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This study aimed to retrospectively investigate the prevalence of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections among blood donors at Anbar Blood Bank in Iraq. The study also explored the correlation between ABO and Rh blood groups with Transfusion-Transmissible Infections (TTIs) and sociodemographic factors and cross-sectional retrospective study was conducted on 100 blood donors at Anbar Blood Bank from March 24, 2023, to June 21, 2023. Inclusion criteria encompassed HBV and HCV-positive patients who provided consent, while exclusion criteria included individuals without HBV and HCV infections. Blood samples (5 mL) were collected, and tests for TTI markers (HBV, HCV) and ABO and Rh blood grouping were performed using enzyme-linked immunosorbent assay (ELISA) and slide method, respectively. Sociodemographic data, TTI marker results, and ABO and Rh blood types were recorded for analysis. Descriptive analysis of sociodemographic data was performed, and a chi-square test was employed to assess the correlation between ABO and Rh blood groups with TTI markers and sociodemographic factors (Age, sex, and living area). Statistical significance was set at P<0.05. The results revealed a male predominance (71%), with the majority aged between 20-30 years (39%) and residing in rural areas (52%). The most common blood group was O+ (39%), while AB- was the least prevalent (0%). In terms of viral infections, 80% of participants were found to be infected with HBs Ag, and 20% with HCV Ab. Notably, blood group O+ exhibited the highest infection rates for both HBs (28%) and HCV (11%), while blood group A- demonstrated the lowest HBs infection rate (3%) and no HCV infection. The study provides valuable insights into the prevalence of HBV and HCV infections among blood donors in Anbar, Iraq. Additionally, correlations between ABO and Rh blood groups, TTI markers, and sociodemographic factors were explored. The findings contribute to the understanding of transfusion

Background The World Health Organization has set a goal to reach world elimination of hepatitis C virus (HCV) by 2030. Needle and syringe programs (NSP) for people who inject drugs (PWID) are crucial to achieve this goal. The NSP in Uppsala, Sweden, was opened in 2016 and has since 2018 provided HCV treatment for PWID. The aim of this study was to investigate HCV prevalence, risk factors and treatment uptake and outcome in NSP participants. Methods Data from 450 PWID registered at the Uppsala NSP between 2016-11-01 and 2021-12-31 were collected from the national quality registry InfCare NSP. Data from the 101 PWID treated for HCV at the Uppsala NSP were collected through patient journal review. Descriptive and inferential analysis was performed. Ethical approval was obtained from the Ethical Review Board in Uppsala (dnr 2019/00215). Results The mean age was 35 years. 75% were males (336/450), and 25% were females (114/450). The overall HCV prevalence was 48% (215/450) with a declining trend over time. Factors associated with a higher risk of HCV were older age at registration (OR 1.025, 95% CI 1.004–1.046), lower age at injection drug debut (OR 0.963, 95% CI 0.932–0.996), lower education level (OR 1.829, 95% CI 1.185–2.821) and higher number of total visits at the NSP (OR 1.005, 95% CI 1.001–1.009). The overall HCV treatment uptake was 47% (101/215), of which 77% (78/101) completed HCV treatment. The HCV treatment compliance was 88% (78/89). 99% (77/78) were cured with a sustained virologic response 12 weeks after completed treatment. The reinfection rate over the study period was 9/77 (11.7%); all were male with mean age of 36. Conclusions HCV prevalence, treatment uptake and treatment outcome have improved since the opening of the Uppsala NSP. However, further measures are needed to reach the HCV elimination goal. Outreach HCV treatment programs for PWID should be explored and evaluated in combination with further implementation of low-threshold programs.

BackgroundMeasuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender.MethodsIn this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884.FindingsOur updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·

BACKGROUND: The trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy. METHODS: We assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1-2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1-2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count). RESULTS: INSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment. CONCLUSIONS: The apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential.

BACKGROUND: Men who have sex with men who ever injected drugs (ever MSM-IDU) carry a high hepatitis C virus (HCV) burden. We estimated whether current HCV testing and treatment in San Francisco can achieve the 2030 World Health Organization (WHO) HCV elimination target on HCV incidence among ever MSM-IDU. METHODS: A dynamic HCV/HIV transmission model among MSM was calibrated to San Francisco data, including HCV antibody (15.5%, 2011) and HIV prevalence (32.8%, 2017) among ever MSM-IDU. MSM had high HCV testing (79%-86% ever tested, 2011-2019) and diagnosed MSM had high HCV treatment (65% ever treated, 2018). Following coronavirus disease 2019 (COVID-19)-related lockdowns, HCV testing and treatment decreased by 59%. RESULTS: Among all MSM, 43% of incident HCV infections in 2022 were IDU-related. Among ever MSM-IDU in 2015, HCV incidence was 1.2/100 person-years (95% credibility interval [CrI], 0.8-1.6). Assuming COVID-19-related declines in HCV testing/treatment persist until 2030, HCV incidence among ever MSM-IDU will decrease by 84.9% (95% CrI, 72.3%-90.8%) over 2015-2030. This decline is largely attributed to HCV testing and treatment (75.8%; 95% CrI, 66.7%-89.5%). Slightly greater decreases in HCV incidence (94%-95%) are projected if COVID-19 disruptions recover by 2025 or 2022. CONCLUSIONS: We estimate that HCV incidence will decline by >80% over 2015-2030 among ever MSM-IDU in San Francisco, achieving the WHO target.

Cirrhosis is an important cause of morbidity and mortality in people with chronic liver disease worldwide. In 2019, cirrhosis was associated with 2.4% of global deaths. Owing to the rising prevalence of obesity and increased alcohol consumption on the one hand, and improvements in the management of hepatitis B virus and hepatitis C virus infections on the other, the epidemiology and burden of cirrhosis are changing. In this Review, we highlight global trends in the epidemiology of cirrhosis, discuss the contributions of various aetiologies of liver disease, examine projections for the burden of cirrhosis, and suggest future directions to tackle this condition. Although viral hepatitis remains the leading cause of cirrhosis worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated cirrhosis are rising in several regions of the world. The global number of deaths from cirrhosis increased between 2012 and 2017, but age-standardized death rates (ASDRs) declined. However, the ASDR for NAFLD-associated cirrhosis increased over this period, whereas ASDRs for other aetiologies of cirrhosis declined. The number of deaths from cirrhosis is projected to increase in the next decade. For these reasons, greater efforts are required to facilitate primary prevention, early detection and treatment of liver disease, and to improve access to care.

BackgroundThe Veterans Health Administration (VA) is the largest integrated healthcare organization in the US and cares for the largest cohort of individuals with hepatitis C (HCV). A national HCV population management dashboard enabled rapid identification and treatment uptake with direct acting antiviral agents across VA hospitals. We describe the HCV dashboard (HCVDB) and evaluate its use and user experience.MethodsA user-centered design approach created the HCVDB to include reports based on the HCV care continuum: 1) 1945-1965 birth cohort high-risk screening, 2) linkage to care and treatment of chronic HCV, 3) treatment monitoring, 4) post-treatment to confirm cure (i.e., sustained virologic response), and 5) special populations of unstably housed Veterans. We evaluated frequency of usage and user experience with the System Usability Score (SUS) and Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) instruments.ResultsBetween November 2016 and July 2021, 1302 unique users accessed the HCVDB a total of 163,836 times. The linkage report was used most frequently (71%), followed by screening (13%), sustained virologic response (11%), on-treatment (4%), and special populations (<1%). Based on user feedback (n = 105), the mean SUS score was 73±16, indicating a good user experience. Overall acceptability was high with the following UTAUT2 rated from highest to least: Price Value, Performance Expectancy, Social Influence, and Facilitating Conditions.ConclusionsThe HCVDB had rapid and widespread uptake, met provider needs, and scored highly on user experience measures. Collaboration between clinicians, clinical informatics, and population health experts was essential for dashboard design and sustained use. Population health management tools have the potential for large-scale impacts on care timeliness and efficiency.

BackgroundIn California, laboratories report all hepatitis C (HCV)-positive antibody tests to the state; however, that does not accurately reflect active infection among those patients without a viral load test confirming a patient's HCV diagnosis. These public health surveillance disease incident records do not include patient details such as comorbidities or insurance status found in electronic medical records (EMRs).ObjectiveThis research seeks to understand how insurance type, insurance status, patient comorbidities, and other sociodemographic factors related to HCV diagnosis as defined by a positive viral load test among HCV antibody-positive persons from January 1, 2010 to March 1, 2020.MethodsHCV antibody-positive individuals reported to the California Reportable Disease Information Exchange (CalREDIE), with a medical record number associated with the University of California, Irvine Medical Center, and an unrestricted EMR (n = 521) were extracted using manual chart review.Main outcomes and measuresHCV diagnosis as indicated in a patient's EMR in the problem list or disease registry.ResultsLess than a quarter of patients in this sample were diagnosed as having HCV in their EMR, with 0.4% of those diagnosed (5/116) patients with indicated HCV treatment in the medication field of their charts. After adjusting for multiple comorbidities, a multinomial logistic regression found that the relative risk ratios (RRRs) of HCV diagnosis found that patients with insurance were more likely to be diagnosed compared to those without insurance. When comparing uninsured patients to those with government insurance at the P < .05 level (RRR = 10.61 (95% confidence interval (CI): 4.14-27.22)) and those uninsured to private insurance (RRR = 6.79 (95% CI: 2.31-19.92).ConclusionsThese low frequencies of HCV diagnosis among the study population, particularly among the uninsured, indicate a need for increased viral load testing and linkage to care. Reflex testing on existing samp

BackgroundPrior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women.MethodsThis was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures.ResultsFEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements.ConclusionsHIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.

BackgroundDue to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine.MethodsIn this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships.ResultsBetween June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement.ConclusionsLocally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

Six refugee screening sites collaborated to estimate the prevalence of hepatitis C virus (HCV) antibodies among newly arrived refugees in the United States from 2010 to 2017, identify demographic characteristics associated with HCV antibody positivity, and estimate missed HCV antibody-positive adults among unscreened refugees. We utilized a cross-sectional study to examine HCV prevalence among refugees (N = 144,752). A predictive logistic regression model was constructed to determine the effectiveness of current screening practices at identifying cases. The prevalence of HCV antibodies among the 64,703 refugees screened was 1.6%. Refugees from Burundi (5.4%), Moldova (3.8%), Democratic Republic of Congo (3.2%), Burma (2.8%), and Ukraine (2.0%) had the highest positivity among refugee arrivals. An estimated 498 (0.7%) cases of HCV antibody positivity were missed among 67,787 unscreened adults. The domestic medical examination represents an opportunity to screen all adult refugees for HCV to ensure timely diagnosis and treatment.

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family of receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, ErbB2, and ErbB4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, proinflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production, and disruption of blood-brain barrier integrity in microfluidics-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof of principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

ImportanceSome payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection.ObjectiveTo evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR).Design, setting, and participantsThis retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023.ExposureAlcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.Main outcomes and measuresThe primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category.ResultsAmong 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result in several metabolic disorders and ApoE genotypes have been associated with multiple diseases. ApoE is synthesized at the endoplasmic reticulum and transported to the Golgi apparatus for LP assembly; however, the ApoE-LPs transport pathway from there to the plasma membrane is largely unknown. Here, we established an integrative imaging approach based on a fully functional fluorescently tagged ApoE. We found that newly synthesized ApoE-LPs accumulate in CD63-positive endosomes of hepatocytes. In addition, we observed the co-egress of ApoE-LPs and CD63-positive intraluminal vesicles (ILVs), which are precursors of extracellular vesicles (EVs), along the late endosomal trafficking route in a microtubule-dependent manner. A fraction of ApoE-LPs associated with CD63-positive EVs appears to be co-transmitted from cell to cell. Given the important role of ApoE in viral infections, we employed as well-studied model the hepatitis C virus (HCV) and found that the viral replicase component nonstructural protein 5A (NS5A) is enriched in ApoE-containing ILVs. Interaction between NS5A and ApoE is required for the efficient release of ILVs containing HCV RNA. These vesicles are transported along the endosomal ApoE egress pathway. Taken together, our data argue for endosomal egress and transmission of hepatic ApoE-LPs, a pathway that is hijacked by HCV. Given the more general role of EV-mediated cell-to-cell communication, these insights provide new starting points for research into the pathophysiology of ApoE-related metabolic and infection-related disorders.

OBJECTIVES To measure the frequency of sustained virologic response in Hepatitis C positive, treatment naïve patients on Sofosbuvir and Daclatasvir.METHODOLOGY This descriptive study was conducted in the Department of Medicine, Khyber Teaching Hospital Peshawar from 15th May 2020 to 14th November, 2020. A sample size of 93 was calculated by using sustained virologic response in 96% patients using Sofosbuvir and Daclatasvir with the confidence level as 95% and 4% margin of error under WHO formula for sample size determination in health studies. Consecutive non probability sampling technique was used in the study.RESULTSNinety Three treatment naïve hepatitis C patients were included in the study containing 53 males (57%) and 40 females (43%) with mean age of 43 + 0.23. 84 (90%) patients were in Child A class according to Child Pugh score. Overall 89 (95.7%) patients showed sustained virologic response following 12 weeks treatment of naïve HCV patients with combination of sofosbuvir and daclastavir. 5 patients developed side effects to the drugs; 2 patients developed anemia with one patient having anemia severe enough to require blood transfusion. 4 patients did not respond to the treatment regime in terms of sustained virologic response for 12 week treatment and were continued for 24 weeks on the same regime. CONCLUSION This study concludes that combined sofosbuvir and daclatasvir for 12 weeks appear to have sustained virologic response in treatment naïve HCV patients. Child score has statistically significant correlation to sustained virologic response with Child A class showing SVR in all patients. Patients in Child class C did not show SVR. Thrombocytopenia has direct and negative affect on SVR.

OBJECTIVES To determine the frequency of the Hepatitis C Virus in patients with chronic kidney disease receiving regular hemodialysis. METHODOLOGY At a tertiary care hospital in Peshawar, 211 patients were observed to ascertain the frequency of the Hepatitis C Virus in chronic kidney disease patients receiving regular hemodialysis. The technique of non-probability sequential sampling was employed to acquire samples. SPSS version 26.0 was used. RESULTSAmong the CKD patients with Hepatitis C Virus (HCV) infection, a higher proportion of males (48.5%) tested positive compared to females (28.1%). Furthermore, the prevalence of HCV infection was significantly higher in CKD patients residing in urban areas (98.5%) compared to those in rural areas (1.5%). The statistical analysis indicated a significant association between the prevalence of Hepatitis and the factors of gender and residency (P value = 0.002). Out of 211, hepatitis C-positive patients 66.2% were diabetics and hypertensive were 77.9%. CONCLUSION Hospitalized CKD patients have a considerably higher frequency of hepatitis C infection. To stop the spread of the hepatitis C virus, nephrology wards should undertake strict universal infection control procedures.

[Background] Once HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH., [Methods] Cross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections., [Results] One hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%)., [Conclusions] After HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver, where 90% of cases of primary liver tumors are caused by this tumor. About 85% of HCC tumor cases also have cirrhosis of the liver. Currently, HCC is the fifth most malignant tumor in the world. Other than that, San HCC's survival is scanty. A patient at Dr. Soetomo complained of an enlarged stomach 5 months ago. The patient was first diagnosed with Hepatitis C 3 months ago but has not been treated for hepatitis C. The patient underwent several examinations in January, March and May 2022. Supportive testing of normal AFP and anti-HCV levels was performed with a positive result for HCV RNA >11.00. When considering liver function tests to assess liver disease severity using the CTP score, the score is 7 (CTP B). X-ray examination, CT scan and tumor size 11.2 x 6.7 cm were obtained, fed from the right a. hepatica, and there was no thrombosis in v. porta/hepatica. In these patients, there was no arterial enhancement, venous phase washout, and pseudocysts. The liver tumor of the aorta to the aorta, the largest size 7.3 x 11.3 x 15.9 cm, is equal to VTh11-VL3. The link expands to ±6.8 inches. Since the AFP test was normal and the CT scan did not show these results, this patient will be followed up with a biopsy. The biopsy method was performed with FNAB considering the safety of the procedure and the patient profile. Atypical FNAB results but favorable histochemistry for HCC, where CK, glypican-3, and AFP are positive. Based on the results of the examination, it was stated that the patient had Hepatoocellular Carcinoma (HCC) accompanied by cirrhosis of the liver due to chronic hepatitis C infection.

Purpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool. Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients >50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients). Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/ VEL regimen was more frequently detected on elderly patients and on those with ≥2 comedications at risk

Background: Hepatitis C virus (HCV) infection has increased among persons who inject drugs (PWID) in the United States with disproportionate burden in rural areas. We use the Risk Environment framework to explore potential economic, physical, social, and political determinants of hepatitis C in rural southern Illinois. Methods: Nineteen in-depth semi-structured interviews were conducted with PWID from August 2019 through February 2020 (i.e., pre-COVID-19 pandemic) and four with key informants who professionally worked with PWID. Interviews were recorded, professionally transcribed, and coded using qualitative software. We followed a grounded theory approach for coding and analyses. Results: We identify economic, physical, policy, and social factors that may influence HCV transmission risk and serve as barriers to HCV care. Economic instability and lack of economic opportunities, a lack of physically available HCV prevention and treatment services, structural stigma such as policies that criminalize drug use, and social stigma emerged in interviews as potential risks for transmission and barriers to care. Conclusion: The rural risk environment framework acknowledges the importance of community and structural factors that influence HCV infection and other disease transmission and care. We find that larger structural factors produce vulnerabilities and reduce access to resources, which negatively impact hepatitis C disease outcomes.

BACKGROUND: Neuroimaging reveals structural brain changes linked with HIV infection and related neurocognitive disorders; however, group-level comparisons between people with HIV and people without HIV do not account for within-group heterogeneity. The aim of this study was to quantify the effects of comorbidities such as cardiovascular disease and adverse social determinants of health on brain ageing in people with HIV and people without HIV. METHODS: In this retrospective case-control study, people with HIV from Washington University in St Louis, MO, USA, and people without HIV identified through community organisations or the Research Participant Registry were clinically characterised and underwent 3-Tesla T1-weighted MRI between Dec 3, 2008, and Oct 4, 2022. Exclusion criteria were established by a combination of self-reports and medical records. DeepBrainNet, a publicly available machine learning algorithm, was applied to estimate brain-predicted age from MRI for people with HIV and people without HIV. The brain-age gap, defined as the difference between brain-predicted age and true chronological age, was modelled as a function of clinical, comorbid, and social factors by use of linear regression. Variables were first examined singly for associations with brain-age gap, then combined into multivariate models with best-subsets variable selection. FINDINGS: In people with HIV (mean age 44·8 years [SD 15·5]; 78% [296 of 379] male; 69% [260] Black; 78% [295] undetectable viral load), brain-age gap was associated with Framingham cardiovascular risk score (p=0·0034), detectable viral load (>50 copies per mL; p=0·0023), and hepatitis C co-infection (p=0·0065). After variable selection, the final model for people with HIV retained Framingham score, hepatitis C, and added unemployment (p=0·0015). Educational achievement assayed by reading proficiency was linked with reduced brain-age gap (p=0·016) for people without HIV but not for people with HIV, indicating a poten

This paper presents a new procedure for vaccine design against highly variable viruses such as Hepatitis C. The procedure uses an optimization algorithm to design vaccines that maximize the coverage of epitopes across different virus variants. Weighted epitopes based on the success ratio of immunological assays are used to prioritize the selection of epitopes for vaccine design. The procedure was successfully applied to design DC vaccines loaded with two HCV peptides, STG and DYP, which were shown to be safe, immunogenic, and able to induce significant levels of anti-viral cytokines, peptide-specific cellular immune responses and IgG antibodies. The procedure could potentially be applied to other highly variable viruses that currently lack effective vaccines

Hepatitis C is the most infectious bloodborne disease in the United States. For my dissertation, I will focus on the study population in Orange County, California. This high-risk area has a significant substance use rehabilitation tourism industry with over 400 rehabilitation facilities).1 and a marked increase in reported HCV cases since 2011. 2 The purpose of this dissertation was to understand why, despite effective HCV treatment, Orange County patients who test antibody-positive are not directly followed up with viral load tests and then initiated on HCV treatment. This question merits further research using routinely collected and reported public health surveillance data and electronic medical records at health care facilities. The goals of this research were to examine socioeconomic individual and group-level correlates of the following outcomes: HCV viral load testing, undetectable HCV viral load, and HCV diagnosis in a health care setting using the University of California, Irvine Medical Center (UCIMC) medical records with chart review. This research utilized secondary data using multivariable logistic regressions and multivariable Cox Proportional Hazard regression to answer these research questions. With an n of 27,389 individuals, that only 3.16 percent of all patients from 2010 to 2020 showed undetectable viral load. Only 37 percent of these patients were not ever viral load tested from 2010 to 2020, leaving the viremic status of these patients unknown. Those over 65 were more likely to have an undetectable HCV viral load than younger adults (HR =2.00). Residents living in census tracts in the third and fourth quartiles of percent enrollment in health insurance showed a greater likelihood of undetectable viral load. When examining 521 electronic medical records (EMRs), only 22 percent of those reported as HCV antibody-positive indicated an HCV-positive diagnosis in their EMR. Less than one percent of patients n=5 were prescribed HCV treatment. These res

Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8+ T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8+ T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an in vitro setting using primary human cells.

BackgroundIn 2017, San Francisco's initiative to locally eliminate hepatitis C virus (HCV) as a public health threat, End Hep C SF, generated an estimate of city-wide HCV prevalence in 2015, but only incorporated limited information about population HCV treatment. Using additional data and updated methods, we aimed to update the 2015 estimate to 2019 and provide a more accurate estimate of the number of people with untreated, active HCV infection overall and in key subgroups-people who inject drugs (PWID), men who have sex with men (MSM), and low socioeconomic status transgender women (low SES TW).MethodsOur estimates are based on triangulation of data from blood bank testing records, cross-sectional and longitudinal observational studies, and published literature. We calculated subpopulation estimates based on biological sex, age and/or HCV risk group. When multiple sources of data were available for subpopulation estimates, we calculated an average using inverse variance weighting. Plausible ranges (PRs) were conservatively estimated to convey uncertainty.ResultsThe total number of people estimated to have anti-HCV antibodies in San Francisco in 2019 was 22,585 (PR:12,014-44,152), with a citywide seroprevalence of 2.6% (PR:1.4%-5.0%)-similar to the 2015 estimate of 21,758 (PR:10,274-42,067). Of all people with evidence of past or present infection, an estimated 11,582 (PR:4,864-35,094) still had untreated, active HCV infection, representing 51.3% (PR:40.5%-79.5%) of all people with anti-HCV antibodies, and 1.3% (PR:0.6%-4.0%) of all San Franciscans. PWID comprised an estimated 2.8% of the total population of San Francisco, yet 73.1% of people with anti-HCV antibodies and 90.4% (n = 10,468, PR:4,690-17,628) of untreated, active HCV infections were among PWID. MSM comprised 7.8% of the total population, yet 11.7% of people with anti-HCV antibodies and 1.0% (n = 119, PR:0-423) of those with untreated active infections. Low SES TW comprised an estimated 0.1% of the to

BackgroundPersons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US).MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals.ResultsWe identified 24 studies published between 1996-2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach).ConclusionsA very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in all other regions. Between 2010 and 2019, non-alcoholic steatohepatitis (NASH) and alcohol had the fastest growing ASDRs, while HCV and HBV declined. Urgent measures are required at a global level to tackle underlying metabolic risk factors and slow the growing burden of NASH-associated liver cancer, especially in the Americas.

BackgroundPeople who inject drugs (PWID) are vulnerable to SARS-CoV-2 infection. We examined correlates of COVID-19 testing among PWID in the U.S.-Mexico border region and described encounters with services representing potential opportunities (i.e., 'touchpoints') where COVID-19 testing could have been offered.MethodsBetween October, 2020 and September, 2021, participants aged ≥18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month completed surveys and SARS-CoV-2, HIV, and HCV serologic testing. Logistic regression identified factors associated with COVID-19 testing including potential touchpoints, comorbidities and COVID-19 related misinformation and disinformation.ResultsOf 583 PWID, 30.5% previously had a COVID-19 test. Of 172 PWID who tested SARS-CoV-2 seropositive (30.1%), 50.3% encountered at least one touchpoint where COVID-19 testing could have been offered within the prior six months. Factors independently associated with at least two fold higher odds of COVID-19 testing were living in San Diego, recent incarceration, receiving substance use treatment, and experiencing ≥1 chronic health condition. Homelessness, having received ≥1 dose of COVID-19 vaccine, and having a HIV or HCV test since the COVID-19 epidemic began were also independently associated with having had a prior COVID-19 test.ConclusionWe identified several factors independently associated with COVID-19 testing and multiple touchpoints where COVID-19 testing could be scaled up for PWID, such as SUD treatment programs and syringe service programs. Integrated health services are needed to improve access to rapid, free COVID-19 testing in this vulnerable population.

PurposeThe Liver Disease and Reproductive Ageing (LIVRA) study leverages the infrastructure of the decades-long multicentre prospective Women's Interagency HIV Study (WIHS) to examine the contributions of HIV, hepatitis C virus (HCV) and ageing to liver disease progression in women.ParticipantsFrom 2013 to 2018, LIVRA enrolled 1576 participants (77 HCV-seropositive only, 248 HIV/HCV-seropositive, 868 HIV-seropositive only and 383 HIV/HCV-seronegative) who underwent vibration controlled transient elastography (VCTE). A VCTE quality assurance programme was established to ensure consistency and accuracy for longitudinal assessment of steatosis (fatty liver) via the controlled attenuation parameter (CAP) and fibrosis via liver stiffness (LS). Demographic, lifestyle factors, anthropometry, clinical and medication history, host genetics, immune markers and hormone levels were collected as part of the WIHS.Findings to dateAt baseline, 737 of 1543 women with CAP measurements had steatosis (CAP ≥248 dB/m) and 375 of 1576 women with LS measurements had significant fibrosis (LS ≥7.1 kPa), yielding a prevalence of 48% and 24%, respectively. On multivariable analysis, waist circumference (WC) and insulin resistance were independently associated with higher CAP (17.8 dB/m per 10 cm (95% CI:16.2 to 19.5) and 1.2 dB/m per doubling (95% CI:0.8 to 1.6), respectively). By contrast, HIV/HCV seropositivity and HCV seropositivity alone were associated with less steatosis compared with HIV/HCV-seronegative women, although the latter did not reach statistical significance (-9.2 dB/m (95% CI:-18.2 to -0.3) and -10.4 dB/m (95% CI: -23.8 to 3.1), respectively). Factors independently associated with higher LS were age (4.4% per 10 years (95% CI: 0.4% to 8.4%)), WC (5.0% per 10 cm (95% CI: 3.3% to 6.6%)), CAP steatosis (0.6% per 10 dB/m (95% CI: 0.1% to 1.0%)), HIV/HCV seropositivity (33% (95% CI: 24% to 44%)) and HCV seropositivity alone (43% (95% CI: 28% to 60%)). Excluding scans that were in

Bakgrund: Hepatit C (HCV) är en virussjukdom som smittar via blodet. Personer sominjicerar droger (PSID) riskerar att drabbas av HCV till följd av injektionsrelateraderiskbeteenden. Idag finns det effektiv behandling mot HCV men det kräver viss följsamhet avden som behandlas. Syfte: Syftet var att undersöka sjuksköterskors upplevelser av följsamhet till behandling avhepatit C hos personer som injicerar droger. Metod: En kvalitativ intervjustudie genomfördes. Totalt intervjuades åtta sjuksköterskor frånfyra mottagningar. Datan analyserades sedan enligt Lundberg och Graneheims modell förkvalitativ innehållsanalys. Resultat: Resultatet sammanfattades under fyra huvudkategorier: Livssituation, Samverkan,Behandlingsrelaterade aspekter och Stigma. Totalt identifierades tretton subkategorier. Slutsats: Sjuksköterskor upplevde stora variationer i följsamhet till behandling hos PSID. Detupplevdes som positivt för följsamheten om PSID fick förutsättningar såsom en stabil tillvarooch regelbunden kontakt med en mottagning. I resultatet framkom att det var viktigt attvården var tillgänglig och att PSID fick ordentlig information om behandlingen. Det upplevdesäven som positivt om det fanns fungerande samverkan med både PSID och mellan deverksamheter som de kom i kontakt med. Stigmatiseringen av HCV och PSID upplevdessom ett centralt hinder för följsamhet., Background: Hepatitis C (HCV) is a viral disease which is transmitted through blood. Peoplewho inject drugs (PWID) are at risk of developing HCV as a result of injection-related riskbehaviors. There is effective treatment for HCV, but it requires some degree of adherence. Aim: The aim was to investigate nurses’ experiences of adherence to treatment for hepatitisC in people who inject drugs. Method: A qualitative interview study was conducted. Eight nurses from four clinics wereinterviewed. The data was analyzed according to Lundberg and Graneheim's model forqualitative content analysis. Results: The results were summarized under four main categories: Life situation,Collaboration, Treatment-related factors and Stigma. Thirteen subcategories were identified. Conclusion: Nurses experienced large variations in adherence to treatment among PWID. Itwas perceived as positive for adherence if PWID had stable living conditions and regularcontact with a clinic. Availability and information about the treatment were important factors.It was also perceived as positive if there was functioning collaboration with PWID andbetween the institutions they came in contact with. The stigmatization of HCV and PWID wasperceived as a key obstacle to adherence.

Hepatitis C virus (HCV) infection is a major global health burden, with an estimated 71 million people infected worldwide. Vaccine design for HCV is challenging for multiple reasons, including high sequence variability of the glycoprotein E2, as well as the lack of a small animal challenge model in which to test vaccine candidates. This thesis addresses aspects of both challenges. Glycoprotein E2 is present on the virion surface and is a major target of neutralizing antibodies which can prevent infection. The N-terminal hypervariable region 1, HVR1 (residues 384-411), of E2 is an immunodominant region within E2 and elicits neutralizing antibodies that are usually isolate specific. We previously identified a novel murine monoclonal antibody, MAb33, which binds to an unusual epitope bridging HVR1 and the adjacent target of broadly neutralizing antibodies referred to as epitope I (residues 412-423). MAb33 potently neutralizes genotype 1a viruses and can cross-neutralize 3 different HCV genotypes. This study defined the epitope of MAb33 to include residues within the E2 region 401-415 and resolved its structure in complex with its epitope. The epitope adopts an alpha-helical conformation with residues G406, A407 and N410 involved in direct polar interaction with the antibody. The helical structure of the epitope differs from the extended conformation of other E2 crystal structures that include this region, suggesting that it could be conformationally flexible. Sero-surveys of HCV positive individuals have identified significant reactivity to a peptide encompassing the MAb33 epitope, indicating a role for MAb33-like antibodies in natural infection. To address the need for an immune competent model for HCV vaccine development, a Rodent hepacivirus (RHV) was investigated as it shows close evolutionary relatedness and virological similarities with HCV and represents an important potential model of HCV pathogenesis and host responses. While the T cell response to RHV has bee

No abstract available

BackgroundAlthough viral hepatitis causes paediatric hepatocellular carcinoma and hepatic and extrahepatic cancers in adults, there are few epidemiologic studies on paediatric-cancer risks from parental viral hepatitis. In a nationwide study in a viral hepatitis endemic region and with confirmation in another population-based sample, we examined associations between parental hepatitis B (HBV) and C (HCV) infections and risks of cancers in offspring.MethodsWe included all children born in Taiwan in 2004-2014 (N = 2 079 037) with 2160 cancer cases ascertained from the Cancer Registry. We estimated risks for paediatric cancers using Cox proportional-hazard regressions. We checked these associations in a nationwide case-control study in Denmark (6422 cases, 160 522 controls).ResultsIn Taiwan, paternal HBV was related to child's hepatoblastoma [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05, 2.97] when identified at any time in the medical record, and when analyses were limited to hepatitis diagnoses occurring before the child's birth, risks increased (HR = 2.08, 95% CI = 1.13-3.80). Paternal HCV was related to child's non-Hodgkin lymphoma (HR = 2.06, 95% CI = 1.13-3.74). Maternal HCV was weakly related to increased risks of all childhood cancers [all types combined; HR = 1.45, 95% CI = 0.95-2.22]. The population-attributable fraction of hepatoblastoma for maternal, paternal and child HBV was 2.6%, 6.8% and 2.8%, respectively.ConclusionsParental HBV and HCV may be risk factors for hepatic and non-hepatic cancers in children. If associations are causal, then parental screening and treatment with antivirals may prevent some paediatric cancers.

BackgroundDirect-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine.MethodsUsing data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status.ResultsAmong the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2]), social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5]) and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants.ConclusionQOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.