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Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator-activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.
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OBJECTIVES: To explore the contribution of avoidable mortality to life expectancy inequalities in Wales during 2002-2020. DESIGN: Observational study. SETTING: Wales, 2002-20, including early data from the COVID-19 pandemic. METHODS: We used routine statistics for 2002-2020 on population and deaths in Wales stratified by age, sex, deprivation quintile and cause of death. We estimated the contribution of avoidable causes of death and specific age-categories using the Arriaga decomposition method to highlight priorities for action. RESULTS: Life expectancy inequalities rose 2002-20 amongst both sexes, driven by serial decreases in life expectancy amongst the most deprived quintiles. The contributions of amenable and preventable mortality to life expectancy inequalities changed relatively little between 2002 and 2020, with larger rises in non-avoidable causes. Key avoidable mortality conditions driving the life expectancy gap in the most recent period of 2018-2020 for females were circulatory disease, cancers, respiratory disease and alcohol- and drug-related deaths, and also injuries for males. CONCLUSIONS: Life expectancy inequalities widened during 2002-20, driven by deteriorating life expectancy in the most deprived quintiles. Sustained investment in prevention post-COVID-19 is needed to address growing health inequity in Wales; there remains a role for the National Health Service in ensuring equitable healthcare access to alongside wider policies that promote equity.
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COVID-19 , Pandemias , Masculino , Feminino , Humanos , Causas de Morte , País de Gales/epidemiologia , Medicina Estatal , Expectativa de Vida , MortalidadeRESUMO
This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK.
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Hospitalização , Hepatopatias/prevenção & controle , Diagnóstico Precoce , Humanos , Hepatopatias/diagnóstico , Reino UnidoRESUMO
BACKGROUND: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS: In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS: We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.
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PURPOSE OF STUDY: This study examines the associations between dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) and gastrointestinal bleeding (GIB), to explore possible predictors of outcomes. STUDY DESIGN: Retrospective analysis of 3342 patients who underwent PCI between 1 August 2011 and 31 December 2018 in a single centre was carried out. Oesophagogastroduodenoscopies (OGDs) for patients 12 months post-PCI were analysed. RESULTS: Blood loss occurred in 2% of all (3342) patients post-PCI within 12 months. 128 patients (63% male, mean age (SD) of 69.8 (10) years) who had PCI subsequently underwent an OGD within 12 months of the index PCI procedure. GIB occurred within the first 30 days of DAPT in 36% (n=13/36) of cases. There were no thrombotic events associated with cessation of one antiplatelet agent. Increased age, haemoglobin (Hb) ≤109 g/L and Glasgow-Blatchford score ≥8 were associated with increased 12-month mortality. An Hb drop of ≥30 g/L was a sensitive and specific marker for significant pathology and evidence of bleeding on OGD (sensitivity=0.83, specificity=0.81). CONCLUSIONS: GIB bleeding occurred infrequently in the patients post-PCI on DAPT. Risk assessment scores (such as Glasgow-Blatchford and Rockall scores) are useful tools to assess the urgency of OGD and need for endoscopic therapy.
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Intervenção Coronária Percutânea , Idoso , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.
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Alcoolismo/epidemiologia , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Obesidade/epidemiologia , Bebidas Alcoólicas/economia , Alcoolismo/complicações , Alcoolismo/terapia , Comércio , Redes Comunitárias/organização & administração , Comorbidade , Efeitos Psicossociais da Doença , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Legislação sobre Alimentos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Transplante de Fígado/estatística & dados numéricos , Obesidade/complicações , Pacotes de Assistência ao Paciente , Escócia , Reino Unido/epidemiologiaRESUMO
This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63â000 preventable deaths over the next 5 years, is to be addressed.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Hepatite Viral Humana/complicações , Hepatopatias Alcoólicas/epidemiologia , Obesidade/complicações , Humanos , Hepatopatias Alcoólicas/economia , Hepatopatias Alcoólicas/terapia , Reino Unido/epidemiologiaRESUMO
This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.
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Política de Saúde , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Bebidas Alcoólicas/economia , Comorbidade , Custos e Análise de Custo , Erradicação de Doenças , Progressão da Doença , Feminino , Indústria Alimentícia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/prevenção & controle , Mortalidade Hospitalar , Humanos , Hepatopatias/mortalidade , Hepatopatias Alcoólicas/epidemiologia , Hepatopatias Alcoólicas/prevenção & controle , Manobras Políticas , Masculino , Neoplasias/epidemiologia , Obesidade/epidemiologia , Obesidade/prevenção & controle , Prevalência , Reino Unido/epidemiologiaRESUMO
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.
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Biomarcadores/sangue , Hepatopatias/diagnóstico , Algoritmos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Gerenciamento Clínico , Medicina Baseada em Evidências/métodos , Humanos , Hepatopatias/etiologia , Hepatopatias/terapia , Testes de Função Hepática/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fatores de RiscoRESUMO
BACKGROUND & AIMS: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103). RESULTS: Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was ≥1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%-27%. When documented, ≥1 antibody was present in 83%. LKM-1-positive and autoantibody-negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH. CONCLUSIONS: This cohort from across the UK is older than other multicentre AIH cohorts. One-fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third and rosettes and emperipolesis were infrequently reported.
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Hepatite Autoimune/diagnóstico , Hepatite Autoimune/epidemiologia , Cirrose Hepática/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Criança , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Reino Unido/epidemiologia , Adulto JovemRESUMO
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.
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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 JovemRESUMO
Reports of pregnancy in liver transplantation (LT) patients have largely favorable outcomes. Concerns remain with regards to maternal and graft risk, optimal immunosuppression (IS), and fetal outcomes. We review all post-LT pregnancies at our center with regard to the outcomes and safety for the patient, graft, and fetus. A total of 117 conceptions occurred in 79 patients. Median age at conception was 29 years. Maternal complications included graft loss (2%), acute cellular rejection (ACR; 15%), pre-eclampsia/eclampsia (15%), gestational diabetes (7%), and bacterial sepsis (5%). ACR was significantly more common in those women who conceived within 12 months of LT (P = 0.001). The live birth rate was 73%. Prematurity occurred in 26 (31%) neonates, and 24 (29%) neonates were of low or very low birth weight. IS choice (cyclosporine versus tacrolimus) had no significant effect on pregnancy outcomes and complications. No congenital abnormalities occurred, and only 1 child born at 24 weeks had delayed developmental milestones. In conclusion, pregnancy following LT has a favorable outcome in the majority, but severe maternal risks remain. Patients should be counseled with regard to the above information so informed decisions can be made, and pregnancy must be considered high risk with regular monitoring by transplant clinicians and specialist obstetricians.
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Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Fígado , Complicações na Gravidez/etiologia , Adulto , Aloenxertos , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/efeitos adversos , Nascido Vivo , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Londres , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/mortalidade , Taxa de Gravidez , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: No standardised definition exists for acute, severe AIH (AS-AIH). However, rapid identification of AS-AIH and early corticosteroid therapy may prevent the need for liver transplantation (LT). We set out to determine the clinical outcomes of patients with AS-AIH presenting to our institution with particular focus on the role of corticosteroids. METHODS: Retrospective analysis of a prospectively collated database identified patients presenting with AS-AIH from 1999 to 2009. We defined AS-AIH as an acute presentation with an INR of ⩾1.5 at any time without histological evidence of cirrhosis. RESULTS: 32 patients were identified with AS-AIH. Among the 32 AS-AIH patients 23 were treated with corticosteroids of whom 10 (48%) required LT, whilst all 9 untreated patients required LT (p = 0.01). Untreated patients demonstrated higher MELD scores at presentation (34 vs. 28 p = 0.01) and a non-significant decrease in episodes of sepsis but no difference in sepsis or mortality was observed between untreated or treated patients (11% vs. 26% p = 0.6 and 22% vs. 17% p = 0.99 respectively). Among treated patients, no difference in MELD scores was observed between responders or failures. Despite 59% undergoing LT, six deaths (19%) occurred. CONCLUSION: In a well characterised cohort of patients with AS-AIH, almost 60% required LT and 20% died. There was no difference in prognostic scores between steroid responders and failures and steroid exposure did not appear to jeopardise survival. Patients with AS-AIH should be considered for a trial of corticosteroids expediently whilst a thorough search for sepsis and assessment for LT should occur if clinical deterioration or encephalopathy develops.
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Corticosteroides , Encefalopatia Hepática , Hepatite Autoimune , Transplante de Fígado/estatística & dados numéricos , Sepse , Doença Aguda , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Intervenção Médica Precoce/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/prevenção & controle , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/mortalidade , Hepatite Autoimune/fisiopatologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Testes de Função Hepática/métodos , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/etiologia , Sepse/prevenção & controle , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
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.
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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 JovemRESUMO
Advanced cirrhosis confers a significant symptom burden and has a 50% 2-year mortality rate in those with decompensated disease. There is increasing demand for supportive and palliative care (SAPC) for these patients, yet no consensus on the best model of delivery. It is necessary to identify the needs of such patients and their carers, and evaluate whether they are being met.A literature search was conducted using key words pertaining to adult patients with liver cirrhosis and their SAPC needs. Study quality was assessed and findings grouped by theme. 51 full texts were selected for inclusion, 8 qualitative studies, 33 quantitative studies, 7 systematic reviews, 2 mixed methods studies and 1 Delphi methods. Key findings were grouped into three main themes: SAPC needs, access to SAPC and models of care.Patients with cirrhosis have significant psychological and physical symptom burden with many unmet needs. These data failed to identify the best service model of care. The impact of specialist palliative care (SPC) referral was limited by small numbers and late referrals. With the majority of studies conducted in the USA, it is unclear how well these findings translate to other healthcare systems. Comparison between hepatology led services and SPC was limited by inconsistent outcome measures and prevented pooling of data sets. These data also had limited evaluation of patient-reported outcome measures. We propose the development of a core outcome set to ensure consistent and meaningful evaluation of the SAPC needs of patients with advanced non-malignant liver cirrhosis.
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Background & Aims: Guidelines for the management of primary biliary cholangitis (PBC) were published by the British Society of Gastroenterology in 2018. In this study, we assessed adherence to these guidelines in the UK National Health Service (NHS). Methods: All NHS acute trusts were invited to contribute data between 1 January 2021 and 31 March 2022, assessing clinical care delivered to patients with PBC in the UK. Results: We obtained data for 8,968 patients with PBC and identified substantial gaps in care across all guideline domains. Ursodeoxycholic acid (UDCA) was used as first-line treatment in 88% of patients (n = 7,864) but was under-dosed in one-third (n = 1,964). Twenty percent of patients who were UDCA-untreated (202/998) and 50% of patients with inadequate UDCA response (1,074/2,102) received second-line treatment. More than one-third of patients were not assessed for fatigue (43%; n = 3,885) or pruritus (38%; n = 3,415) in the previous 2 years. Fifty percent of all patients with evidence of hepatic decompensation were discussed with a liver transplant centre (222/443). Appropriate use of second-line treatment and referral for liver transplantation was significantly better in specialist PBC treatment centres compared with non-specialist centres (p <0.001). Conclusions: Poor adherence to guidelines exists across all domains of PBC care in the NHS. Although specialist PBC treatment centres had greater adherence to guidelines, no single centre met all quality standards. Nationwide improvement in the delivery of PBC-related healthcare is required. Impact and implications: This population-based evaluation of primary biliary cholangitis, spanning four nations of the UK, highlights critical shortfalls in care delivery when measured across all guideline domains. These include the use of liver biopsy in diagnosis; referral practice for second-line treatment and/or liver transplant assessment; and the evaluation of symptoms, extrahepatic manifestations, and complications of cirrhosis. The authors therefore propose implementation of a dedicated primary biliary cholangitis care bundle that aims to minimise heterogeneity in clinical practice and maximise adherence to key guideline standards.
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The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials.
Assuntos
Terminologia como Assunto , Humanos , Fígado Gorduroso/classificação , Hepatopatia Gordurosa não Alcoólica/classificação , Gastroenterologia , Fígado Gorduroso Alcoólico/classificação , Fatores de Risco , Estigma SocialRESUMO
Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.
Assuntos
Continuidade da Assistência ao Paciente , Disparidades em Assistência à Saúde , Hepatopatias , Humanos , Hepatopatias/terapia , Doença Crônica , Transplante de Fígado , Equidade em Saúde , Acessibilidade aos Serviços de Saúde , Cirrose Hepática/terapiaRESUMO
BACKGROUND: Liver disease incidence and hence demand on hepatology services is increasing. AIM: To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services. METHODS: The registry is populated by International Classification of Diseases-10 (ICD-10) code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019. Pseudo-anonymised linkage of: (1) Causative diagnoses; (2) Cirrhosis; (3) Portal hypertension; (4) Decompensation; and (5) Liver cancer diagnoses enabled tracking liver disease progression. RESULTS: The population of Wales in 2019 was 3.1 million. Between 1999 and 2019 73054 individuals were diagnosed with a hepatic disorder, including 18633 diagnosed with cirrhosis, 10965 with liver decompensation and 2316 with hepatocellular carcinoma (HCC). Over 21 years the incidence of liver diseases increased 3.6 fold, predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease (NAFLD); the leading cause of liver disease from 2014. The incidence of cirrhosis, decompensation, HCC, and all-cause mortality tripled. Liver-related mortality doubled. Alcohol-related liver disease (ArLD), autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality. CONCLUSION: A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years. Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD. Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.