Editorial

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Open AccessEditorial

Special Issue “Chronic HCV Infection: Clinical Advances and Eradication Perspectives”

by Maria Carla Liberto and Nadia Marascio

J. Clin. Med. 2022, 11(2), 359; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11020359 - 12 Jan 2022

Cited by 2 | Viewed by 955

The latest report of global hepatitis estimated 58 million people with Hepatitis C virus (HCV) chronic disease and 1 [...] Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

Research

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10 pages, 3599 KiB

Open AccessArticle

Out-of-Hospital Treatment of Hepatitis C Increases Retention in Care among People Who Inject Drugs and Homeless Persons: An Observational Study

by Bianca Granozzi, Viola Guardigni, Lorenzo Badia, Elena Rosselli Del Turco, Alberto Zuppiroli, Beatrice Tazza, Pietro Malosso, Stefano Pieralli, Pierluigi Viale and Gabriella Verucchi

J. Clin. Med. 2021, 10(21), 4955; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10214955 - 26 Oct 2021

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Abstract

Background. People who inject drugs (PWID) and homeless people represent now a large reservoir of Hepatitis C virus (HCV) infection. However, Hepatis C elimination programs can barely reach these subgroups of patients. We aimed to evaluate and compare the retention in care among [...] Read more.

Background. People who inject drugs (PWID) and homeless people represent now a large reservoir of Hepatitis C virus (HCV) infection. However, Hepatis C elimination programs can barely reach these subgroups of patients. We aimed to evaluate and compare the retention in care among these difficult-to-treat patients when managed for HCV in hospital or in an out-of-hospital setting. Methods. In our retrospective study, we categorized the included patients (PWID and homeless persons) into two groups according to whether anti-HCV treatment was offered and provided in a hospital or an out-of-hospital setting. We run logistic regressions to evaluate factors associated with retention in care (defined as the completion of direct antiviral agents (DAAs) therapy). Results. We included 56 patients in our study: 27 were in the out-of-hospital group. Overall, 33 patients completed DAAs therapy. A higher rate of retention in care was observed in the out-of-hospital group rather than in-hospital group (p = 0.001). At the univariate analysis, retention in care was associated with the out-of-hospital management (p = 0.002) and with a shorter time between the first visit and the scheduled start of DAAs (p = 0.003). Conclusions. The choice of treatment models that can better adapt to difficult-to-treat populations, such as an out-of-hospital approach, will be important for achieving the eradication of HCV infection. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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12 pages, 760 KiB

Open AccessArticle

The Netherlands Is on Track to Meet the World Health Organization Hepatitis C Elimination Targets by 2030

by Marleen van Dijk, Sylvia M. Brakenhoff, Cas J. Isfordink, Wei-Han Cheng, Hans Blokzijl, Greet Boland, Anthonius S. M. Dofferhoff, Bart van Hoek, Cees van Nieuwkoop, Milan J. Sonneveld, Marc van der Valk, Joost P. H. Drenth and Robert J. de Knegt

J. Clin. Med. 2021, 10(19), 4562; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10194562 - 30 Sep 2021

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Abstract

Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to [...] Read more.

Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well-supported timeline towards HCV elimination in The Netherlands. Methods: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (≤5 per 100,000). Results: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO’s elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver-related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liver-related death from 2020–2030. Conclusions: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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10 pages, 718 KiB

Open AccessArticle

Real-Life Experience with Ledipasvir/Sofosbuvir for the Treatment of Chronic Hepatitis C Virus Infection with Genotypes 1 and 4 in Children Aged 12 to 17 Years—Results of the POLAC Project

by Maria Pokorska-Śpiewak, Anna Dobrzeniecka, Małgorzata Aniszewska and Magdalena Marczyńska

J. Clin. Med. 2021, 10(18), 4176; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10184176 - 15 Sep 2021

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Abstract

Background: Available real-world data on the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) in pediatric patients are limited. In this prospective, open-label, single-center study, we aimed to present our real-life experience with a fixed dose of LDV/SOF (90/400 mg) for the treatment of chronic [...] Read more.

Background: Available real-world data on the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) in pediatric patients are limited. In this prospective, open-label, single-center study, we aimed to present our real-life experience with a fixed dose of LDV/SOF (90/400 mg) for the treatment of chronic hepatitis C (CHC) genotypes 1 and 4 in children aged 12 to 17 years. Methods: We analyzed intention-to-treat (ITT) and per-protocol (PP) rates of sustained virological response (SVR), defined as undetectable HCV viral load at posttreatment week 12, in 37 participants treated with LDV/SOF according to the HCV genotype, baseline liver fibrosis, duration of treatment, and experience of the previous ineffective antiviral treatment. There were 32 patients infected with genotype 1 and 5 with genotype 4. Fourteen (38%) participants were treatment-experienced, two were coinfected with HIV, and three were cirrhotic. Two patients qualified for 24 weeks of therapy, and the remaining 35 received 12 weeks of LDV/SOF treatment. Results: The overall ITT SVR12 rate was 36/37 (97%). One patient was lost to follow-up after week 4 of therapy when his HCV RNA was undetectable. All 36 patients who completed the full protocol achieved SVR (36/36, 100%). PP analyses of SVR12 rates according to the HCV genotype, baseline liver fibrosis, duration of the treatment, and previous ineffective treatment were all 100%. A significant decrease in aminotransferase serum levels was observed in the subsequent weeks of the treatment and at SVR assessment compared to baseline. No serious adverse events were reported. Conclusions: The results of this study confirm previous observations of a suitable efficacy and safety profile of LDV/SOF for the treatment of CHC genotypes 1 and 4 in adolescents. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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14 pages, 670 KiB

Open AccessArticle

Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics

by Dorota Zarębska-Michaluk, Jerzy Jaroszewicz, Anna Parfieniuk-Kowerda, Ewa Janczewska, Dorota Dybowska, Małgorzata Pawłowska, Waldemar Halota, Włodzimierz Mazur, Beata Lorenc, Justyna Janocha-Litwin, Krzysztof Simon, Anna Piekarska, Hanna Berak, Jakub Klapaczyński, Piotr Stępień, Barbara Sobala-Szczygieł, Jolanta Citko, Łukasz Socha, Magdalena Tudrujek-Zdunek, Krzysztof Tomasiewicz, Marek Sitko, Beata Dobracka, Rafał Krygier, Jolanta Białkowska-Warzecha, Łukasz Laurans and Robert Flisiak Show full author list Hide full author list

J. Clin. Med. 2021, 10(15), 3280; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10153280 - 25 Jul 2021

Cited by 15 | Viewed by 2064

Abstract

There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this [...] Read more.

There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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11 pages, 738 KiB

Open AccessArticle

Phylogenetic and Molecular Analyses of More Prevalent HCV1b Subtype in the Calabria Region, Southern Italy

by Nadia Marascio, Angela Costantino, Stefania Taffon, Alessandra Lo Presti, Michele Equestre, Roberto Bruni, Giulio Pisani, Giorgio Settimo Barreca, Angela Quirino, Enrico Maria Trecarichi, Chiara Costa, Maria Mazzitelli, Francesca Serapide, Giovanni Matera, Carlo Torti, Maria Carla Liberto and Anna Rita Ciccaglione

J. Clin. Med. 2021, 10(8), 1655; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081655 - 13 Apr 2021

Cited by 3 | Viewed by 1241

Abstract

Hepatitis C virus subtype 1b (HCV1b) is still the most prevalent subtype worldwide, with massive expansion due to poor health care standards, such as blood transfusion and iatrogenic procedures. Despite safe and effective new direct antiviral agents (DAA), treatment success can depend on [...] Read more.

Hepatitis C virus subtype 1b (HCV1b) is still the most prevalent subtype worldwide, with massive expansion due to poor health care standards, such as blood transfusion and iatrogenic procedures. Despite safe and effective new direct antiviral agents (DAA), treatment success can depend on resistance-associated substitutions (RASs) carried in target genomic regions. Herein we investigated transmission clusters and RASs among isolates from HCV1b positive subjects in the Calabria Region. Forty-one NS5B and twenty-two NS5A sequences were obtained by Sanger sequencing. Phylogenetic analysis was performed using the maximum likelihood method and resistance substitutions were analyzed with the Geno2pheno tool. Phylogenetic analysis showed sixteen statistically supported clusters, with twelve containing Italian sequences mixed with foreign HCV1b isolates and four monophyletic clusters including only sequences from Calabria. Interestingly, HCV1b spread has been maintained by sporadic infections in geographically limited areas and by dental treatment or surgical intervention in the metropolitan area. The L159F NS5B RAS was found in 15 isolates and in particular 8/15 also showed the C316N substitution. The Y93H and L31M NS5A RASs were detected in three and one isolates, respectively. The A92T NS5A RAS was found in one isolate. Overall, frequencies of detected NS5B and NS5A RASs were 36.6% and 22.7%, respectively. For the eradication of infection, improved screening policies should be considered and the prevalence of natural RASs carried on viral strains. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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13 pages, 4408 KiB

Open AccessArticle

Impact of Interferon-Based Therapy on Hepatitis C-Associated Rheumatic Diseases: A Nationwide Population-Based Cohort Study

by Jur-Shan Cheng, Yu-Sheng Lin, Jing-Hong Hu, Ming-Yu Chang, Hsin-Ping Ku, Rong-Nan Chien and Ming-Ling Chang

J. Clin. Med. 2021, 10(4), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040817 - 17 Feb 2021

Cited by 4 | Viewed by 1534

Abstract

Whether hepatitis C virus (HCV) infection-associated risk of rheumatic diseases is reversed by anti-HCV therapy remain elusive. A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted. Of 19,298,735 subjects, 3 cohorts (1:4:4, propensity score-matched), including HCV-treated (6919 [...] Read more.

Whether hepatitis C virus (HCV) infection-associated risk of rheumatic diseases is reversed by anti-HCV therapy remain elusive. A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted. Of 19,298,735 subjects, 3 cohorts (1:4:4, propensity score-matched), including HCV-treated (6919 HCV-infected subjects with interferon and ribavirin therapy ≥ 6 months), HCV-untreated (n = 27,676) and HCV-uninfected (n = 27,676) cohorts, were enrolled and followed (2003–2015). The HCV-uninfected cohort had the lowest cumulative incidence of rheumatic diseases (95% confidence interval (CI): 8.416–10.734%), while HCV-treated (12.417–17.704%) and HCV-untreated (13.585–16.479%) cohorts showed no difference in the cumulative incidences. Multivariate analyses showed that HCV infection (95% CI hazard ratio (HR): 1.54–1.765), female sex (1.57–1.789), age ≥ 49 years (1.091–1.257), Charlson comorbidity index ≥ 1 (1.075–1.245), liver cirrhosis (0.655–0.916), chronic obstruction pulmonary disease (1.130–1.360), end-stage renal disease (0.553–0.98), diabetes mellitus (0.834–0.991) and dyslipidemia (1.102–1.304) were associated with incident rheumatic diseases. Among the 3 cohorts, the untreated cohort had the highest cumulative incidence of overall mortality, while the treated and un-infected cohorts had indifferent mortalities. Conclusions: HCV infection, baseline demographics and comorbidities were associated with rheumatic diseases. Although HCV-associated risk of rheumatic diseases might not be reversed by interferon-based therapy, which reduced the overall mortality in HCV-infected patients. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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Review

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19 pages, 357 KiB

Open AccessReview

Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography

by Mira Florea, Teodora Serban, George Razvan Tirpe, Alexandru Tirpe and Monica Lupsor-Platon

J. Clin. Med. 2021, 10(12), 2575; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10122575 - 10 Jun 2021

Cited by 4 | Viewed by 2171

Abstract

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as [...] Read more.

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods. Full article

(This article belongs to the Special Issue Chronic HCV Infection: Clinical Advances and Eradication Perspectives)

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