Countermeasures against viral hepatitis in Japan: road to HCV elimination

The World Health Organization (WHO) has set a goal of elimination of viral hepatitis by 2030. In Japan, the estimated people of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections were 1.7-2.2 and 1.3-1.5 million in 2000, respectively. Although the mortality due to hepatocellular carcinoma (HCC) had been increasing until around 2002, it has been gradually decreasing to date, and approximately 24,000 people died from HCC in 2021 in Japan. Japan has a national action plan for addressing viral hepatitis called, ''Basic Act on Hepatitis Measures'', established in 2009. ''Basic Guidelines for Promotion of Control Measures for Hepatitis'' was issued in 2011 and was updated in 2016 and 2022, comprising 9 principles in order to promote measures to prevent HBV and HCV. According to these guidelines, national and local government share screening costs for testing HBV and HCV for those residents who are over 40 years old. Thus, out-of-pocket expenses from examinees are free of charge or reduced to a minimum. In addition, for patients with chronic HBV or HCV infections treated with nucleotide analogues, interferon, and direct antiviral agents, the drug prices and examination expenses were covered by a medical-expenses support system for viral hepatitis. By these countermeasures against viral hepatitis, the estimated people of chronic HCV infection revealed a decrease to 1.0-1.6 million in 2011 (30-40% decrease from 2000 level) and 0.9-1.3 million in 2015 (40- 50% decrease from 2000 level). If the current situation had been continuing, the number of HCV patients is expected to decrease to 0.2-0.5 million (80-90% decrease from 2000 level and 60-80% decrease from 2015 level) by 2030. However, the COVID-19 pandemic since December 2019 is thought to have affected testing, linkage to care, treatment uptake, and follow-up, and new efforts that do not slow the progress to date toward HCV elimination, which is finally becoming visible, will be necessary in the future. In this lecture, I would also like to talk about the efforts at our hospital to achieve the sustainable development goal targeted by WHO.

Taiwan's national strategies and actions toward HCV elimination before 2025

In 1990, the seroprevalence of antibody against hepatitis C virus (anti- HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been well-documented by REVEL-HCV study. A national program of antiviral therapy for chronic viral hepatitis was launched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO's 2030 goals in 2025. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. There are triple focuses of hepatitis C elimination in Taiwan including (1) therapy spearheads prevention, (2) screening supports therapy, and (3) prevention secures outcome. A total of US$1.7 billion will be allocated from 2017 to 2025 for the elimination of HCV. The coverage of HCV screening and treatment has been increasing significantly since 2017. The HCV screening coverage was almost 100% for dialytic patients, 96% for HIV-infected patients, 65% for patients under opioid substitution treatment, 63% for patients in the pre-end-stage renal disease care program, 57% for patients in the early chronic kidney disease care program, 52% for patients in diabetes care program, 39% for prisoners, and 38% for adults aged 45-79 years old in the general population by April 30, 2020. The budget to cover the cost of DAA increased from US$101 million in 2017 to US$219 million in 2019. The number of chronic hepatitis C patients receiving DAA therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,806 in 2019. However, the number of DAA-treated CHC patients reduced to 36,159 in 2020 and 20,559 in 2021 due to the COVID-19 pandemic. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, over 98.6% after 2019. It is expected that Taiwan will achieve WHO's HCV elimination goal by 2025.

Features of the diagnosis and course of COVID-19 in HIV-infected patients hospitalized in a hospital

The global pandemic of coronavirus infection (COVID-19) has set complex diagnostic tasks for doctors of polyclinics and hospitals. Considering the simultaneous pandemic spread of two infectious diseases - COVID-19 and HIV infection, the problem of studying the clinical features of combined COVID-19/HIV infection becomes urgent. The aim of the study was to determine the features of the diagnosis and course of COVID-19 against the background of HIV infection in patients undergoing inpatient treatment. Material and methods. The study was conducted on the basis of the temporary Clinical Medical Center COVID-19 of the A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation in Moscow from October 2020 to January 2022. The study included 31 233 patients with COVID-19 complicated by pneumonia. To analyze the features of the course of combined COVID-19/HIV infection, a group of 51 HIV-infected patients was identified. The diagnosis of COVID-19 was determined based on the detection of SARS-CoV-2 RNA by PCR in nasal/oropharyngeal smears and/or according to computed tomography of the lungs (CT). During the study, age, gender, anamnesis, objective examination data were analyzed, taking into account the results of CT scans of the chest organs, data from routine laboratory blood tests, oxygen support regimens, treatment outcomes and duration of detection of SARS-CoV-2 RNA. All patients were treated according to the Temporary Clinical Guidelines for the Diagnosis and Treatment of COVID-19, 14 version dated 12/27/2021. Results. The number of patients with combined HIV infection and SARS-CoV-2 out of the total number of hospitalized COVID-19 patients (n=31 233) was 0.16%. Upon admission, 30 (59%) patients reported having HIV infection and receiving antiretroviral therapy (ART). HIV infection was first diagnosed in 21 patients at 2-3 weeks of inpatient treatment. The average age of patients with SARS-Cov-2/HIV co-infection was 1.5 times less than in patients without HIV (41.1+/-5.3 and 64.4+/-10.1, respectively) (p<=0.05). Concomitant pathology (hypertension, type 2 diabetes mellitus, chronic kidney disease and chronic lung diseases) was less common (51%) in the group of combined infection than in the group without HIV (83%). However, in 41% of patients with coinfection, chronic viral hepatitis B, C was detected, in contrast to 0.3% of cases of COVID-19 patients without HIV. 26 (51%) patients were discharged with improvement, while the average bed-day did not differ from patients without HIV infection (13.4+/-4.5 days and 11.7+/-5.2, respectively) (p>=0.05). 7 (24%) patients at the time of discharge (16.8+/-4.2 days) with clinical and laboratory improvement maintained a positive result of PCR RNA on SARS-Cov-2. In 22 (43%) patients with coinfection, hospitalization was fatal for 3 to 21 days of treatment, with ARDS with respiratory and multiple organ failure, which is 3.6 times higher than in patients without HIV infection. The analysis showed that, regardless of the result of PCR on SARS-CoV-2 RNA, in non-specialized hospitals, HIV testing is indicated for young patients with fever for more than 14 days, with lung damage in the form of bilateral interstitial changes according to CT, a history of chronic hepatitis C, B, with progressive severity of the condition on against the background of COVID-19 therapy. Early consultation of an infectious disease specialist, examination of sputum/lavage by PCR for pathogens of opportunistic infections and the appointment of ART and drugs for the treatment of opportunistic diseases will improve the quality of medical care for patients in a non-core HIV hospital will improve the prognosis of COVID-19.Copyright © Eco-Vector, 2022.

Results of an Automatic Alert System from Microbiology to Link Diagnosis to Treatment in Patients with Chronic Hepatitis C

Introduction and Objectives: Strategies to simplify the care circuit for patients with the hepatitis C virus (HCV) are vital to achieving its eradication. To achieve this aim, we introduced an electronic system of HCV serology detection to link diagnosis with specialized assistance in order to minimize the loss of patients. Material(s) and Method(s): A retrospective single-center study of HCV patients developed by Microbiology Department from February 15th, 2020, to December 15th, 2021. In the event of a positive HCV antibody, the anti-HCV core was directly measured by the electronic system. If positive, an encrypted e-mail with the patient data was automatically sent to HCV specialized physicians, who, after evaluating the benefits of antiviral therapy in each patient, contacted them by phone for an appointment. In the first face-to-face consultation FibroScan, HCV genotype and viral load measurement were performed, and antiviral therapy was prescribed. Patient diagnosis origin and public health characteristics were recorded. We analyzed the association between antiviral therapy prescription and these variables. Statistical significance was set at p<0.005. Result(s): Of 171 patients identified, with a mean age of 59.6 +/- 15.9, 61.5 % of males and 81.2% of Spanish nationals. HCV origin from out-of-hospital settings predominated (50.9%, 87/171), particularly primary care (28.7%), penitentiary (11.6%) and addiction units (8.2%). In all, 43.3% (74/171) were aware of their diagnosis, but 64.9% (48/74) hadn't previously received antiviral therapy. Genotype 1 predominated. We recorded 19.4% (20/103) of patients F3 fibrosis and 27.2% (26/103) F4. Finally, 58.5% (100/171) attended a physician consultation. They were all treated with pangenotypic interferon-free therapy. A 100% rate of sustained viral response was achieved. The main reasons for not being treated were high comorbidity (43.7%,31/71), not located (23.9%, 17/71), patient refusal to treatment (23.9%,17/71) and death (8.5%,6/71). The sole association found between antiviral therapy and patient variables was that of comorbidities with being untreated (OR=7.14, p<0.001). Conclusion(s): Our alert system is simple and easily reproducible. It allows for minimizing the loss of HCV patients, even considering it was performed during the COVID-19 pandemic.Copyright © 2023

Liver and COVID-19 - A Review and Clinical Approach

Liver enzyme abnormalities occur frequently in patients diagnosed with Coronavirus disease 2019 (COVID-19). It has been suggested that patients with severe acute liver injury are more likely to be admitted to intensive care, require intubation or renal replacement therapy and their mortality rate is higher than patients without severe acute liver injury. This review article explores the possible aetiologies of liver dysfunction seen in patients with COVID-19 and also the effect of COVID-19 on patients with pre-existing liver disease. Finally, we suggest clinical approaches to treating a patient with liver enzyme disturbance and COVID-19 and also caring for patients who require liver transplantation in the COVID-19 era.Copyright © 2022 Bentham Science Publishers.

Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases.

Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Distinct profiles and kinetics of soluble infammatory markers in patients with acute and chronic HCV-infections and SARS-CoV-2-infections: Implications for the long-term consequences of viral infections?

Background and Aims Viral infections occur acutely but can also progress chronically, with the immune system having a central role in immunopathoge-nesis. The question arises whether all alterations in immune responses are reversible after viral elimination (spontaneously or by therapy). Therefore, the aim of this study is to compare soluble infammatory markers (SIM) during and after infection with SARS-CoV-2 and acute and chronic HCV-infections. Patients and Method Patients with acute HCV (n = 29), chronic HCV (n = 54), SARS-CoV-2 (n = 39) and 31 healthy-controls were included. Blood samples were tested at baseline, end of treatment/infection, and follow-up ( >= 9 months after baseline). IL-12p70, IL-1b, IL-4, IL-5, IL-6, IL-8, TNF, IFN-g, IL-10, IL-22, CXCL-10, MCP-1, MIP-1b, ITAC were quantified using the HD-SP-X Imaging and Analysis SystemTM. Results SIM profiles in patients with acute HCV were substantially elevated at baseline and the decrease during follow-up was considerably less compared to the SARS-CoV-2 cohort. In chronic HCV-patients, viral elimination by therapy resulted in a decrease in SIM, although not always to those of controls. Cirrhotic HCV patients had higher SIM levels after HCV elimination than non-cirrhotic chronic HCV-patients. In the SARS-CoV-2 cohort, most SIM returned to levels of controls 3 months after baseline. Conclusions SIM profiles and kinetics after viral elimination difer between blood-borne acute and chronic HCV- and respiratory SARS-CoV-2-infections. The immunologic imprint 9 months after cured HCV-infection (both acute and chronic) appears to be more pronounced than after SARS-CoV-2-infection. Further analysis is needed to correlate the SIM profle with the clinical pheno-type (long-HepC vs. long-COVID-19).

Relinkage of Patients with Chronic Hepatitis C Infection in the Context of the Covid-19 Pandemic

Introduction and Objectives: In Argentina, it is estimated that around 50% of patients infected with hepatitis C virus (HCV) have been diagnosed and only 5% of those have accessed treatment after several months;this reality got worse with the pandemic. World Health Organization proposed a global health sector strategy to eliminate HCV as a public health threat by 2030. Key elements of the elimination plan include increased diagnosis and treatment access. This study aimed to describe the implementation of "Relinkage and simplified care pathway program" as a strategy for micro-elimination of HCV. Material(s) and Method(s): : Hospital outpatients aged over 18 years, with a confirmed or suspected diagnosis of HCV infection and without follow-up during the last year, were included. Patient selection was made by collecting data from medical records. Selected patients were contacted by telephone and scheduled for a clinic visit with a simplified care pathway. "Reflex Testing," which is an HCV antibody test, was used;if the result was positive, an HCV RNA and genotype test on the same specimen was performed. Untreated and non-responder patients were treated. Result(s): : A total of 938 patients were included, and 409 (44%) could be reached. Out Of these, 16.3% (67) died, 1.7% (7) developed hepatocellular carcinoma, and 6.75% (15) progressed to cirrhosis. We found that 21.7% were candidates for treatment, and the treatment was delivered in two clinic visits with an average time of 29 days (7-69). However, 41% (34) of patients with cirrhosis could not be contacted. Conclusion(s): : Program implementation improved the diagnosis and treatment access. Furthermore, it reduces the number of clinical visits and may increase adherence to follow-up. On the other hand, we are concerned that half of the patients were lost on the follow-up and about their progression to cirrhosis rate. If we are looking for different results, we should take different measures.Copyright © 2023

Four Weeks Treatment with Glecaprevir/Pibrentasvir + Ribavirin-A Randomized Controlled Clinical Trial.

Enhancing treatment uptake for hepatitis C to achieve the elimination goals set by the World Health Organization could be achieved by reducing the treatment duration. The aim of this study was to compare the sustained virological response at week 12 (SVR12) after four weeks of glecaprevir/pibrentasvir (GLE/PIB) + ribavirin compared to eight weeks of GLE/PIB and to estimate predictors for SVR12 with four weeks of treatment through a multicenter open label randomized controlled trial. Patients were randomized 2:1 (4 weeks:8 weeks) and stratified by genotype 3 and were treatment naïve of all genotypes and without significant liver fibrosis. A total of 27 patients were analyzed for predictors for SVR12, including 15 from the first pilot phase of the study. In the 'modified intention to treat' group, 100% (7/7) achieved cure after eight weeks and for patients treated for four weeks the SVR12 was 58.3% (7/12). However, patients with a baseline viral load <2 mill IU/mL had 93% SVR12. The study closed prematurely due to the low number of included patients due to the COVID-19 pandemic. Our results suggest that viral load should be taken into account when considering trials of short course treatment.

Covid-19 In HCV Treated Versus Non-Treated Patients: A Case Control Study

Background: COVID-19 poses a major health threat to healthy individuals and those with comorbidities. SARS-CoV-2 virus causes liver damage and worsens pre-existing chronic liver disease that yields higher mortality rates. However, it remains unknown whether those with chronic liver disease are at increased risk for SARS-CoV-2 virus infection and how these risks were further affected by the patient's demographics. Aim(s): this study aimed to determine the incidence of mortality and degree of severity of covid-19 infection among the studied cohort. Subject and methods: This case-control study was conducted on 124 patients: (Group A): COVID-19 patients with previous history of treated HCV and (Group B): COVID-19 patients with previous history of untreated HCV. Result(s): There was high significant difference between both groups as regard mortality rate. Also, active HCV infection was associated with more severe disease and higher mortality in patients co-infected with SARS-CoV-2, HCV viral load being an independent risk factor for all-cause mortality and liver impairment. The severity of liver impairment was associated with poor clinical outcomes in COVID-19 patients. Conclusion(s): These results suggested that close monitoring and careful treatment for active- HCV patients with COVID-19 are needed to avoid health deterioration and fatal outcome. Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Experience in managing action research on hepatitis C survey in the prison community

We aimed to report the experience in managing action research on hepatitis C investi-gation in the prison community in the Triangulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and mo-nitoring of positive cases. We adopted intersecto-ral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are descri-bed: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommoda-tion of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invi-sible population, the prison community when it highlights the strategies adopted to conduct the research. Copyright © 2022, Associacao Brasileira de Pos - Graduacao em Saude Coletiva. All rights reserved.

Frequency of Mutations in Abcb1 and Abcb11 Genes in Patients with Chronic Hepatitis C (Hcv) in Rio De Janeiro

Introduction: The post-COVID-19 syndrome is characterized by the appearance of symptoms and sequelae up to four weeks after the acute symptoms of COVID-19 and can affect various systems, such as respiratory, hematological and hepatic. Cases of chronic fatigue, thromboembolism events, myalgia and the increase in enzymes associated with liver damage have been reported. It is known that individuals with chronic liver disease, cirrhosis and/or hepatocellular carcinoma are more likely to develop post-COVID-19 syndrome. In addition, mutations in the ABCB1 gene (G2677T, C3435T and C1236T) that encode the drug-export pump (P-glycoprotein) are associated with drug resistance and hepatotoxicity. The T1331C mutation in the ABCB11 gene encodes the bile salt-exporting pump and is associated with cholestasis. Therefore, these mutations may be an aggravating factor for the post-COVID-19 syndrome, especially in hepatocompromised individuals. Objective(s): The aim of this study was to assess the frequencies of mutations in the ABCB1 and ABCB11 genes and to monitor the post-COVID-19 syndrome in patients with liver disease. Material(s) and Method(s): We analyzed 197 samples from patients with chronic hepatitis C from the Liver Disease Outpatient Clinic of the Gaffree and Guinle University Hospital. Extraction and mutation analysis by qPCR was performed using TaqMan Assays. Result(s): In the ABCB1 gene, the most frequent mutation was C3435T (rs1045642) in 13.7% (TT), in this group 40.1% were wild-type (CC) and 46.2% were heterozygous (CT). For the C1236T (rs1128503) the frequency of wild-type (CC) was 45.2%, of heterozygotes (CT) 43.6% and mutants (TT) 11.2%. The lowest frequency of mutations in the ABCB1 gene was G2677T (rs2032582) in 8.6% of patients, 52.8% are wild-type (GG) and 38.6% are heterozygous (GT). As for the T1331C (rs2287622) in the ABCB11 gene, most individuals were heterozygotes - TC (51.8%), followed by wild-type - TT (34.0%) and mutants - CC (14.2%). Discussion(s): This is the first study to evaluate the association of cases and severity of post-COVID-19 syndrome with mutations in the ABCB1 and ABCB11. So far, there are only reports in the literature of the association of this mutations with liver damage and resistance to drugs used in the treatment of COVID-19, such as lopinavir and dexamethasone. Therefore, the presence of these mutations could influence the presence of the post-COVID-19 syndrome. Conclusion(s): We observed a greater presence of heterozygous individuals than the other genotypes in the population studied. It is necessary to investigate its association with cases of post-COVID-19 syndrome in hepatocompromised patients, in order to establish the risks associated with the syndrome in these individuals and to understand the influence of these polymorphisms on the clinical picture and evolution of these individuals. Support: CAPES and FAPERJ. Copyright © 2022

PATIENTS WITH CHRONIC HEPATITIS C COULD BE TREATED WITH SOFOSBUVIR/ VELPATASVIR FOR 12 WEEKS BY NON-SPECIALISTS: 2nd INTERIM ANALYSIS OF PROSPECTIVE STUDY HELIOS-3

Background: In France, prescribing authorization for hepatitis C virus (HCV) treatment has been expanded to all physicians including non-specialists working in addiction and psychiatric centers and in jails. Patient management includes a Test and Treat approach (TnT) to expedite treatment initiation and a pathway for severe patients followed-up by specialists. This is a descriptive, interim analysis of an ongoing study to assess the efficacy and safety of Sofosbuvir/Velpatasvir (SOF/VEL) for 12 weeks after prescription expansion in patients treated by specialists and non-specialists. Method(s): Included patients are HCV-infected adults following SOF/VEL-based regimens prescribed by primary care physicians and specialists. Data collected from available information in medical records include patient characteristics, number of days between positive PCR/fibrosis assessment and start of therapy, and proportion of patients with sustained virologic response (SVR) 12 weeks after treatment end. Qualitative variables are described as number and percentage (%);quantitative measures as mean (standard deviation;SD) or median (range) as indicated. Result(s): Table) As of January 2022, 286 patients had received at least one dose of SOF/VEL treatment;217 were managed by specialists and 69 by non-specialists. Median patient age was 53.14 years (19.8-88.7), 80 (28%) were F3/F4 and 185 (64.7%) were male. Occasional and excessive consumption of alcohol was reported in 43 (62.3%) and 87 (40.8 %) patients managed by specialists and non-specialists respectively. Current recreational drug use was reported more frequently in 37 patients (53.6%) managed by non-specialists and 40 patients (18.6%) managed by specialists. Mean number of days between SOF/VEL initiation and fibroscan and Fib 4 were 62.16 +/- 306.39 and 40.35 +/- 60.24, respectively. Median number of days between positive PCR and start of therapy was 89.19 +/- 311.17 and 60.65 +/- 80.71 for patients managed by specialists and non-specialists respectively, and only 2 were lost to follow-up. Among 167 eligible patients who achieved an SVR12, 124 (97.6%) [93.28;99.19] were managed by specialists and 40 (100.0%) [91.24;100.00] by non-specialists;according to fibrosis stage, 107 F0-F2 patients (100.0%) and 39 F3-F4 (92.9%) achieved SVR12. Overall, at least one adverse event was observed in 34 patients (11.9%), of which only 2 (0.7%) lead to drug withdrawal. Conclusion(s): This interim analysis describes a French study population benefiting from SOF/VEL in real world use after treatment prescription expansion. SVR12 rates were high, regardless of the type of patient management and stage of fibrosis suggesting that HCV patients could be treated by SOF/VEL for 12 weeks by non-specialists. Despite the COVID 19 situation this study suggested that HCV patient pathway could be more optimized regarding fibrosis assessment or genotype determination.

Psychiatrist-led treatment of hepatitis C (HCV) at an opioid agonist treatment (OAT) clinic in Stockholm - enhancing the HCV treatment care cascade

Introduction: People who inject drugs (PWID) and opioid agonist treatment (OAT) patients have an increased hepatitis C (HCV) prevalence. Studies among these populations show promising HCV treatment results, which is essential to reach the WHO goal of eliminating HCV as a major public health threat by 2030. Objective(s): To introduce psychiatrist-led HCV treatment at an OAT clinic and to investigate HCV treatment results, i.e. sustained virological response at 12 weeks post treatment (SVR12) and numbers of reinfections. Method(s): Prima Maria OAT clinic in Stockholm, provides OAT for 450 patients. The majority have a history of injection drug use. Baseline HCV prevalence (January 2018) was retrospectively investigated through medical charts. In January 2018, psychiatristled HCV treatment (with consultation support from infectious diseases specialists) was introduced at the clinic. Prospective treatment results, numbers of reinfections and incidence rates between January 2018 and April 2021 were further investigated. Result(s): Baseline data (n=418), showed that 46% were not tested for HCV. Of those tested (n=225), 64% had a chronic HCV infection. By January 2021, 104 HCV treatments were initiated. 97/97 (100%) were HCV RNA negative at end-of-treatment. 78/88 (89%) reached SVR12. Overall, 2 reinfections were noted after SVR12 corresponding to a reinfection rate of 3.5/100 PY. Numbers of HCV treatment did not decrease during the COVID-19 pandemic. Conclusion(s): To enhance the HCV treatment cascade, targeted HCV diagnosis efforts are needed. Bringing HCV treatment to OAT clinics enhance the HCV care cascade. HCV treatment education for psychiatrists/addiction specialists makes HCV treatment more sustainable, as specifically noted during the COVID-19 pandemic. (Figure Presented).

Treatment of chronic hepatitis c in children during the covid-19 pandemic

The introduction of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C (CHC) has revolutionized the treatment of this disease. DAAs are almost 100% effective, have a good safety profile, with a short duration of therapy. The first DAAs were registered for children in 2017. Currently, the first real-life therapeutic program is conducted in Po-land, in which children aged 12-18 from all over Poland with chronic hepatitis C are treated using DAAs. Pandemic caused by severe acute respiratory syndrome coronavirus (SARS--CoV-2), which disrupted the functioning of the healthcare systems around the world, also affected the possibility of continuing therapeutic programs for chronic hepatitis C. This paper presents current recommendations on antiviral therapy in children with chronic hepatitis C during the COVID-19 pandemic, with particular emphasis on the role and cooper-ation between specialistic treatment centers, pediatricians, and primary care physicians. Copyright © 2020, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

SESSION TITLE: Lung Transplantation Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: A shortage of lungs persists despite the addition of increased-risk donors to the transplantation pool. Waitlist mortality increased from 14.7 to 16.1 deaths per 100 waitlist years from 2019 to 2020. (1) Novel strategies are needed to further expand the donor pool. We report a case of intentional transplant of recently infected acute respiratory virus syndrome 2 (SARS-CoV-2) donor lungs to a patient with end-stage Idiopathic Pulmonary Fibrosis (IPF). CASE PRESENTATION: A 67 year old man with IPF, former tobacco and alcohol abuse, hypertension and gastroesophageal reflux disease underwent a sequential bilateral lung transplant on cardiopulmonary bypass. His post-operative course was complicated by Pseudomonas Aeruginosa pneumonia and bilateral pleural effusions status-post bilateral chest tube placement. He was extubated 4 days after surgery and had his chest tubes removed within 1 week. He discharged on room air 17 days after transplant and appeared well at his 3 week post-operative clinic visit. The donor lungs came from a 28 year old woman with chronic hepatitis C and recent asymptomatic SARS-CoV-2 infection. She tested positive for SARS-CoV-2 on reverse transcriptase polymerase chain reaction (RT-PCR) nasopharyngeal (NP) swabs at 12 and 7 days prior to surgery. She had negative SARS-CoV-2 results on lower respiratory tract testing via bronchioalveolar lavage (BAL) at 7 and 2 days prior to surgery. Recipient RT-PCR NP testing was negative on post-operative days 3, 10, and 17. Two subsequent BAL samples were negative in the first week post-operation. The recipient consented to transplant and was aware of the donor's recent SARS-CoV-2 and chronic hepatitis C infections. Infectious disease did not recommend any SARS-CoV-2 anti-viral therapy or post-exposure prophylaxis. Hepatology prescribed treatment for donor derived hepatitis C viremia on discharge. DISCUSSION: Emerging pathogens present a challenge in minimizing donor-derived diseases. The utilization of lungs, including patients with recent SARS-CoV-2 infection, should be considered carefully. Institutional guidelines vary in donor exclusion criteria based on history of prior SARS-CoV-2 infection, severity of prior infection, timing of last SARS-CoV-2 result, and type of screening test. (2,3) We report a case of intentional lung transplant with asymptomatic SARS-CoV-2 infection on NP swab 1 week prior to transplant and negative lower respiratory tract testing 2 days prior to transplant. Our recipient patient has remained SARS-CoV-2 free at 3 weeks post-operation on serial testing. We propose that the timing of recent donor infection, even within 10 days of positive results, is less important as infectious status based on lower respiratory tract testing at the time of transplant. CONCLUSIONS: We demonstrate that donor lung donation following very recent asymptomatic SARS-CoV-2 infection can be done safely with good short-term outcomes. Reference #1: (1) 2020 Annual Data Report. Scientific Registry of Transplant Recipients https://srtr.transplant.hrsa.gov/annual_reports/2020/Lung.aspx Accessed [03/23/22] Reference #2: (2) Querrey, M, Kurihara, C, Manerikar, A, et al. Lung donation following SARS-CoV-2 infection. Am J Transplant. 2021;21: 4073– 4078. https://doi.org/10.1111/ajt.16777 Accessed [03/23/22] Reference #3: (3) Summary of Current Evidence and Information– Donor SARS-CoV-2 Testing & Organ Recovery from Donors with a History of COVID-19. Version Release Date: January 21, 2022. US Department of Health & Human Services. Organ Procurement and Transplantation Network https://optn.transplant.hrsa.gov/media/kkhnlwah/sars-cov-2-summary-of-evidence.pdf Accessed [03/23/22] DISCLOSURES: No relevant relationships by Thomas Meehan No relevant relationships by Jagadish Patil No relevant relationships by Huddleston Stephen

HCV core antigen and residual HCV RNA in the native liver of living donor liver transplant recipients with chronic hepatitis C

Background: With the highly effective direct-acting antiviral (DAA) therapy, the number of liver transplants for hepatitis C virus (HCV) has decreased worldwide. However, similar to the phenomenon occurring in COVID-19 infection, the residual virus reservoirs in target organ is warranted to be explored due to the potential replication and disease recurrence. Hence, we aim to investigate the significance of hepatic HCV RNA identification as well as the discrepancy between HCV RNA and HCV core antigen (HCV Ag) in native liver of chronic hepatitis C recipients undergoing living donor liver transplantation (LDLT). Methods: Between Feb 2016 to Aug 2019, we prospectively enrolled 80 serum anti-HCV positive recipients who underwent LDLT. HCV RNA extracted from the native liver tissues was subjected to one-step reverse transcribed qPCR, using the TopScript One Step qRT PCR Probe Kit with HCV qPCR probe assay and human GAPDH qPCR probe assay on ViiA 7 Real Time PCR System. Hepatic HCV Ag was identified from the native liver tissues by employing the qualitative enzyme immunoassay technique. All experimental steps were based on the protocol provided by Human HCV Ag ELISA Kit (Cat. No. MBS167758). Results: Among 80 recipients, 85% (68/80) positive HCV-RNA was significantly higher in the native liver tissues than in the serum before (29/80, 36.3%;p = 0.000) and after LDLT (3/80, 4.4%;p = 0.000). In contrast, hepatic HCV Ag was 100% negative identified in all 80 explanted native liver. Conclusions: Significant positive HCV-RNA identification in the native liver suggested that pre-LDLT serum HCV RNA should be underestimated in the real status of HCV activity. HCV Ag assay may have lack of sensitivity and negative predictive value in liver tissues. In contrast to serum HCV RNA and HCV Ag, a great discrepancy might be described between hepatic HCV RNA and HCV Ag in the liver tissue. (Figure Presented).

Results from a nationwide hepatitis C serosurvey and progress towards HCV elimination in the country of Georgia

Background and aims: The country of Georgia launched its national Hepatitis C Virus (HCV) Elimination Program in 2015, and a serosurvey the same year showed prevalence of HCV antibody (anti-HCV) and HCV RNA among adults aged ≥18 years was 7.7%, and 5.4%, respectively. Since then, over 76, 000 people with chronic HCV have been treated, with a cure rate of 98.9%. To monitor progress, a second serosurvey was conducted in 2021 to estimate the prevalence of hepatitis C, hepatitis B, and anti-SARS-CoV-2. This analysis reports hepatitis C results of the serosurvey and progress towards elimination. Method: The serosurvey used a stratified, multi-stage cluster design with systematic sampling. Adults and children ≥5 years consenting (or assenting with parental consent) to the interviewand blood draw were eligible to participate. All blood samples were tested for anti- HCV and if positive, HCV RNA. Nationally representative weighted proportions and 95% confidence intervals (CI) were calculated and compared with 2015 age-adjusted estimates for adults. Results: A total of 7, 237 adults and 1, 473 children participated in the survey. For adults, the median age was 46 years (interquartile range: 32–60), and 53.3% (95% CI: 51.3–55.2)were female. The prevalence of anti-HCV was 6.8% (95% CI: 5.9–7.7), which was not significantly different from 2015 (7.7% [95% CI: 6.6–8.8];p = 0.20). The HCV RNA prevalencewas 1.8% (95% CI: 1.3–2.4), compared to 5.4% [95% CI: 4.5– 6.3] in 2015 (p < 0.001). This represents a 67% reduction in persons with chronic HCV infection, despite the program having treated 51% of the estimated 150, 000 infected. HCV RNA prevalence decreased among all age groups, most notably among those aged 40–59 years (9.3% in 2015 to 2.2% in 2021;p < 0.001). Substantial decreases were also observed among both males (9.0% to 3.1%;p < 0.001) and females (2.2% to 0.6%;p < 0.001). HCV RNA prevalence also decreased from 51.1% to 17.8% among persons who ever injected drugs, and 13.1% to 3.8% among those who received a blood transfusion (both p < 0.001). No children tested positive for anti-HCV or HCV RNA. Conclusion: These results demonstrate the substantial progress made since Georgia launched its HCV Elimination Program in 2015. The 67% reduction in chronic HCV infections during 2015–2021 also supports treatment as a means for prevention, as the reduction is larger than would be expected based on those treated alone. These findings can inform strategies to meet HCV elimination targets.

CRIVALVIR-FOCUS: low HIV and chronic Hepatitis B and C infection prevalence among women in reproductive and sexual health services in Valencia, Spain

Background and Aims: In Spain, HIV, HBV, and HCV prevalence are lower in females. A 2017–2018 Ministry of Health serosurvey in 7, 675 primary care patients found 0.35% and 0.08% chronic HCV infection in men and women. A previous opportunistic, population-based screening program in 11, 449 primary care patients seen in our health department found 0.18% and 0.06% HIV infection prevalence, 1.11% and 0.56% chronic HBV infection prevalence, and 0.73% and 0.25% chronic HCV infection prevalence in men and women from February to December 2019. We aimed to assess HIV, HBV, and HCV prevalence among women seeking care in our health department’s 5 Sexual and Reproductive Health Units (SRHU), in the Human Reproduction Unit (HRU), and the Obstetrics and Gynecology Service (OGS). Method: We implemented opportunistic HIV, HBV, and HCV screening from March to October 2021, despite challenges related to a fifth wave of the SARS-CoV-2 pandemic. We used existing infrastructure and staff, aided by electronic health record system modifications, to identify screening eligibility and request serologies. Patients were eligible for testing upon verbal consent if they were between 18 and 80, and had no record of testing in the previous year, and required blood tests in their current health care visit. Follow-up or discharge was given, regardless of test results. A case manager contacted positive patients to ensure and monitor linkage to specialist medical care. Herein we analyze data from patients aged 18 to 45 — the maximum age of patients seen in the HRU. Results: We screened 934 women, of whom 48.1% (449) in SRHUs, 26.0% (243) in the HRU, and 25.9% (242) in the OGS (26%). Regarding age and nationality,14.6.% (136)were aged 18 to 25, 45.5% (425)were 26 to 35, 39.9% (373) were 36 to 45, and 20.6% (192) were foreigners. We found 1 (0.1%) HIV antibody positive patient (a 45-year-old from the Dominican Republic), 1 (0.1%) HBV surface antigen positive patient (a 36-year-old from China), 1 (0.1%) HCV antibody positive patient, and no HCV RNA positive patients. Conclusion: HIV prevalence among Valencian women in reproductive and sexual health serviceswas similar to the general population in primary health care in the area. In contrast, chronic HBV infection prevalence was low, and chronic HCV infection was not found. Our data suggest that opportunistic HBV and HCV screening of women aged 18 to 45 out of populations at increased risk is an inefficient public health strategy in our area

A novel hepatitis C intervention in Denmark to test and treat people who inject drugs

Background and aims: Providing testing and treatment for hepatitis C (HCV) for people who inject drugs (PWID) is critical in eliminating HCV, but reaching this population with traditional healthcare services can be challenging. Combining point-of-care (PoC) testing with peer support and counselling is a model of care (MoC) that can be effective for PWID. This study aims to investigate if a peer-led mobile van equipped with rapid PoC tests for HCV antibodies (Ab) and RNA could simplify testing and link PWID to care and treatment. Method: In Copenhagen, Denmark, a peer-led mobile service providing counselling, Ab testing (In-Tec™) and linkage to standard of care was equipped with a PoC HCV-RNA finger-prick test (Xpert HCV Viral Load Finger-Stick Point-of-Care Assay, Cepheid). Eligible HCV-RNA+ individuals were offered assisted referral to a fast-track hospital clinic for evaluation and treatment, with peer support available if needed. Results: From 1 May 2019 to 25 October 2021, 1013 people were tested for HCV-RNA and 10.2% (n = 103) were positive. Nine additional individuals with HCV infection contacted the service to be linked to care. Of the 112 individuals with chronic HCV infection, 72.3% (n = 81) were evaluated for treatment at the hospital clinic, of whom86.4% (n = 70) initiated direct-acting antiviral therapy and 3.7% (n = 3) are waiting to initiate treatment. Major reasons for not being evaluated for treatment included being undocumented (38.7%;n = 12) and being lost to follow-up (32.3%;n = 10). Among those who initiated treatment, 20.0% (n = 14) were connected to drug addiction treatment services. The peer-led service assisted all treated with communication with the hospital nurse, collection of treatment medicine and accompaniment to follow-up visits. Conclusion: We found that a peer-led mobile PoC service is an MoC that can engage PWID in HCV testing and link them to treatment, even during the COVID-19 pandemic. We identified being an undocumented migrant as a major cause for not accessing care. This poses a challenge for HCVelimination in Denmark due to the risk of onward transmission. Next steps include engaging with health authorities to provide care for these migrants.