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1.
Gut ; 72(2): 381-391, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35788059

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.


Assuntos
Carcinoma Hepatocelular , Predisposição Genética para Doença , Cirrose Hepática Alcoólica , Neoplasias Hepáticas , Telomerase , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Variação Genética , Estudo de Associação Genômica Ampla , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/genética , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Telomerase/genética
2.
Ann Neurol ; 90(2): 315-318, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34114269

RESUMO

Although SARS-CoV-2 vaccines are very safe, we report 4 cases of the bifacial weakness with paresthesias variant of Guillain-Barré syndrome (GBS) occurring within 3 weeks of vaccination with the Oxford-AstraZeneca SARS-CoV-2 vaccine. This rare neurological syndrome has previously been reported in association with SARS-CoV-2 infection itself. Our cases were given either intravenous immunoglobulin, oral steroids, or no treatment. We suggest vigilance for cases of bifacial weakness with paresthesias variant GBS following vaccination for SARS-CoV-2 and that postvaccination surveillance programs ensure robust data capture of this outcome, to assess for causality. ANN NEUROL 2021;90:315-318.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/diagnóstico , Vacinas contra COVID-19/administração & dosagem , Glucocorticoides/administração & dosagem , Síndrome de Guillain-Barré/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Vacinação/efeitos adversos , Adulto Jovem
3.
Br J Nurs ; 29(20): 1155-1158, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180617

RESUMO

The target set by the World Health Organization to eliminate viral hepatitis as a public health problem by 2030 first requires methods of testing for hepatitis B and C virus that are acceptable to diverse populations. One such test is the dried blood spot sample method. This article explains what a dried blood spot sample is, how it is collected, and how it can help increase the viral hepatitis test uptake in prisons, drug and alcohol services, and other populations at risk of hepatitis B or C infection.


Assuntos
Teste em Amostras de Sangue Seco , Hepatite Viral Humana , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/epidemiologia , Humanos , Prisões
4.
J Viral Hepat ; 27(10): 1003-1011, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32488916

RESUMO

The prison population is central to the campaign to eliminate hepatitis C virus as a public health threat. In the UK, this has led to the introduction of a national 'opt-out' policy, requiring people in prison to be tested for HCV unless they decline, with a target to test 75% of those admitted. However, in a representative prison estate in the East Midlands of England (20,000 prison entrants per annum) testing rates were only 13.4%. This qualitative study explains why the rates of test uptake are so far short of target. This qualitative study examines the experiences of 45 people in prison about hepatitis C virus testing in an English category C (low security) prison. The data collection method was semi-structured interviews. The data were coded and analysed according to the research questions, and interpretation of the data was aided by the use of a thematic network approach. The themes Fear, Insufficient Knowledge, Stigma, Privacy, Choice and Prison Life emerged as the principal barriers to test uptake. Test Uptake Facilitators that promoted testing were identified by participants and benefits presented of prison health care being a Health Farm. In order to increase hepatitis C virus test uptake, significant changes and flexibility in the timing, location, and staff deployed to test are required. Providing information to people in prison about hepatitis C virus transmission and treatment may reduce fears and enable the test uptake target to be met and sustained.


Assuntos
Hepatite C , Prisioneiros , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Humanos , Prisões , Estigma Social
5.
Gut ; 67(11): 2017-2024, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29615488

RESUMO

OBJECTIVE: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. DESIGN: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case-control study comparing results with those obtained with the Abbott RealTime HCV test. RESULTS: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. CONCLUSION: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. TRIAL REGISTRATION NUMBER: NCT02992184 .


Assuntos
Hepacivirus/genética , Hepatite C Crônica/virologia , RNA Viral/genética , Carga Viral/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Open Forum Infect Dis ; 3(1): ofv218, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26900576

RESUMO

Background. Engagement of individuals infected with hepatitis C virus (HCV) with care pathways remains a major barrier to realizing the benefits of new and more effective antiviral therapies. After an exploratory study, we have undertaken an evidence-based redesign of care pathways for HCV, including the following: (1) reflex testing of anti-HCV-positive samples for HCV RNA; (2) annotation of laboratory results to recommend referral of actively infected patients to specialist clinics; (3) educational programs for primary care physicians and nurses; and (4) the establishment of needs-driven community clinics in substance misuse services. Methods. In this study, we conducted a retrospective cohort study of progression through care pathways of individuals with a new diagnosis of HCV infection made between January 2010 and January 2012. We also analyzed patient flow through new care pathways and compared this with our baseline study of identical design. Results. A total of 28 980 samples were tested for anti-HCV antibody during the study period and yielded 273 unique patients with a new diagnosis of HCV infection. Of these, 38% were tested in general practice, 21% were tested in substance misuse services, 23% were tested in secondary care, and 18% were tested in local prisons. Overall, 80% of patients were referred to specialist clinics, 70% attended for assessment, and 38% commenced treatment, in comparison to 49%, 27%, and 10%, respectively, in the baseline study. Referral rates from all testing sources improved. Conclusions. This study provides timely evidence that progression through care pathways can be enhanced, and it demonstrates reduction of key barriers to eradication of HCV.

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