The Severity of Depressive Symptoms as an Independent Predictor of Sustained Virological Response During Treatment of Hepatitis C With Pegylated Interferon-α2a and Oral Ribavirin.

BACKGROUND: Sustained virological response (SVR) is the best indicator of successful therapy for hepatitis C virus (HCV) infection. Patients with chronic HCV infection treated with pegylated interferon-α and ribavirin (PEG-IFN-α/RBV) can achieve SVR 56% of the time. OBJECTIVES: This study aimed to evaluate baseline predictors of SVR in patients treated with PEG-IFN-α/RBV for HCV chronic infection. METHODS: A total of 101 patients receiving PEG-IFN-α/RBV for chronic HCV infection participated in the prospective cohort study. Symptoms of depression were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) before the treatment. The multivariate regression analysis was applied to determine predictors of SVR. RESULTS: Of a total of 101 patients included, 99 patients reached the primary end point-24 weeks after completing treatment. After the initial analysis of probable predictive variables, the logistic analysis included age, sex, HCV genetic type, and MADRS score. The HCV genotype (odds ratio = 0.22 [confidence interval = 0.073-0.68, p = .008) and MADRS score (OR = 0.88 [confidence interval = 0.80-0.98), p = .013]) predicted an SVR outcome. CONCLUSIONS: The severity of depressive symptoms before treatment and HCV genotype are independent predictors of SVR.

Modified E2 Glycoprotein of Hepatitis C Virus Enhances Proinflammatory Cytokines and Protective Immune Response.

Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. In addition, CD81/E2 binding on immunity-related cells may also influence host response outcome to HCV infection. Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate the potential of the resulting immunogen as an HCV vaccine candidate. The modified sE2 protein (F442NYT), unlike unmodified sE2, exhibited a significant reduction in CD81 binding, induced higher levels of proinflammatory cytokines, repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen-presenting cells, and stimulated CD4+ T cell proliferation. Immunization of BALB/c mice with an E1/sE2F442NYT nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine resulted in improved IgG1-to-IgG2a isotype switching, an increase in neutralizing antibodies against HCV pseudotype virus, a B and T cell proliferative response to antigens, and improved protection against infection with a surrogate recombinant vaccinia virus-expressing HCV E1-E2-NS2aa134-966 challenge model compared to E1/unmodified sE2 mRNA-LNP vaccine. Further investigation of the modified E2 antigen may provide helpful information for HCV vaccine development. IMPORTANCE Hepatitis C virus (HCV) E2-CD81 binding dampens protective immune response. We have identified that an alteration of amino acids in the front layer of soluble E2 (sE2) disrupts CD81 interaction and alters the cytokine response. Immunization with modified sE2F442NYT (includes an added potential N-linked glycosylation site and reduces CD81 binding activity)-mRNA-LNP candidate vaccine generates improved proinflammatory response and protective efficacy against a surrogate HCV vaccinia challenge model in mice. The results clearly suggested that HCV E2 exhibits immunoregulatory activity that inhibits induction of robust protective immune responses. Selection of engineered E2 antigen in an mRNA-LNP platform amenable to nucleic acid sequence alterations may open a novel approach for multigenotype HCV vaccine development.

A personal journey through Oral medicine: The tale of hepatitis C virus and oral lichen planus.

Around 30 years ago, the hepatitis C virus (HCV) was identified and soon it was shown that this virus, further to the liver, could affect a variety of organ systems. This article summarizes how an association between HCV and a relatively common oral disorder, oral lichen planus (OLP), was revealed. Through key publications, many of them published in Journal of Oral Pathology and Medicine, it is shown the building of strong epidemiologic evidence supporting the association and how a plausible pathogenic link between HCV and OLP was discovered. As HCV infection is now potentially curable, modern direct antiviral agents can be used to effectively cure also OLP in HCV-infected patients.

Training Providers of People Who Use Drugs to Offer Hepatitis C Treatment: A Washington State Initiative.

To address hepatitis C infection (HCV) treatment gaps among people who use drugs (PWUD), a statewide initiative trained buprenorphine waiver trainers to offer an optional HCV treatment module to waiver trainees. Five of twelve trained buprenorphine trainers went on to conduct HCV sessions at waiver trainings, reaching 57 trainees. Word-of-mouth led to multiple additional presentations by the project team, suggesting an unmet need for more education about treating HCV among PWUD. A post-session survey suggested that participant views on the importance of treating HCV among PWUD changed and that almost all felt confident to treat uncomplicated HCV. While limitations of this evaluation include that no baseline survey was conducted and that the survey response rate was low, findings suggest that among providers who care for PWUD, limited training may be adequate to change views about treating HCV. Future research is needed to explore models of care that will support providers to prescribe lifesaving direct-acting antiviral medications to PWUD with HCV.

A Rare Case of Isolated Hepatocellular Carcinoma Metastasis in Left Mandibular Region in a Patient with Hepatitis C Virus Liver Cirrhosis Diagnosed after the Onset of COVID-19 Infection.

Background and Objectives: Hepatocellular carcinoma (HCC) most frequently metastasizes in the lungs, abdominal lymph nodes and adrenal glands. Metastatic spread to the head and neck area is extremely rare. In the presented case, an uncommon site of solitary metastatic spread of HCC to the mandible confirmed after the core biopsy of the lesion is reported. There have been only about 80 cases of mandibular HCC metastases described in the literature to date. We contribute our experience to the pool of data. Case presentation: A 65-year-old female with HCV-related liver cirrhosis was diagnosed with an HCC that was successfully treated with liver resection. Subsequently, the patient had developed COVID-19 disease, which was associated with a painless swelling in the left jaw. A neck MDCT scan demonstrated an osteolytic soft-tissue mass in the left mandible, with the characteristics consistent for the metastasis of HCC. In order to confirm the diagnosis, a core biopsy of the mandibular mass was performed. The pathohistological evaluation confirmed the presence of a metastatic HCC in the mandible. No other sites of disease dissemination were identified in extensive MDCT scans. Despite considering various treatments, including symptomatic and palliative, the patient's overall prognosis remained poor. Conclusions: Isolated metastases of HCC to the orofacial region are extremely rare; however, it should be considered in patients with known risk factors for HCC development. Early diagnosis is critical, and clinicians should consider this possibility of HCC spread when assessing patients with orofacial swelling, among those patients with risk factors for HCC. The overall prognosis for such patients remains poor, emphasizing the challenges in managing these cases.

The Payer License Agreement, or "Netflix model," for hepatitis C virus therapies enables universal treatment access, lowers costs and incentivizes innovation and competition.

BACKGROUND AND AIMS: High unit prices of treatments limit access. For epidemics like that of hepatitis C virus (HCV), reduced treatment access increases prevalence and incidence, making the infectious disease increasingly difficult to manage. The objective of the current study was to construct and test an alternative pricing model, the Payer License Agreement (PLA), and determine whether it could improve outcomes, cut costs and incentivize innovation versus the current unit-based pricing model. METHODS: We built and used computational models of hepatitis C disease progression, treatment, and pricing in historical and future scenarios and quantitatively analyzed their economic and epidemiological impact in three high-income countries. RESULTS: This study had three key results regarding HCV treatment. First, if the PLA model had been implemented when interferon-free direct-acting antiviral (DAA) combinations launched, the number of patients treated and cured would have more than doubled in the first three years, while the liver-related deaths (LRDs) would have decreased by around 40%. Second, if the PLA model had been implemented beginning in 2018, the year that several Netflix-like payment models were under implementation, the number of treated and cured patients would nearly double, and the LRDs would decline by more than 55%. Third, implementing the PLA model would result in a decline in total payer costs of more than 25%, with an increase to pharmaceutical manufacturer revenues of 10%. These results were true across the three healthcare landscapes studied, the USA, the UK and Italy, and were robust against variations to critical model parameters through sensitivity analysis. CONCLUSIONS AND RELEVANCE: These results suggest that implementation of the PLA model in high-income countries across a variety of health system contexts would improve patient outcomes at lower payer cost with more stable revenue for pharmaceutical manufacturers. Health policy-makers in high-income countries should consider the PLA model for application to more cost-effective management of HCV, and explore its application for other infectious diseases with curative therapies available now or soon.

A Cross-Sectional Questionnaire-Based Survey on Blood-Borne Infection Control among Romanian Dental Students.

Background and Objectives: According to the CDC estimates, 5.6 million healthcare workers worldwide are exposed to the risk of occupationally contracting blood-borne pathogens, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and others. The aim of the present study was to assess the knowledge level on blood-borne infection control (IC) among Romanian undergraduate dental students. Materials and Methods: A cross-sectional, questionnaire-based survey with 21 items was conducted from May 2022 to June 2022. The study had α = 0.620 and Cronbach's Alpha = 0.660. The Chi-square test was used for data comparison. The data were analyzed using IBM SPSS version 26 (IBM, Armonk, NY, USA), and p ≤ 0.05 was considered statistically significant. Results: The study sample included 207 subjects with a mean age of 21.38 (±1.9) years, 59.9% F (female), 40.1% M (male), 38.2% students from year II and 61.8% from year III. Most of the subjects did not have knowledge on the indirect mode of IC, the persistence of HBV, HCV, or HIV, or the existence of rapid tests (p < 0.05). PEP (post-exposure prophylaxis) was known as follows: HBV, 32.36% (67); HCV, 25.60% (53); and HIV, 36.71% (76); p < 0.05. Only 50.24% (104) had knowledge on the recommended testing moments (p = 0.019 by gender, p = 0.752 by year of study). The optimal time to access PEP was considered by 28.01% (58), p ˃ 0.05. Only 37.68% (78) strongly agreed that the one-hand covering technique of the needle was efficient in IC (p < 0.05). Conclusions: The evaluation of the knowledge regarding IC highlighted major gaps in the perception of the subjects, which underlined the need to implement sustained forms of continuing medical education on this topic.

[The diagnostic potential of Golgi protein 73 for cirrhosis in patients with chronic hepatitis C].

Objective: To explore the diagnostic value and model of serum Golgi protein 73 (GP73) in patients with hepatitis C cirrhosis. Methods: 271 cases with chronic hepatitis C virus infection who were treated in the Fifth Medical Center of PLA General Hospital from January 2010 to December 2017 were retrospectively collected as the research objects, including 126 cases with hepatitis and 145 cases with liver cirrhosis. Serum GP73 and liver stiffness measurement (LSM) based on transient elastography test were performed in all patients. Simultaneously, blood routine, liver function, coagulation function and other related indicators were collected. GP73 diagnostic efficiency for liver cirrhosis was evaluated by receiver operating characteristic curve (ROC). GP73 diagnostic value was clarified after comparison with aspartate aminotransferase/platelet ratio index (APRI), FIB-4 index (FIB-4) and LSM. Compensated hepatitis C virus-related cirrhosis diagnostic model based on serological index was established by logistic regression analysis. Results: The area under the receiver operating characteristic curve (AUC) of GP73, LSM, FIB-4 and APRI in the diagnosis of compensated hepatitis C virus-related cirrhosis were 0.923, 0.839, 0.836 and 0.800 respectively, and GP73 had the best diagnostic efficiency (P <0.001). LSM and GP73 combined use had improved the diagnostic sensitivity of cirrhosis to 97.24%. Multivariate logistic regression analysis revealed that GP73, age, and platelets were independent predictors of cirrhosis.Compensated hepatitis C virus-related cirrhosis diagnostic model (GAP) was established based on the result: LogitP=1/[1+exp(6.145+0.013×platelet-0.059×age-0.059×GP73)].AUC model for diagnosing compensated liver cirrhosis was 0.944, and the optimal cut-off value was 0.56, with sensitivity and specificity of 84.03% and 92.06%, respectively, and the diagnostic efficiency of this model was better than that of APRI, FIB-4, LSM and GP73 alone (P<0.05). Conclusion: GP73 is a reliable serum biomarker for the diagnosis of compensated hepatitis C virus-related cirrhosis. The GAP diagnostic model based on GP73, platelet count, and age can further improve the diagnostic efficiency and help to diagnose patients with compensated hepatitis C virus-related cirrhosis.

KNOWLEDGE, ATTITUDE AND PRACTICE SURVEY AMONG GEORGIAN HEALTH CARE WORKERS TOWARDS BLOOD BORNE INFECTIONS.

The prevalence of viral hepatitis B and C in Georgia is among the highest in the region. US Centers for Disease Control and Prevention (CDC) has selected Georgia as a pilot country for hepatitis C elimination program. Since 2015, Georgia launched a multi-year program of HCV elimination, including treatment of infected individuals with Direct Acting Antivirals (DAAs) and implementation of prevention programs, including infection control in health care facilities. The objective of this study was to evaluate the attitude and knowledge of blood borne infections (HIV, HCV, HBV) among Georgian Health Care Workers (HCWs). HCWs were recruited from six participating multi-profile hospitals and dental care institutions in three large cities of Georgia (Batumi (Western Georgia), Rustavi (Eastern Georgia) and the capital city, Tbilisi). A self - administered questionnaire included sections regarding sociodemographic and professional characteristics; awareness of blood-borne infections; practice for transmission risk reduction and perceived educational interventions acceptable among HCWs. The selection of HCWs was done through simple random sampling from the list of staff as a sampling frame. HCW's survey results were compared to the one from Dental health care workers (DHCWs). The total number of surveyed individuals was 442. Among them, 246 (55.6%) were HCWs (physicians, nurses, physician assistants and residents) from different departments, including family medicine (38.6 %), surgery (21.7%), gynecology (23.4%) and intensive care (13.9%) and 196 DHCWs (44.6%). Only few respondents (15.6%) correctly identified the prevalence of HIV infection in Georgia. HCWs have better understanding about the prevalence of viral hepatitis compared to DHCWs (Prevalence of HBsAg was correctly identified by 33.2 % vs 22.3%; prevalence of HCV- by 18.9 % vs 17.3%). Knowledge regarding transmission risks of blood-borne infections (HIV, HCV, HBV) among HCWs is higher compared to DHCWS (for HIV 73% vs 45.3%, for HCV 49.2% vs 37.9% and for HBV 54.8% vs 33.7%) (p<0.005). Vast majority of DHCWs as well as HCWs believed that probability of transmission of blood-borne infections after contaminated needle stick is 50-70% (p<0.05). There was a poor knowledge on availability of post exposure prophylaxis (42.9% of HCWs compare to 36.1% DHCWs believed that HCV post-exposure prophylaxis is available) (p<0.005). The practice of using facemasks (81% vs 74.4% always use, respectively), protective clothes (96.8% vs 83.3% always use) and eyewears (46.9% vs 27.4% always use) was reported by DHCWs and HCWs. Some nosocomial risk events were reported by higher proportion of DHCWs, compared to HCWs and included accidental needle stick injuries (65.1% vs 45.5%) and blood splashes (48.3% vs 28.2%). Cuts with contaminated instruments was more common among HCWs compared to DCHWs (41.4% vs 35.1%) during medical procedures. The study suggests that level of knowledge on blood borne infections among both HCWs and DHCWs is not adequate. Data from this study can be utilized to design educational programs for Georgian HCWs/DHCWs to improve knowledge and practice about blood borne diseases.

Effects of Hepatitis C Virus (HCV) Eradication on Bone Mineral Density in Human Immunodeficiency Virus/HCV-Coinfected Patients.

BACKGROUND: Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κß ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. RESULTS: A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/µL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. CONCLUSIONS: SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Reduced incidence of hepatitis C in 9 villages in rural Egypt: Progress towards national elimination goals.

BACKGROUND & AIMS: Egypt has a major HCV burden and a well established treatment programme, with an ambitious goal of HCV elimination. Our aim was to assess the impact of a comprehensive HCV prevention, test and treat programme on the incidence of new HCV infections in 9 villages in rural Egypt. METHODS: An HCV "educate, test and treat" project was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. In 2018, in 9 of the villages we re-tested individuals who originally tested HCV antibody (HCV-Ab) and HBsAg negative using rapid diagnostic tests (RDTs); confirmatory HCV RNA testing was performed for positive cases. The incidence rate per 1,000 person-years (py) was calculated, and risk factors for incident HCV infections assessed through an interviewer-administered questionnaire in 1:3 age- and gender-matched cases and controls. RESULTS: Out of 20,490 individuals who originally tested HCV-Ab negative in the 9 villages during the 2015-2016 implementation of the "educate, test and treat" programme, 19,816 (96.7%) were re-tested in 2018. Over a median of 2.4 years (IQR 2.1-2.7), there were 19 new HCV infections all of which were HCV RNA positive (incidence rate 0.37/1,000 py) (95% CI 0.24-0.59). Compared to a previous estimate of incidence in the Nile Delta region (2.4/1,000 py) from 2006, there was a substantial reduction in overall incidence of new HCV infections. Exposures through surgery (odds ratio 51; 95% CI 3.5-740.1) and dental procedures (odds ratio 23.8; 95% CI 2.9-194.9) were significant independent predictors of incident infections. CONCLUSIONS: This is the first study to show a substantial reduction in incidence of new HCV infections in a sample of the general population in Egypt following attainment of high testing and treatment coverage. New infections were significantly associated with healthcare-associated exposures. LAY SUMMARY: Egypt has a major national HCV testing and treatment programme with the goal of eliminating HCV infection. We assessed the impact of a comprehensive HCV prevention, test and treat programme in 73 villages that achieved high coverage of testing and treatment on the subsequent incidence of new HCV infections in nine of the villages. We re-tested people who were previously HCV antibody negative and found that the rate of new HCV infections was greatly reduced compared to previous estimates. We also found that exposure through surgery and dental procedures were associated with these new infections. This highlights the importance of continued strengthening of infection control and prevention measures, alongside treatment scale-up.

Responsive polymer-assisted 3D cryogel supports Huh7.5 as in vitro hepatitis C virus model and ectopic human hepatic tissue in athymic mice.

The three-dimensional (3D) cell culture models serve as the interface between conventional two-dimensional (2D) monolayer culture and animal models. 3D culture offers the best possible model system to understand the pathophysiology of human pathogens such as hepatitis C virus (HCV), which lacks a small animal model, due to narrow host tropism and non-permissiveness of murine hepatocytes. In this study, functionally robust spheroids of HCV permissive Huh7.5 cells were generated, assisted by the temperature or pH-responsive polymers PNIPAAm and Eudragit respectively, followed by the long-term growth of the multilayered 3D aggregates in poly(ethylene glycol) (PEG)-alginate-gelatin (PAG) cryogel. The human serum albumin (HSA), marker of hepatic viability was detected up to 600 ng/ml on 24th day of culture. The 3D spheroid culture exhibited a distinct morphology and transcript levels with the upregulation of hepato-specific transcripts, nuclear factor 4α (HNF4α), transthyretin (TTr), albumin (Alb), phase I and phase II drug-metabolizing genes. The two most important phase I enzymes CYP3A4 and CYP2D6, together responsible for 90% metabolism of drugs exhibited up to 9- and 12-fold increment, respectively in transcripts. The 3D culture was highly permissive to HCV infection and supported higher multiplicity of infection compared to monolayer Huh7.5 culture. Quantitation of high levels of HSA (500-200 ng/ml) in circulation in mice for 32 days asserted integration with host vasculature and in vivo establishment of 3D culture implants as an ectopic human hepatic tissue in mice. The study demonstrates the 3D spheroid Huh7.5 culture as a model for HCV studies and screening potential for anti-HCV drug candidates.

In Vivo and In Vitro Potency of Polyphosphazene Immunoadjuvants with Hepatitis C Virus Antigen and the Role of Their Supramolecular Assembly.

Two well-defined synthetic polyphosphazene immunoadjuvants, PCPP and PCEP, were studied for their ability to potentiate the immune response to the hepatitis C virus (HCV) E2 glycoprotein antigen in vivo. We report that PCEP induced significantly higher serum neutralization and HCV-specific IgG titers in mice compared to other adjuvants used in the study: PCPP, Alum, and Addavax. PCEP also shifted the response toward the desirable balanced Th1/Th2 immunity, as evaluated by the antibody isotype ratio (IgG2a/IgG1). The in vivo results were analyzed in the context of antigen-adjuvant molecular interactions in the system and in vitro immunostimulatory activity of formulations. Asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) analysis showed that both PCPP and PCEP spontaneously self-assemble with the E2 glycoprotein with the formation of multimeric water-soluble complexes, which demonstrates the role of polyphosphazene macromolecules as vaccine delivery vehicles. Intrinsic in vitro immunostimulatory activity of polyphosphazene adjuvants, which was assessed using a mouse macrophage cell line, revealed comparable activities of both polymers and did not provide an explanation of their in vivo performance. However, PCEP complexes with E2 displayed greater stability against agglomeration and improved in vitro immunostimulatory activity compared to those of PCPP, which is in line with superior in vivo performance of PCEP. The results emphasize the importance of often neglected antigen-polyphosphazene self-assembly mechanisms in formulations, which can provide important insights on their in vivo behavior and facilitate the establishment of a structure-activity relationship for this important class of immunoadjuvants.

Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey.

BACKGROUND: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. METHODS: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. RESULTS: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). CONCLUSIONS: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.

Long-term follow-up of HCV patients with sustained virological response after treatment with pegylated interferon plus ribavirin.

BACKGROUND: The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). METHODS: Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. RESULTS: In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). CONCLUSIONS: The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

A CROSS-SECTIONAL STUDY OF HEPATITIS B AND HEPATITIS C KNOWLEDGE AMONG DENTAL MEDICINE STUDENTS AT THE UNIVERSITY OF ZAGREB.

Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb, and analyze how enrolment in obligatory and supplemental courses affects knowledge and NSI reporting practice. The knowledge was assessed by our questionnaires based on the Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data were analyzed by descriptive statistical analysis, independent-samples t-test, proportion analyses, and combined factor analyses of categorical and quantitative variables in SPSS and R. In total, 206 students participated in the survey. The overall level of HBV- and HCV-related knowledge was poor, with the mean scores of 61.90% and 51.35%, respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants, 18.2% had sustained a NSI and the majority of them (78.95%) had never reported the injury. In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form has failed to significantly improve student competence and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.

Prevalence, risk factors and impact of occult HCV infection on liver morbidity among haemodialysis patients: hospital-based cross-sectional study.

OBJECTIVES: Haemodialysis (HD) patients are at risk for blood-borne infections as occult HCV infection, which justifies comprehensive studies. We aimed to determine the prevalence and risk factors of occult HCV infection (OCI) among HD patients. MATERIAL AND METHODS: One hundred eligible HD patients, with no evidence of overt HCV or HBV and HBV vaccinated were recruited, and tested for HCV, HBV markers and HCV RNA. Two HCV-positive patients were excluded and peripheral mononuclear cells of 98 patients were verified for viraemia. RESULTS: OCI was detected in eight (8.16%); with a median viral load of 7010copies/ml. Their mean age was 30.63 (±18.87 years) compared to others (41.73 ± 15.93) (p = .069). History of surgery, dental procedure, and blood transfusion was comparably high in both groups (p > .05). All OCI patients underwent dialysis twice weekly compared to 48.9% of non-OCI patients (p = .006). OCI patients had a significantly higher mean duration of dialysis (12.63 ± 6.74 years), and a significantly higher frequency (50%) of HCV Ab compared to 6.48 ± 4.76, and 10%, respectively, in non-OCI patients. None of OCI patients was reactive to HBcAb compared to 34 (37.8%) patients without (p = .048). Evidence of liver morbidity was detected in 5 (62.5%) OCI patients compared to 43 (47.7%) of non-OCI patients (p > .05). CONCLUSION: Among our HD patients, OCI is considered a comorbid finding associated with mild liver morbidity that warrants strict infection control and periodic testing for blood borne infections.

AMSSM Position Statement Update: Blood-Borne Pathogens in the Context of Sports Participation.

This AMSSM position statement update is directed toward health care providers of patients involved in sport and exercise. There have been significant advances in clinical and scientific research in the understanding of blood-borne pathogens (BBPs), and this update incorporates these advancements. This document is intended as a general guide to clinical practice based on the current state of evidence, while acknowledging the need for modification as new knowledge becomes available. Confirmed transmission of BBPs during sport is exceedingly rare. There are no well-documented reports of HIV, hepatitis C virus, or hepatitis D virus transmission during sport. There is also no evidence for universal testing for BBPs as a specific requirement for participation in sports. Competitive athletes and nonathletes should follow appropriate general public health agency recommendations for screening for BBPs, considering their individual risk factors and exposures. Standard (universal) precautions must be followed by those providing care to athletes. Exercise and athletic participation can help promote a healthy lifestyle for persons living with BBPs. Those with acute symptomatic BBP infection should limit exercise intensity based on their current health status. Education is the key tool for preventing BBP transmission. Research gaps include evaluation of the prevalence of BBP infections in competitive athletes, the effects of long-term, intense training on infected athletes, and the effects of BBP treatment therapies on performance.

Comparative safety and efficacy of conventional interferon versus pegylated-interferon based therapy for HCV: A retrospective cohort study from Gujranwala, Pakistan.

Numerous studies on risk factors, clinical presentation and treatment of hepatitis C are known to the world. However, no data is available about the safety and efficacy of anti-hepatitis C therapy among the patients of Gujranwala, Pakistan. This retrospective study compared two dosage forms of interferon; conventional interferon (IR) and Pegylated interferon (PIR) in 370 Hepatitis C patients selected through non probability convenient sampling technique. Clinical data were collected related to therapy outcomes at the start of therapy, after each follow up and at the end of therapy. The study indicated that HCV 3 was the most prevalent genotype of hepatitis C. Main side effects associated with therapies were pain at injection site (PIR; 49%, IR; 48%), inflammation at injection site (PIR; 34%, IR; 48%), fever (PIR; 56.12%, IR; 61.5%), myalgia (PIR; 24.5%,IR; 22.99%), malaise (PIR; 7.14%, IR; 5.75%), anorexia (PIR; 46%, IR; 39%), vomiting (PIR; 43%, IR; 41%), irritability (PIR; 4%, IR; 11.5%) and impaired concentration (PIR; 13%, IR; 21). The sustained viral response rate was significantly better in PIR group as compared to IR group (PIR; 80.61%, IR; 66.67%). In conclusion Pegylated interferon based therapy showed better clinical response with less adverse events as compared to conventional interferon based therapy. However, there is dire need to shift from these intravenous dosage forms to relatively new oral dosage forms for the treatment of hepatitis C to further improve clinical outcome and minimize the risks of adverse events.

Routine screening for HIV, hepatitis B virus and hepatitis C virus in individuals undergoing oral and maxillofacial surgery.

OBJECTIVES: Given the effectiveness of treatment of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, there are considerable benefits associated with determining HIV/HBV/HCV status. We evaluated the feasibility and acceptability of systematic screening and subsequent care in an oral and maxillofacial surgery department. METHODS: The anaesthesiologists proposed screening for HIV, HBV and HCV to all individuals of unknown infection status undergoing surgery between 19 April 2016 and 19 April 2017. The endpoints were the rates of test offer, acceptance/refusal and new diagnoses. Seropositive individuals were referred to infectious disease specialists. Associations between age, sex or surgery type and test offer (eligible individuals) or acceptance/refusal (those offered testing) were investigated. RESULTS: Of the 1407 individuals attending the department, 1322 were eligible for inclusion in the study. Testing was proposed to 899 individuals [68%; 95% confidence interval (CI) 65-71%], 831 of whom accepted the offer (92.4%; 95% CI 90.5-94.1%). Results were obtained for 787 individuals (41 samples were uncollected and three were invalid). Age was the only factor associated with test offer in multivariable analysis [odds ratio (OR) 0.90; 95% CI 0.84-0.97, per additional 10 years], and no factor was associated with acceptance. Of the five, three and eight individuals testing positive for HIV, HBV and HCV, four, two and one patient, respectively, reported prior knowledge of seropositivity. The new diagnosis rate was 0.13% (95% CI 0-0.7%) for HIV and HBV, and 0.89% (95% CI 0.36-1.82%) for HCV [three positive polymerase chain reaction (PCR) tests]. All individuals newly diagnosed with HIV or HCV infection received specific antiviral treatment. CONCLUSIONS: Rates of screening offer and acceptance were high. Substantial screening resources are required to decrease the impact of the hidden epidemics of HIV, HBV and HCV infections.