An in vitro CD8 T-cell priming assay enables epitope selection for hepatitis C virus vaccines.

For the rational design of epitope-specific vaccines, identifying epitopes that can be processed and presented is essential. As algorithm-based epitope prediction is frequently discordant with actually recognized CD8+ T-cell epitopes, we developed an in vitro CD8 T-cell priming protocol to enable the identification of truly and functionally expressed HLA class I epitopes. The assay was established and validated to identify epitopes presented by hepatitis C virus (HCV)-infected cells. In vitro priming of naïve CD8 T cells was achieved by culturing unfractionated PBMCs in the presence of a specific cocktail of growth factors and cytokines, and next exposing the cells to hepatic cells expressing the NS3 protein of HCV. After a 10-day co-culture, HCV-specific T-cell responses were identified based on IFN-γ ELISpot analysis. For this, the T cells were restimulated with long synthetic peptides (SLPs) spanning the whole NS3 protein sequence allowing the identification of HCV-specificity. We demonstrated that this protocol resulted in the in vitro priming of naïve precursors to antigen-experienced T-cells specific for 11 out of 98 SLPs tested. These 11 SLPs contain 12 different HLA-A*02:01-restricted epitopes, as predicted by a combination of three epitope prediction algorithms. Furthermore, we identified responses against 3 peptides that were not predicted to contain any immunogenic HLA class I epitopes, yet showed HCV-specific responses in vitro. Separation of CD8+ and CD8- T cells from PBMCs primed in vitro showed responses only upon restimulation with short peptides. We established an in vitro method that enables the identification of HLA class I epitopes resulting from cross-presented antigens and that can cross-prime T cells and allows the effective selection of functional immunogenic epitopes, but also less immunogenic ones, for the design of tailored therapeutic vaccines against persistent viral infections and tumor antigens.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.

Predictors of Frailty in Patients With Liver Cirrhosis.

Introduction Frailty is noticed in a large number of cirrhotic patients with advanced liver disease. Frailty not only disposes cirrhotic patients to increased rates of decompensation and hospitalization but also leads to prolonged hospital stay and increased psychological and social impact, resulting in the delisting of these patients from the transplant list. Therefore, our aim was to identify the factors that are independent predictors of frailty in patients with liver cirrhosis. Methods This cross-sectional study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from March 1, 2022, to August 31, 2022. All the patients diagnosed with liver cirrhosis and aged 18-70 years were included in the study. The excluded patients comprised those with disorders that over-estimate frailty such as cardiopulmonary disease and hepatocellular carcinoma. The measurement of the Liver Frailty Index (LFI) was done using the hand grip strength method, timed chair stands, and balance testing. Patients with LFI >4.5 were considered frail. All data was entered and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, New York, United States). Continuous variables were analyzed using the student-t test while categorical variables were analyzed using the chi-square test. Variables with significance on univariate analysis then underwent multivariate analysis to identify the independent predictors of frailty in cirrhotic patients. A p-value < 0.05 was considered statistically significant. Results A total of 132 patients were included in the study. Out of them, 89 (67.4%) were males. On assessment, 51 (38.6%) patients were frail on presentation. On univariate analysis, female gender, advanced age, raised total leucocyte count, increased percentage of neutrophils on peripheral smear, raised serum creatinine, raised total bilirubin, raised prothrombin time, high Child Turcotte Pugh (CTP) score, and high model for end-stage liver disease along with low hemoglobin and low serum albumin levels were statistically significantly associated with frailty in cirrhosis. On multivariate analysis, female gender, age >40 years, CTP>B7, Hemoglobin <10g/dl, and neutrophils >60% on peripheral smear were independent predictors of liver frailty in cirrhotic patients. Conclusion Female gender, advanced age, increased neutrophils on peripheral smear, decreased hemoglobin along with increased degree of liver dysfunction were independent predictors of increased frailty in patients with chronic liver disease.

Memory impacts in hepatitis C: A global analysis of a fractional-order model with an effective treatment.

BACKGROUND AND OBJECTIVE: Hepatitis virus infections are affecting millions of people worldwide, causing death, disability, and considerable expenditure. Chronic infection with hepatitis C virus (HCV) can cause severe public health problems because of their high prevalence and poor long-term clinical outcomes. Thus a fractional-order epidemic model of the hepatitis C virus involving partial immunity under the influence of memory effect to know the transmission patterns and prevalence of HCV infection is studied. Investigating the transmission dynamics of HCV makes the issue more interesting. The HCV epidemic model and worldwide dynamics are examined in this study. Calculate the basic reproduction number for the HCV model using the next-generation matrix technique. We determine the model's global dynamics using reproduction numbers, the Lyapunov functional approach, and the Routh-Hurwitz criterion. The model's reproduction number shows how the disease progresses. METHODS: A fractional differential equation model of HCV infection has been created. Maximum relevant parameters, such as fractional power, HCV transmission rate, reproduction number, etc., influencing the dynamic process, have been incorporated. The model's numerical solutions are obtained using the fractional Adams method. Finally, numerical simulations support the theoretical conclusions, showing the great agreement between the two. RESULTS: In the fractional-order HCV infection model, the memory effect, which is not seen in the classical model, was shown on graphs so that disease dynamics and vector compartments could be seen. We found that the fractional-order HCV infection model has more stages of freedom than regular derivatives. Fractional-order derivations, which may be the best and most reliable, explained bodily approaches better than classical order. CONCLUSION: The current study modeled and analyzed a fractional-order HCV infection model. The current approach results in a much better understanding of HCV transmission in a population, which leads to important insights into its spread and control, such as better treatment dosage for different age groups, identifying the best control measure, improving health, prolonging life, reducing the risk of HCV transmission, and effectively increasing the quality of life of HCV patients. The creation of a fractional-order HCV infection model, which provides a better understanding of HCV transmission dynamics and leads to significant insights for better treatment dosages, identification of optimal control measures, and ultimately improvement of the quality of life for HCV patients, is the study's major outcome.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

A community-based participatory research approach to evaluating and improving hepatitis C risk, knowledge, and stigma associations among people who inject substances in Indiana.

OBJECTIVES: To explore hepatitis C risk, knowledge, and stigma among individuals who inject substances in South Central Indiana. DESIGN: A cross-sectional study design was employed using a community-based participatory research approach. The community partner was a grassroots harm reduction organization. SAMPLE: Participants in this study were at least 18 years of age, current residents of Indiana, and self-identified as injection substance users (n = 179). MEASUREMENTS: The survey measured hepatitis C risk, knowledge, and stigma, as well as differences in hepatitis C risk scores among key demographic characteristics. RESULTS: Most participants identified as male (n = 106, 59%), White (n = 139, 78%), and straight (n = 143, 80%). People of color reported lower hepatitis C knowledge than White participants. Women had significantly lower hepatitis C knowledge compared with men. LGBTQ participants reported increased hepatitis C risk compared with straight participants. Increased frequency of substance use was associated with decreased stigma. Unhoused participants demonstrated significantly lower hepatitis C knowledge compared with housing-secure participants. CONCLUSIONS: Our findings increase understanding that knowledge and risk around hepatitis C are associated with demographic characteristics. Results underscore the need for tailored public health interventions to increase hepatitis C knowledge, reduce stigma, and improve testing and treatment among vulnerable populations.

Epidemiology of Hepatocellular Carcinoma in India - An Updated Review for 2024.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a significant cause of morbidity and mortality, especially in patients with chronic liver disease. As a reflection of geographical variations in India, there is significant variation in the prevalence and etiological factors of HCC. In contrast to previous studies reporting viral hepatitis as the most common etiology, recent data indicates a changing etiological pattern of cirrhosis and HCC, with alcohol and metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as the foremost cause. Thus, there was a need for an updated review of the current literature and databases for the changing epidemiology and etiological spectrum of HCC in India. The review included data primarily from the National Cancer Registry Program and the Global Burden of Diseases, Injuries, and Risk Factors Study, with the inclusion of other studies from India. The highlights of the present review are summarized in the following lines. Although the current incidence (2.15 per 100,000), prevalence (2.27 per 100,000), and mortality (2.21 per 100,000) rate of HCC in India remain lower compared to the global data, the annual rates of change in these parameters are higher in India. Among Indians, the present incidence, prevalence, and mortality related to HCC are higher in males, while the annual rate of change is higher in females. The Northeastern states have higher incidence, prevalence, and mortality related to HCC, but the Western states of Gujarat, Maharashtra, Goa, and Kerala are emerging as newer hotspots with higher annual rates of change in incidence, prevalence, and mortality. The incidence of HCC related to hepatitis B is on a downtrend, while those related to alcohol and MASLD are rising. Public health initiatives, awareness campaigns, and focused treatments are all necessary to combat these changes, particularly in areas with high incidence rates.

HCV prevalence and phylogenetic characteristics in a cross-sectional, community study of young people who inject drugs in New York City: Opportunity for and threats to HCV elimination.

Background and Aims: In the United States, the opioid epidemic has led many young people who use opioids to initiate injection drug use, putting them at risk for hepatitis C virus (HCV) infection. However, community surveys to monitor HCV prevalence among young people who inject drugs (YPWID) are rare. Methods: As part of Staying Safe (Ssafe), a trial to evaluate an HCV-prevention intervention, a community-recruited sample of 439 young people who use opioids (ages 18-30) in New York City (NYC) were screened from 2018 to 2021. Screening procedures included a brief verbal questionnaire, a visual check for injection marks, onsite urine drug testing, rapid HCV antibody (Ab) testing, and dried blood spot (DBS) collection. DBS specimens were sent to a laboratory for HCV RNA testing and phylogenetic analysis to identify genetic linkages among HCV RNA-positive specimens. Multivariable logistic regression was used to assess associations between HCV status (Ab and RNA) and demographics and drug use patterns. Results: Among the 330 participants who reported injecting drugs (past 6 months), 33% (n = 110) tested HCV Ab-positive, 58% of whom (n = 64) had HCV RNA-positive DBS specimens, indicating active infection. In multivariable analysis, visible injection marks (AOR = 3.02; p < 0.001), older age (AOR = 1.38; p < 0.05), and female gender (AOR = 1.69; p = 0.052) were associated with HCV Ab-positive status. Visible injection marks were also associated with HCV RNA-positive status (AOR = 5.24; p < 0.01). Twenty-five percent of RNA-positive specimens (14/57) were genetically linked. Conclusion: The relatively low prevalence of active infection suggests the potential impact of treatment-as-prevention in reducing HCV prevalence among YPWID. Targeted community serosurveys could help identify actively infected YPWID for treatment, thereby reducing HCV incidence and future transmissions.

Best Practices for Hepatitis C Linkage to Care in Pregnant and Postpartum Women: Perspectives from the TiP-HepC Community of Practice.

There is an increasing burden of hepatitis C virus (HCV) among persons of reproductive age, including pregnant and breastfeeding women, in many regions worldwide. Routine health services during pregnancy present a critical window of opportunity to diagnose and link women with HCV infection for care and treatment to decrease HCV-related morbidity and early mortality. Effective treatment of HCV infection in women diagnosed during pregnancy also prevents HCV-related adverse events in pregnancy and HCV vertical transmission in future pregnancies. However, linkage to care and treatment for women diagnosed in pregnancy remains insufficient. Currently, there are no best practice recommendations from professional societies to ensure appropriate peripartum linkage to HCV care and treatment. We convened a virtual Community of Practice (CoP) to understand key challenges to the HCV care cascade for women diagnosed with HCV in pregnancy, highlight published models of integrated HCV services for pregnant and postpartum women, and preview upcoming research and programmatic initiatives to improve linkage to HCV care for this population. Four-hundred seventy-three participants from 43 countries participated in the CoP, including a diverse range of practitioners from public health, primary care, and clinical specialties. The CoP included panel sessions with representatives from major professional societies in obstetrics/gynecology, maternal fetal medicine, addiction medicine, hepatology, and infectious diseases. From this CoP, we provide a series of best practices to improve linkage to HCV treatment for pregnant and postpartum women, including specific interventions to enhance co-location of services, treatment by non-specialist providers, active engagement and patient navigation, and decreasing time to HCV treatment initiation. The CoP aims to further support antenatal providers in improving linkage to care by producing and disseminating detailed operational guidance and recommendations and supporting operational research on models for linkage and treatment. Additionally, the CoP may be leveraged to build training materials and toolkits for antenatal providers, convene experts to formalize operational recommendations, and conduct surveys to understand needs of antenatal providers. Such actions are required to ensure equitable access to HCV treatment for women diagnosed with HCV in pregnancy and urgently needed to achieve the ambitious targets for HCV elimination by 2030.

Awareness of chronic hepatitis B and C in men who have sex with men in Belgium: epidemiological survey and on-site screening.

OBJECTIVES: To eliminate hepatitis B and C virus (HBV/HCV) as a public health threat by 2030, the WHO focuses on screening key populations, including men who have sex with men (MSM).This study aims to assess HBV and HCV knowledge and awareness and HCV prevalence in MSM in Belgium. METHODS: First, a questionnaire was designed to assess MSM's knowledge of HBV and HCV infection (disease process, vaccination, treatment and transmission routes). This questionnaire was conducted online, and by means of a tablet-based face-to-face questionnaire at the Antwerp and Belgian Pride. Second, HCV and HIV prevalence data were collected during outreach projects and office screening for sexually transmitted infections (STIs) organised by Sensoa and Exaequo, a Flemish and Walloon sexual health organisation. RESULTS: 300 MSM completed the questionnaire (median age 36 years; 7.7% HIV+). Mean overall survey scores were low (HBV: 41.1%; HCV: 39.8%). Few participants identified all transmission routes correctly (HBV: 15%; HCV 1%).The degree of education was significantly correlated with HBV knowledge and showed a trend towards correlation with HCV knowledge. HCV knowledge was significantly correlated with high-risk sexual behaviour.The prevalence of HCV and HIV was 0.3% and 1.0%, respectively, in MSM attending commercial gay venues and 0% and 1.9% in MSM attending office STI screening. CONCLUSIONS: Knowledge of HBV and HCV infection in MSM is poor. More awareness campaigns are needed, focusing on frequent HCV risk factors (group sex, chemsex, receptive fisting, and sharing of anal toys and anal douching devices), especially targeting low-educated MSM. HBV vaccination of MSM requires continued attention.The prevalence of HCV and HIV was remarkably low in commercial gay venues and may be higher in older MSM or in subcultures where risk factors coexist (eg, chemsex). The cost-effectiveness of internet-based approaches with subsequent at-home testing needs to be evaluated in the future.

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus.

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.

Hepatitis C Presenting Like Endocarditis in a Young Patient With Substance Use Disorder: A Case Report.

This case report details a 21-year-old male patient who initially presented with endocarditis-like symptoms but ultimately had hepatitis C in the setting of substance use disorder. It highlights the value of prompt diagnosis and effective treatment. He had a medical history of chronic heroin use over two years and presented inconsistently to the emergency department with generalized body aches. He had generalized body pain and right upper and lower quadrant abdominal pain. He had been unable to tolerate any oral intake and had been vomiting after every meal for the last three weeks. Physical examination was significant only for large, ovoid, erythematous nodules on the left dorsal foot, blanching and slightly painful to touch; diffuse scabs and sores on extremities; and nodules on dorsal interphalangeal joints on the left hand. Urine drug screen was noted to be positive for cannabinoids, methamphetamines, and opioids. The initial electrocardiogram did not show typical T wave flattening changes for hypokalemia. Transthoracic echocardiogram ruled out infective endocarditis, with no valvular vegetation. He was ultimately found to be hepatitis C virus antibody positive. This case illustrates the importance of keeping a wide differential in mind. The patient had hepatitis C despite being asymptomatic throughout presentation-keeping. The patient's history of heroin use was critical while ordering testing.

Seroprevalence of transfusion-transmitted infections among blood donors in Makkah, Saudi Arabia.

INTRODUCTION: Blood donation is vital for healthcare; however, transfusion-transmitted infections (TTIs) pose a serious risk. This study investigated the seroprevalence of TTIs among Saudi blood donors. METHODOLOGY: This retrospective study included male blood donors aged ≥ 18 years who donated blood at Al-Noor Specialist Hospital in Makkah from January 2017 to December 2022. The blood units were screened for hepatitis B surface antigen (HBsAg) and core antibodies (HBc-IgG), hepatitis C antibodies (HCV-Abs), syphilis, HIV-1 antigen/antibody (HIV-1 Ag/Ab), human T-lymphotropic virus 1, 2 (HTLV-1/2), and malaria. RESULTS: There were 40,287 donors with an average age of 44.33 ± 18.12 years, and 62.3% (n = 25103) were Saudis. The overall rate of TTIs seropositivity was 7.4% (n = 2953); HBc-IgG (6.1%; n = 2473) was the most common, followed by HCV-Abs (0.4%; n = 177), and syphilis (0.34%; n = 136). All cases were negative for malaria, whilst HIV and HTLV positive donors were 0.06% (n = 24) and 0.13% (n = 52), respectively. Syphilis was more prevalent among non-Saudis (0.24%; n = 83) than among Saudis (0.1%; n = 53), whereas anti-HBc antibodies seropositivity was significantly higher among Saudi (3.4%; n = 1373) than non-Saudi donors (2.7%; n = 1100). CONCLUSIONS: Hepatitis B virus was the most frequently detected bloodborne pathogen, followed by hepatitis C virus and syphilis. Hepatitis B virus was also more prevalent among Saudi donors, whilst expatriates had higher rates of syphilis. Additional prospective multicenter studies are needed to accurately determine the prevalence of TTIs in Saudi Arabia.

HIV and hepatitis C virus-related misinformation may contribute to rising rates of infection and suboptimal clinical outcomes among persons with substance use.

HIV and hepatitis C virus (HCV) infection rates among persons, who use drugs, have risen during the US overdose crisis. We elicited patient perspectives about these interconnected infections to identify the areas of misinformation that might prevent appropriate management. We used in-depth interviews and thematic analysis of coded data collected from patients (N = 24) at detox and from key informants (N = 10). Seventy-one per cent reported injecting drugs. We found that patient narratives included misinformation about HIV and HCV transmission, natural history and treatment. Some participants thought that activities such as sharing drinkware or food with persons with HIV could lead to infection, while others believed that mainly men who have sex with men were at risk. Despite significant improvements in treatment, some participants still believed that HIV was a fatal condition, while others noted that treatment was only necessary at later stages. Some participants thought that HCV was a common, mild infection that might not need immediate attention, and others stated that individuals who were actively using drugs were ineligible for treatment. The current study exposes a considerable level of misinformation about HIV prevention and about the importance and benefits of HCV therapy. Educational interventions are necessary to counter misinformation identified.

Disengagement from Care Among People Co-Infected with HIV and HCV: A Scoping Review.

Disengagement from care among people with HIV (PWH) and hepatitis C (HCV) increases the risks of adverse health outcomes and poses significant barriers to achieving global HIV and HCV elimination goals. In accordance with the Joanna Briggs Institute framework, a scoping review was conducted to synthesize and highlight existing gaps in the literature on (dis)engagement in care among PWH and HCV. We searched for original studies on (dis)engagement in care among PWH and HCV in high-income countries using eight electronic databases from inception to May 2023. Our search yielded 4462 non-duplicated records, which were scoped to 27 studies. Definitions of (dis)engagement in care were diverse, with considerable heterogeneity in how retention was operationalized and temporally measured. Studies identified predictors of (dis)engagement to be related to drug and substance use (n = 5 articles), clinical factors (n = 5), social and welfare (n = 4), and demographic characteristics (n = 2). When engagement in care was treated as an exposure, it was associated with HCV treatment initiation (n = 3), achieving sustained virological response (n = 2), and maintaining HIV viral suppression (n = 1). Interventions to improve care engagement among PWH and HCV were limited to five studies using cash incentives (n = 1) and individual case management (n = 4). (Dis)engagement in care is a dynamic process influenced by shifting priorities that may 'tip the balance' towards or away from regularly interacting with healthcare professionals. However, inconsistent definitions render cross-study comparisons and meta-analyses virtually impossible. Further research needs to establish a standardized definition to identify patients at high risk of disengagement and develop interventions that leverage the nested HIV/HCV care cascades to retain and recover patients lost from care.

Prevalence of hepatitis B and C virus infections among visceral leishmaniasis patients: a systematic review and meta-analysis.

Background: Visceral leishmaniasis (VL) patients are at high risk of acquiring hepatitis B virus (HBV) and hepatitis C virus (HCV) infections during multiple injections and the anti-leishmanial treatment possesses a potential hepatotoxic effect. This systematic review and meta-analysis determined the pooled prevalence of HBV and HCV infections in VL patients. Methods: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned number CRD42024516889, and conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Medline, EMBASE, Google Scholar, Web of Science, and Science Direct databases. Data were extracted using Microsoft Excel and analyzed using STATA version 11.0 software. A random-effects model was used to estimate the pooled effect size of outcome variables across studies with a 95% confidence interval and was displayed in a forest plot. The I 2 statistic was used to check for heterogeneity. The presence of publication bias was determined using a funnel plot and Egger's test with a p value <0.05 evidence of statistically significant bias. Results: Among 216 retrieved records, seven studies were eligible for systematic review and meta-analysis. A total of 937 VL patients were examined, revealing that 105 and 93 were infected with HBV and HCV, respectively. The pooled prevalence of HBV was 16.15% (95% CI: -4.10 to 36.39), with a significant heterogeneity (I 2 = 91.4%, p < 0.001). The combined prevalence of HCV was 13.74% (95% CI: 1.32-26.16, I 2 = 71.6%, p = 0.003). The funnel plot (symmetry), and Egger's test in both HBV (p value = 0.650) and HCV (p value = 0.841) revealed no publication bias. In subgroup analysis, high HBV and HCV prevalence was detected in Sudan; 20.64% (95% CI: -13.60 to 54.88) and India; 18.26% (95% CI: -0.40 to 36.92%), respectively. Conclusion: This study revealed a high prevalence of both HBV and HCV infections in VL patients. In subgroup analysis, the prevalence of HBV and HCV was high in Sudan and India, respectively. Therefore, screening of VL patients for HBV and HCV, vaccination of VL patients in endemic regions, and collaboration between kala-azar and hepatitis elimination programs are required. Systematic review registration: https://www.crd.york.ac.uk/prospero/export_details_pdf.php#page=1.00&gsr=0, identifier: CRD42024516889.

Glecaprevir-Pibrentasvir and Ethinyl Estradiol-Induced Liver Injury in a Patient Without Cirrhosis.

Most drug liver injury cases are the result of an unexpected interaction with medications. We present a 33-year-old woman, four months postpartum, on ethinyl estradiol/norgestrel, who presented in the ED with nausea, vomiting, abdominal pain, and severe pruritus six weeks after starting glecaprevir-pibrentasvir (GP) treatment. The patient was suspected to have a drug-induced liver injury (DILI), and GP was discontinued. Other potential causes of liver injury were ruled out via labs, imaging, and liver biopsy. The patient's liver function significantly improved after discontinuing GP. Few cases of DILI secondary to GP have been reported. However, to the best of our knowledge, DILI from the interaction of ethinyl estradiol and GP does not exist in published literature. In our case, DILI was likely due to the effect of GP and ethinyl estradiol on the liver's cytochrome 450 (CYP 450) system. The aim of this report is to raise awareness and improve pharmacovigilance, especially in patients receiving medications that are metabolized by the liver's CYP 450 system. Early detection of DILI secondary to drug-interaction and discontinuation of the culprit medication is the mainstay of treatment. However, there is a lack of evidence-based management strategies for premature discontinuation of GP in the setting of DILI while treating chronic hepatitis C virus (HCV) infection. Further investigations are warranted.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

Understanding hepatitis C virus (HCV) health literacy and educational needs among people in prison to enhance HCV care in prisons.

BACKGROUND: Hepatitis C virus (HCV) is a significant concern within prison populations. Provision of HCV testing and treatment for people in prison is expanding and a key component of global elimination efforts. Despite growing service availability, several challenges remain in HCV testing and treatment engagement during incarceration. The PIVOT study demonstrated that a 'one-stop-shop' intervention (point-of-care HCV RNA testing, Fibroscan®, nurse-led clinical assessment, and fast-tracked direct-acting antiviral prescription) enhanced HCV testing and treatment at a reception prison in Australia. Utilising Squier et al's Health Literacy Skills Framework, this analysis aimed to understand HCV health literacy and educational needs among people at a reception prison in Australia. METHODS: Semi-structured interviews were conducted with twenty-four male PIVOT study participants. Purposive sampling ensured comparable representation of those with: 1) prior HCV testing history (standard pathology / no prior testing), and 2) injecting drug use history (IDU; ever / never). RESULTS: Varied HCV health literacy levels and educational needs were evident amongst people in prison. Whilst those with multiple incarceration episodes and IDU history (prior knowledge) appeared to have stronger HCV health literacy than those without, substantial gaps in HCV health literacy were evident. Knowledge of HCV transmission risks in prison was high, and most understood the importance of HCV testing and treatment in prison (comprehension), but ability to engage with HCV testing and treatment services, participation in safe injecting behaviours (health-related behaviours), and knowledge of re-infection and re-treatment, within the context of the prison environment, were suboptimal. There was a general desire for increased HCV education in prison. CONCLUSION: Gaps in HCV health literacy among people in prison were evident, indicating opportunities for improvement. A targeted HCV education program for people in prison, addressing the gaps identified in this analysis, may enhance HCV testing, treatment, and prevention by fostering stronger HCV health literacy among people in prison.