Challenges of transferring rural adults with chronic HCV infection for further HCV RNA confirmation and free DAAs treatment: a success story of the interdisciplinary collaboration approach

Abstract Background Chronic hepatitis C virus (HCV), which is a concern in many countries, is the leading cause of liver cancer around the world. Since Taiwan launched its national health insurance system in 1995, it has managed to extend health coverage to 99% of the Taiwanese population, providing free but limited antiviral treatment each year since 2017. However, many people in rural areas are unaware that they have chronic HCV; nor do they realize that new drugs with high cure rates could drastically reduce their health burden. The aim of this study is to explore the implementation facilitators of and barriers to inviting potentially infected patients in rural areas to be transferred for HCV ribonucleic acid (RNA) confirmation and new drug treatment. Methods A descriptive and prospective study design with an interdisciplinary collaboration approach was implemented. After five elements of referral were developed, telephone counseling was conducted between August 2018 and May 2019 in Yunlin, Taiwan. The elements of referral developed by the research team were: (1) forming and coordinating physicians’ schedules, (2) recruiting and training volunteers, (3) training the nursing staff, (4) raising funds or resources, and (5) connecting with village leaders. Thereafter, we collaborated with two district health centers, a private local hospital, and health clinics. Based on the medical records provided by these agencies, community adults that were HCV antibody (anti-HCV) positive were invited to join the program. Results Of the 1795 adults who were serum anti-HCV positive, 1149 (64%) accepted transfer to a qualified hospital; of these, 623 (54.2%) had an HCV infection. 552 (88.6%) of those infected started receiving direct-acting antivirals (DAAs) treatment. The top four barriers to accepting transfer were: (1) they perceived themselves to be healthy (n = 98, 32.3%); (2) mistrust of treatment/healthcare (n = 60, 20.2%); (3) limited transportation to the hospital (n = 52, 17.5%); and (4) work conflict (n = 30, 10.1%). Conclusion An interdisciplinary collaboration approach significantly contributed to the invitation of CHC patients, as well as their acceptance of HCV RNA confirmation and free DAAs treatment. Using anti-HCV data from previous medical records for case-finding and collaborating with a hospital and health clinics proved to be an efficient strategy.

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Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2022/7348755 ◽

2022 ◽

Vol 2022 ◽

pp. 1-17

Author(s):

Geane Lopes Flores ◽

Jurema Corrêa Mota ◽

Larissa Tropiano da Silva Andrade ◽

Renata Serrano Lopes ◽

Francisco Inácio Bastos ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Meta Analysis ◽

Antiviral Treatment ◽

Hcv Infection ◽

Hcv Rna ◽

Eligibility Criteria ◽

Cross Sectional ◽

High Concordance ◽

Chronic Hcv

Background and Aims. Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. Methods. The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. Results. Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% ( 95 % CI = 98.04 %; 99.30%) and 98.95% ( 95 % CI = 97.84 %; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. Conclusions. According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.

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Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

Orvosi Hetilap ◽

10.1556/oh.2011.29113 ◽

2011 ◽

Vol 152 (22) ◽

pp. 876-881

Author(s):

Alajos Pár

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Genetic Polymorphisms ◽

Chronic Hepatitis C ◽

Genome Wide Association Study ◽

Antiviral Treatment ◽

Hcv Infection ◽

Snp Analysis ◽

Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

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Hepatitis C Virus Prevalence and Risk Factors in a Village in Northeastern Romania—A Population-Based Screening—The First Step to Viral Micro-Elimination

Healthcare ◽

10.3390/healthcare9060651 ◽

2021 ◽

Vol 9 (6) ◽

pp. 651

Author(s):

Laura Huiban ◽

Carol Stanciu ◽

Cristina Maria Muzica ◽

Tudor Cuciureanu ◽

Stefan Chiriac ◽

...

Keyword(s):

Risk Factors ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Treatment ◽

Population Based ◽

Hcv Infection ◽

World Health ◽

Hcv Rna ◽

Virus Eradication ◽

Tertiary Center

(1) Background: The World Health Organization adopted a strategy for the Global Health Sector on Viral Hepatitis in 2016, with the main objective of eliminating hepatitis C virus (HCV) by 2030. In this work, we aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village using population-based screening as part of the global C virus eradication program. (2) Methods: We conducted a prospective study from March 2019 to February 2020, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults in a village located in Northeastern Romania. (3) Results: In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests (RDOT). Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found to have positive HCV antibodies and were scheduled for further evaluation in a tertiary center of gastroenterology/hepatology in order to be linked to care. In total, 66 (85%) subjects presented for evaluation and 55 (83%) had detectable HCV RNA. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained a sustained virological response. (4) Conclusions: The elimination of hepatitis C worldwide has a higher chance of success if micro-elimination strategies based on mass screening are adopted.

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Hepatitis C virus infection and risk of liver-related and non-liver-related deaths: a population-based cohort study in Naples, southern Italy

BMC Infectious Diseases ◽

10.1186/s12879-021-06336-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Pierluca Piselli ◽

Diego Serraino ◽

Mario Fusco ◽

Enrico Girardi ◽

Angelo Pirozzi ◽

...

Keyword(s):

Southern Italy ◽

Population Based ◽

Hcv Infection ◽

Hcv Rna ◽

Risk Of Death ◽

High Prevalence ◽

Specific Mortality ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Related Mortality

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

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Demonstration and Distribution of HCV RNA Sequences by in situ Hybridization and HCV-Related Proteins by Immunohistochemistry in the Liver Tissue of Patients with Chronic HCV Infection

Pathobiology ◽

10.1159/000163956 ◽

1995 ◽

Vol 63 (5) ◽

pp. 239-248 ◽

Cited By ~ 10

Author(s):

Domenico Sansonno ◽

Vito Cornacchiulo ◽

Anna Rina Iacobelli ◽

Pietro Gatti ◽

Maria Di Stasi ◽

...

Keyword(s):

In Situ Hybridization ◽

Liver Tissue ◽

Hcv Infection ◽

Hcv Rna ◽

Rna Sequences ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Related Proteins

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Effect of Direct Acting Anti-Viral Drugs on Insulin Resistance and sensitivity Among Egyptian Chronic HCV Infected Patients

QJM ◽

10.1093/qjmed/hcab100.111 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Tareq M Yosef ◽

Wesam A Ibrahim ◽

Sarah A El-Nakeep ◽

Ahmed M ElGhandour ◽

Soha saied attiya

Keyword(s):

Insulin Resistance ◽

Fasting Blood Glucose ◽

Hcv Infection ◽

Military Hospital ◽

Hcv Rna ◽

Matsuda Index ◽

Treatment Naïve ◽

Chronic Hcv ◽

Direct Acting ◽

The Impact

Abstract Background Hepatitis C virus (HCV) infection is a worldwide infection, affecting up to 185 million people across the world. It carries a high risk for developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Aim of the Work to assess the impact of direct acting anti-viral drugs on the status of insulin resistance and sensitivity in non-diabetic chronic HCV infection patients Patients and Methods study included 100 treatment naive patients with chronic infection of HCV attending the out-patient clinic at Gastro-enterology and Hepatology Department, Ain shams University and Kobry El Kobba Military Hospital between September 2017 till June 2019. Patients were diagnosed by HCV antibodies & HCV RNA by PCR. Results The fasting blood glucose, seum insulin and HbA1c were significantly decreased between the baseline and after SVR12. The 2Hrs PP was significantly increased between the baseline and after SVR12. The HOMA-IR showed significant decrease between the baseline and SVR12. The QUICKI and Matsuda Index showed significant increase at SVR12. Conclusion HOMA-IR, QUICKI and Matsuda index showed significant improvement between the baseline and after SVR12.

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French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

BMC Infectious Diseases ◽

10.1186/s12879-020-05478-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Cécile Brouard ◽

Josiane Pillonel ◽

Marjorie Boussac ◽

Victor de Lédinghen ◽

Antoine Rachas ◽

...

Keyword(s):

Hepatitis C ◽

Antiviral Treatment ◽

Hcv Infection ◽

World Health ◽

Direct Acting Antivirals ◽

Substantial Impact ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

The Impact

Abstract Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

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Hepatic Stress Response in HCV Infection Promotes STAT3-Mediated Inhibition of HNF4A-miR-122 Feedback Loop in Liver Fibrosis and Cancer Progression

Cancers ◽

10.3390/cancers11101407 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1407 ◽

Cited By ~ 7

Author(s):

Aydin ◽

Kurt ◽

Song ◽

Lin ◽

Osman ◽

...

Keyword(s):

Stress Response ◽

Cancer Progression ◽

Antiviral Treatment ◽

Hcv Infection ◽

Infection Model ◽

Related Factor ◽

Nuclear Factor ◽

Survival Signaling ◽

Chronic Hcv ◽

Hepatic Stress

Hepatitis C virus (HCV) infection compromises the natural defense mechanisms of the liver leading to a progressive end stage disease such as cirrhosis and hepatocellular carcinoma (HCC). The hepatic stress response generated due to viral replication in the endoplasmic reticulum (ER) undergoes a stepwise transition from adaptive to pro-survival signaling to improve host cell survival and liver disease progression. The minute details of hepatic pro-survival unfolded protein response (UPR) signaling that contribute to HCC development in cirrhosis are unknown. This study shows that the UPR sensor, the protein kinase RNA-like ER kinase (PERK), mediates the pro-survival signaling through nuclear factor erythroid 2-related factor 2 (NRF2)-mediated signal transducer and activator of transcription 3 (STAT3) activation in a persistent HCV infection model of Huh-7.5 liver cells. The NRF2-mediated STAT3 activation in persistently infected HCV cell culture model resulted in the decreased expression of hepatocyte nuclear factor 4 alpha (HNF4A), a major liver-specific transcription factor. The stress-induced inhibition of HNF4A expression resulted in a significant reduction of liver-specific microRNA-122 (miR-122) transcription. It was found that the reversal of hepatic adaptive pro-survival signaling and restoration of miR-122 level was more efficient by interferon (IFN)-based antiviral treatment than direct-acting antivirals (DAAs). To test whether miR-122 levels could be utilized as a biomarker of hepatic adaptive stress response in HCV infection, serum miR-122 level was measured among healthy controls, and chronic HCV patients with or without cirrhosis. Our data show that serum miR-122 expression level remained undetectable in most of the patients with cirrhosis (stage IV fibrosis), suggesting that the pro-survival UPR signaling increases the risk of HCC through STAT3-mediated suppression of miR-122. In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.

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