Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
Int J Mol Sci ; 24(16)2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37628898

RESUMO

Patients with non-alcoholic steatohepatitis (NASH) show significantly faster progress in the stages of fibrosis compared to those with non-alcoholic fatty liver (NAFL) disease. The non-invasive diagnosis of NASH remains an unmet clinical need. Preliminary data have shown that sphingolipids, especially ceramides, fatty acids, and other lipid classes may be related to the presence of NASH and the histological activity of the disease. The aim of our study was to assess the association of certain plasma lipid classes, such as fatty acids, acylcarnitines, and ceramides, with the histopathological findings in patients with NASH. The study included three groups: patients with NASH (N = 12), NAFL (N = 10), and healthy [non non-alcoholic fatty liver disease (NAFLD)] controls (N = 15). Plasma samples were collected after 12 h of fasting, and targeted analyses for fatty acids, acylcarnitines, and ceramides were performed. Baseline clinical and demographic characteristics were collected. There was no significant difference in baseline characteristics across the three groups or between NAFL and NASH patients. Patients with NASH had increased levels of several fatty acids, including, among others, fatty acid (FA) 14:0, FA 15:0, FA 18:0, FA 18:3n3, as well as Cer(d18:1/16:0), compared to NAFL patients and healthy controls. No significant difference was found between NAFL patients and healthy controls. In conclusion, patients with NASH exhibited a distinctive plasma lipid profile that can differentiate them from NAFL patients and non-NAFLD populations. More data from larger cohorts are needed to validate these findings and examine possible implications for diagnostic and management strategies of the disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Estudos de Casos e Controles , Ceramidas , Ácidos Graxos , Hepatopatia Gordurosa não Alcoólica/diagnóstico
2.
Clin Med (Lond) ; 23(3): 213-218, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37236795

RESUMO

In 2017 the Royal College of Physicians launched a voluntary accreditation process supported by British Association for the Study of the Liver (BASL) and the British Society of Gastroenterologists (BSG) to improve the quality and consistency of liver services across the UK and Ireland. This article describes the approach that we took and the challenges that we met on the way to achieving accreditation.


Assuntos
Acreditação , Fígado , Humanos , Irlanda
3.
World J Transplant ; 12(11): 347-358, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36437846

RESUMO

Coronavirus disease-2019 (COVID-19) has led to a temporary suspension of liver transplant activity across the world and the remodeling of care for patients on the waiting list and transplant recipients with the increasing use of remote consultations. Emerging evidence shows that patients with more advanced liver disease are at increased risk of severe COVID-19 and death, whereas transplant recipients have similar risk with the general population which is mainly driven by age and metabolic comorbidities. Tacrolimus immunosuppression might have a protective role in the post-transplant population. Vaccines that have become rapidly available seem to be safe in liver patients, but the antibody response in transplant patients is likely suboptimal. Most transplant centers were gradually able to resume activity soon after the onset of the pandemic and after modifying their pathways to optimize safety for patients and workforce. Preliminary evidence regarding utilizing grafts from positive donors and/or transplanting recently recovered or infected recipients under certain circumstances is encou raging and may allow offering life-saving transplant to patients at the greatest need. This review summarizes the currently available data on liver trans plantation in the context of a major pandemic and discusses areas of uncertainty and future challenges. Lessons learnt from the COVID-19 pandemic might provide invaluable guidance for future pandemics.

4.
Pharmacol Ther ; 237: 108252, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35926664

RESUMO

Colorectal cancer (CRC) is the third most common cancer in both sexes and the second in terms of mortality. Apart from genetic predisposition, dietary and lifestyle factors have been implicated in the development of CRC. Several studies suggested that vitamin D (VitD) might be a promising strategy in CRC prevention, while other studies did not confirm this finding. The aim of our study was to examine the role of Vit-D supplementation in the prevention of colorectal neoplasms (CRC and polyps). We conducted a systematic search in Pubmed, Embase and Web of Science databases for Randomized Controlled Trials (RCTs) examining the incidence of colorectal neoplasms in patients taking Vit-D supplementation compared to placebo. We synthetized results using Risk Ratio along with 95% Confidence Intervals (CIs). Nine RCTs (N = 71,386) were included. Non-significant correlations were observed between Vit-D supplementation and CRC incidence (RR:1.06, p = 0.52). Similarly, non-significant associations were observed between the use of Vit-D supplements and colorectal adenoma incidence (RR:1.00, p = 0.91). Advanced adenomas (OR:1.05, p = 0.63) and serrated polyps (RR:1.03, p = 0.63) were also not significantly inversely associated with Vit-D supplementation. Our study shows that Vit-D does not seem to have a role in the chemoprevention of colorectal neoplasms. However, additional well-designed studies are needed in order to draw safe conclusions. A potentially beneficial role of Vit-D supplementation in CRC primary prevention in individuals with severe vitamin D deficiency as well in the primary prevention of early-onset CRC, requires further investigation.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/epidemiologia , Adenoma/prevenção & controle , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/uso terapêutico , Vitaminas
5.
Viruses ; 13(10)2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34696525

RESUMO

The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence of resistance-associated substitutions (RASs), in particular in the context of incomplete drug pressure, has an impact on sustained virological response (SVR) rates. Several RASs in NS3, NS5A and NS5B have been linked with reduced susceptibility to DAAs. RAS vary based on HCV characteristics and the different drug classes. DAA-resistant HCV variant haplotypes (RVs) are dominant in cases of virological failure. Viruses with resistance to NS3-4A protease inhibitors are only detected in the peripheral blood in a time frame ranging from weeks to months following completion of treatment, whereas NS5A inhibitor-resistant viruses may persist for years. Novel agents have been developed that demonstrate promising results in DAA-experienced patients. The recent approval of broad-spectrum drug combinations with a high genetic barrier to resistance and antiviral potency may overcome the problem of resistance.


Assuntos
Hepacivirus/genética , Hepatite C/tratamento farmacológico , Antivirais/farmacologia , Combinação de Medicamentos , Farmacorresistência Viral/genética , Quimioterapia Combinada/métodos , Genótipo , Inibidores da HCV NS3-4A Protease/metabolismo , Inibidores da HCV NS3-4A Protease/farmacologia , Hepacivirus/patogenicidade , Hepatite C/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , RNA Polimerase Dependente de RNA/antagonistas & inibidores , RNA Polimerase Dependente de RNA/metabolismo , Serina Proteases/efeitos dos fármacos , Serina Proteases/metabolismo , Resposta Viral Sustentada , Falha de Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/efeitos dos fármacos , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
6.
J Hepatol ; 74(6): 1407-1415, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33460690

RESUMO

BACKGROUND & AIMS: Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for accurate counselling is paramount. To date, minimal data exist on outcomes of IVF in patients with chronic liver disease, cirrhosis, or post-LT. We report the largest experience of IVF in women with liver-related subfertility (LRSF). METHODS: A retrospective analysis was performed on 42 women with LRSF who had undergone 57 IVF cycles between 1990 and 2019. RESULTS: Forty-two women with LRSF received IVF; 9 cycles in 6 women with cirrhosis, 14 cycles in 11 women post-LT, and 34 cycles in 25 women without cirrhosis. The main aetiologies of liver disease included HBV, HCV, and autoimmune hepatitis (AIH). Of 57 IVF cycles evaluated, 43 (75%) resulted in successful implantation. Eight (2 post-LT, 3 with cirrhosis, 4 without cirrhosis) resulted in miscarriage. The live birth rate (LBR) was 74% (32/43). Two of 9 (22%) patients with cirrhosis, 4/14 (29%) patients who were post-LT, and 6/34 (18%) patients without cirrhosis had unsuccessful IVF attempts. Nine of 57 (16%) IVF cycles resulted in new liver enzyme derangement during therapy, which improved after treatment completion. Six pregnancies (2 in patients who were post-LT, 4 without cirrhosis) were complicated by obstetric cholestasis (OC). Ovarian hyperstimulation syndrome (OHSS) was rare (n = 3, 7%). One patient with AIH-related cirrhosis decompensated after initiating IVF, warranting discontinuation of therapy. There were no maternal deaths. Three women developed a hypertensive disorder of pregnancy. Half the pregnancies resulted in premature deliveries (range 27-36 weeks). CONCLUSIONS: In selected cases, IVF in women with LRSF can be successful. However, patients should be counselled on the potential increased risks of OHSS, OC, and prematurity. LAY SUMMARY: Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.


Assuntos
Aborto Espontâneo/etiologia , Colestase Intra-Hepática/etiologia , Fertilização in vitro/efeitos adversos , Infertilidade Feminina/complicações , Infertilidade Feminina/terapia , Cirrose Hepática/complicações , Transplante de Fígado , Síndrome de Hiperestimulação Ovariana/etiologia , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Adulto , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Aliment Pharmacol Ther ; 52(5): 855-865, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32683724

RESUMO

BACKGROUND: In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions. AIM: To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis. METHODS: Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival. RESULTS: Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge. Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry. CONCLUSION: Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/mortalidade , Biomarcadores/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Linfócitos/patologia , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Doença Hepática Terminal/sangue , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Contagem de Leucócitos , Cirrose Hepática/sangue , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Escores de Disfunção Orgânica , Prognóstico , Análise de Sobrevida
9.
Am J Transplant ; 20(9): 2437-2448, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32185866

RESUMO

The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2  ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF-3.


Assuntos
Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Estado Terminal , Humanos , Cirrose Hepática/cirurgia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Clin Liver Dis ; 23(2): 177-189, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947870

RESUMO

Patients with sickle cell disease can develop liver disease as a result of intrahepatic sickling of erythrocytes, viral hepatitis and iron overload secondary to multiple blood transfusions, and gallstone disease as a result of chronic hemolysis. The spectrum of clinical liver disease is wide and often multifactorial. Some patients develop cirrhosis that may progress to end-stage liver failure. Limited evidence exists for medical treatments. Exchange blood transfusions may improve outcomes in the acute liver syndromes. Liver transplantation may be an option for chronic liver disease. The role for prophylactic cholecystectomy in preventing complications of gallstone disease is controversial.


Assuntos
Anemia Falciforme/complicações , Colelitíase/etiologia , Hepatopatias/etiologia , Reação Transfusional/complicações , Anemia Falciforme/terapia , Transfusão de Sangue , Colestase Intra-Hepática/etiologia , Hemólise , Hepatite Viral Humana/etiologia , Humanos , Sobrecarga de Ferro/etiologia , Cirrose Hepática/etiologia , Hepatopatias/terapia
11.
Dig Dis Sci ; 64(6): 1686-1694, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30659471

RESUMO

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.


Assuntos
Testes de Função do Córtex Suprarrenal , Córtex Suprarrenal/metabolismo , Insuficiência Adrenal/diagnóstico , Taxa de Filtração Glomerular , Síndrome Hepatorrenal/diagnóstico , Hidrocortisona/sangue , Rim/fisiopatologia , Cirrose Hepática/diagnóstico , Insuficiência Adrenal/sangue , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Grécia/epidemiologia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Síndrome Hepatorrenal/sangue , Síndrome Hepatorrenal/epidemiologia , Síndrome Hepatorrenal/fisiopatologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Adulto Jovem
12.
Curr Pharm Des ; 24(31): 3654-3657, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30317984

RESUMO

BACKGROUND: Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD. OBJECTIVE: The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type- 9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD. RESULTS: Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD. The findings of animal and human studies, aiming to reduce PCSK9 with inhibitors (human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies) point towards liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of hepatic HNF1a protein, insulin resistance (IR), and other mechanisms. CONCLUSIONS: The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently of low density lipoprotein cholesterol level reduction.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/enzimologia , Inibidores de PCSK9 , Animais , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo
13.
Ann Gastroenterol ; 31(5): 613-620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30174399

RESUMO

BACKGROUND: This study evaluated the efficacy, safety, and impact on renal function of everolimus in patients after liver transplantation (LT) with or without mycophenolate mofetil (MMF). METHODS: We evaluated LT recipients with calcineurin inhibitor (CNI)-related renal dysfunction after everolimus initiation. Laboratory data, including evaluation of renal function based on glomerular filtration rate (GFR) at baseline (i.e., everolimus initiation) and at the end of follow up, were analyzed. RESULTS: Fifty consecutive patients started taking everolimus at 30 months post-LT (range: 1-240), 6 as monotherapy and 44 in combination with MMF. After 30.5 months (range: 6-112), all patients were alive, without any biochemical evidence of a rejection episode or recurrence of hepatocellular carcinoma. The mean GFR, based on the Modification of Diet in Renal Disease equation, was 53±13 mL/min at baseline and 59±12 mL/min at the end of follow up (P=0.031). Eleven (22%) of the patients had GFR <60 mL/min at baseline but returned to GFR >60 mL/min by the end of follow up. In multivariate analysis, the time between the development of renal dysfunction and everolimus initiation was the only factor independently associated with GFR improvement (odds ratio [OR] 0.85, 95% confidence interval [95%CI] 0.76-0.96; P=0.007). Everolimus was stopped in 11 patients (22%) at the end of follow up because of adverse events. CONCLUSION: A CNI-free everolimus-based regimen was effective in LT recipients with renal dysfunction and was associated with an improvement in GFR.

14.
Neuroendocrinology ; 107(3): 292-304, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30153671

RESUMO

BACKGROUND: Small intestinal neuroendocrine tumours (SI NETs) represent 30-50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. AIM: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. RESULTS: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. CONCLUSIONS: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.


Assuntos
Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Tumores Neuroendócrinos/secundário , Idoso , Neoplasias Ósseas/secundário , Feminino , Fibrose/patologia , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
Liver Transpl ; 24(8): 1113-1118, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29893056

RESUMO

Autoimmune liver diseases (AILDs) can recur following liver transplantation (LT) despite immunosuppressive therapy, with implications for graft survival. Although the evidence is not robust, disease recurrence seems to occur in the presence of less intense and/or steroid-free immunosuppression (IS) in particular in the case of autoimmune hepatitis (AIH). The main risk factor for AIH recurrence is the severity of disease activity in the explant and potential donor/recipient human leukocyte antigen D-related 3 (DR3) mismatch. The treatment for AIH recurrence includes reintroduction or increase in the dose of steroids with or without the addition of azathioprine. T cell-mediated rejection episodes are also more common in AILD. Steroid withdrawal is the common practice in LT for non-AILD, eliminating the risks associated with longterm exposure to steroids. In AILD, maintenance of steroids at a low dose in the long term may reduce the risk of disease recurrence and rejection. This strategy is safe when there is vigilance for steroid-related adverse effects. Alternatively, identifying patients who are at the greatest risk for disease recurrence and who would benefit from intensified IS might be an option.


Assuntos
Glucocorticoides/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Hepatite Autoimune/cirurgia , Terapia de Imunossupressão/normas , Transplante de Fígado/efeitos adversos , Relação Dose-Resposta a Droga , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Humanos , Terapia de Imunossupressão/métodos , Transplante de Fígado/normas , Recidiva , Prevenção Secundária/métodos , Prevenção Secundária/normas , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Suspensão de Tratamento/normas
16.
Br J Hosp Med (Lond) ; 79(3): 151-159, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29528732

RESUMO

Autoimmune hepatitis occurs in genetically susceptible individuals as a result of loss of immunological tolerance to hepatic autoantigens that can be precipitated by environmental triggers. The clinical manifestation is usually insidious but can be also acute with liver failure. The diagnosis is made on the basis of antibody positivity, elevated immunoglobulin G levels and interface hepatitis on liver histology. Induction of remission is achieved with high-dose steroids in the majority of cases, and maintenance of remission with azathioprine. Treatment withdrawal is achievable only in a small proportion of patients. Patients with acute liver failure unresponsive to steroids or those with end-stage liver failure or hepatocellular carcinoma may require liver transplantation. Variant forms of overlapping autoimmune hepatitis with either primary biliary cholangitis or sclerosing cholangitis are associated with worse outcomes. New insights into the pathophysiology of the disease may provide novel therapeutic targets and a more individualized approach to treatment of autoimmune hepatitis.


Assuntos
Hepatite Autoimune/diagnóstico , Hepatite Autoimune/fisiopatologia , Hepatite Autoimune/terapia , Humanos
17.
J Am Heart Assoc ; 6(10)2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29018026

RESUMO

BACKGROUND: The recent finding that aortic pulse wave velocity (aPWV) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. METHODS AND RESULTS: A systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer-reviewed publications on clinical studies reporting original data. This study followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data 2015 guidelines. Data were provided for 4 cohorts in 3 countries (151 participants with ulcerative colitis, 159 with Crohn's disease, and 227 control patients). Using aPWV, cohort-specific z scores were calculated after loge-transform and combined in meta-analysis to form pooled effects using a random-effects model. Compared with controls, aPWV was increased in patients with Crohn's disease (mean difference 0.78 z score; 95% confidence interval, 0.56-1.00 z score [P<0.001]) and ulcerative colitis (mean difference 0.75 z score; 95% confidence interval, 0.52-0.97 z score [P<0.001]). In an outlier-robust multivariate linear regression model adjusted for prespecified confounders, aPWV was associated with disease duration (years, ß=0.05 z score; 95% confidence interval, 0.02-0.08 z score [P<0.001]) and white blood cell count (billion cells/L, ß=0.07 z score; 95% confidence interval, 0.02-0.11 z score [P=0.002]) but not with markers of acute inflammation (C-reactive protein and erythrocyte sedimentation rate), cardiovascular risk factors, and therapy. CONCLUSIONS: The increased aPWV reported in patients with inflammatory bowel disease is associated with inflammation. CLINICAL TRIAL REGISTRATION: URL: http://www.crd.york.ac.uk. Unique identifier: PROSPERO 2016: CRD42016053070.


Assuntos
Doenças Cardiovasculares/etiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Inflamação/complicações , Rigidez Vascular , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Contagem de Leucócitos , Modelos Lineares , Análise Multivariada , Prognóstico , Análise de Onda de Pulso , Fatores de Risco
19.
Gastroenterol Res Pract ; 2017: 8270310, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28584525

RESUMO

Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.

20.
Ann Intensive Care ; 7(1): 33, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28321803

RESUMO

BACKGROUND: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. METHODS: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). RESULTS: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88). CONCLUSIONS: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...