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Esophageal varices are dilated submucosal esophageal veins that connect the portal and systemic circulations. Bleeding esophageal varices is a well-recognized complication of liver cirrhosis.It is known that in active variceal bleeding, treatment needs to be started promptly. Treatments comprise band ligation, sclerotherapy, removable stent placement, balloon tamponade, and transjugular intrahepatic portosystemic shunt (TIPS).We report a case in which hemodynamic stability can be maintained with the use of Purastat to control bleeding.
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Background: Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals. Methods: Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool. Results: Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH: in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital. Conclusion: Management of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.
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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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BACKGROUND: The low FODMAP diet (LFD) is effective in managing irritable bowel syndrome (IBS) in the short term. This study assessed the long-term effect of the LFD on symptoms, nutritional composition and socialising. METHODS: Patients with IBS who received dietetic-led LFD advice were approached at long term follow up (>6 months post LFD advice) from six centres across the United Kingdom. Participants completed questionnaires assessing gastrointestinal symptoms, adherence, nutritional intake, dietary acceptability and food related quality of life (QOL). RESULTS: 205 participants completed the study, with a mean follow up of 44 months (3.7 years). Adequate symptom relief was noted in 60% of individuals at long term follow up, with 76% being on the personalisation phase of the LFD (pLFD). Mean nutritional intake did not differ between individuals on the pLFD versus habitual diet, with no difference in fructan intake (2.9â¯g/d vs 2.9â¯g/d, pâ¯=â¯0.96). The majority (80%) of individuals on the pLFD consumed specific 'free-from' products at the long term, with the purchase of gluten or wheat free products being the commonest (68%). CONCLUSION: The majority of patients follow the pLFD in the long term, with a large proportion purchasing gluten or wheat free products to manage their symptoms.
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Dieta com Restrição de Carboidratos/métodos , Dieta Livre de Glúten/métodos , Síndrome do Intestino Irritável/dietoterapia , Adulto , Idoso , Dieta com Restrição de Carboidratos/efeitos adversos , Dieta Livre de Glúten/efeitos adversos , Ingestão de Energia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Reino UnidoRESUMO
PURPOSE: Clinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn's disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events. MATERIALS AND METHODS: A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI ≤4 or pMS <2 with a combined stool frequency and rectal bleeding sub score of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. RESULTS: One hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7-29.6] and 14.1 [QR: 6.0-21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7-15.4] and CD was 9.5 [IQR: 6.1-18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. CONCLUSIONS: Results in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile.
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Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Reino UnidoRESUMO
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
OBJECTIVES: Colonoscopy can be uncomfortable. To increase safety, there is a trend, in the UK, towards reduced sedative use. We aimed to determine factors predictive of discomfort during colonoscopy. METHODS: Prospectively recruited patients were asked to grade anticipated discomfort on a Numeric Rating Scale ranging from 0 to 10. Discomfort scores were recorded every 2 min during the procedure and during peaks of discomfort. An overall discomfort score was recorded. RESULTS: One hundred and nine patients [44 male, 65 female; median 61.5 (21-80) years] were recruited. One hundred and three procedures were completed. Forty-five patients received midazolam [median 2 (1.5-5) mg]. Mean overall Numeric Rating Scale score was 4.7 (men 4.0; women 5.2; P<0.01) and median peak score 7. Discomfort was usually greatest at the beginning of the procedure, while in the sigmoid colon. Discomfort scores were higher in patients with irritable bowel syndrome (P = 0.03); diverticular disease (P<0.01); midazolam (P = 0.02), buscopan (P<0.001) or nitrous oxide (P<0.001) use; endoscope tracker use (P = 0.01); incomplete procedures (P<0.001) or a preceding gastroscopy (P = 0.02), but were not correlated with discomfort during venous cannulation or digital rectal examination. Multivariate analysis showed that female sex, high anxiety, anticipation of high discomfort, longer intubation time and higher endoscopist's grade of procedural difficulty were independent factors significantly related to overall discomfort scores. Recollected discomfort scores 2-3 months later were lower (P<0.01). Low-dose midazolam had no appreciable amnesic effect. CONCLUSION: Factors indicative of difficult colonoscopy, and preceding gastroscopy, are associated with greater discomfort, as are the presence of female sex, irritable bowel, anxiety and anticipated discomfort. Low-dose midazolam neither relieves discomfort nor makes patients forget it. Selected patients may benefit from increased analgesia.
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Dor Abdominal/etiologia , Colonoscopia/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Dor Abdominal/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgesia , Competência Clínica , Colonoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Bladder augmentation using colonic patches is being increasingly performed and a substantial risk of neoplasia in such patches has been reported. We present the case of a 62-year-old man who developed a large flat adenoma in the colonic mucosa of an augmented bladder. The adenoma was indigo-carmine dye sprayed and completely resected via a cystoscope using an endoscopic mucosal resection technique. We discuss how methods used at colonoscopy to detect and remove early neoplastic lesions may readily be employed during colonic patch surveillance at cystoscopy.
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Adenoma/cirurgia , Colo/transplante , Cistoscopia , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Adenoma/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Human defensin (HD)-5 is an antimicrobial peptide expressed in small intestinal Paneth cells, and alterations in HD-5 expression may be important in Crohn's disease (CD) pathogenesis. Levels of HD-5 in Paneth cells and ileostomy fluid from control and CD patients were studied by quantitative immunodot analysis, immunohistochemistry, acid urea-polyacrylamide gel electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western blotting, reverse phase-high performance liquid chromatography, N-terminal amino acid sequencing, and ES-QToF mass spectrometry. In both control and CD patients, HD-5 in Paneth cell extracts was present almost exclusively in the precursor form. HD-5 levels in ileostomy fluid were lower in CD patients (n = 51) than in controls (n = 20): median (range), 7.9 (5.5 to 35.0) microg/ml versus 10.5 (6.0 to 30.4) microg/ml; P = 0.05; this difference was most marked in CD patients with homozygous/compound heterozygous mutations in NOD2 (P = 0.03). In control ileostomy fluid, HD-5 was present in the mature form only. In contrast, CD patient ileostomy fluid contained both precursor and mature forms of HD-5, with the majority present in a complex with trypsin, chymotrypsinogen/chymotrypsin, and alpha1-anti-trypsin. Pro-HD-5 was not associated with trypsin or chymotrypsinogen in Paneth cell extracts. In conclusion, pro-HD-5 in the intestinal lumen is processed by trypsin in a complex in which chymotrypsinogen is also cleaved for activation. The persistence of this complex in CD may be attributable to increased luminal levels of proteinase inhibitors such as alpha1-anti-trypsin.
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Quimotripsinogênio/metabolismo , Doença de Crohn/metabolismo , Defensinas/metabolismo , Mucosa Intestinal/metabolismo , Processamento de Proteína Pós-Traducional , Tripsina/metabolismo , alfa-Defensinas/metabolismo , Adulto , Sequência de Aminoácidos , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Defensinas/farmacocinética , Feminino , Humanos , Ileostomia , Intestino Delgado/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Dados de Sequência Molecular , Complexos Multiproteicos/metabolismo , Precursores de Proteínas/metabolismo , Extratos de Tecidos/metabolismo , alfa 1-Antitripsina/metabolismo , alfa-Defensinas/farmacocinéticaRESUMO
BACKGROUND: In presumed decompensated alcoholic liver disease (ALD; liver decompensation, heavy alcohol intake, and negative results of noninvasive screening for other causes), liver biopsy is often performed to assess severity of liver injury and to rule out other liver diseases. AIM: The aim of the study is to describe the spectrum of liver histology in such patients. METHODS: We reviewed all patients with presumed decompensated ALD seen between 1998 and 2004, in whom liver tissue was available for histology (N = 110). RESULTS: A total of 104 of the 110 patients had at least one of the histological features suggestive of ALD: fat, Mallory's hyalin, neutrophilic infiltrate, and hepatocyte ballooning. These features were more prevalent in tissue obtained within a month after presentation with decompensation than in that obtained before decompensation or more than 1 month after. These features were also associated with more severe liver dysfunction. Histology revealed a major additional diagnosis (Budd-Chiari syndrome) in only one case. In 41 patients biopsied within a month of first presentation with decompensation, Child score and Maddrey discriminant function (DF), but none of the histological features, were predictive of survival by Cox multivariate analysis. Of the 26 of these 41 patients with a Maddrey DF >32, 22 (85%) had alcoholic hepatitis. CONCLUSIONS: In patients with presumed decompensated ALD, other liver diseases are uncommon. Routine liver biopsy is of limited added value but biopsy should be considered in those in whom the noninvasive workup, or failure to recover despite abstinence, raises the possibility of other liver diseases.
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Hepatopatias Alcoólicas/patologia , Adulto , Biópsia , Distribuição de Qui-Quadrado , Feminino , Humanos , Hepatopatias Alcoólicas/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estatísticas não ParamétricasRESUMO
Small bowel bacterial overgrowth (SBBO) is an important and under-recognized clinical syndrome in the elderly. It is the most common cause of malabsorption among older adults. Presentation of SBBO syndrome is often occult, which makes it imperative to maintain a high index of suspicion for this disorder. When symptomatic bacterial overgrowth is appropriately identified and treated there can be positive dramatic results. This article discusses the importance of considering a diagnosis of bacterial overgrowth in those predisposed to its development and the mechanisms by which nutrient malabsorption occurs. Signs and symptoms of bacterial overgrowth, differential diagnosis, investigation, and current treatment options are discussed.
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Bactérias/crescimento & desenvolvimento , Intestino Delgado/microbiologia , Síndromes de Malabsorção/microbiologia , Desnutrição/microbiologia , Idoso , Testes Respiratórios , Diagnóstico Diferencial , HumanosAssuntos
Doenças do Esôfago/etiologia , Gastrostomia/efeitos adversos , Acidente Vascular Cerebral/complicações , Doenças do Esôfago/fisiopatologia , Esfíncter Esofágico Inferior/fisiopatologia , Humanos , Pneumonia Aspirativa/etiologia , Acidente Vascular Cerebral/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: Patients with advanced liver diseases tend to develop a hyperdynamic circulation which complicates cirrhosis. Impairment of nitric oxide (NO) metabolism has been implicated in the pathogenesis of portal hypertension. The aim of this study was to determine nitric oxide synthase (NOS)-dependent whole body NO production in patients with decompensated liver cirrhosis and portal hypertension. MATERIAL AND METHODS: Ten patients with decompensated alcoholic liver disease and portal hypertension (Child-Pugh Classifications B and C with no signs of infection) and 10 age- and gender-matched control subjects received an intravenous infusion of L-[15N]2-arginine (50 micromol/min for 30 min). Urine and serum nitrite and nitrate concentrations were determined using ion chromatography-mass spectrometry. RESULTS: NOS-dependent whole body NO synthesis was estimated by the conversion of [15N]guanidino nitrogen of arginine to urine 15N-nitrite and 15N-nitrate. The amount of 15N-nitrite and 15N-nitrate in the urine of patients and control subjects was significantly correlated with the amount of urine nitrite and nitrate over 36 h (r=0.91 and 0.77, respectively, p<0.0001). However, neither a median of 12 h 15N-nitrite and 15N-nitrate nor nitrite and nitrate excretion in the urine was different between patients and control subjects, 46.4 (9.4-152.2) versus 98.7 (29.9-146.5) nmol/mmol creatinine and 20.6 (2.1-69.0) versus 40.0 (27.0-70.1) micromol/mmol creatinine, respectively. No differences were found in serum nitrite and nitrate concentrations and glomerular filtration rates between patients and control subjects, 111.4 (73.2-158.8) versus 109.3 (83.5-176.4) micromol/l. CONCLUSION: Our results contraindicate a greater basal NOS-dependent whole body NO production in patients with decompensated liver disease and portal hypertension.