Impact of educational interventions on hepatitis B and C awareness among school students of Delhi NCR, India.

BACKGROUND: Viral hepatitis, particularly B and C, is a major cause of liver cirrhosis and cancer, leading to about 1.4 million deaths annually. Alarmingly, less than 20% of those with hepatitis are aware of their status, with only 6.3% receiving treatment. School children can play a pivotal role in raising awareness and preventing the spread of infections. This intervention study focuses on understanding and enhancing the knowledge, attitudes, and practices related to Hepatitis B and C, among school children in Delhi NCR to foster dialogue and awareness. METHODS: An intervention study was conducted in selected schools across Delhi NCR between September and October 2022 to assess baseline knowledge, attitudes, and practices related to Hepatitis B and C. Three of seven schools were randomly selected by probability sampling, representing 9-12 grade students, and 901 students participated. Following this, an educational interventional program was conducted using educational material, interactive sessions, and audiovisual aids. Post-intervention assessments were done to measure the impact on knowledge improvement. RESULTS: The study is expected to provide insights into the current level of awareness regarding Hepatitis B and C. Furthermore, the intervention's effectiveness was analysed using the pre-formed questionnaire. The average pre-test knowledge score was 8.9 ± 3.2, while the post-test average was 15.6 ± 4.4, indicating a substantial increase of 6.7 ± 4.7 points (+ 75.2%). There was a positive correlation of 0.240 between pre and post-test scores. Attitude change before and after the session showed a positive percentage change of + 38.0% with a correlation of 0.351. The study indicated substantial improvements in knowledge about hepatitis B and C, notably regarding awareness about transmission methods and risk factors. CONCLUSION: This interventional study seeks to bridge the knowledge gap among school children regarding Hepatitis B and C in Delhi NCR, fostering a proactive approach towards prevention, detection, and treatment. The considerable rise in awareness and favourable changes in perspectives post-intervention say that specific health education initiatives are pivotal in raising awareness and comprehension of infectious diseases, ultimately contributing to improving community health.

Progress Toward the Elimination of Hepatitis B and Hepatitis C in the Country of Georgia, April 2015-April 2024.

Hepatitis B and hepatitis C are leading causes of cirrhosis and liver cancer and caused 1.3 million deaths worldwide in 2022. Hepatitis B is preventable with vaccination, and hepatitis C is curable with direct-acting antivirals. In 2015, in collaboration with CDC and other partners, Georgia, a country at the intersection of Europe and Asia, launched a hepatitis C elimination program to reduce the prevalence of chronic hepatitis C; at that time, the prevalence was 5.4%, more than five times the global average of 1.0%. In 2016, the World Health Assembly endorsed a goal for the elimination of viral hepatitis as a public health problem by 2030. In 2024, 89% of the Georgian adult population have received screening for hepatitis C, 83% of persons with current chronic HCV infection have received a diagnosis, and 86% of those with diagnosed hepatitis C have started treatment. During 2015-2023, vaccination coverage with the hepatitis B birth dose and with 3 doses of hepatitis B vaccine among infants exceeded 90% for most years. In 2021, the prevalence of hepatitis B surface antigen was 0.03% among children and adolescents aged 5-17 years and 2.7% among adults. Georgia has demonstrated substantial progress toward hepatitis B and hepatitis C elimination. Using lessons from the hepatitis C elimination program, scale-up of screening and treatment for hepatitis B among adults would prevent further viral hepatitis-associated morbidity and mortality in Georgia and would accelerate progress toward hepatitis B and hepatitis C elimination by 2030.

Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review.

Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.

Development of an evidence-based hepatitis C education program to enhance public health literacy in the Australian prison sector: The Hepatitis in Prisons Education program (HepPEd).

BACKGROUND: Australia's prisons have a high chronic hepatitis C (HCV) prevalence (8 %). Antiviral therapies and prison-based hepatitis services are available, but only a minority of those eligible are being treated. Improving the HCV public health literacy of the prison sector via targeted education may overcome key barriers to scale-up treatment. This paper describes the: i) HCV public health literacy of the prison setting; ii) barriers and solutions for HCV education and service engagement; iii) HCV education program co-design and development processes; and iv) HepPEd resources. METHODS: A national needs assessment was conducted to analyse the HCV public health literacy of the target audience groups in the prisons (healthcare providers; custodial officers; people in prison) to inform development of a prison-specific HCV education program (HepPEd). Structured interviews were conducted with key informants (n = 40). Three National Steering Committees, one for each target group, were convened to co-design and develop HepPEd. RESULTS: Only healthcare providers involved with hepatitis care were considered to have 'good' to 'very good' HCV health literacy (including knowledge, attitudes, and capabilities), with all other groups considered less favourably. Key barriers identified included being time poor (healthcare providers), poor motivation (custodial officers) and stigma (people in prison). Peer education delivery was considered a key facilitator for custodial officers and people in prison. A suite of multi-modal resources addressing the perceived gaps in HCV health literacy was developed, with a broad theme of 'Let's talk about hep C'. Delivery of HepPEd was designed to overcome key barriers and utilise facilitators for each group. CONCLUSIONS: Significant gaps in HCV health literacy were perceived amongst the target audience groups. The comprehensive co-design and development processes utilised in HepPEd suggest the program will be well-placed to improve the HCV public health literacy of the prison sector and thereby enhance HCV testing and treatment rates amongst people in prison.

Immunogenicity study of a Novel DNA-Based HCV vaccine candidate.

In this study, we aimed to evaluate the immunogenic profile of a chimeric DNA-based hepatitis C virus (HCV) vaccine candidate encoding the full-length viral core-E1-E2 (HCV-CE) fragment. The vaccine candidate was designed to uniformly express the HCV genotype 4 core-E1-E2 protein. The recombinant HCV-CE protein was bacterially expressed in C41 (DE3) cells, and then BALB/c mice were immunized with different combinations of DNA/DNA or DNA/protein prime/boost immunizations. The proper construction of our vaccine candidate was confirmed by specific amplification of the encoded fragments and basic local alignment search tool (BLAST) results of the nucleotide sequence, which revealed a high degree of similarity with several HCV serotypes/genotypes. The platform for bacterial expression was optimized to maximize the yield of the purified recombinant HCV-CE protein. The recombinant protein showed high specific antigenicity against the sera of HCV-infected patients according to the ELISA and western blot results. The predicted B- and T-cell epitopes showed high antigenic and interferon-γ (IFN-γ) induction potential, in addition to cross-genotype conservation and population coverage. The mice antisera further demonstrated a remarkable ability to capture 100% of the native viral antigens circulating in the sera of HCV patients, with no cross-reactivity detected in control sera. In conclusion, the proposed HCV vaccination strategy demonstrated promising potential regarding its safety, immunogenicity, and population coverage.

Hepatitis C virus infection is uncommon at baseline and during follow-up among individuals using PrEP in the Dutch national PrEP programme between 2019 and 2022.

OBJECTIVES: Studies showed that men who have sex with men (MSM), including those using pre-exposure prophylaxis (PrEP), are at increased risk of hepatitis C virus (HCV) infection. We evaluated HCV prevalence and incidence, along with their associated determinants, in a cohort of PrEP-using individuals in the Netherlands. METHODS: In 2019, the Netherlands launched a 5-year national programme that offers subsidised PrEP to eligible individuals. We used prospectively collected data from individuals registered in this programme between 2019 and 2022. Individuals underwent annual testing for HCV antibodies and additional HCV-RNA testing when antibodies were present. We calculated the prevalence of past/current HCV infection at first visit and overall incidence rate (IR) during follow-up. Univariable logistic and Poisson regression models were used to identify determinants associated with past/current prevalent or incident HCV infection, respectively. Behavioural factors referred to those occurring in the previous 6 months. RESULTS: A total of 10 563 (n=10 319, 97.7% MSM) were included. At first visit, 66 of 10 563 (0.6%) had a past/current HCV infection, which was associated with older age [odds ratio (OR) per 10 years=1.57, 95% confidence interval (CI)=1.31 to 1.88], the use of PrEP before first visit (OR=3.03, 95% CI=1.79 to 5.13), receptive condomless anal sex (CAS) (OR=2.73, 95% CI=1.25 to 5.98), chemsex (OR=2.44, 95% CI=1.49 to 3.99) and injecting drug use (IDU) (OR=6.61, 95% CI=2.35 to 18.61). Among 9851 individuals contributing to 17 150 person-years (PYs) of follow-up, 64 incident HCV infections (IR=0.37 per 100 PYs, 95% CI=0.29 to 0.48) were identified. Factors associated with incident HCV infection were receptive CAS [incidence rate ratio (IRR)=2.59, 95% CI=1.12 to 6.02], chemsex (IRR=1.78, 95% CI=1.06 to 2.98), sexually transmitted infection diagnosis (IRR=2.30, 95% CI=1.23 to 4.31) and IDU (IRR=6.15, 95% CI=2.20 to 17.18). CONCLUSIONS: Past/current prevalence and incidence of HCV were low among individuals in the Dutch PrEP programme. Infections were associated with behaviour known to be associated with HCV. Instead of annual HCV testing, as stated in most PrEP care guidelines, testing frequency for HCV could be based on behaviours associated with HCV acquisition.

Opportunistic population screening as a hepatitis elimination strategy: the CRIVALVIR-FOCUS program.

OBJECTIVES: Hepatitis B (HBV) and hepatitis C (HCV) viruses are significant causes of primary liver cancer, responsible for over a million deaths annually. We aimed to develop a screening strategy for viral hepatitis elimination in Spain, aligned with WHO's 2030 objectives. DESIGN: The CRIVALVIR-FOCUS program, conducted at the Consortium General University Hospital of Valencia, aimed to identify individuals with active blood-borne viral infections through opportunistic population screening. The hospital's Health Department serves more than 280,000 adults. RESULTS: Of the 31,995 adults screened (52% women; 15% immigrants), HBV prevalence was 0.44%, with higher rates in men (0.57%) than women (0.32%), and notably higher in migrants (1.27%) compared to Spanish nationals (0.30%). The 45-64 age group had the highest HBV prevalence (0.65%). HCV prevalence was 0.35%, again higher in men than women (0.51% vs 0.20%) and in migrants compared to Spanish nationals (0.58% vs 0.31%), with the 45-64 age group showing the highest HCV prevalence (0.76%). From the positive tests, 78.0% (110/141) of HBV cases and 71.4% (80/112) of HCV cases were patients previously unaware of their infections. CONCLUSION: Opportunistic screening effectively identifies early cases, potentially enhancing prevention of new infections. Our study highlights the need for targeted interventions for individuals aged 45-64 and migrants. Designing specific screening programs, in collaboration with social workers and cultural mediators, is critical to improve access to care. Training and involving primary care professionals are vital actions for the program's success.

Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

INTRODUCTION: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. METHODS: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. RESULTS: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. CONCLUSIONS: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.

Hepatitis C virus (HCV) is a major medical health burden and the leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations, making vaccine development a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been the development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches.

Infection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful.

The 'missing' in the 'endgame' of hepatitis C elimination: A qualitative study in New South Wales, Australia.

INTRODUCTION: After a promising start in Australia, elimination efforts for hepatitis C are not on track. Following the global campaign to 'find the missing' in hepatitis C response, this qualitative study explores stakeholder perspectives on the 'missing' in the 'endgame' of hepatitis elimination in the state of New South Wales, Australia. METHOD: Twenty-eight key informants working in New South Wales, elsewhere in Australia and internationally in high income countries participated in a semi-structured qualitative interview. Analysis examined key informant accounts of the 'missing' in efforts to eliminate hepatitis C. RESULTS: Participants' accounts framed the missing in relation to epidemiological knowledge, making-up four population categories 'missing' or 'missed' in hepatitis C response. In turn, accounts situated the missing in relation to where and how individuals were presumed to connect, or not, with existing health-care infrastructures. This gave rise to concerns about the capacity of health services to be made available for those at risk or in need, with systems said to create opportunities for people to 'miss out' on hepatitis C services. DISCUSSION AND CONCLUSIONS: The 'missing' in the 'endgame' of hepatitis C elimination effort is not simply a function of who-populations missed-but of where and how, that is, situation and context. Our findings encourage a focus on how services, systems and contexts may create situations in which people become missed or are 'made missing' from care. We therefore advocate for a systemic, and not only population-based, approach in the final push towards hepatitis C's elimination.

Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Advancing Diagnosis of Current Hepatitis C Virus Infection: A Key to Hepatitis C Elimination in the United States.

More than 2 million adults have hepatitis C virus (HCV) infection in the United States, and new infections continue to increase. Without treatment, HCV infection can lead to advanced liver disease and death. Treatment is recommended for nearly everyone with hepatitis C, resulting in a cure in >95% of people treated and raising the possibility of hepatitis C elimination. Testing is the first step to accessing life-saving treatment. The Centers for Disease Control and Prevention recommends hepatitis C screening for all adults, all pregnant persons, and anyone with risk; yet about one-third of people with hepatitis C remain unaware of their infection. Testing begins with a hepatitis C antibody test, followed, when reactive, by a nucleic acid test to detect HCV RNA. This antibody-first, 2-step testing strategy misses early infections and can result in incomplete diagnoses. Advancements in hepatitis C diagnostics and the US regulatory landscape have created an opportunity to include viral-first testing strategies and improve hepatitis C diagnosis. This journal supplement features 8 articles detailing challenges and opportunities for improving hepatitis C diagnostics in support of advancing hepatitis C elimination in the United States.