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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 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.

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.

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·

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.

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.

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.

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.

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.

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.

[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.

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

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.

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: The objective of this study was to evaluate the effectiveness of formal hepatitis C virus (HCV) education on engagement in therapy in persons experiencing homelessness in an on-site shelter-based model of care. As policies to eliminate Medicaid access restrictions to HCV treatment are expanded, patient education is paramount to achieving HCV elimination targets in difficult-to-engage populations including persons experiencing homelessness. METHODS: This prospective study was conducted at 4 shelters in San Francisco and Minneapolis from August 2018 to January 2021. Of the 162 HCV Ab-positive participants, 150 participated in a 30-minute HCV education session. Posteducation changes in knowledge, beliefs, barriers to care, and willingness to accept therapy scores were assessed. RESULTS: Following education, knowledge scores (mean change, 4.4 ± 4.4; P < .001) and willingness to accept therapy (70% to 86%; P = .0002) increased. Perceived barriers to HCV care decreased (mean change, -0.8 ± 5.2; P = .001). Higher baseline knowledge was associated with lesser gain in knowledge following education (coef., -0.7; P < .001). Posteducation knowledge (odds ratio, 1.2; P = .008) was associated with willingness to accept therapy. CONCLUSIONS: An HCV educational intervention successfully increased willingness to engage in HCV therapy in persons experiencing homelessness in an on-site shelter-based HCV model of care.

Hepatitis C virus (HCV) prevalence is high among people experiencing homelessness, but barriers to scaling up HCV testing and treatment persist. We aimed to implement onsite HCV testing and education and evaluate the effectiveness of low-barrier linkage to HCV therapy among individuals accessing homeless shelters. HCV rapid testing was performed at four large shelters in San Francisco (SF) and Minneapolis (MN). Sociodemographic status, HCV risk, barriers to testing, and interest in therapy were captured. Participants received information about HCV. Those testing positive underwent formal HCV education and onsite therapy. Multivariable modeling assessed predictors of receipt of HCV therapy and sustained virologic response (SVR). A total of 766 clients were tested. Median age was 53.7 years, 68.2% were male participants, 46.3% were Black, 27.5% were White, 13.2% were Hispanic, and 57.7% had high school education or less; 162 (21.1%) were HCV antibody positive, 107 (66.0%) had detectable HCV RNA (82.1% with active drug use, 53.8% history of psychiatric illness), 66 (61.7%) received HCV therapy, and 81.8% achieved SVR. On multivariate analysis, shelter location (MN vs. SF, odds ratio [OR], 0.3; P = 0.01) and having a health care provider (OR, 4.1; P = 0.02) were associated with receipt of therapy. On intention to treat analysis, the only predictor of SVR when adjusted for age, sex, and race was HCV medication adherence (OR, 14.5; P = 0.01). Conclusion: Leveraging existing homeless shelter infrastructure was successful in enhancing HCV testing and treatment uptake. Despite high rates of active substance use, psychiatric illness, and suboptimal adherence, over 80% achieved HCV cure. This highlights the critical importance of integrated models in HCV elimination efforts in people experiencing homelessness that can be applied to other shelter settings.

We analyzed the rate of patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection diagnosed by pre-operative screening and estimated its cost. We retrospectively analyzed patients who underwent elective surgery at our maxillofacial surgery department between April 2014 and March 2022. We compared the number of patients with each infection identified by pre-operative screening and a pre-operative questionnaire. We also compared the prevalence of infections with varying age, sex, and oral diseases, and calculated the cost of screening per positive result. The prevalence of HBV, HCV, and HIV was 0.39% (62/15,842), 0.76% (153/15,839), and 0.07% (10/12,745), respectively. The self-reported rates were as follows: HBV, 63.4% (26/41); HCV, 50.4% (62/123); HIV, 87.5% (7/8). Differences in sex were statistically significant for all infectious diseases; age significantly affected HBV and HCV rates. There was no association between the odds ratio of oral disease and viral infections. The cost per positive result was $1873.8, $905.8, and $11,895.3 for HBV, HCV, and HIV, respectively. Although self-assessment using questionnaires is partially effective, it has inadequate screening accuracy. Formulating an auxiliary diagnosis of infectious diseases with oral diseases was challenging. The cost determined was useful for hepatitis, but not HIV.

Testing and treatment resource guide for chlamydia, gonorrhea, syphilis, herpes, hepatitis C, and HIV/AIDS. This testing guide was developed as a resource and is not a comprehensive list of providers.

Hepatitis is inflammation of the liver. Hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are some of the most common types of viral hepatitis. Hepatitis A is a vaccine-preventable liver infection caused by the hepatitis A virus (HAV). It is spread when someone unknowingly ingests the virus—even in microscopic amounts—through close personal contact with an infected person or through consumption of contaminated food or drink. Most people with hepatitis A do not have long-lasting illness. HBV is spread through blood, sexual fluid, or other body fluids. HCV is spread through blood only. While HAV and HBV are vaccine-preventable, there are currently no curative treatments. There is no vaccine available for HCV, but highly effective medication is available to clear the virus. Illness from viral hepatitis may last a few weeks (acute) or become a lifelong illness (chronic; HBV and HCV only). Acute HBV and HCV infection can range in severity from a very mild illness with few or no symptoms to a serious condition which requires hospitalization, while chronic infection can cause serious health problems, including liver disease, liver failure, liver cancer, and even death. Symptoms, including fever, fatigue, loss of appetite, nausea, vomiting, dark urine, gray-colored stool, joint pain, and yellow skin and eyes, are common with HAV but rare with HBV and HCV. The Utah Department of Health and Human Services (DHHS) Disease Response, Evaluation, Analysis, and Monitoring (DREAM) Program’s Viral Hepatitis Program manages and conducts surveillance for viral hepatitis cases, which are reportable conditions in Utah through Utah Administrative Code, Title R386-702 Communicable Disease Rule (CD rule). Labs reporting electronically are required to report both negative and positive results. More than 90% of labs in Utah report electronically. Demographics, risk factors, and laboratory results are collected in the National Electronic Disease Surveillance System

The Utah Department of Health and Human Services (DHHS) Disease Response, Evaluation, Analysis, and Monitoring (DREAM) Program’s Viral Hepatitis Program manages and conducts surveillance for viral hepatitis cases, which are reportable conditions in Utah through Utah Administrative Code, Title R386-702 Communicable Disease Rule (CD rule). Labs reporting electronically are required to report both negative and positive results. More than 90% of labs in Utah report electronically. Demographics, risk factors, and laboratory results are collected in the National Electronic Disease Surveillance System (NEDSS), called EpiTrax. This report presents hepatitis A, B, and C surveillance data collected by DHHS in 2020.

Disease investigation plan about hepatitis C. Includes information on the disease and epidemiology, public health control measures, and case investigation.

BackgroundAcute rejection (AR) and recurrent hepatitis C virus (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management.MethodsWe performed small RNA sequencing and microRNA (miRNA) microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized real-time quantitative PCR (RT-qPCR) assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve.ResultsNine miRNAs-miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210, and miR-885-5p-were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P < 0.0001) as the best statistical model and miR-122 + miR-210 (P < 0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis.ConclusionsCirculating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to R-HCV.

In 2019, Mexico was one of the first countries in Latin America to commit resources to achieve hepatitis C elimination by 2030. One year after this commitment, the global COVID-19 pandemic diverted attention to address immediate health needs to combat the spread of the disease. As a result, efforts to implement hepatitis C prevention and management programs were indefinitely postponed. Furthermore, populations at high risk of contracting the hepatitis C virus (HCV) and who bear the greatest burden of HCV national epidemic, including people who inject drugs and people who live with human immunodeficiency virus infection, remain exposed to extreme health disparities, which have potentially been exacerbated during the COVID-19 pandemic. In this article, we discuss the potential impact the COVID-19 pandemic has had on HCV elimination efforts in Mexico and the urgent need to resume them, since without these efforts, HCV elimination goals are likely not be achieved in the country by 2030.

BackgroundThe current opioid epidemic across the United States has fueled a surge in the rate of new hepatitis C virus (HCV) infections among young persons who inject drugs (PWIDs). Paramount to interrupting transmission is targeting these high-risk populations and understanding the underlying network structures facilitating transmission within these communities.MethodsDeep sequencing data were obtained for 52 participants from 32 injecting partnerships enrolled in the U-Find-Out (UFO) Partner Study, which is a prospective study of self-described injecting dyad partnerships from a large community-based study of HCV infection in young adult PWIDs from San Francisco. Phylogenetically linked transmission events were identified using traditional genetic-distance measures and viral deep sequence phylogenies reconstructed to determine the statistical support of inferences and the direction of transmission within partnerships.ResultsUsing deep sequencing data, we found that 12 of 32 partnerships were genetically similar and clustered. Three additional phylogenetic clusters were found describing novel putative transmission links outside of the injecting relationship. Transmission direction was inferred correctly for 5 partnerships with the incorrect transmission direction inferred in more than 50% of cases. Notably, we observed that phylogenetic linkage was most often associated with a lower number of network partners and involvement in a sexual relationship.ConclusionsDeep sequencing of HCV among self-described injecting partnerships demonstrates that the majority of transmission events originate from outside of the injecting partnership. Furthermore, these findings caution that phylogenetic methods may be unable to routinely infer the direction of transmission among PWIDs especially when transmission events occur in rapid succession within high-risk networks.

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.

PurposeHepatitis C virus (HCV) is the most common blood-borne infection in the United States, and a leading cause of liver disease, transplant, and mortality. CDC HCV elimination goals include reducing HCV-related mortality by 65% (from 2015) by 2030.MethodsWe used vital registry data (CDC WONDER) to estimate overall and demographic-specific HCV-related mortality from 1999 to 2019 in San Francisco and then used an exponential model to project progress toward HCV elimination. Local trends were compared to state and national trends.ResultsBetween 1999 and 2019, there were 1819 HCV-related deaths in San Francisco, representing an overall age-adjusted mortality rate of 9.4 (95% CI 9.0, 9.9) per 100,000 population. The age-adjusted HCV-related mortality rates were significantly higher among males (13.7), persons aged 55 years and older (28.0), Black and/or African Americans (32.2) compared to other racial groups, and Hispanic/Latinos (11.6) compared to non-Hispanic and/or Latinos. Overall and in most subgroups, mortality rates were lowest between 2015 and 2019. Since 2015, San Francisco observed a significantly larger reduction in agbe-adjusted HCV-related mortality than California or the U.S. Projected age-adjusted HCV-related mortality rates for San Francisco for 2020 and 2030 were 4.7 (95% CI 3.5, 6.2) and 1.1 (95% CI 0.7, 1.8), respectively.ConclusionsBased on trends between 2015 and 2019, San Francisco, California, and the U.S. are projected to achieve 65% reduction in HCV-mortality at or before 2030. Based on current trends, San Francisco is projected to achieve this goal earlier.

BackgroundIncarceration is associated with increased risk of hepatitis C virus (HCV) among people who inject drugs (PWID). Mexico's previous attempt in implementing a public health-oriented drug law reform resulted in minimal impact on incarceration among PWID. However, implementation of reforms alongside Mexico's HCV elimination program has the potential to reshape the HCV epidemic among PWID in the next decade. We use data from a cohort of PWID in Tijuana, Mexico, to inform epidemic modeling to assess the contribution of incarceration and fully implemented drug reform on HCV transmission and elimination among PWID.MethodsWe developed a dynamic, deterministic model of incarceration, HCV transmission and disease progression among PWID. The model was calibrated to data from Tijuana, Mexico, with 90% HCV seroprevalence among 10,000 PWID. We estimated the 10-year population attributable fraction (PAF) of incarceration to HCV incidence among PWID and simulated, from 2022, the potential impact of the following scenarios: 1) decriminalization (80% reduction in incarceration rates); 2) fully implemented drug law reform (decriminalization and diversion to opiate agonist therapy [OAT]); 3) fully implemented drug law reform with HCV treatment (direct-acting antivirals [DAA]). We also assessed the number DAA needed to reach the 80% incidence reduction target by 2030 under these scenarios.ResultsProjections suggest a PAF of incarceration to HCV incidence of 5.4% (95% uncertainty interval [UI]:0.6-11.9%) among PWID in Tijuana between 2022-2032. Fully implemented drug reforms could reduce HCV incidence rate by 10.6% (95%UI:3.1-19.2%) across 10 years and reduce the number of DAA required to achieve Mexico's HCV incidence reduction goal by 14.3% (95%UI:5.3-17.1%).ConclusionsAmong PWID in Tijuana, Mexico, incarceration remains an important contributor to HCV transmission. Full implementation of public health-oriented drug law reform could play an important role in reducing HCV incid

Until the COVID-19 pandemic, San Francisco's hepatitis C virus (HCV) elimination initiative, End Hep C SF, was expanding and refining HCV testing and treatment strategies citywide, making progress toward local HCV elimination goals. Although a shelter-in-place health order issued in March 2020 categorized HCV testing as an "essential service," most HCV testing and treatment immediately stopped until COVID-19-safe protocols could be implemented. During the 14 months of pandemic-related organizational closures, End Hep C SF transitioned to a 100% virtual model, maintaining regularly scheduled meetings. Community-based HCV antibody testing decreased 80% from February to April 2020, and HCV treatment initiation also decreased, although both services started to rebound in mid-to-late 2020, partially as a result of End Hep C SF collaborations. End Hep C SF service providers, clinicians, and advocates reported that the continuous communication and common agenda of End Hep C SF-2 principles of the collective impact initiative-served as a familiar touchpoint and helpful source of information during this isolating and uncertain time. Ultimately, End Hep C SF allowed us to continue HCV elimination strategies through 6 lessons learned: maintaining HCV treatment access through telehealth and mobile services; leveraging research studies that provided HCV testing and treatment; offering HCV screening and linkage to care in tandem with COVID-19-related initiatives; being flexible and inventive, such as administering HCV treatment to residents of shelter-in-place hotels; establishing a data dashboard to track HCV testing and treatment; and relying on partnerships to solve problems and avoid burnout.

BackgroundPrior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany.MethodsTo evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic.ResultsContinuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo.ConclusionsHCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.

BackgroundChina and the United States (US) ranked first and third in terms of new liver cancer cases and deaths globally in 2020. Therefore, a comprehensive assessment of trends in the incidence of primary liver cancer with four major etiological factors between China and the US during the past 30 years with age-period-cohort (APC) analyses is warranted.MethodsData were obtained from the Global Burden of Disease 2019, and period/cohort relative risks were estimated by APC modeling from 1990 to 2019.ResultsIn 2019, there were 211,000 new liver cancer cases in China and 28,000 in the US, accounting for 39.4% and 5.2% of global liver cancer cases, respectively. For China, the age-standardized incidence rate (ASIR) consecutively decreased before 2005 but increased slightly since then, whereas the ASIR continuously increased in the US. Among the four etiological factors of liver cancer, the fastest reduction in incidence was observed in hepatitis B virus-related liver cancer among Chinese women, and the fastest increase was in nonalcoholic steatosis hepatitis (NASH)-related liver cancer among American men. The greatest reduction in the incidence of liver cancer was observed at the age of 53 years in Chinese men (-5.2%/year) and 33 years in Chinese women (-6.6%/year), while it peaked at 58 years old in both American men and women (4.5%/year vs . 2.8%/year). Furthermore, the period risks of alcohol- and NASH-related liver cancer among Chinese men have been elevated since 2013. Simultaneously, leveled- off period risks were observed in hepatitis C viral-related liver cancer in both American men and women.ConclusionsCurrently, both viral and lifestyle factors have been and will continue to play an important role in the time trends of liver cancer in both countries. More tailored and efficient preventive strategies should be designed to target both viral and lifestyle factors to prevent and control liver cancer.

SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.

PurposeInformation is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment.MethodsNewly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6 months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test.ResultsOf 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6 months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy.ConclusionMany patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.

BackgroundHarm reduction is an accumulation of strategies aimed at preventing adverse health outcomes associated with illicit substance use. Several harm reduction programs and services exist within Los Angeles County (LAC), however their success relies in part on the application of harm reduction principles by local primary care providers serving patients with substance use disorders. This study aims to assess the readiness of patient-centered medical homes in the San Fernando Valley to provide effective harm reduction to patients who use injection drugs and identify barriers to doing so.MethodsAn online survey was distributed to primary care providers and social workers via email at federally qualified health centers and LAC Department of Health Services clinics in the San Fernando Valley between May and June 2019. It consisted of 22 multiple-choice, Likert scale, and short answer questions. The survey assessed knowledge of injection drug use (IDU), familiarity and utilization of harm-reduction and resources, and self-evaluation of attitudes and skills.ResultsThere were a total of 41 survey respondents across all clinics. Of respondents, 98% correctly identified heroin as a drug typically injected, and 93% identified Hepatitis C as an infectious risk of IDU. 63% of respondents use harm reduction strategies every few months or less. 34% prescribe buprenorphine routinely, and 76% prescribe pre-exposure prophylaxis to those at risk for Human Immunodeficiency Virus (HIV). 76% are comfortable discussing IDU with their patients, but 59% indicate that they lack the necessary skills, and 42% agree that they lack the time to address it.ConclusionKnowledge of IDU was adequate among those surveyed, although overall utilization of harm reduction was infrequent. There is a perceived deficit in skills and time to effectively provide harm reduction to primary care patients in the San Fernando Valley.

BackgroundPeople who inject drugs (PWID) have likely borne disproportionate health consequences of the COVID-19 pandemic. PWID experienced both interruptions and changes to drug supply and delivery modes of harm reduction, treatment, and other medical services, leading to potentially increased risks for HIV, hepatitis C virus (HCV), and overdose. Given surveillance and research disruptions, proximal, indirect indicators of infectious diseases and overdose should be developed for timely measurement of health effects of the pandemic on PWID.MethodsWe used group concept mapping and a systems thinking approach to produce an expert stakeholder-generated, multi-level framework for monitoring changes in PWID health outcomes potentially attributable to COVID-19 in the U.S. This socio-ecological measurement framework elucidates proximal and distal contributors to infectious disease and overdose outcomes, many of which can be measured using existing data sources.ResultsThe framework includes multi-level components including policy considerations, drug supply/distribution systems, the service delivery landscape, network factors, and individual characteristics such as mental and general health status and service utilization. These components are generally mediated by substance use and sexual behavioral factors to cause changes in incidence of HIV, HCV, sexually transmitted infections, wound/skin infections, and overdose.ConclusionThis measurement framework is intended to increase the quality and timeliness of research on the impacts of COVID-19 in the context of the current pandemic and future crises. Next steps include a ranking process to narrow the drivers of change in health risks to a concise set of indicators that adequately represent framework components, can be written as measurable indicators, and are quantifiable using existing data sources, as well as a publicly available web-based platform for summary data contributions.

BACKGROUND: People who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran. METHODS: This study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients. RESULTS: A total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis. CONCLUSION: Our integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Over 70 million people worldwide are living with chronic hepatitis C virus (HCV) infection. Untreated, HCV infection can progress to cirrhosis, advanced liver disease, and hepatocellular carcinoma. Our improved understanding of HCV transmission, coupled with significant advances in treatment have the potential to dramatically reduce the incidence and prevalence of HCV-related diseases. Based on these advances, the World Health Organization (WHO) has established a goal to eliminate HCV infection by 2030; however, a significant impediment to this goal is the lack of infection awareness, which perpetuates the spread of the virus. By improving the detection of HCV infection, we can connect patients to treatment to reduce its prevalence and curtail transmission to reduce future incidence of infection. This dissertation reviews the literature on known risk factors for HCV infection in the United States (US) and uses a large, contemporary, publicly available national dataset, the National Health and Nutrition Examination Survey (NHANES), to look for additional risk factors and to build an algorithm to identify individuals with a high probability of HCV infection. NHANES participants are randomly selected from the non-institutionalized and housed US population and screened for HCV RNA, regardless of insurance status or known risk factors, providing meaningful insights into the characteristics associated with HCV infection.The results of an umbrella review of circumstances associated with an increased prevalence of HCV infection in the US can be found in Chapter two. Risk factors were categorized as behavioral/lifestyle factors, risks associated with a medical condition, risks related to an occupation, or vulnerable populations. These findings can be used to improve outreach, education, and prevention programs, as many of the identified risk factors are present in marginalized groups that may not have access to regular healthcare or may be missed by existing HCV diagnosis an

Hepatitis B virus (HBV) causes either acute or chronic liver diseases. Chronic hepatitis B (CHB) often progresses to the development of cirrhosis and hepatocellular carcinoma. As HBV is extremely noncytopathic, immunological events play a key role in the infection outcome. Indeed, adaptive immune responses trigger viral clearance during acute infection and viral persistence reflects the failure to generate and maintain such responses. Current therapies for patients with CHB rely on direct-acting antivirals (DAAs) that suppress viral replication without eradicating HBV from the liver. Cure of CHB may well require combining these and forthcoming DAAs with immune-stimulating approaches of different nature and function. Here, we review the relative potential of these combination therapies.

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols.

Background: Following the introduction of direct-acting antiviral therapy in 2013, WHOlaunched the first Global Health Sector Strategy on Viral Hepatitis. We describe a hepatitis C virus (HCV) cascade of care in people with HIV (PWH) across Europe in terms of reaching the WHO elimination targets of diagnosing 90% and treating 80% of HCV-infected individuals. Methods: HIV/HCV-coinfected participants in the EuroSIDA cohort under prospective follow-up at October 1, 2019, were described using a nine-stage cascade of care. Care cascades were constructed across Europe, on a regional (n 5) and country (n 21) level. Results: Of 4773 anti-HCV positive PWH, 4446 [93.1%, 95% confidence interval (CI) 92.4-93.9)] were ever tested for HCV RNA, and 19.0% (95% CI 16.4-21.6) were currently HCV RNA positive, with the highest prevalence in Eastern and Central-Eastern Europe (33.7 and 29.6%, respectively). In Eastern Europe, 78.1% of the estimated number of chronic infections have been diagnosed, whereas this proportion was above 95% in the other four regions. Overall, 3116 persons have ever started treatment (72.5% of the ever chronically infected, 95% CI 70.9-74.0) and 2404 individuals (55.9% of the ever chronically infected, 95% CI 53.9-57.9) were cured. Cure proportion ranged from 11.2% in Belarus to 87.2% in Austria. Conclusion: In all regions except Eastern Europe, more than 90% of the study participants have been tested for HCV-RNA. In Southern and Central-Western regions, more than 80% ever chronically HCV-infected PWH received treatment. The proportion with cured HCV infection did not exceed 80% in any region, with significant heterogeneity between countries. Summary: In a pan-European cohort of PWH, all regions except Eastern Europe achieved the WHO target of diagnosing 90% of chronic HCV infections, while the target of treating 80% of eligible persons was achieved in none of the five regions.