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1.
Georgian Med News ; (306): 76-81, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33130651

RESUMO

HCV infection and its complications, especially hepatocellular carcinoma, is a substantial public health burden. In 2015 "Nationwide hepatitis C elimination program" was launched in Georgia. According to the protocol, patients with HCC also receive DAA antiviral treatment. We study the effect of the different DAA therapy regiments on the incidence or recurrence of HCC and its prognosis. Overall, 408 patients were recruited in Georgian-French Joint Hepatology Clinic HEPA between April 2015-March 2016. The selection criteria were as follows: 1 - age 50-65 years; 2. Liver fibrosis level F3-F4 or cirrhosis at least 15 years of disease history; 3. HCV positive diagnosed by PCR method, whatever the level of viral load and genotype; 4. absence of previous complications of cirrhosis (ascites, gastrointestinal bleeding or HCC; 5. Child-Pugh class A or B; and 6. absence of severe extrahepatic disease. Essential clinical and biological parameters were recorded. Clinical monitoring and management of adverse events were performed on a regular base. HCV All patients included in the study received anti-HCV treatment with direct-acting antivirals (DAAs) within the national hepatitis C elimination program in accordance with national protocols. During April 2015-March 2016 treatment was provided with sofosbuvir (SOF) in combination with ribavirin (RBV), with or without pegylated interferon (IFN). Since March 2016, ledipasvir/sofosbuvir (LDV/SOF) was prescribed to all patients with or without RBV depending on the HCV genotype, level of fibrosis, and previous treatment experience. In conclusion, we find that neither different DAA regimens nor different treatment duration affects HCC risk after antiviral treatment. Moreover, there are no significant changes in mortality rate due to HCC in these groups. Therefore, it can be concluded, that HCC status is not a contraindication for DAA treatment, especially at the early stages of cancer, when a tumor is curative.


Assuntos
Antivirais , Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Criança , Quimioterapia Combinada , Genótipo , Georgia , República da Geórgia , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
2.
Sci Rep ; 10(1): 16577, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024223

RESUMO

SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2. We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase. Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity. Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Exonucleases/metabolismo , Pneumonia Viral/tratamento farmacológico , Pró-Fármacos/farmacologia , RNA Viral/efeitos dos fármacos , Sofosbuvir/farmacologia , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/química , Alanina/farmacologia , Alanina/uso terapêutico , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/enzimologia , Infecções por Coronavirus/virologia , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , Pró-Fármacos/uso terapêutico , RNA Replicase/antagonistas & inibidores , RNA Replicase/metabolismo , RNA Viral/química , RNA Viral/metabolismo , Sofosbuvir/química , Sofosbuvir/uso terapêutico , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
3.
J Exp Med ; 217(3)2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33002101

RESUMO

Eliminating the burden of disease caused by hepatitis C virus infection is proving difficult, despite the availability of curative drug treatments. Progress will require innovations in healthcare delivery and a deeper understanding of how the liver and other vital organs survive damage caused by chronic injury.


Assuntos
Hepatite C/patologia , Cirrose Hepática/patologia , Fígado/patologia , Progressão da Doença , Hepatite C/tratamento farmacológico , Humanos , Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico
4.
Medicine (Baltimore) ; 99(41): e22650, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031326

RESUMO

RATIONALE: Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS: In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES: This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS: The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES: Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS: Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.


Assuntos
Antivirais/efeitos adversos , Vírus da Hepatite B/isolamento & purificação , Hepatite C/tratamento farmacológico , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Feminino , Hepatite B/virologia , Humanos , Pessoa de Meia-Idade , Recidiva
5.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 809-811, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105921

RESUMO

Hepatitis C infection is a serious public health threat, and the World Health Organization has recommended the elimination of public health threats from viral hepatitis, including hepatitis C, by 2030. Many countries and regions are actively exploring strategies and models to eliminate the public health threat of hepatitis C. It is estimated that there are at least 7.6 million cases of chronic hepatitis C in China, with both diagnosis and treatment rates far away to 2030 target. China's government, social organizations and doctors at different levels are also actively exploring the mode of eliminating the public health threat of hepatitis C in China, including the main mode supported by national standards, government-led mode, social institution undertaking and government-supported mode, medical alliance mode, screening in high-prevalence areas and services contracted with family doctors. China can have a lessons learning from international and ourselves experience, particularly as "Test and treat all based on needs and demand" strategy in Covid-19 control, finally achieve eliminate the public health threat of hepatitis C as soon as possible.


Assuntos
Hepatite C , China/epidemiologia , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos
6.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 812-816, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105922

RESUMO

Recently, global hepatitis C testing and treatment have made some progress with the popularization of direct-acting antiviral drugs (DAAs), application of new detection technologies and service models. By 2017, 5 million hepatitis C patients had received DAA treatment, which has surpassed the 2020 treatment target set by the World Health Organization's hepatitis strategy. However, on a global scale, the scope of hepatitis C testing and treatment remains severely inadequate, especially in countries with a high burden of hepatitis C and low-and middle-income countries. In addition, the coverage of harm reduction interventions for injecting drug users is low and the progress is slow. Therefore, achieving the goal of eliminating hepatitis C by 2030 is a huge challenge. Overcoming barriers to prevention and treatment, thereby accelerating progress in eliminating hepatitis C, depends on the strong political will, increasing fund, epidemic and prevention analysis based on the deeper implementation of existing effective measures and rapid use and promotion of new detection and treatment tools. Importantly, Universal Health Coverage (UHC) provides an opportunity to countermeasures the challenges and expands effective prevention and control measures.


Assuntos
Antivirais , Erradicação de Doenças , Hepatite C , Antivirais/uso terapêutico , Saúde Global , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos
7.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 844-849, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105929

RESUMO

Objective: To understand the hepatitis C diagnosis type, progression and treatment in medical institutions. Methods: Monitoring posts were set up in the secondary and tertiary-level hospitals in some parts of the country. Reported infectious diseases cases of hepatitis C in sentinel hospitals during the three consecutive years from 2017 to 2019 were investigated to understand their general demographic characteristics, diagnosis, liver fibrosis degree, and treatment. The diagnosis, treatment and related factors were analyzed by chi square test and trend. Results: A total of 16 241 cases of hepatitis C were investigated in three years. Among them, 7 538 cases were clinically diagnosed (46.41%) and 8703 cases (53.59%) were confirmed as hepatitis C. Among the confirmed cases, 60 cases (0.69%) were acute and 8643 cases (99.31%) were chronic. In the past three years, the proportion of cases diagnosed by liver diseases related departments decreased from 62.23% to 40.01%, while the proportion of medical and surgical cases of non-liver diseases increased from less than 30% to nearly 60%. The proportion of confirmed cases in secondary hospitals (26.27%) was significantly lower than that in tertiary hospitals (62.48%), and the difference was statistically significant (χ (2) = 1594.833, P < 0.001). There were also differences in the proportion of confirmed cases in different regions (P < 0.001). The cases with FIB-4 > 3.25 accounted for 35.78%, and the proportion was increased significantly with age (χ (2) trend = 1159.624, P < 0.001). The average proportion of antiviral treatment was less than 10%, and the proportion of antiviral treatment in secondary hospitals was very low (2.13%); however, the proportion of liver-protective monotherapy treatment was decreased from 30.40% in 2017 to 11.14% in 2019, and the difference was statistically significant (P < 0.001). Conclusion: The large-scale screening of hepatitis C by medical institutions is increasing year by year, but only about half of the cases can be diagnosed, and the diagnostic capacity of secondary hospitals is particularly unsatisfactory. Most of the confirmed cases are chronic hepatitis C, and more than one third of them have abnormal liver fibrosis indicators, and the proportion increases with age. The proportion of antiviral treatment for hepatitis C is lower in secondary than tertiary-level hospitals. Therefore, there is an urgent need to raise the attention of both parties (doctors and patients) to enhance diagnostic capabilities and expand the coverage of antiviral treatment for hepatitis C.


Assuntos
Antivirais , Hepatite C , Antivirais/uso terapêutico , China/epidemiologia , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Vigilância de Evento Sentinela
8.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 893-896, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105938

RESUMO

HCV prevalence among people who inject drugs (PWID) is up to 67%. PWID is a population that needs priority attention to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030. Although the SVR of HCV patients treated with direct-acting antiviral drugs (DAAs) can reach over 95%, especially in medical practice, there are still major obstacles to PWID treatment, because PWID is usually accompanied with concurrent infection, multiple-genotype infections, low compliance, substance abuse, methadone maintenance therapy, and risky behavior and re-infection conditions. Therefore, physicians often concern that these factors will affect the treatment efficacy, and refuse to provide hepatitis C treatment in PWID. This article reviews the relevant studies status and effects of hepatitis C treatment in PWID with different infection states and special behavior characteristics, and further highlights that the multidisciplinary cooperation for hepatitis C treatment in PWID is safe and effective, and can ensure treatment compliance.


Assuntos
Antivirais , Usuários de Drogas , Hepatite C , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Humanos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico
9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(10): 1161-1164, 2020 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-33115205

RESUMO

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.


Assuntos
Antivirais , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Saúde Pública
10.
BMC Infect Dis ; 20(1): 759, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059617

RESUMO

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.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , França/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Value Health ; 23(9): 1137-1141, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32940230

RESUMO

OBJECTIVES: Hepatitis C virus (HCV) antivirals have been shown to be highly effective with minimal adverse effects, but they are costly. Little is known about the national spending on this drug class in either Canada or the United States, 2 countries with different drug pricing regulations. Thus the objective of this study was to compare drug expenditure on HCV medications in the United States and Canada. METHODS: This was a retrospective cross-sectional study using the IQVIA National Sales Perspectives (United States) and Geographic Prescription Monitor (Canada) databases, which contains prescription transactions from American and Canadian pharmacies. All prescription claims for the period between January 1, 2014, and June 30, 2018, were used to describe HCV antiviral expenditure in both countries. RESULTS: The United States and Canada spent $59.7 billion and $2.8 billion on HCV medications, respectively. Population-adjusted HCV medication costs were higher in the United States ($1 million per 100 000 population) compared with Canada ($0.4 million per 100 000 population). CONCLUSIONS: Although the rates of HCV infection are similar in the 2 countries, these findings highlight the differences in both the reimbursement utilization policy for HCV treatments in the countries and the major differences in drug pricing policies. As policies to reduce drug spending in the United States are explored, this article highlights the potential cost implications of implementing Canadian index pricing.


Assuntos
Antivirais/economia , Custos de Medicamentos/estatística & dados numéricos , Hepatite C/tratamento farmacológico , Canadá , Estudos Transversais , Política de Saúde , Humanos , Estudos Retrospectivos , Estados Unidos
13.
BMC Infect Dis ; 20(1): 702, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972393

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infections in people who inject drugs (PWID) can now be treated and cured. However, the impact that HCV treatment has on drug-user health, practices and wellbeing is not known. The aim of this research was to understand the non-clinical impact that HCV treatment has in PWID and their reasons for accessing and completing treatment. METHODS: Participants aged 25-67 years who had injected opioids or stimulants (currently or in the past) and had completed direct-acting antiviral treatment were recruited from seven European countries. Participants completed a 30-min online survey administered face-to-face between September 2018 and April 2019. The questionnaire responses were used to assess the mental and physical impact of having completed treatment. RESULTS: Of the 124 participants who completed the survey questionnaire, 75% were male, 69% were over 45 years old and 65% were using opioids and/or stimulants at the start of HCV treatment. Participants reported improvements in the following areas after completing HCV treatment: outlook for the future (79%); self-esteem (73%); ability to plan for the future (69%); belief in their abilities (68%); confidence (67%); empowerment (62%); energy levels (59%); and ability to look after themselves (58%). The most common reasons for starting HCV treatment were: becoming aware of treatments that were well tolerated (77%) and effective (75%); and understanding the potentially severe consequences of HCV (75%). CONCLUSIONS: The benefits of HCV treatment go beyond clinical outcomes and are linked to improved drug-user health and wellbeing. Sharing information about well-tolerated and effective HCV treatments, and raising awareness about the potentially severe consequences of untreated HCV are likely to increase the number of PWID who are motivated to access and complete HCV treatment in future.


Assuntos
Usuários de Drogas , Hepatite C/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Atitude Frente a Saúde , Usuários de Drogas/psicologia , Usuários de Drogas/estatística & dados numéricos , Emoções , Emprego , Europa (Continente) , Feminino , Hepatite C/psicologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
14.
BMC Infect Dis ; 20(1): 632, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847527

RESUMO

BACKGROUND: Viral relapse is a major concern in hepatitis C virus (HCV) antiviral therapy. Currently, there are no satisfactory methods to predict viral relapse, especially in the era of direct acting antivirals in which the virus often quickly becomes undetectable using PCR-based approaches that focus on a small viral region. Next-generation sequencing (NGS) provides an alternative option for viral detection in a genome-wide manner. However, owing to the overwhelming dominance of human genetic content in clinical specimens, direct detection of HCV by NGS has a low sensitivity and hence viral enrichment is required. METHODS: Based on template-dependent multiple displacement amplification (tdMDA), an improved method for whole genome amplification (Wang et al., 2017. Biotechniques 63, 21-27), we evaluated two strategies to enhance the sensitivity of NGS-based HCV detection: duplex-specific nuclease (DSN)-mediated depletion of human sequences and HCV probe-based capture sequencing. RESULTS: In DSN-mediated depletion, human sequences were significantly reduced in the two HCV serum samples tested, 65.3% → 55.6% → 33.7% (#4727) and 68.6% → 56% → 21% (#4970), respectively for no normalization, self- and driver-applied normalization. However, this approach was associated with a loss of HCV sequences perhaps due to its micro-homology with the human genome. In capture sequencing, HCV-mapped sequencing reads occupied 96.8% (#4727) and 22.14% (#4970) in NGS data, equivalent to 1936x and 7380x enrichment, respectively. Capture sequencing was then applied to ten serum samples collected at the end of HCV antiviral therapy. Interestingly, the number of HCV-mapped reads was significantly higher in relapsed patients (n = 5) than those from patients with sustained virological response (SVR) (n = 5), 102.4 ± 72.3 vs. 2.6 ± 0.55, p = 0.014. CONCLUSIONS: Our data provides concept evidence for a highly sensitive HCV detection by capture sequencing. The abundance difference of HCV sequencing reads at the end of HCV antiviral therapy could be applied to predict treatment outcomes.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Feminino , Genoma Viral/genética , Hepatite C/sangue , Humanos , Masculino , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resposta Viral Sustentada
15.
BMC Infect Dis ; 20(1): 588, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770955

RESUMO

BACKGROUND: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. METHODS: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. RESULTS: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. CONCLUSION: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.


Assuntos
Infecções por HIV/patologia , Hepatite C/diagnóstico , Modelos Teóricos , Antivirais/uso terapêutico , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/patologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos Prospectivos , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Resposta Viral Sustentada
16.
Intern Med ; 59(15): 1811-1817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741890

RESUMO

Objective Although most patients who obtain a sustained virological response (SVR) show an improved liver function, some show decreased platelet counts after the eradication of hepatitis C virus (HCV). The aim of this retrospective study was to clarify the association of the liver and spleen volumes with the platelet count after SVR achieved by direct-acting antiviral (DAA) treatment. Methods This study enrolled 36 consecutive patients treated by DAAs who obtained an SVR between September 2014 and December 2018. The liver and spleen volumes were derived from computed tomography scans obtained at pretreatment, SVR, and 48 weeks after SVR. No patient developed hepatocellular carcinoma during this study. Results Compared with pretreatment, the median aspartate aminotransferase, alanine aminotransferase, albumin serum levels, and platelet counts were significantly improved at SVR and 48 weeks after SVR. The liver/spleen volumes per body weight had decreased significantly from 22.5/4.2 mL/kg at baseline to 21.1/3.6 mL/kg at 48 weeks after SVR. The change in the liver volume was associated with the change in the platelet count, and the change in the spleen volume was negatively associated with the change in the serum albumin level. A multivariate analysis identified the change in the liver volume (≥95%, odds ratio 76.9, p=0.005) as the factor associated with improvement in the platelet count at 48 weeks after SVR. The patients with an increased liver volume at 48 weeks after SVR showed an increased platelet count. Conclusion Both the liver and spleen volume decreased significantly after the eradication of HCV. The patients with a re-increased liver volume showed a rapid increase in the platelet count.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Cirrose Hepática/patologia , Tamanho do Órgão/fisiologia , Contagem de Plaquetas/estatística & dados numéricos , Baço/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepacivirus , Hepatite C/complicações , Humanos , Cirrose Hepática/etiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resposta Viral Sustentada
17.
PLoS One ; 15(8): e0237162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750098

RESUMO

Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Coinfecção/genética , Variação Genética , HIV , Hepacivirus/genética , Hepatite C/genética , Proteínas não Estruturais Virais/genética , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Sequência de Aminoácidos , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Filogenia , RNA Replicase/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Uracila/uso terapêutico
18.
Life Sci ; 258: 118205, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777300

RESUMO

AIMS: Coronavirus disease 2019 (COVID-19) has appeared in Wuhan, China but the fast transmission has led to its widespread prevalence in various countries, which has made it a global concern. Another concern is the lack of definitive treatment for this disease. The researchers tried different treatment options which are not specific. The current study aims to identify potential small molecule inhibitors against the main protease protein of SARS-CoV-2 by the computational approach. MAIN METHODS: In this study, a virtual screening procedure employing docking of the two different datasets from the ZINC database, including 1615 FDA approved drugs and 4266 world approved drugs were used to identify new potential small molecule inhibitors for the newly released crystal structure of main protease protein of SARS-CoV-2. In the following to validate the docking result, molecular dynamics simulations were applied on selected ligands to identify the behavior and stability of them in the binding pocket of the main protease in 150 nanoseconds (ns). Furthermore, binding energy using the MMPBSA approach was also calculated. KEY FINDINGS: The result indicates that simeprevir (Hepatitis C virus NS3/4A protease inhibitor) and pyronaridine (antimalarial agent) could fit well to the binding pocket of the main protease and because of some other beneficial features including broad-spectrum antiviral properties and ADME profile, they might be a promising drug candidate for repurposing to the treatment of COVID-19. SIGNIFICANCE: Simeprevir and pyronaridine were selected by the combination of virtual screening and molecular dynamics simulation approaches as a potential candidate for treatment of COVID-19.


Assuntos
Antimaláricos/farmacologia , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Naftiridinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Simeprevir/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Reposicionamento de Medicamentos , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Hepatite C/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Inibidores de Proteases/farmacologia , Serina Proteases , Bibliotecas de Moléculas Pequenas/farmacologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
19.
PLoS One ; 15(8): e0237236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764799

RESUMO

We previously reported that the non-immunosuppressive cyclophilin inhibitors (CypIs)-cyclosporin A analog CRV431 and sanglifehrin analog NV556-efficiently inhibit HCV replication in vitro. In this study, we asked whether they can also reduce HCV replication in vivo. We found that a single oral administration of CRV431 and NV556 to HCV-infected humanized-liver mice drastically reduced HCV blood levels. The antiviral effect was observed when CRV431 or NV556 were each individually administered with HCV, 3, 6 weeks or even 3 months post-infection when viral replication is robust. These results were confirmed in chimeric mice implanted with human hepatocytes isolated from three distinct donors. Remarkably, no viral rebound was observed 5 months after a single dose administration of 50 mg/kg of CRV431 or NV556 four weeks post-HCV infection, indicating the possibility of suppression of an established viral infection. Since we recently demonstrated that both CRV431 and NV556 also inhibit the development of liver fibrosis and hepatocellular carcinoma in nonviral-induced non-alcoholic steatohepatitis mouse models, our present data suggest that the two entirely structurally different CypIs-CRV431 and NV556-derived from unrelated natural products, represent attractive partners to current direct-acting agent (DAA) regimens for the treatment of hepatitis C and liver diseases.


Assuntos
Antivirais/uso terapêutico , Ciclosporinas/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Animais , Antivirais/farmacologia , Ciclosporinas/farmacologia , Hepacivirus/fisiologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Camundongos , Camundongos SCID , Camundongos Transgênicos , Replicação Viral/efeitos dos fármacos
20.
PLoS One ; 15(6): e0235445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603349

RESUMO

BACKGROUND: Hepatitis C elimination will require widespread access to treatment and responses at the health-service level to increase testing among populations at risk. We explored changes in hepatitis C testing and the cascade of care before and after the introduction of direct-acting antiviral treatments in Victoria, Australia. METHODS: De-identified clinical data were retrospectively extracted from eighteen primary care clinics providing services targeted towards people who inject drugs. We explored hepatitis C testing within three-year periods immediately prior to (pre-DAA period) and following (post-DAA period) universal access to DAA treatments on 1st March 2016. Among ever RNA-positive individuals, we constructed two care cascades at the end of the pre-DAA and post-DAA periods. RESULTS: The number of individuals HCV-tested was 13,784 (12.2% of those with a consultation) in the pre-DAA period and 14,507 (10.4% of those with a consultation) in the post-DAA period. The pre-DAA care cascade included 2,515 RNA-positive individuals; 1,977 (78.6%) were HCV viral load/genotype tested; 19 (0.8%) were prescribed treatment; and 12 had evidence of cure (0.5% of those RNA-positive and 63.6% of those eligible for cure). The post-DAA care cascade included 3,713 RNA-positive individuals; 3,276 (88.2%) were HCV viral load/genotype tested; 1,674 (45.1%) were prescribed treatment; and 863 had evidence of cure (23.2% of those RNA-positive and 94.9% of those eligible for cure). CONCLUSION: Marked improvements in the cascade of hepatitis C care among patients attending primary care clinics were observed following the universal access of DAA treatments in Australia, although improvements in testing were less pronounced.


Assuntos
Antivirais/uso terapêutico , Hepatite C , Adolescente , Adulto , Serviços de Saúde Comunitária , Feminino , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Abuso de Substâncias por Via Intravenosa/complicações , Vitória/epidemiologia , Adulto Jovem
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