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1.
J Viral Hepat ; 31(2): 66-77, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38018328

RESUMO

Achieving hepatitic C virus (HCV) elimination requires linking people who use drugs (PWUD) into care. We report final direct-acting antivirals (DAAs)-based outcomes from the Integrated-Test-stage -Treat (ITTREAT) study. Project ITTREAT (2013-2021), based at an addiction centre, was a 'one-stop' service with innovative linkage to care strategies. Primary outcome was sustained virological response (SVR12) (intention to treat ITT) including whether individuals were recruited in first (period 1) versus last four (period 2 included the COVID-19 pandemic) years of the study. Number recruited were n = 765, mean age 40.9 ± 10.1 years, 78% males, history of current/past injecting drug use (IDU) and alcohol use being 77% and 90%, respectively. Prevalence of a positive HCV PCR was 84% with 19% having cirrhosis. Comparing those recruited in period 2 versus period 1, there was increasing prevalence of IDU, 90% versus 72% (p < .001); homelessness, 67% versus 50% (p < .001); psychiatric diagnosis, 84% versus 50% (p < .001); overdose history 71% versus 31% (p < .001), receiving opioid agonist treatment (OAT) 75% versus 52% (p < .001) and comorbidity 44% versus 25% (p < .001). Of those treated with DAAs (n = 272), ITT SVR rates were 86% (95% CI: 81%-90%), being similar in period 2 versus period 1. Predictors of non-SVR were receiving OAT (OR 0.33, 95% CI: 0.12-0.87, p = .025) and ≥80% adherence (OR 0.01, 95% CI: 0.003-0.041, p < .001). Reinfection rates period 2 versus period 1 (per 100 person-years) were 1.84 versus 1.70, respectively. In the treated cohort, mortality was 15%, being mostly drug-related. Despite increasing complexity of PWUD, high SVR12 rates are achievable with use of OAT and good adherence.


Assuntos
Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Hepacivirus/genética , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Pandemias , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia
2.
J Hepatol ; 79(5): 1236-1253, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37419393

RESUMO

Patients with advanced chronic liver disease have a complex symptom burden and many are not candidates for curative therapy. Despite this, provision of palliative interventions remains woefully inadequate, with an insufficient evidence base being a contributory factor. Designing and conducting palliative interventional trials in advanced chronic liver disease remains challenging for a multitude of reasons. In this manuscript we review past and ongoing palliative interventional trials. We identify barriers and facilitators and offer guidance on addressing these challenges. We hope that this will reduce the inequity in palliative care provision in advanced chronic liver disease.

3.
Liver Int ; 43(4): 917-927, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36708150

RESUMO

BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Cirrose Hepática/terapia , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/tratamento farmacológico , Hepacivirus , Reino Unido/epidemiologia , Antivirais/uso terapêutico , Resposta Viral Sustentada
4.
Liver Int ; 42(3): 628-639, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34846794

RESUMO

BACKGROUND/AIMS: Community-based assessment and management of chronic liver disease (CLD) in people who are homeless (PWAH) remain poorly described. We aimed to determine prevalence/predictors of CLD in PWAH and assess the performance of non-invasive liver fibrosis and injury markers. METHODS: The Vulnerable Adult LIver Disease (VALID) study provided a "one-stop" liver service based at homeless hostels. Our primary outcome was the prevalence of clinically significant hepatic fibrosis (CSHF; liver stiffness measurement (LSM) ≥8 kPa). RESULTS: Total individuals recruited were 127, mean ± SD age 47 ± 9.4 years, 50% (95% CI 41%-59%) and 39% (95% CI 31%-48%) having alcohol dependence and a positive HCV RNA respectively. CSHF was detected in 26% (95% CI 17%-35%), independent predictors being total alcohol unit/week (OR 1.01, 95% CI 1.00-1.02, P = .002) and HCV RNA positivity (OR 2.93, 95% CI 1.12-7.66, P = .029). There was moderate agreement between LSM and Enhanced Liver Fibrosis (ELF) score (kappa 0.536, P < .001) for CSHF as assessed by LSM ≥8 kPa. Those with CSHF had significantly higher levels of IFN-γ (P = .002), IL-6 (P = .001), MMP-2 (P = .006), ccCK-18 (P < .001) and ELF biomarkers (P < .001), compared to those without CSHF. Service uptake was ≥95%. Direct acting antiviral (DAA) treatment completion was 93% (95% CI 77%-99%), sustained virological response (SVR) being 83% (95% CI 64%-94%). CONCLUSION: There is a significant liver disease burden from HCV and alcohol in PWAH. Non-invasive liver fibrosis and injury markers can help in identifying such individuals in the community. Despite a challenging cohort, excellent service uptake and high DAA-based SVRs can be achieved.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite C Crônica , Adulto , Antivirais/uso terapêutico , Biomarcadores , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Pessoa de Meia-Idade
5.
Gut ; 70(1): 9-29, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33067334

RESUMO

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.


Assuntos
Ascite/diagnóstico , Ascite/terapia , Cirrose Hepática/complicações , Ascite/etiologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/terapia
6.
J Viral Hepat ; 27(2): 176-187, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31566851

RESUMO

Achieving hepatitis C virus (HCV) elimination by 2030 requires an increased linkage to care for people who inject drugs (PWID). Project ITTREAT was established to mitigate barriers to HCV care by providing an integrated service within a local drug and alcohol treatment centre. This study aimed to explore the experiences of clients and staff involved in Project ITTREAT and assess the facilitators and barriers to a community-based HCV service. Between October 2014 and April 2016, drug and alcohol treatment attendees were interviewed using one-to-one semi-structured interviews. Drug and alcohol treatment staff took part in focus groups. All data were recorded, transcribed verbatim and analysed using thematic content analysis. Fifteen drug and alcohol treatment attendees with current/previous HCV infection were interviewed, and 15 staff members contributed across two focus groups. Drug and alcohol treatment staff and attendees reported that Project ITTREAT facilitated access to HCV care by mitigating previous negative hospital-based experiences. Other key facilitators were positive narratives around HCV care, and drug and alcohol treatment attendees being well engaged in their drug/alcohol recovery. Barriers included a lack of stability in drug and alcohol treatment attendees, negative discourse around testing/treatment and stigma associated with attending the drug and alcohol treatment to access HCV treatment in some who had successfully achieved drug rehabilitation. Our findings indicate the positive impact of an integrated and personalized community-based service delivered by a dedicated hepatitis nurse. This played a crucial role in reducing barriers to HCV care for PWID. Our work also highlights areas for future investment including non-DAT-based community services and increasing awareness of new treatments amongst this cohort.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Acessibilidade aos Serviços de Saúde , Hepatite C/terapia , Abuso de Substâncias por Via Intravenosa/terapia , Abuso de Substâncias por Via Intravenosa/virologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estigma Social , Reino Unido
7.
Liver Int ; 40(5): 1021-1031, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32048798

RESUMO

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) provide an unprecedented opportunity for a "find-and-treat strategy." We aimed to report real-world clinical, patient reported and health economic outcomes of community-based hepatitis C virus (HCV) screening/treatment in people who use drugs (PWUDs). METHODS: Project ITTREAT (2013-2021), established at a drug and alcohol treatment centre, offered a comprehensive service. Generic (SF-12v2 and EQ-5D-5L) and liver-specific (SFLDQoL) health-related quality of life (HRQoL) were assessed before and after HCV treatment. Costs/case detected and cured were calculated. Primary outcome measure was sustained virological response (SVR) (intention to treat). RESULTS: Till March 2018, 573 individuals recruited, 462 (81%) males, mean age 40.5 ± 10.0 years. Of the 125 treated, 115 (92%) had past/current history of injecting drug use, 88 (70%) were receiving opioid agonist treatment and 50 (40%) were homeless. Twenty-six per cent received interferon-based and 74% DAA-only regimens. SVR (ITT) was 87% (90% with DAAs). Service uptake/HCV treatment completion rates were >95%, HCV reinfection being 2.63/100 person years (95% CI 0.67-10.33). HRQoL improved significantly at end of treatment (EOT) in those with SVR: SFLDQoL (symptoms, memory, distress, loneliness, hopelessness, sleep and stigma) (P

Assuntos
Hepatite C Crônica , Hepatite C , Preparações Farmacêuticas , Adulto , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
8.
J Med Virol ; 91(11): 1979-1988, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31329295

RESUMO

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Reino Unido
9.
Liver Int ; 39(9): 1594-1607, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152623

RESUMO

BACKGROUND & AIMS: The incidence and mortality from end-stage liver disease is increasing, with a minority eligible for liver transplantation. Ascites is the commonest complication of end-stage liver disease and large volume paracentesis (LVP) the accepted management strategy where refractory to medical treatment. In malignant ascites, permanent indwelling peritoneal catheters (PIPC) are an established palliative intervention. The aims are to describe available data using permanent indwelling peritoneal catheters in refractory ascites due to end-stage liver disease. METHODS: Using systematic review methodology, databases were searched (MEDLINE, EMBASE, CINAHL [The Cumulative Index to Nursing and Allied Health Literature], Google Scholar and Cochrane Database of Systematic Reviews from inception-March 2018), for studies combining ascites and palliative care. Inclusion and exclusion criteria were applied to results. RESULTS: Following initial and updated searches, 225 studies were identified for full text review, 18 were eligible for final analysis. The studies displayed heterogeneity in design, reported on different indwelling catheters and were overall of low quality. Only one pilot randomised controlled trial was identified, of PIPC versus LVP, recruiting one patient into each arm. Technical insertion success was 100%, with low rates of non-infectious complications (<12%), none life threatening. Rates of bacterial peritonitis were not unacceptably high (12.7%), considering this was an end-stage liver disease population and only a minority utilising long-term prophylactic antibiotics. Only one study attempted quality-of-life assessments; none addressed potential health economic benefits. CONCLUSIONS: Despite lack of well-designed studies, preliminary data suggests low significant complication rates; however safety and efficacy of permanent indwelling peritoneal catheters in end-stage liver disease remains to be confirmed. Further prospective randomised controlled trials are warranted, potentially translating permanent indwelling peritoneal catheters into improved palliative care in end-stage liver disease.


Assuntos
Ascite/terapia , Cateteres de Demora , Drenagem/instrumentação , Doença Hepática Terminal/terapia , Cuidados Paliativos/métodos , Antibioticoprofilaxia , Ascite/etiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Cateteres de Demora/efeitos adversos , Drenagem/efeitos adversos , Humanos , Paracentese/efeitos adversos , Peritonite/complicações , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Clin Gastroenterol Hepatol ; 15(12): 1950-1956.e1, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28603052

RESUMO

BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.


Assuntos
Hepatite Autoimune/tratamento farmacológico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Adolescente , Adulto , Idoso , Canadá , Criança , China , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
11.
Liver Int ; 37(3): 449-457, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27541063

RESUMO

BACKGROUND: Concurrent extrahepatic autoimmune disease (CEHAID) associated with autoimmune hepatitis (AIH) have been incorporated into the diagnostic criteria stipulated by the International Autoimmune Hepatitis Group (IAIHG). Large comprehensive cohort data on the extrahepatic autoimmunity in AIH remain scanty. AIM: To systematically assess features and clinical impact of CEHAID on AIH. METHODS: Clinical records of 562 patients with AIH from two tertiary centres in the UK were retrospectively reviewed. RESULTS: Prevalence of CEHAID in patients with AIH was 42%. Autoimmune thyroid disease was the commonest CEHAID associated with AIH (101/562, 18%). Autoimmune skin diseases were more prevalent in AIH-2 than AIH-1 (21.9% vs 7%, P=.009). Personal history of CEHAID was more commonly found in AIH patients with than without first-degree family history of CEHAID [48/86 (55.8%) vs 169/446 (37.9%), P=.002]. AIH patients with CEHAID were more often women (85.2% vs 76.1%, P=.008), had higher post-treatment IAIHG score (22 vs 20, P<.001), less reactivity to smooth muscle antibodies (49.8% vs 65%, P<.001), more likely to have mild fibrosis at diagnosis (20.9% vs 6.5%, P<.001) and less often had ascites (6.3% vs 13.6%, P=.008) and coagulopathy (1.18 vs 1.27, P=.013) at presentation. Presence of CEHAID, however, did not significantly affect disease progression, prognosis and survival in AIH. CONCLUSIONS: Our study confirms the strong association of CEHAID with AIH. Association between personal and familial extrahepatic autoimmunity especially among first-degree relatives was evident. Presence of CEHAID may influence clinical phenotype of AIH at presentation, but without notable impact on the long-term clinical outcomes.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Hepatite Autoimune/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/classificação , Criança , Pré-Escolar , Bases de Dados Factuais , Progressão da Doença , Saúde da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Reino Unido/epidemiologia , Adulto Jovem
12.
Palliat Med ; 31(7): 671-675, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27707955

RESUMO

BACKGROUND: Ascites, the commonest complication of cirrhosis, leads to frequent hospitalisations. Refractory ascites confers a median survival of 6 months without liver transplantation. In many, the management remains palliative (large-volume paracentesis). Despite calls for improvement, palliative and end-of-life care is not yet integrated into end-stage liver disease. Long-term abdominal drains are a palliative strategy in malignant ascites, but not end-stage liver disease. CASE PRESENTATION: A retrospective, single centre, case series review was performed of patients undergoing long-term abdominal drain placement for refractory ascites secondary to end-stage liver disease at a large teaching hospital between August 2011 and March 2013. Case management: Patients with end-stage liver disease and refractory ascites, where liver transplantation was not an option, were considered for long-term abdominal drains. Seven patients underwent successful long-term abdominal drain insertion after multi-professional assessment. Case outcome: Following long-term abdominal drain insertion, mean hospital attendances reduced to 1 (0-4) from 9 (4-21), with none for ascites management. Median survival after long-term abdominal drain insertion was 29 days (8-219). The complication rate was low and none life threatening. CONCLUSION: Palliative and end-of-life care needs in end-stage liver disease remain under-addressed. Our data suggest that long-term abdominal drains may be a safe and effective palliative intervention in end-stage liver disease. Prospective randomised controlled trials comparing large-volume paracentesis versus long-term abdominal drains in refractory ascites secondary to end-stage liver disease are warranted.


Assuntos
Ascite/etiologia , Ascite/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Cuidados Paliativos/métodos , Paracentese/métodos , Assistência Terminal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
15.
AIDS Care ; 28(12): 1522-1527, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27263666

RESUMO

Recent advances in antiviral therapy have improved outcomes in HIV-positive individuals co-infected with hepatitis B and C virus (HBV/HCV). Our aim was to assess prevalence and predictors of chronic liver disease (CLD) due to the metabolic syndrome (MS), alcohol and antiretrovirals (ARVs) use in HIV-monoinfected individuals. This was a retrospective cohort study (2005-2012). HIV-positive patients with negative HBV/HCV serology and at least two elevated alanine aminotransferase (ALT) levels six months apart were included. Data are presented as mean ± SD or percentage. Despite negative viral serology, 27% (1047/3872) of HIV-positive individuals had persistently elevated ALT. Only 243 (23.2%) were investigated (by imaging in the majority, only 58 undergoing liver biopsy/transient elastography). CLD was identified in 66.2%, this being clinically significant in one in four individuals. Potential CLD risk factors were alcohol (44.2%), hepatotoxic ARVs (74.1%) and MS risk factors (68%) with 68.7% having >1 risk factor. On multivariate logistic regression analysis serum triglyceride (OR 1.482, 95% CI 1.053-2.086, p = .024) was the only independent predictor of CLD. Overall, 4.3% were referred to Hepatology services. In conclusion, less than 6% of HIV-monoinfected individuals with persistently elevated ALT undergo objective assessment of hepatic fibrosis. Despite non-stringent criteria, some degree of non-viral CLD is identified in approximately two-thirds of those investigated, risk factors being synonymous with those for the MS. This increasing yet under-recognised non-viral CLD burden warrants timely recognition to prevent long-term morbidity and mortality.


Assuntos
Alcoolismo/complicações , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/complicações , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Síndrome Metabólica/complicações , Adulto , Alanina Transaminase/sangue , Doença Crônica , Feminino , Humanos , Hepatopatias/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos/sangue
16.
Hepatol Res ; 46(3): E79-88, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25943838

RESUMO

AIM: Drug-induced autoimmune hepatitis (DIAIH) remains poorly characterized. Our aim was to assess natural history and outcomes in DIAIH. METHODS: This was a retrospective cohort study. RESULTS: Eighty-two patients with autoimmune hepatitis (AIH) were identified, 11 (13.4%) with DIAIH, implicated drugs being nitrofurantoin (n = 4), statins (n = 4), herbal remedies (n = 2) and diclofenac (n = 1). Female sex, acute onset, elevated serum globulins/immunoglobulin G, fibrosis stage (Ishak), cirrhosis at onset, moderate-severe portal inflammation, interface and lobular hepatitis, remission, relapse and poor outcome were similar in those with DIAIH and AIH (P > 0.05). The former were however more likely to be aged 60 years or more and take longer to relapse on immunosuppression discontinuation (P = <0.05). On Kaplan-Meier analysis, probability of poor outcome was similar in those with DIAIH and AIH (log-rank test, 0.339). On comparing those with (n = 4) and without nitrofurantoin (n = 7) DIAIH, the former were older, had longer duration of drug use prior to DIAIH diagnosis, higher fibrosis stage and were less likely to relapse upon immunosuppression discontinuation. CONCLUSION: Approximately 15% of patients with AIH have DIAIH with similar outcomes, although the latter are older with a propensity for late relapse, mandating long-term follow up.

17.
Ann Hepatol ; 15(2): 277-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26845607

RESUMO

 Multiple genetic and environmental factors interact to determine an individual's predisposition to non-alcoholic fatty liver disease and its phenotypic characteristics. Association studies have found a number of alleles associated with the development of non-alcoholic steatohepatitis. Our aim was to investigate whether multiple risk-associated alleles may be present in affected monozygotic twins, indicating underlying genetic predisposition to non-alcoholic steatohepatitis. We determined the genotype of 14 candidate gene polymorphisms (at 11 unlinked loci) in a set of monozygotic twins who presented with cirrhosis within 18 months of each other. Genotyping revealed multiple single nucleotide polymorphisms at 9 independent loci in genes PNPLA3, APOC3, GCKR, TRIB1, LYPLAL1, PPP1R3B, COL13A1, and EFCAB4B, previously implicated in contributing to non-alcoholic steatohepatitis pathogenesis. In conclusion, this case series illustrates the potential cumulative effect of multiple polymorphisms in the development and potential progression of a complex trait such as NASH cirrhosis.


Assuntos
Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/genética , Gêmeos Monozigóticos/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Apolipoproteína C-III/genética , Proteínas de Ligação ao Cálcio/genética , Colágeno Tipo XIII/genética , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipase/genética , Cirrose Hepática/etiologia , Lisofosfolipase/genética , Masculino , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Polimorfismo de Nucleotídeo Único , Proteína Fosfatase 1/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética
18.
Lancet ; 382(9902): 1433-44, 2013 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-23768844

RESUMO

Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.


Assuntos
Hepatite Autoimune/imunologia , Adolescente , Adulto , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Criança , Modelos Animais de Doenças , Feminino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/terapia , Humanos , Tolerância Imunológica/imunologia , Complexo Principal de Histocompatibilidade/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Linfócitos T/imunologia , Adulto Jovem
19.
AJR Am J Roentgenol ; 203(3): 643-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25148170

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease is associated with hepatic inflammation. An emerging technique to image inflammation is PET using the glucose tracer, (18)F-FDG. The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte. MATERIALS AND METHODS: Hepatic FDG uptake, as SUV = [voxel counts / administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate, SUVmax) and average SUV ( SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLV). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). RESULTS: The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUVave. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. CONCLUSION: FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Simulação por Computador , Fluordesoxiglucose F18/sangue , Humanos , Modelos Biológicos , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Regulação para Cima
20.
Int J Palliat Nurs ; 30(6): 286-293, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38913640

RESUMO

BACKGROUND: Palliative care is often suboptimal for patients with end-stage liver disease (ESLD). Ascites remains the most common complication in ESLD. Though long-term abdominal drains (LTAD) are commonly used in refractory malignant ascites, the standard care for ESLD is hospital drainage (large volume paracentesis (LVP)). There is an ongoing National Institute for Health and Care Research (NIHR) funded trial (REDUCe 2 Study) (ISRCTN269936824) comparing palliative LTAD to LVP in ESLD. This 35-site trial is being conducted in England, Scotland and Wales. AIM: To understand the views and experience of healthcare professionals (HCP) on the use of palliative LTAD in ESLD. METHODS: An electronic survey comprised of seven questions with fixed quantitative options and three exploratory questions was used between August-December 2019. The survey was distributed electronically via the British Association for Study of Liver newsletter and to relevant hospital departments in Southeast England and Northeast London. An email reminder was sent at 4 and 8 weeks after the initial invitation to the survey. RESULTS: There were 211 respondents (hepatologists (36.5%), specialist nurses (24.6%), gastroenterologists (16.6%), trainees (17%) and others (5.2%)). All respondents had access to LVP, 86% to a transjugular intrahepatic portosystemic shunt procedure for patients, 67% to LTADs and 10% to other options, such as the automated low-flow ascites (ALFA) pump. The majority of respondents to the survey (68%) reported their experience of using LTAD. Almost all respondents (91%) were willing to consider LTAD in ESLD. However, the main deterrents of this were the perceived risk of infection (90%), followed by LTAD management in community (57%). Some 51% of those with prior experience of using LTAD reported clinical complications for patients (including bleeding, infection and renal impairment), 41% reported technical issues and 35% inadequate community support. CONCLUSIONS: Almost all HCPs are willing to consider palliative LTAD in refractory ascites due to ESLD, but the main deterrents are the perceived infection risk and lack of published data to guide community management. The REDUCe 2 trial will clarify if these concerns are real and provide conclusive evidence on role, if any, of palliative LTADs in this vulnerable and under researched cohort with ESLD.


Assuntos
Ascite , Cirrose Hepática , Cuidados Paliativos , Humanos , Ascite/terapia , Ascite/etiologia , Cuidados Paliativos/métodos , Cirrose Hepática/complicações , Feminino , Masculino , Inquéritos e Questionários , Paracentese , Pessoa de Meia-Idade , Drenagem
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