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1.
J Clin Virol ; 139: 104738, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33933822

RESUMEN

Hepatitis E Virus (HEV) is emerging as a public health concern across Europe and tools for complete genome data to aid epidemiological and virulence analysis are needed. The high sequence heterogeneity observed amongst HEV genotypes has restricted most analyses to subgenomic regions using PCR-based methods, which can be unreliable due to poor primer homology. We designed a panel of custom-designed RNA probes complementary to all published HEV full genome NCBI sequences. A target enrichment protocol was performed according to the NimbleGen® standard protocol for Illumina® library preparation. Optimisation of this protocol was performed using 40 HEV RNA-positive serum samples and the World Health Organization International Reference Panel for Hepatitis E Virus RNA Genotypes for Nucleic Acid Amplification Technique (NAT)-Based Assays and related reference materials. Deep sequencing using this target enrichment protocol resulted in whole genome consensus sequences from samples with a viral load range of 1.25 × 104-1.17 × 107 IU/mL. Phylogenetic analysis of these sequences recapitulated and extended the partial genome results obtained from genotyping by Sanger sequencing (genotype 1, ten samples and genotype 3, 30 samples). The protocol is highly adaptable to automation and could be used to sequence full genomes of large sample numbers. A more comprehensive understanding of hepatitis E virus transmission, epidemiology and viral phenotype prediction supported by an efficient method of sequencing the whole viral genome will facilitate public health initiatives to reduce the prevalence and mitigate the harm of HEV infection in Europe.

2.
Viruses ; 13(5)2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33946211

RESUMEN

Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that generate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development.

3.
Am J Kidney Dis ; 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33940114

RESUMEN

RATIONALE & OBJECTIVE: Hemodialysis facilities are high-risk environments for hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model. STUDY DESIGN: Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists and public health practitioners. SETTING & PARTICIPANTS: All dialysis patients in the Changhua county of Taiwan were treated using an inter-disciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C). QUALITY IMPROVEMENT ACTIVITIES: Provision of an HCV care cascade to fill three gaps including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau. OUTCOMES: Outcome measures included quality indicators pertaining to six steps in HCV care ranging from HCV screening to complete treatment and cure from treatment with DAA ANALYTICAL APPROACH: A descriptive analysis. RESULTS: A total of 3657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 96.0% (166/173). No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferon-based therapy (2017) to 25.6% after restricted provision of DAA (2017-2018) and then to 89.1% after universal access to DAA (2019). LIMITATIONS: Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease. CONCLUSIONS: A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization.

4.
Diagnostics (Basel) ; 11(3)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33804260

RESUMEN

The World Health Organization has established an elimination plan for hepatitis C virus (HCV) by 2030. In Sub-Saharan Africa (SSA) access to diagnostic tools is limited, and a number of genotype 4 subtypes have been shown to be resistant to some direct-acting antivirals (DAAs). This study aims to analyze diagnostic assays for HCV based on dried blood spots (DBS) specimens collected in Kinshasa and to characterize genetic diversity of the virus within a group of mainly HIV positive patients. HCV antibody detection was performed on 107 DBS samples with Vidas® anti-HCV and Elecsys anti-HCV II, and on 31 samples with INNO-LIA HCV. Twenty-six samples were subjected to molecular detection. NS3, NS5A, and NS5B regions from 11 HCV viremic patients were sequenced. HCV seroprevalence was 12.2% (72% with detectable HCV RNA). Both Elecsys Anti-HCV and INNO-LIA HCV were highly sensitive and specific, whereas Vidas® anti-HCV lacked full sensitivity and specificity when DBS sample was used. NS5B/NS5A/NS3 sequencing revealed exclusively GT4 isolates (50% subtype 4r, 30% 4c and 20% 4k). All 4r strains harbored NS5A resistance-associated substitutions (RAS) at positions 28, 30, and 31, but no NS3 RAS was detected. Elecsys Anti-HCV and INNO-LIA HCV are reliable methods to detect HCV antibodies using DBS. HCV subtype 4r was the most prevalent among our patients. RASs found in subtype 4r in NS5A region confer unknown susceptibility to DAA.

5.
J Coll Physicians Surg Pak ; 30(4): 393-398, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33866723

RESUMEN

OBJECTIVE: To evaluate the vitamin D receptor (VDR) gene polymorphisms and vitamin D levels in inactive hepatitis B virus (HBV) carriers. STUDY DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: From March to September 2017 at the Izmir Katip Celebi University (IKCU) Ataturk Training and Research Hospital, Izmir, Turkey. METHODOLOGY: Eighty-six inactive hepatitis B carriers and 86 control individuals were included in the study. Individuals with diseases or under medication that could affect vitamin D levels were excluded from the study. Serum vitamin D concentration of >30 ng/mL was considered as sufficient, between 20-30 ng/mL as insufficient, <20 ng/mL as deficiency and <10 ng/mL as severe deficiency. VDR gene Bsm I, Fok I, Apa I and Taq I polymorphisms were identified by the polymerase chain reaction-fragment length polymorphism (PCR-RFLP) method. RESULTS: When vitamin D levels were examined, 52.3% (n = 45) of the inactive HBV carriers had severe deficiency, 38.4% (n = 33) deficiency, 7% (n = 6) insufficiency; 45.3% (n = 39) of the control group had severe deficiency, 43% (n = 37) deficiency, and 7% (n = 6) insufficiency. There was no statistically significant relationship between VDR gene and Bsm I, Fok I, Apa I, Taq I polymorphisms and vitamin D levels in inactive hepatitis B carriers and control group (p>0.05). CONCLUSION: Vitamin D deficiency is highly prevalent both among control population as well as in chronic hepatitis patients. Key Words: Inactive HBV carrier, Vitamin D, Polymorphism, Vitamin D receptor (VDR).

6.
Artículo en Inglés | MEDLINE | ID: mdl-33867444

RESUMEN

BACKGROUND: Underdiagnosis of HCV infection may hinder the obtainment of 2030 elimination goal. OBJECTIVE: To estimate the pre-DAA HCV diagnosis rate to inform future public health effort. METHODS: Data were obtained from three nationwide databases (Truven Health MarketScan Research Database 2007-2014, US Census Bureau 2012-2016 and NHANES 2007-2014). HCV diagnosis was defined with either one inpatient or two outpatient HCV International Classification of Disease 9 codes, providing the number of patients with diagnosed HCV (Truven). US Census Bureau data were used for age- and sex-standardization. We derived the total (diagnosed and undiagnosed) HCV infection using the NHANES database. To determine the rate and number of undiagnosed HCV, we subtracted diagnosed HCV burden (Truven) from the total HCV burden (NHANES). RESULTS: Of the 198 073 302 privately insured Americans, 1.49% (2 951 490 persons) had HCV infection. However, only 362 672 (12.29%) persons were diagnosed with HCV, leaving 2 588 818 (87.71%) undiagnosed. About two-third (68.04%) and one-third (33.04%) of diagnosed HCV patients had HCV RNA or genotype tests overall, with even lower rates for the ≥65 age group, respectively. CONCLUSION: In the pre-DAA era, only 12% of insured Americans with HCV were diagnosed. While this grim statistic is expected to rise, much more effort is needed to enhance the HCV care cascade.

7.
Epidemiol Mikrobiol Imunol ; 70(1): 18-25, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33853334

RESUMEN

OBJECTIVES: Long-term monitoring of the mutual effects of chronic viral hepatitis C (VHC) treatment and tailored addiction treatment. In 2016, the World Health Organization (WHO) published an action plan to eliminate viral hepatitis C globally by 2030. People who inject drugs (PWID) are a key population that needs increased attention and care. Two decades before the announcement of the WHO plan for the global elimination of HCV (hepatitis C virus), the Remedis Medical Facility, where the study was conducted, established a “Comprehensive Care Program for patients with substance use disorders and addictive behaviour”. METHODS: We evaluated all patients who were in the methadone program as of 1 March 2020, regardless of OST duration, OST dosage, age or gender. Their epidemiological and demographic data obtained during a structured clinical interview and laboratory test results were analysed. RESULTS: Of 24 patients on methadone substitution therapy, 12 (50%) were anti-HCV negative before starting OST. None of them became newly infected with hepatitis C virus (HCV) during OST. The remaining 12 of the study patients were anti-HCV positive. Ten of them have already undergone successful treatment for viral hepatitis. Two patients were re-infected with HCV. CONCLUSION: The presented work confirms the high efficacy of chronic VHC treatment among PWID in inducing suitable conditions. We consider combination of HCV infection treatment and targeted tailored addiction treatment as a starting point for achieving control over the HCV epidemic in the Czech Republic, with a possible positive impact on other blood-borne infections related to risky behaviour.


Asunto(s)
Hepatitis C , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Antivirales/uso terapéutico , República Checa , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Organización Mundial de la Salud
8.
World J Gastroenterol ; 27(12): 1117-1131, 2021 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-33828389

RESUMEN

Chronic hepatitis C virus (HCV) infection presents a significant global public health burden. In 2015, over 400000 deaths worldwide were attributed to HCV infection. This led the World Health Organization (WHO) in 2016 to set the ambitious goal of eliminating HCV by 2030. Adult-centered guidelines have been established in order to provide direction for healthcare professionals, allowing integration of the newest screening policies and therapeutic strategies into their practices. However, for children and adolescents, HCV is a significant, unrecognized public health problem. HCV infection rates in the United States in women of childbearing age and those who are pregnant have increased in parallel with the rising opioid epidemic. An estimated 29000 women with HCV infection gave birth each year from 2011 to 2014 in the United States, with approximately 1700 of their infants being infected with HCV. Newer HCV-specific therapeutics, namely direct acting antivirals (DAA), has brought a new and highly successful approach to treatment of hepatitis C. Recent studies have confirmed similar levels of effectiveness and safety of DAA therapies in the pediatric population. Thus, an enhanced cascade of care, which should include the population under 18 years of age, can help achieve the WHO goal by focusing on elimination in the youngest populations. This review will present an overview of the natural history, clinical features, and management of HCV in children and adolescents.

9.
J Viral Hepat ; 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33797190

RESUMEN

Very few low-income countries have developed national plans to achieve the viral hepatitis elimination targets set in the World Health Organization (WHO) strategy. We reviewed the policy environment, strategies and challenges on the fight against viral hepatitis in Zimbabwe. The review focussed on the Ministry of Health and Child Care (MoHCC) policy documents, strategic plans and reports. We performed key informant interviews to enhance evidence generated from the document review. Twelve documents were reviewed and interviews with 10 key informants were completed. The MoHCC established a technical working group to work towards elimination of viral hepatitis. The technical working group drafted a strategic plan for elimination of viral hepatitis; however, it is still awaiting implementation. Key strategies that are working well include screening of donated blood for transfusion, safe injection practices and hepatitis B virus (HBV) three-dose vaccination. Current challenges in the drive towards elimination of viral hepatitis include poor to non-existent surveillance systems, lack of epidemiological data, absence of the HBV vaccine birth dose and lack of systematic screening and treatment services for viral hepatitis. In conclusion, despite political will demonstrated towards achieving viral hepatitis elimination, substantial investment and work are required to implement the strategic plan and realize significant success.

10.
Braz J Infect Dis ; 25(2): 101573, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33836175

RESUMEN

A retrospective cohort of 11,308 chronic hepatitis C infected patients treated with regimens that included Sofosbuvir (SOF), Daclatasvir (DCV), Simeprevir (SMV), or an association of Ombitasvir, Veruprevir/Ritonavir and Dasabuvir (3D) with or without Ribavirin (RBV) were assessed for sustained virologic response (SVR) or viral cure after a 12-week treatment. Logistic regression analyses were used to identify factors independently associated with positive response to direct-acting antivirals (DAA)-based therapies. Overall 57.1% were male; 48.3% self-identified as white; 78.3% were over 50 years old; 44.1% were from the Southeast region; 47.7% had genotype 1b; and 84.5% were treated for 12 weeks. The SVR rates with DAAs ranged from 87% to 100%. Genotypes 1 and 4 had higher SVR rates (96.3-100%), and genotypes 2 and 3 had SVR of 90.6-92.2%, respectively. Treatment durations of 12 and 24 weeks were associated with an average SVR of 95.0% and 95.9%, respectively. Females were half as likely (OR 0.5; 95% CI 0.4-0.6) to have a negative response to therapy compared to males, and those with genotypes 2 and 3 were one and half fold more likely (OR 1.5-2.2; 95 CI% 0.7-2.9; 1.2-3.6 and OR 2.7-2.8; 95% CI 2.0-3.8, respectively) to not have SVR compared to genotype 1. Patients in the age-range of 50-69 years old were 1.2-fold (OR 1.2; 95% CI 0.7-1.9) more likely to not have SVR compared to other age groups, although not statistically significant. This study is the first of this magnitude to be held in a Latin-American country with high SVR results, supported by a free-of-charge universal and public health system. The high performance found in this study gives support to the Brazilian public health policy decision of adopting DAA-based therapies as a strategy to eliminate HCV by 2030.

11.
Artículo en Inglés | MEDLINE | ID: mdl-33896315

RESUMEN

INTRODUCTION: The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8-12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030. AREAS COVERED: This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges. EXPERT OPINION: The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4-5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.

12.
Vaccine ; 2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33896665

RESUMEN

BACKGROUND: Risk-group HBV vaccination for men who have sex with men (MSM) was introduced in the Netherlands in 2002, followed by universal infant vaccination in 2011, that will enable termination of risk-group vaccination over time. The introduction of pre-exposure prophylaxis (PrEP) for HIV prevention might result in increased HBV testing and vaccination against HBV. The aim of this study was to investigate the impact of the transition from risk-group to universal HBV vaccination, accounting for improvements in HBV testing and treatment, as well as the introduction of PrEP. METHODS: We developed a mathematical model for HBV transmission among MSM. Universal vaccination was modelled by assigning some MSM (5-15% in 2028 increasing to 80-90% in 2033 and thereafter) to be vaccinated when they become sexually active. We investigated different scenarios assuming 0.5% extra vaccination rate and 0.5% extra testing rate due to PrEP consultations; and 5% of HIV-negative MSM on PrEP, that will reduce the probability of HBV acquisition by 88%. RESULTS: Universal vaccination resulted in a reduction of 24% (interquartile range; 22-25%) of the total number of HBV infections among MSM estimated to occur from 2020 to 2070. With universal vaccination, terminating risk-group vaccination in 2030 or 2040 resulted in 30% or 10% more HBV infections over 2020-2070, respectively, compared to continuation of risk-group vaccination until 2070. With PrEP and continued risk-group vaccination, the total number of HBV infections over 2020-2070 was reduced by 13%. CONCLUSIONS: Universal HBV vaccination can lead to a major reduction in HBV incidence among MSM in the future. The reduction becomes smaller when ending risk-group HBV vaccination, but larger by PrEP use for HIV prevention. Efforts to keep high levels of HBV vaccination, testing, and treatment have to be continued in the coming decades in order to eliminate HBV as a health threat for MSM.

13.
Mar Drugs ; 19(4)2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33808126

RESUMEN

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, Thais clavigera (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.

14.
Turk J Gastroenterol ; 32(1): 88-96, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33893771

RESUMEN

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is the only viral infection that can be treated with oral antiviral agents. However, CHC awareness is a major barrier to the World Health Organization's target of eliminating hepatitis C virus (HCV) by 2030. Here, CHC awareness trends were analyzed in Hacettepe University Hospital, Turkey, between January 2000 and December 2017. MATERIALS AND METHODS: Central laboratory data were retrospectively analyzed for HCV test results (anti-HCV, HCV RNA, HCV genotype). After combining 548,141 anti-HCV test results, 395,103 cases were analyzed. The following two parameters were defined for CHC awareness: (1) the presence of HCV RNA results for anti-HCV positives and (2) the presence of a genotype result for HCV RNA positives. RESULTS: Anti-HCV positives were older than negatives (mean age-years ± SD, 59.4 ± 19.0 vs. 44.0 ± 18.9), and the positivity rate was higher in women than in men (1.4% vs. 1.0%). Anti-HCV positivity decreased from 3.1% to 0.6% from 2000 to 2015 and subsequently stabilized. The overall percentage of RNA testing among anti-HCV positives was 53.1% (range, 20%-70%), which stabilized at approximately 50% after 2010. The genotyping rate for RNA positives varied between 40% and 70%. The main genotype identified was genotype 1 (85.7%). CONCLUSION: In an ideal CHC awareness state, all anti-HCV positives should undergo RNA testing, and genotyping should be performed when RNA tests are positive. However, even in our referral center, the combined rate of RNA and genotype testing was only approximately 50% during the last 10 years.

15.
PLoS One ; 16(4): e0250347, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33905426

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) is a major global health challenge with approximately 250-350 million chronically infected individuals. An improved understanding of the demographic features and outcomes of chronic HBV infection and hepatitis D virus (HDV) infection in low-endemic areas may improve prevention, early identification and management both at individual and community levels. Here, we retrospectively analyzed the demographic and clinical characteristics, treatment rates and outcomes of adult patients with chronic HBV infection with or without HDV coinfection examined at Lausanne University Hospital, Switzerland over a 10-year period. METHODS: We analyzed the medical records of all adult patients with chronic HBV and HDV infection examined in our center between 2007 and 2016. Liver-related outcome was defined as the occurrence of cirrhosis, hepatocellular carcinoma, liver transplantation or liver-related death. Analyses were performed using logistic regression and results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Of 672 consecutive patients, 421 (62.6%) were male, median age was 36 years (interquartile range, 28-46 years), and 233 (34.7%) were of African origin. The prevalence of HDV coinfection was 7.1% and the proportion of anti-HDV-positive patients with detectable HDV RNA was 70.0%. In multivariate analysis, HDV coinfection was the strongest predictor for liver-related outcome (OR 6.06, 95% CI 2.93-12.54, p<0.001), followed by HBeAg positivity (OR 2.47, 95% CI 1.30-4.69, p = 0.006), age (OR per 10-year increase 2.03, 95% CI 1.63-2.52, p<0.001) and sex (OR for female 0.39, 95% CI 0.22-0.71, p = 0.002). The predictive accuracy of the multivariate model was high (receiver operator characteristic area under the curve 0.81). CONCLUSION: This retrospective study underscores the importance of migration in the epidemiology of chronic hepatitis B in low-endemic areas. HDV coinfection, HBeAg positivity and age predicted liver-related outcomes while female sex had a protective effect.

16.
Medicina (B Aires) ; 81(2): 252-256, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33906144

RESUMEN

The clinical management of hepatitis C virus (HCV) infection presents several challenges today. WHO's goal is to eliminate it by 2030. It is an ambitious goal and difficult to meet given the barriers to care that arise. This is possible today thanks to the discovery of direct-acting antivirals (DAAs). This treatment achieves a high cure rate and is virtually free of adverse effects. To try to comply with this, in addition to the use of DAAs, it is necessary to reduce the rate of undiagnosed patients and facilitate the access of those diagnosed to care and treatment. For that, it is proposed to carry out a simplified treatment of HCV. This involves reducing controls during and after treatment. This simplification varies according to whether patients have cirrhosis or not. In this way, it seeks to increase significantly the number of patients treated and cured to reduce the burden on public health of this disease.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática
17.
World J Gastroenterol ; 27(14): 1369-1391, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33911462

RESUMEN

Infection with the hepatitis B virus (HBV) is still a major global health threat as 250 million people worldwide continue to be chronically infected with the virus. While patients may be treated with nucleoside/nucleotide analogues, this only suppresses HBV titre to sub-detection levels without eliminating the persistent HBV covalently closed circular DNA (cccDNA) genome. As a result, HBV infection cannot be cured, and the virus reactivates when conditions are favorable. Interferons (IFNs) are cytokines known to induce powerful antiviral mechanisms that clear viruses from infected cells. They have been shown to induce cccDNA clearance, but their use in the treatment of HBV infection is limited as HBV-targeting immune cells are exhausted and HBV has evolved multiple mechanisms to evade and suppress IFN signalling. Thus, to fully utilize IFN-mediated intracellular mechanisms to effectively eliminate HBV, instead of direct IFN administration, novel strategies to sustain IFN-mediated anti-cccDNA and antiviral mechanisms need to be developed. This review will consolidate what is known about how IFNs act to achieve its intracellular antiviral effects and highlight the critical interferon-stimulated gene targets and effector mechanisms with potent anti-cccDNA functions. These include cccDNA degradation by APOBECs and cccDNA silencing and transcription repression by epigenetic modifications. In addition, the mechanisms that HBV employs to disrupt IFN signalling will be discussed. Drugs that have been developed or are in the pipeline for components of the IFN signalling pathway and HBV targets that detract IFN signalling mechanisms will also be identified and discussed for utility in the treatment of HBV infections. Together, these will provide useful insights into design strategies that specifically target cccDNA for the eradication of HBV.

18.
Artículo en Inglés | MEDLINE | ID: mdl-33837565

RESUMEN

BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

19.
Artículo en Inglés | MEDLINE | ID: mdl-33909923

RESUMEN

BACKGROUND: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications: cirrhosis decompensation, hepatocellular carcinoma (HCC, the fourth most common cause of cancer-related mortality worldwide), liver transplantation and death. It is now 40 years since development of the first plasmatic vaccine which has been proven to prevent (liver) cancer. AIMS: To update firstly the molecular and epidemiological aspects of HBV-related HCC and its natural history together with the benefits associated with viral suppression and secondly the safety, immunogenicity and efficacy of HBV vaccination. METHODS: Analysis of recent published data regarding HBV replication, anti-viral treatments and vaccination. RESULTS: The nuclear HBV replication cycle in the hepatocyte combines two limiting steps to achievement of HBV cure during chronic infection: the formation of a minichromosome, the supercoiled cccDNA, and host-genome integration of HBV DNA which triggers direct viral hepatocarcinogenesis. Even if specific anti-viral treatments significantly reduce viral replication, they decrease but do not cancel the risk of liver-related events in contrast with the prevention of HBV through HBV vaccination. CONCLUSIONS: To achieve the 2030 viral hepatitis elimination plan, the HBV vaccine is a priority tool for achieving the sustainable development goals of the World Health Organization.

20.
J Virol ; 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33910953

RESUMEN

Whereas the mode of action of lamivudine (LAM) against hepatitis B virus (HBV) is well established, the inhibition mechanism(s) of interferon-α are less completely defined. To advance our understanding, we mathematically modelled HBV kinetics during 14-day pegylated interferon-α-2a (pegIFN), LAM or pegIFN+LAM treatment of 39 chronically HBV-infected humanized uPA/SCID chimeric mice. Serum HBV DNA and intracellular HBV DNA were measured frequently. We developed a multicompartmental mathematical model and simultaneously fit it to the serum and intracellular HBV DNA data. Unexpectedly, even in the absence of an adaptive-immune response, a biphasic decline in serum HBV DNA and intracellular HBV DNA was observed in response to all treatments. Kinetic analysis and modeling indicate that the 1st phase represents inhibition of intracellular HBV DNA synthesis and secretion which was similar under all treatments with overall mean efficacy of 98%. In contrast, there were distinct differences in HBV decline during the 2nd phase which was accounted for in the model by a time-dependent inhibition of intracellular HBV DNA synthesis with the steepest decline observed during pegIFN + LAM (1.28/d) and the slowest (0.1/d) during pegIFN monotherapy. Reminiscent of observations in patients treated with pegIFN and/or LAM, a biphasic HBV decline was observed in treated humanized mice in the absence of adaptive immune response. Interestingly, combination treatment does not increase the initial inhibition of HBV production, but rather enhanced 2nd phase decline providing insight into the dynamics of HBV treatment response and the mode of action of interferon-α against HBV.ImportanceChronic hepatitis B virus (HBV) infection remains a global health care problem as we lack sufficient curative treatment options. Elucidating the dynamics of HBV infection and treatment response at the molecular level could facilitate the development of novel, more effective HBV antivirals. Currently, the only well-established small animal HBV infection model available is the chimeric uPA/SCID mice with humanized livers; however, the HBV inhibition kinetics under pegylated interferon-α (pegIFN) in this model system have not been determined in sufficient detail. In this study, viral kinetics in 39 humanized mice treated with pegIFN and/or lamivudine were monitored and analyzed using a mathematical-modelling approach. We found that the main mode of action of interferon-α is blocking HBV DNA synthesis and that the majority of synthesized HBV DNA is secreted. Our study provides novel insights into HBV DNA dynamics within infected human hepatocytes.

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