and 15 statements on their personal ‘pros and cons’ views to start such a treatment assessed with the means of a 6-point Likert scale.ResultsA total of 153 patients (average age 45 years, male 78%; 106 (69.3%) currently in opioid maintenance treatment, 47 (30.7%) currently admitted to an inpatient detoxification) with an opioid use disorder were investigated. All of them reported having injected drugs at least once in their lives; 97 participants (63.3%) stated that they had been previously diagnosed with HCV infection. Among them, 27/97 patients (27.8%) reported a previous treatment with interferon; 27/97 (27.8%) with DAAs; and 32/97 (33.0%) reported a currently active hepatitis C. Most patients knew about the availability and efficacy of DAAs. However, DAAs’ low rate of side effects, their short treatment duration, and their replacement of interferon, were not correctly evaluated by up to 50.3% of patients. 25–40% of 32 patients with currently active hepatitis C prioritized handling of social and other medical issues, e.g., reduction of heroin use, over treatment of hepatitis C.ConclusionsAlthough current levels of risky behavior have reportedly been reduced by active PWID over the past few years, educational and motivational interventions to increase hepatitis C treatment uptake should address the gaps in patients’ knowledge.

Epidemiology of Hepatitis C over 28 years of monitoring Canadian blood donors: Insight into a low-risk undiagnosed population

BackgroundHepatitis C is a blood-borne infection with the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% (50–80%) of infections become chronic and exhibit anti-HCV and HCV nucleic acid (NAT) positivity. Direct acting oral pan genotypic antiviral treatment became available in 2014 and was free for most Canadians in 2018. Clinical screening for HCV infection is risk-based. About 1% of Canadians have been infected with HCV, with 0.5% chronically infected (about 25% unaware) disproportionately impacting marginalized groups. Blood donors are in good health, are deferred for risks such as injection drug use and can provide insight into the low-risk undiagnosed population. Here we describe HCV epidemiology in first-time blood donors over 28 years of monitoring.MethodsAll first-time blood donors in all Canadian provinces except Quebec (1993 to 2021) were analyzed. All blood donations were tested for HCV antibodies (anti-HCV) and since late 1999 also HCV NAT. A case-control study was also included. All HCV positive donors (cases) since 2005 and HCV negative donors (1:4 ratio controls) matched for age, sex and location were invited to complete a risk factor interview. Separate logistic regression models for anti-HCV positivity and chronic HCV assessed the association between age cohort, sex, region and neighbourhood material deprivation and ethnocultural concentration. Case: control data were analysed by logistic regression.ResultsThere were 2,334,238 donors from 1993 to 2021 included. Prevalence for anti-HCV was 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021 (p < 0.0001). In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar, for chronic HCV were male sex (OR 1.8, 1.6,2.1), birth between 1945 and 1975 (OR 7.1, 5.9,8.5), living in the western provinces (OR 1.4, 1.2,1.7) and living in material deprived (OR 2.7, 2.1,3.5) and more ethnocultural concentrated neighbourhoods (OR 1.8, 1.3,2.5). There were 318 (35.4%) of chronic HCV positive and 1272 (39.6%) of controls who participated in case control interviews. The strongest risks for acquisition were injection drug use (OR 96.9, 22.3,420.3) and birth in a high prevalence country (OR 24.5, 11.2,53.6).ConclusionsBlood donors have 16 times lower HCV prevalence then the general population. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risks for acquisition missed by risk-based patient screening.

Assessment of Thyroid Profile in Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection remains a major public health concern in Pakistan, with potential impacts on thyroid function. Long-term HCV infection has been associated with thyroid dysfunction, but the extent of this relationship is not fully understood.Objective: This study aimed to evaluate the thyroid hormone profile in HCV-positive patients to assess the prevalence of thyroid dysfunction in this population.Methods: A cross-sectional study was conducted on 120 HCV-positive patients aged 18-70 years. Patients with liver cirrhosis, known thyroid disorders, or medications affecting thyroid function were excluded. Blood samples were collected, and thyroid hormones (TSH, FT3, FT4) were measured using an automated immunoassay system. Data were analyzed using SPSS version 25.0, with a p-value &lt;0.05 considered statistically significant.Results: The study found that 17.50% of patients had elevated TSH levels, while 11.66% and 10.83% had elevated FT3 and FT4 levels, respectively. The mean values for TSH, FT3, and FT4 were 1.15 ± 0.515 µIU/mL, 1.10 ± 0.351 pg/mL, and 1.12 ± 0.361 ng/dL.Conclusion: The study demonstrated a significant association between HCV infection and thyroid dysfunction, highlighting the need for regular thyroid function monitoring in HCV-positive patients.

Prevalence and associated risk factors of current hepatitis C infection among U.S. general population and injection drug users aged 20-59 years: NHANES 2009-2018.

The people who inject drugs (PWID) are attributed to high-risk groups for transmission of the Hepatitis C virus (HCV). This study assessed the prevalence and associated factors of current HCV infection (CHI) among U.S. general population and PWID of ages between 20 and 59 years old. This study utilized cross-sectional data from the 2009-2018 National Health and Nutrition Examination Survey, conducting separate analyses for the U.S. general population, including PWID and non-PWID, as well as specific analyses focusing solely on PWID. The analytical methods included the estimation of CHI prevalence, Rao-Scott chi-square test to compare CHI-positive and CHI-negative groups, and univariate and multivariable logistic regressions models to evaluate the associated risk factors of CHI. The prevalence of CHI among general population and PWID were 1% and 19%, respectively. Compared to non-PWID, the odds of CHI were significantly higher among PWID (OR = 32.6, 95% CI = 17.7-60.3) in general population. Among PWID, male vs. female (OR = 2.6, 95% CI = 1.1-5.9), adults aged 40-59 vs. 20-39 years old (OR = 2.9, 95% CI = 1.2-7.3), Non-Hispanic Black vs. White (OR = 4.6, 95% CI = 1.5-13.6), with high school diploma or less educational attainment vs. above college degree (OR = 3.5, 95% CI = 1.4-9.2) showed higher odds of having CHI. The prevalence of CHI was found to be higher among PWID especially those who were male, aged 40-59 years old, Non-Hispanic Black, and had lower educational attainment. Targeted intervention such as screening and awareness program among PWID population is recommended to reduce the burden of new HCV infections in the U.S.

Hepatitis C Virus Reinfection Among People Who Inject Drugs

Hepatitis C virus (HCV) reinfection after curative treatment remains a concern for people who inject drugs. To assess the incidence of HCV reinfection and associated risk factors. This cohort study is a secondary analysis of a randomized clinical trial that was conducted across opioid treatment programs and community health centers in the US between September 2016 and August 2018. The current analyses were performed in March 2022. People who inject drugs who achieved sustained virologic response (SVR) were followed for up to 42 months. Patients were randomly assigned to receive modified directly observed therapy or patient navigation. The primary outcome was rate of HCV reinfection. Change in reinfection rates over time was assessed using a Poisson regression model. A total of 415 participants (mean [SD] age, 44.7 [11.5] years; 302 male [72.8%]) achieved a SVR and had 1 or more post-SVR assessments for HCV RNA. Overall, 302 (72.8%) reported recent injection drug use, 192 (46.3%) were living in unstable housing, and 313 (75.4%) had received recent methadone or buprenorphine for opioid use disorder. The overall reinfection rate was 11.4 per 100 person-years at risk (95% CI, 8.7-14.7 per 100 person-years at risk) over 518 person-years of follow-up. Reinfection rates varied significantly across sites, ranging from 2.9 per 100 person-years at risk (95% CI, 0.1-16.3 per 100 person-years) to 25.2 per 100 person-years at risk (95% CI, 15.6-38.5 per 100 person-years at risk) (P = .006). There was a significant decrease in incident reinfection with increasing post-SVR follow-up (weeks 0-24, 15.5 per 100 person-years; 95% CI, 10.3-22.3 per 100 person-years; weeks 73-144, 4.3 per 100 person-years; 95% CI, 0.9-12.5 per 100 person-years; P = .008). Reinfection rates were lower for participants aged 40 years or older than for younger participants (adjusted incidence rate ratio, 0.32; 95% CI, 0.18-0.57) and for participants for whom methamphetamine was not detected in urinary drug screening compared with participants for whom methamphetamine was detected (adjusted incidence rate ratio, 0.41; 95% CI, 0.21-0.82). Participants who reported injection drug use within the preceding 3 months had higher risk of reinfection than those who did not have recent injection drug use (adjusted incidence rate ratio, 3.33; 95% CI, 1.86-5.97). In this cohort study of people who injected drugs and were treated for HCV infection in community settings, reinfection was high in the period immediately after SVR but decreased significantly over time. These findings highlight the importance of early intervention to prevent reinfection. ClinicalTrials.gov Identifier: NCT02824640.

Computer-aided molecular modeling and design studies of some N-(4-(dimethyl amino) phenyl)-4-methoxy-3-propionamidobenzamide derivatives as NS5B polymerase inhibitors

Hepatitis C Virus (HCV) is a stealthy ailment, and most people are unaware they have it in the early stages. Insilco modeling was used to develop a model with high predictive power for N-(4-(dimethyl amino) phenyl)-4-methoxy-3-propionamidobenzamide inhibitors. The inhibitors were optimized using Density Functional Theory (DFT) based on a notion of B3LYP/6–31 G* levels. The genetic function algorithm (GFA) was utilized to create the QSAR models. The best model was chosen based on its statistical fitness using the subsequent measurement parameters: R2trng = 0.828181, R2adj = 0.800468, Q2cv = 0.734795, R2test = 0.7028, and LOF = 0.613985, led to its selection and publication. The model underwent additional assessments, including the Y-scrambling test, and applicability domain, and was considered to have statistical significance. The docking results demonstrate that compound 17 has the greatest inhibitory effect on NS5B-polymerase of any drug in the dataset. Using this compound as a template, novel anti-hepatitis C compounds were developed by including a few beneficial substituents. The docking results of the proposed compounds yielded a high MolDock score (−152.12), indicating effective binding to the target's active sites. Two comparable compounds (SBD4 and SBD3) were shown to be superior to the food drug administration (FDA) approved medication, revibirin/pegylated interferon. The chemicals were determined to be orally accessible after passing Lipinski's criteria, a drug similarity test. Furthermore, the synthesized compounds were found to have favorable pharmacokinetic (absorption, distribution, metabolism, excretion, and toxicity) properties. In conclusion, using the QSAR model, a model with excellent prediction power for certain Biaryl amide inhibitors was constructed. The model was validated and determined to have good internal and external assessment criteria. According to the docking results, compound 17 inhibits NS5B-polymerase the most out of the compounds in the dataset. Furthermore, the compounds' oral bioavailability met drug-like standards. The ultimate goal of this research is to contribute to the development of new therapeutic agents for the treatment of HCV infections, addressing the pressing need for effective antiviral medications.

Pregnancy Outcomes in Patients With Hepatitis C Virus Infection.

To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection. This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal intensive care (NICU); small-for-gestational-age (SGA) birth weight; and neonatal infection, defined as sepsis or pneumonia. Models were adjusted for maternal age, body mass index, injection drug use, and maternal medical comorbidities. The 249 individuals in the case group were prospectively matched to 486 individuals in the control group who met eligibility criteria. There were significant differences in demographic characteristics between the groups, including race, socioeconomic markers, education, insurance status, and drug and tobacco use. The frequencies of maternal outcomes of gestational diabetes, preeclampsia, and abruption were similar between the case and control groups. Preterm birth was similar between groups, but neonates born to individuals in the case group were more likely to be admitted to the NICU (45.1% vs 19.0%, adjusted odds ratio [aOR] 2.6, 95% CI, 1.8-3.8) and to have SGA birth weights below the 5th percentile (10.6% vs 3.1%, aOR 2.9, 95% CI, 1.4-6.0). There were no increased odds of hyperbilirubinemia or neonatal infection. Despite no increased odds of preterm birth or other adverse maternal outcomes in adjusted analyses, maternal HCV infection was associated with twofold increased odds of NICU admission and nearly threefold increased odds of SGA birth weight below the 5th percentile.

Racial and ethnic disparities in testing of Hepatitis C virus-exposed children across the United States.

Despite rising hepatitis C virus (HCV) prevalence among pregnant individuals in the United States, HCV testing among exposed infants remains low. Although recent guidelines recommend early RNA testing for HCV-exposed children to help improve testing rates, national studies describing factors associated with HCV testing and type of testing completed are lacking. In this retrospective national study, we characterized HCV testing and care among HCV-exposed infants born 2010-2020 captured in the electronic health record-based TriNetX Research Network. We analyzed factors associated with appropriate HCV testing completion (negative or positive HCV RNA testing or negative HCV antibody testing at any age through study end in 2022) and with RNA compared with antibody testing, using univariable and multivariable logistic regression with clustered standard errors by healthcare organization. Of 8,516 HCV-exposed children, 45.8% completed any HCV testing and 42.1% completed appropriate testing (25% of whom had RNA testing only). 182 (5.1% of appropriately tested children) had evidence of HCV infection. Of 104 treatment-eligible children, 14.4% were treated. Black (OR 0.38, 95% CI 0.26-0.55), Asian/Pacific Islander (OR 0.06, 95% CI 0.03-0.11), and Hispanic/Latinx children (OR 0.56, 95% CI 0.36-0.88) had lower odds of appropriate testing compared with White and non-Hispanic/Latinx children, respectively. Fewer than half of HCV-exposed children in this national sample were tested for HCV, with lower testing odds among Black, Asian/Pacific Islander, and Hispanic/Latinx children. Substantial work to increase testing and treatment and decrease disparities in testing among HCV-exposed children is needed to help reach US HCV elimination goals.

Hepatitis C Virus Seroprevalence and Genotypic Distribution Among Hemodialysis Patients at a Teaching and Training Hospital in Western Rajasthan, India.

Background Hepatitis C virus (HCV) infection is a chronic hepatotropic blood-borne infection. The transmission of HCV in patients undergoing hemodialysis (HD) is more common in comparison to the general population due to factors such as frequent blood transfusions, prolonged vascular access, and the potential for nosocomial infections. Western Rajasthan in India is home to numerous teaching and training hospitals that cater to a large number of HD patients. Understanding the seroprevalence and genotypic distribution of HCV in this specific patient population is crucial for assessing the extent of infection within this vulnerable group for targeted surveillance and developing effectively tailored treatment protocolsin healthcare settings. Hence, this study was conducted with an aim to determine seroprevalence, seroconversion, and genotypes of HCV in HD patients at a tertiary care hospital. Methods This was a cross-sectional observational study. The duration of the study was from July 2019 to March 2022. In this study, the patients undergoing maintenance HD due to chronic kidney disease (CKD) were recruited. The data collected include patients' demographics, etiology of CKD, underlying other co-morbidities, duration of dialysis, and biochemical and blood count parameters. The patients recruited at the start of the study were screened for anti-HCV antibodies by HCV enzyme-linked immune sorbent assay (ELISA). The anti-HCV antibody-negative patients were followed up for the detection of anti-HCV antibodies. At the end of the follow-up period, all anti-HCV antibody negative samples in the pool of five and all anti-HCV antibody positive samples were subjected to a real-time polymerase chain reaction (RT-PCR) of 5' untranslated region (5'UTR) and core region, followed by line probe assay (LiPA). Results In this study, after applying inclusion and exclusion criteria, a total of 109 patients were recruited, out of which 64 (58.7%) were males and 45 (41.3%) were females. The age range of participants was 11-88 years with a mean and standard deviation of 46.75 and 16.35 years, respectively. A total of 39 patients (20 on screening, 19 on follow-up) were detected anti- HCV antibody positive. By RT-PCR, 24 patients tested HCV RNA positive (10 on screening, 14 on follow-up). Among 24 HCV RNA-positive samples, LiPA showed, HCV genotype 1a (n=21), genotype 3b (n=1), and two samples were detected to be inconclusive. Conclusion The increasing duration of dialysis is significantly associated with acquiring HCV infection. The majority of the cases of CKD in this geographical region are due to hypertensive nephropathy. There can be discordance between antibody and viral RNA positivity in HCV infection. The predominant HCV genotype identifiedin the dialysis ward of tertiary care hospital was genotype 1a.

Publisher's Note

BackgroundPrevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57% in 2015 to 32% in 2022. We aimed to investigate potential explanations for this decline. MethodsChanges in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours. ResultsOverall prevalence of DBS HCV Ab declined rapidly and significantly from 57% in 2015 to 32% in 2022 (p<0.001) however modified HCV Ab prevalence remained stable over time (85% and 88% in 2015 and 2022, respectively, p=0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20% in 1995 to 40% in 2022 (p<0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3% in 1999 to 67% in 2022 (p<0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p<0.001) however the short-term trend was not significant for recent receptive syringe sharing. ConclusionThe temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting.

Forecasting Hepatitis C Virus Status for Children in the United States: A Modeling Study.

Virtually all cases of hepatitis C virus (HCV) infection in children in the United States occur through vertical transmission, but it is unknown how many children are infected. Cases of maternal HCV infection have increased in the United States, which may increase the number of children vertically infected with HCV. Infection has long-term consequences for a child's health, but treatment options are now available for children ≥3 years old. Reducing HCV infections in adults could decrease HCV infections in children. Using a stochastic compartmental model, we forecasted incidence of HCV infections in children in the United States from 2022 through 2027. The model considered vertical transmission to children <13 years old and horizontal transmission among individuals 13-49 years old. We obtained model parameters and initial conditions from the literature and the Centers for Disease Control and Prevention's 2021 Viral Hepatitis Surveillance Report. Model simulations assuming direct-acting antiviral treatment for children forecasted that the number of acutely infected children would decrease slightly and the number of chronically infected children would decrease even more. Alone, treatment and early screening in individuals 13-49 years old reduced the number of forecasted cases in children and, together, these policy interventions were even more effective. Based on our simulations, acute and chronic cases of HCV infection are remaining constant or slightly decreasing in the United States. Improving early screening and increasing access to treatment in adults may be an effective strategy for reducing the number of HCV infected children in the United States.

Differences in the course of hepatocellular carcinoma depending on the DAA treatment

Background and aims: 58 million people live with chronic hepatitis C virus (HCV) infection which can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Currently, a non-interferon therapy based on direct-acting antivirals (DAA) is the standard treatment of HCV infection. This study aimed to assess the occurrence of HCC after treatment with DAA and evaluate whether the course of the disease and liver function is different in patients treated with DAA compared to those who did not receive such therapy. Materials and methods: We studied the population of adult patients from the 2015-2021 period and analyzed the demographic and clinical data, including alcohol abuse, liver enzymes, Child-Pugh and model for end-stage liver disease scores, imaging tests, liver biopsy and elastography, if performed. The Mann-Whitney U and the McNemar’s tests were used. The p-value was set at 0.05. Results: The study included n=34 patients with HCC. In this group n=22 patients (61%) were diagnosed with a chronic HCV infection and n=11 (50%) were receiving DAA treatment. Patients who were receiving DAA developed multiple HCC significantly less often compared to patients not treated with DAA (45.5% vs. 69.6%). We also observed a significantly less common occurrence of portal vein thrombosis (8.7% vs. 18.2%) and distant metastases (0.0% vs. 13.0%) in patients with HCC receiving DAA. Patients with HCC who underwent DAA therapy had significantly lower levels of serum liver enzymes in comparison with patients diagnosed with HCC and not receiving DAA. Conclusions: HCC occurring in patients treated with DAA was more often associated with lymphadenopathy, multiple tumors, portal vein thrombosis and distant metastases probably due to restricted treatment qualification criteria. DAA treatment led to a decrease in the inflammatory activity in the liver. It is important to adjust qualification protocols so that all patients suffering from chronic HCV infection could receive the treatment as soon as possible.

Trends in the prevalence of HIV, HCV, and co-infection and associated factors among young people who inject drugs (PWID) in Catalonia (2008–2019)

ABSTRACT People who inject drugs (PWID) face a significantly increased risk of blood-borne virus (BBV) infections, including HIV and hepatitis C virus (HCV), as well as co-infections. To better understand this issue, bio-behavioral surveillance studies were conducted among PWID attending harm reduction facilities in Catalonia, forming part of the comprehensive Integrated HIV/STI Surveillance System since 2008. The goal of this study was to describe the prevalence of HIV, HCV, and HIV-HCV coinfection and associated socio-demographic and behavioural factors among young PWID in Catalonia by gender and to examine trends over time, from 2008 to 2019. We first estimated the prevalence of HIV, HCV, and their co-infection and sample characteristics, and then, we calculated prevalence ratios (PR) and adjusted prevalence ratios (aPR) to identify the variables associated with HIV infection, HCV infection, and HIV-HCV co-infection. We found that the overall prevalence of HIV, HCV and HIV-HCV co-infection in 2019 was 20.1%, 66.2%, and 16.8%, respectively. In multivariable analysis, we found that being female (aPR: 1.55, 95% CI: 1.05–2.30), age (aPR: 1.09, 95% CI: 1.04–1.14), having born outside of Spain (aPR: 1.67, 95% CI: 1.19–2.34), homelessness (aPR: 1.90, 95% CI: 1.34–2.68), daily injection (aPR: 1.46, 95% CI: 1.04–2.04), sharing needles (aPR: 1.93, 95% CI: 1.32–2.82), involvement in sex work (aPR: 1.82, 95% CI: 1.09–3.03), and imprisonment (aPR: 2.54, 95% CI: 1.75–3.67) was associated with increased prevalence of HIV and HCV co-infection, while being a new injector (aPR: 0.64, 95% CI: 0.43–0.93) was associated with decreased prevalence. Overall, this research provides valuable insights into the risks and determinants of HIV and HCV co-infection among young PWID. The study’s findings contribute to the existing body of knowledge on blood-borne virus transmission in this population, informing evidence-based strategies for prevention and harm reduction.

Design and Proof of Concept of a Web-Based Questionnaire to Identify Patients at Risk for HIV and HCV Infection.

Despite remarkable improvement in the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) care continuum, the rate of late diagnosis of HIV and HCV in high-income countries remains unacceptably high. Testing relies mainly on primary care physicians' identification of risk factors. We aimed to adapt an analogic to an online questionnaire to help HIV and HCV screening and perform a pilot study to assess its accuracy and acceptability. We used the Delphi method to adapt a previously validated analogical questionnaire to a user-friendly online tool. It aimed to identify participants who should be screened for HIV or HCV and those who should be referred for pre-exposure prophylaxis (PrEP). We then designed a proof-of-concept pilot study from July to October 2022 to test its feasibility and suitability for use on a larger scale and to assess its accuracy in identifying patients at risk for HIV or HCV or with indication for PrEP. The final questionnaire consisted of 37 questions. A total of 142 participants provided informed consent, and 102 completed the questionnaire: 41 random patients recruited at the primary care level, 10 participants recently diagnosed with HIV, 20 participants with HIV on follow-up, 21 participants from the PrEP program, and 10 patients diagnosed with HCV. The tool adequately indicated the need for testing in more than 98% of participants with confirmed HIV/HCV infections or in the PrEP program. Furthermore, it adequately assessed PrEP referral in 94% of participants already on PrEP or with known HIV infection. Participants were highly satisfied with the tool, and 98% of them recommended its use. A self-administered web-based tool to identify patients who should be tested for HIV or HCV or referred to PrEP could simplify patient selection and help reduce late diagnosis.

Adopting the 2023 CDC Early Testing for Perinatal Hepatitis C: Call to Action for Pediatric Primary Care Providers.

In the US, the burden of hepatitis C virus (HCV) infection is disproportionately high among young adults including pregnant persons, resulting in increased infections among children as perinatal transmission remains the main route of HCV infection in children. Hence, in 2020, the Centers for Disease Control and Prevention (CDC) recommended universal HCV screening during each pregnancy. HCV infection in infancy is usually asymptomatic, so the diagnosis entirely relies on testing of perinatally-exposed infants which, historically, included anti-HCV antibody testing at ≥ 18 months of age. However, nation-wide perinatal HCV testing rates have been suboptimal with significant loss to follow up. To address this problem, in 2023, the CDC introduced early single HCV RNA testing at 2-6 months of age with an alternative for HCV RNA testing up to 17 months of age if not previously tested. The high sensitivity and specificity of the HCV real-time PCR laid the grounds for this policy shift. In this review we highlight how these new CDC recommendations will enhance testing of infants and children and ultimately contribute to overall HCV elimination efforts. We also emphasize the role of all pediatric providers and obstetricians in implementing these new guidelines. Additionally, we offer our perspective and practical advice for testing of perinatally exposed infants and children. Currently, curative oral antivirals for HCV-infection treatment are approved for children ≥ 3 years of age. As pediatricians, advocating for children's wellness, it is our utmost duty to ensure that every child exposed to perinatal hepatitis C has been tested, diagnosed, linked to care, treated, and achieved cure.

The Role of Epigenetic Mechanisms in the Pathogenesis of Hepatitis C Infection.

Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC.

Risk Factors Associated with Hepatitis C Subtypes and the Evolutionary History of Subtype 1a in Mexico.

The Hepatitis C Virus (HCV), with its diverse genotypes and subtypes, has significantly impacted the health of millions of people worldwide. Analyzing the risk factors is essential to understanding the spread of the disease and developing appropriate prevention strategies. This study aimed to identify risk factors associated with HCV subtype transmission and calculate the emergence time of subtype 1a in Mexico. A cross-sectional study was conducted from January 2014 to December 2018, involving 260 HCV-infected adults. HCV infection was confirmed via Enzyme-Linked Immunosorbent Assay, and viral load was measured by real-time PCR. Genotyping/subtyping tools were the Line Probe Assay and Sanger sequencing of the non-structural region 5B (NS5B). The most frequent HCV subtype was 1a (58.5%), followed by subtypes 1b (19.2%), 3a (13.1%), 2b (5.4%), 2a/2c (2.7%), 2a (0.8%), and 4a (0.4%). Intravenous drug use and tattoos were significant risk factors for subtypes 1a and 3a, while hemodialysis and blood transfusion were linked with subtype 1b. For the evolutionary analysis, 73 high-quality DNA sequences of the HCV subtype 1a NS5B region were used, employing a Bayesian coalescent analysis approach. This analysis suggested that subtype 1a was introduced to Mexico in 1976, followed by a diversification event in the mid-1980s. An exponential increase in cases was observed from 1998 to 2006, stabilizing by 2014. In conclusion, this study found that HCV subtypes follow distinct transmission routes, emphasizing the need for targeted prevention strategies. Additionally, the findings provide valuable insights into the origin of HCV subtype 1a. By analyzing the history, risk factors, and dynamics of the HCV epidemic, we have identified these measures: limiting the harm of intravenous drug trafficking, enhancing medical training and infrastructure, and ensuring universal access to antiviral treatments. The successful implementation of these strategies could lead to an HCV-free future in Mexico.

Modeling hepatocyte apoptosis in chronic HCV infection with impulsive drug control

Chronic hepatitis C virus (HCV) infection is one of the leading life-threatening diseases owing to its non-cytopathic nature and scarcity of vaccines to combat. Hepatocyte apoptosis casts extensive impact in regulating chronic HCV infection. We propose a four dimensional deterministic model scheming the role of hepatocyte apoptosis and significance of HCV-specific CTL response in the intermediate stages of chronic HCV infection. Numerical simulation indicates that unregulated behavior of hepatocyte apoptosis triggers hepatocellular carcinoma and prolonged continuation of apoptosis induces liver damages. The system undergoes backward bifurcation and the value of the basic reproduction number R0=0.98<1 shows recurrence of infection. Local sensitivity analysis has been performed to reveal the most sensitive parameters responsible for the progression and mitigation of infection. In order to control of chronic HCV infection through pan-genotypic direct acting antiviral drugs (DAAs), impulsive differential equations are considered to study the effect of perfect drug adherence to both fixed and non-fixed dosing. For possible eradication of the chronic HCV infection, impulsive drug control suggests significant viral load reduction. The analytical results obtained for both non-impulsive and impulsive models are quantified biologically.

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact.

Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment. A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases. Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution. By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.