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2.
World J Gastroenterol ; 27(28): 4603-4638, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34366625

RESUMO

In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.


Assuntos
Hepatite B Crônica , Vírus da Hepatite E , Hepatite E , Animais , Objetivos , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Humanos , Zoonoses
4.
Artigo em Inglês | MEDLINE | ID: mdl-34126911

RESUMO

INTRODUCTION: HCV infection elimination is set to be carried out by 2030. To achieve this goal, the WHO has set minor achievable short-term "mini-goals." One of these is the treatment of "difficult to reach and treat populations," such as prisoners. One of the biggest obstacles to reaching this mini goal is the poor knowledge of the real HCV prevalence in such a population and the barriers to its detection, treatment, and follow-up. Even if HCV testing in Italian prisons is feasible and recommended, it is not always carried out. To worsen the picture, the peculiar status of conviction is correlated with the difficulty in carrying out the antiviral therapy due to challenges in follow-up and the refusals by inmates. AIMS: A point-of-care test-and-treat program was set up in a penitentiary in Southern Italy to reduce the number of patients lost-to-follow-up (LTFU) between detection and treatment. A secondary aim was to evaluate the prevalence of HCV-infected patients in a cohort of new inmates. METHODS: This prospective-observational study was carried out from January 2020 to February 2020. We performed a quick HCV-RNA blood capillary test on all new arriving inmates. As a routine, the new inmates underwent clinical and laboratory assessments. To those who were detected as HCV-RNA positive, the shortest possible antiviral treatment was offered, according to genotype and clinical features. RESULTS: We observed 122 new inmates in the period between January and February of 2020. Overall, 62 (50.8%) subjects accepted HCV-RNA quick testing through blood sampling. Four (6.4%) subjects were found to be HCV-RNA positive; 1 refused antiviral therapy while 3 accepted, obtaining 100% SVR. None of the HCV-active inmates were lost-to-follow-up between detection and treatment proposal. CONCLUSION: The use of a very fast test-and-treat protocol for HCV infection demonstrated to be effective to avoid LTFU in HCV-positive new inmates in the period between detection and treatment. We observed an apparent prevalence of HCV incident cases in newly arriving inmates of 6.4%. Antiviral therapy was quickly provided, secure, and successful.

5.
Nutrients ; 13(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063372

RESUMO

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition's capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients' clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context.


Assuntos
Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Nutrigenômica , Dieta , Humanos , Imunidade , Estilo de Vida , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Medicina de Precisão/métodos
6.
BMJ Open ; 11(5): e043112, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972332

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic has infected millions of people and has caused more than 2.30 million deaths worldwide to date. Several doubts arise about the role of asymptomatic carriers in virus transmission. During the first epidemic outbreak in Italy a large screening with nasopharyngeal swab (NS) was performed in those who were considered 'suspect' for infection. AIMS: To report the results of the SARS-CoV-2 screening in a province in Southern Italy and to provide data on the COVID-19 epidemic and the burden of asymptomatic subjects. PATIENTS AND METHODS: A retrospective cohort study was set up in all healthcare facilities of the province (12 hospitals and 13 sanitary districts: primary, secondary and tertiary centres) with the aim to analyse the results of NS performed on all subjects suspected to be infected with SARS-CoV-2, either because they presented symptoms suggestive of SARS-CoV-2 infection, they were 'contacts' of positive subjects, they came from areas with high prevalence or they were healthcare workers. NS were performed and managed as indicated by international guidelines. The specimens were processed for SARS-CoV-2 detection by real-time PCR. RESULTS: A total of 20 325 NS were performed from 13 March to 9 May 2020. Of these, 638 (3.14%) were positive. 470 were asymptomatic, or 75.3% of persons who were positive. They were mostly among 'contacts' of symptomatic cases (428 of 470, 91%) and were in domiciliary isolation. Expression of three SARS-CoV-2 genes did not differ between asymptomatic and symptomatic subjects. The strict measures with regard to social distancing led to a continuous decrease in cases during phase 1. CONCLUSIONS: In a large area in Southern Italy, 3.14% (638 of 20 325) of the total subjects tested were positive for SARS-CoV-2. Most of them were asymptomatic (470 of 624, 75.3%), and of these 91% (428 of 470) were 'close contacts' of symptomatic subjects. The combination of social distancing together with the systematic screening of close contacts of COVID-19-positive symptomatic subjects seems to be an efficacious approach to limit the spread of the epidemic.


Assuntos
COVID-19 , SARS-CoV-2 , Estudos de Coortes , Humanos , Itália/epidemiologia , Estudos Retrospectivos
7.
Nutrients ; 13(4)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923525

RESUMO

Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression.


Assuntos
Dieta/efeitos adversos , Açúcares da Dieta/efeitos adversos , Frutose/efeitos adversos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Progressão da Doença , Ácidos Graxos/biossíntese , Humanos , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenótipo
8.
Nutrients ; 13(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805795

RESUMO

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.


Assuntos
Antioxidantes/uso terapêutico , Hepatopatias/tratamento farmacológico , Resveratrol/uso terapêutico , Humanos , Técnicas In Vitro
9.
Infect Dis Ther ; 10(2): 763-774, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33655410

RESUMO

INTRODUCTION: In Italy, hepatitis C virus (HCV) elimination is achievable; however, barriers remain to achieving the World Health Organization's elimination targets, and have become more pronounced with the spread of COVID-19. Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral therapy for HCV, approved for 8-week treatment in patients without cirrhosis, and with compensated cirrhosis (CC). Previously, 12 weeks of therapy was recommended for patients with CC. Shortened treatment may reduce the burden on healthcare resources, allowing more patients to be treated. This study presents the benefits that 8-week vs 12-week treatment with G/P may have in Italy. METHODS: A multicohort Markov model was used to assess the collective number of healthcare visits and time on treatment with 8-week vs 12-week G/P in the HCV-infected population of Italy from 2019 to 2030, using healthcare resource data from post-marketing observational studies of G/P. Increased treatment capacity and downstream clinical and economic benefits were also assessed assuming the reallocation of saved healthcare visits to treat more patients. RESULTS: Modeled outcomes showed that by 2030, 8-week treatment saved 27,006 years on therapy compared with 12-week treatment, with 21,065 fewer hepatologist visits. Reallocating these resources to treat more patients could increase capacity to treat 5064 (1.4%) more patients with 8 weeks of G/P, all with CC. This increased treatment capacity would further avoid 2257 cases of end-stage liver disease, 893 liver-related deaths, and provide net savings to the healthcare system of nearly €70 million. CONCLUSION: The modeled comparisons between 8- and 12-week treatment with G/P show that shorter treatment duration can lead to greater time and resource savings, both in terms of healthcare visits and downstream costs. These benefits have the potential to enable the treatment of more patients to overcome elimination barriers in Italy through programs aimed to engage and treat targeted HCV populations.

10.
Metabolomics ; 17(2): 12, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33458794

RESUMO

INTRODUCTION: Non-Alcoholic Fatty Liver Disease encompasses a spectrum of diseases ranging from simple steatosis to steatohepatitis (or NASH), up to cirrhosis and hepatocellular carcinoma (HCC). The challenge is to recognize the more severe and/or progressive pathology. A reliable non-invasive method does not exist. Untargeted metabolomics is a novel method to discover biomarkers and give insights on diseases pathophysiology. OBJECTIVES: We applied metabolomics to understand if simple steatosis, steatohepatitis and cirrhosis in NAFLD patients have peculiar metabolites profiles that can differentiate them among each-others and from controls. METHODS: Metabolomics signatures were obtained from 307 subjects from two separated enrollments. The first collected samples from 69 controls and 144 patients (78 steatosis, 23 NASH, 15 NASH-cirrhosis, 8 HCV-cirrhosis, 20 cryptogenic cirrhosis). The second, used as validation-set, enrolled 44 controls and 50 patients (34 steatosis, 10 NASH and 6 NASH-cirrhosis).The "Partial-Least-Square Discriminant-Analysis"(PLS-DA) was used to reveal class separation in metabolomics profiles between patients and controls and among each class of patients, and to reveal the metabolites contributing to class differentiation. RESULTS: Several metabolites were selected as relevant, in particular:Glycocholic acid, Taurocholic acid, Phenylalanine, branched-chain amino-acids increased at the increase of the severity of the disease from steatosis to NASH, NASH-cirrhosis, while glutathione decreased (p < 0.001 for each). Moreover, an ensemble machine learning (EML) model was built (comprehending 10 different mathematical models) to verify diagnostic performance, showing an accuracy > 80% in NAFLD clinical stages prediction. CONCLUSIONS: Metabolomics profiles of NAFLD patients could be a useful tool to non-invasively diagnose NAFLD and discriminate among the various stages of the disease, giving insights into its pathophysiology.


Assuntos
Fígado Gorduroso/diagnóstico , Cirrose Hepática/diagnóstico , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Idoso , Algoritmos , Biomarcadores , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Humanos , Cirrose Hepática/congênito , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Redes e Vias Metabólicas , Metaboloma , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo
11.
Dig Liver Dis ; 53(5): 612-619, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32917546

RESUMO

BACKGROUND AND AIMS: The MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. PATIENTS AND METHODS: Achievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naïve and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity and Activity Impairment) were also evaluated. RESULTS: The SVR12 rate was 99.4% (319/321; 95% CI: 97.8-99.8%) in the core population with sufficient follow-up (n = 321), 99.7% (289/290) in 8-week treated patients, and high (>96%) across subgroups. Only three patients (0.9%) had treatment-related adverse events that led to treatment discontinuation. In total, 30.1% of patients showed an improvement of ≥2.5 points in the Physical Component Summary of the SF-36 from baseline to the end of treatment, and this figure raised to 37.5% with the achievement of SVR12. Corresponding values for MCS were 42.2% and 42.8%, respectively. CONCLUSION: Glecaprevir/pibrentasvir is safe and effective across subpopulations who are underserved in clinical trials.

12.
Life (Basel) ; 10(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352991

RESUMO

Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment.

14.
Adv Ther ; 37(9): 4033-4042, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32754824

RESUMO

INTRODUCTION: More than 70 million people are estimated to be infected with hepatitis C virus globally. Glecaprevir/pibrentasvir is a widely used treatment and has recently been approved for an 8-week regimen for treatment-naïve patients with compensated cirrhosis in Europe and the USA, who would previously have received glecaprevir/pibrentasvir for 12 weeks. This label update was based on the EXPEDITION-8 study, which included 343 treatment-naïve patients with compensated cirrhosis. However, there is currently a lack of similarly large-scale real-world studies of the 8-week glecaprevir/pibrentasvir regimen in this population. METHODS: This summary of seven separate smaller real-world studies aims to validate the results seen in EXPEDITION-8 and provide an up-to-date real-world reference for clinicians making treatment decisions for patients with compensated cirrhosis (Child-Pugh A) who may benefit from a shorter-duration therapy with glecaprevir/pibrentasvir. The newly emerging real-world effectiveness data on treatment-naïve patients with compensated cirrhosis treated with 8 weeks of glecaprevir/pibrentasvir help to understand where further research is needed to support patients with hepatitis C virus. RESULTS: Across all seven studies, glecaprevir/pibrentasvir showed high effectiveness with an average sustained virologic response rate of 98.1%, similar to that found in a clinical trial setting (99.7%). Only one patient (0.5%) experienced virologic failure and treatment was well tolerated. CONCLUSION: Expanding the number of patients eligible for the shortened treatment duration will potentially increase treatment initiation and completion, particularly in underserved populations, contributing to the elimination of hepatitis C virus.


Assuntos
Ácidos Aminoisobutíricos/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Ciclopropanos/uso terapêutico , Combinação de Medicamentos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Lactamas Macrocíclicas/uso terapêutico , Leucina/análogos & derivados , Cirrose Hepática/tratamento farmacológico , Prolina/análogos & derivados , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Variação Genética , Hepacivirus/efeitos dos fármacos , Humanos , Leucina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-32408667

RESUMO

: Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 g of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. METHODS: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. RESULTS: A direct proportionality between TBARS levels and BPA exposure was shown (p < 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p < 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p < 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). CONCLUSIONS: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.


Assuntos
Compostos Benzidrílicos , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Fenóis , Adulto , Compostos Benzidrílicos/toxicidade , Humanos , Itália , Fígado , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade
16.
Dig Liver Dis ; 52(5): 541-546, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32234417

RESUMO

BACKGROUND: An unmet objective in the pursuit of HCV elimination is the creation of a simple and fast operating model to identify difficult-to-treat populations, like prisoners. Of many obstacles, the first is represented by the poor knowledge of inmates HCV-Ab prevalence. Moreover, due to the peculiar status of conviction, often their access to antiviral therapy is neglected. AIMS: To evaluate the prevalence of HCV infection in a penitentiary Institution of Southern Italy through a point-of-care screening and treatment program. METHODS: We conducted a prospective observational study in two phases: first, we reviewed all the prisoners' clinical records, to verify HCV-Ab execution. Subsequently, we performed a universal point-of-care screening and treatment program. RESULTS: We enrolled 670 patients. Overall, 310(46.27%) were already HCV-Ab tested. At the screening initiation, 23.28% patients were discharged, whereas 8.35% refused. Of the remaining 458 subjects, 58(12.67%) were HCV-Ab positive and 46 HCVRNA positive. All these underwent DAA, obtaining 100% SVR. At the end of the program, a total of 491(73.28%) subjects had HCV-Ab available. Sixty-nine (14.05%) were positive. A total of 214(31.94%) subjects were lost to follow-up. CONCLUSIONS: We revealed a prevalence of 14.05% of HCV-Ab in conviction. Antiviral treatment was safe and efficacious. More efforts are advisable to provide screening for HCV-Ab in conviction.


Assuntos
Antivirais/uso terapêutico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Prisões , Adulto , Idoso , Feminino , Hepacivirus/genética , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/análise , Humanos , Itália/epidemiologia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Prevalência , Estudos Prospectivos , Recusa do Médico a Tratar/estatística & dados numéricos , Resposta Viral Sustentada , Adulto Jovem
17.
J Hepatol ; 72(6): 1112-1121, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32061651

RESUMO

BACKGROUND & AIMS: Glecaprevir/pibrentasvir is approved for treating adults infected with HCV genotypes 1-6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken. METHODS: Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naïve pooling was used to calculate adverse event (AE) rates. RESULTS: Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment week 12 data, SVR12 rates were 96.7% (95% CI 95.4-98.1) in the ITT population (n = 8,583, 15 cohorts) and 98.1% (95% CI 97.1-99.2) in the mITT population (n = 7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts). CONCLUSIONS: Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients. LAY SUMMARY: It is important to assess treatments for hepatitis C virus (HCV) in the real world, as patient populations tend to be more diverse and potentially less adherent to treatment compared to those in clinical trials. Results from 18 studies performed in real-world clinics were pooled and analyzed to investigate the effectiveness and safety of a direct-acting antiviral combination (glecaprevir/pibrentasvir) in routine clinical practice. This analysis showed that glecaprevir/pibrentasvir is highly effective and well tolerated across all HCV genotypes and patient groups studied. It also showed that results seen in the real world are similar to the results seen in clinical trials, even in patients historically considered more challenging to treat.

18.
Liver Int ; 40(5): 1032-1041, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31821716

RESUMO

BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Previously available direct-acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. METHODS: EXPEDITION-5 is a phase 3 study to evaluate efficacy and safety of the fixed-dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty-four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty-five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6-99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug. CONCLUSIONS: G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected. CLINICALTRIALS. GOV IDENTIFIER: This Phase 3 clinical trial was funded by AbbVie and registered with clinicaltrials.gov as NCT03069365 (EXPEDITION-5).


Assuntos
Hepatite C Crônica , Adulto , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Benzimidazóis , Ciclopropanos , Combinação de Medicamentos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , Sulfonamidas
19.
Oxid Med Cell Longev ; 2019: 8742075, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737175

RESUMO

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α, transforming growth factor ß, interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline (p < 0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients (p < 0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome (p < 0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome.


Assuntos
Células Endoteliais/fisiologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Silibina/uso terapêutico , Vitamina D/uso terapêutico , Vitamina E/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Peso Corporal , Citocinas/sangue , Quimioterapia Combinada , Feminino , Humanos , Resistência à Insulina , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
20.
Artigo em Inglês | MEDLINE | ID: mdl-31540048

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.


Assuntos
Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipotireoidismo/epidemiologia , Osteoporose/epidemiologia , Periodontite/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Psoríase/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Disfunções Sexuais Fisiológicas/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Urolitíase/epidemiologia
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