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2.
Hepatol Commun ; 8(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696372

RESUMO

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.


Assuntos
Colangiocarcinoma , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante , Humanos , Colangite Esclerosante/mortalidade , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Austrália/epidemiologia , Adulto , Colangiocarcinoma/mortalidade , Colangiocarcinoma/diagnóstico por imagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Idoso
3.
Dig Dis Sci ; 69(6): 1979-1989, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38637459

RESUMO

BACKGROUND: There is a need to improve psychological care for people with Inflammatory Bowel Diseases (IBD), noting the high psychosocial burden of disease. AIMS: This study qualitatively explored the views of people living with IBD to help inform future co-design of services that better meet the psychological needs of consumers. METHODS: Adults with IBD were recruited to attend virtual focus groups to discuss what they want most in an IBD-specific psychological service. The discussions were recorded and transcribed, and data were analyzed using conventional qualitative content analysis. Draft results were summarized midway and reviewed by remaining focus groups and a final expert consumer. A quantitative dataset was created of comment frequencies. RESULTS: Thirty-one participants took part in the study: 10 focus groups were held with an average of three participants per group. The analysis identified 254 codes, 38 sub-categories and six categories. Five main categories were identified for an IBD-specific psychological service: People-Centered Healthcare (commented on by 90% of participants), Education and Preparation (83%), Social Connection (83%), Psychological Input (93%), and Accessible Services (97%). Results were summarized in a set of proposed clinical guidelines. CONCLUSIONS: The findings of this study identify important insights from people living with IBD regarding priorities for psychological services. IBD services should focus on improving education, addressing social connection, and integrating psychological input, as well as becoming more people-centered and accessible. It is hoped that IBD services consult the proposed clinical guidelines to inform co-designed service improvements.


Assuntos
Grupos Focais , Doenças Inflamatórias Intestinais , Humanos , Feminino , Masculino , Adulto , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Pessoa de Meia-Idade , Idoso , Pesquisa Qualitativa , Adulto Jovem , Serviços de Saúde Mental/organização & administração
4.
Aliment Pharmacol Ther ; 57(1): 23-36, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36324251

RESUMO

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested. AIM: To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis. METHODS: We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC. RESULTS: A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking. CONCLUSIONS: The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.


Assuntos
Colangite Esclerosante , Humanos , Colangite Esclerosante/terapia
5.
Dig Dis Sci ; 68(3): 889-896, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35687221

RESUMO

BACKGROUND: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP). TDM of thiopurines involves measurement and interpretation of metabolites 6-TGN and 6-MMPR. AIMS: This study aimed to assess long-cterm outcomes of patients on thiopurines following therapeutic drug monitoring. METHODS: A multicenter retrospective observational study of outcomes post thiopurine TDM was conducted. Demographics, disease characteristics, physician global assessment, IBD therapy at baseline TDM and again at 12 months were collected. Clinical outcomes were analyzed according to TDM result, and indication for TDM including proactive and other indications. RESULTS: The study included 541 patients. Only 39% of patients had appropriate dosing of thiopurines. AZA/6MP TDM informed a management change in 61.9%, and enabled 88.8% of the cohort to continue AZA/6MP following TDM. At 12 months following TDM the majority (74.1%) of the cohort remained on AZA/6MP. Clinical remission was higher at 12-months following thiopurines TDM (68%) compared to baseline (37%), including proactive TDM. Post TDM, 13.0% of patients were identified as shunters and commenced on thiopurine-allopurinol co-therapy. CONCLUSION: Thiopurine TDM resulted in a change in management for the majority of patients. Post TDM significantly more patients were in remission. TDM allowed the identification of non-adherence and shunters who, without intervention, would not reach therapeutic drug levels. Proactive TDM allowed identification and management of inappropriate dosing, and was associated with increased levels of clinical remission.


Assuntos
Azatioprina , Doenças Inflamatórias Intestinais , Humanos , Azatioprina/efeitos adversos , Mercaptopurina/efeitos adversos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Estudos Retrospectivos , Metiltioinosina/uso terapêutico , Imunossupressores/efeitos adversos
6.
Intern Med J ; 52(6): 1070-1074, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35583312

RESUMO

The majority of the Australian public are willing to have a Coronavirus disease 2019 (COVID-19) vaccination. It is unclear whether people with inflammatory bowel disease (IBD) have the same attitude towards COVID-19 vaccination. A survey was performed to assess the attitude of patients with IBD towards COVID-19 vaccination in South Australia. Two-thirds of surveyed patients with IBD were willing to accept COVID-19 vaccine. Females and younger patients were less likely to accept the COVID-19 vaccine, as were those who had never had a discussion around vaccines.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Austrália/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Doença Crônica , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Vacinação
7.
Br Med Bull ; 133(1): 95-104, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32282030

RESUMO

INTRODUCTION: Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). SOURCES OF DATA: In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC.No medications are currently approved in Europe or the USA for the treatment of NASH.In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. AREAS OF AGREEMENT: OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. AREAS OF CONTROVERSY: The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1-10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH.In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. GROWING POINTS: Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. AREAS TIMELY FOR DEVELOPING RESEARCH: New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.


Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Cirrose Hepática Biliar , Hepatopatia Gordurosa não Alcoólica , Receptores Citoplasmáticos e Nucleares/agonistas , Ácido Quenodesoxicólico/farmacologia , Fármacos Gastrointestinais/farmacologia , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Resultado do Tratamento
8.
Clin Gastroenterol Hepatol ; 18(10): 2295-2304.e2, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32068151

RESUMO

BACKGROUND & AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. METHODS: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. RESULTS: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083). CONCLUSIONS: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.


Assuntos
Colangite Esclerosante , Doenças Inflamatórias Intestinais , Adalimumab/efeitos adversos , Colangite Esclerosante/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
9.
Clin Gastroenterol Hepatol ; 18(1): 179-187.e6, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100458

RESUMO

BACKGROUND & AIMS: Gut-homing lymphocytes that express the integrin α4ß7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4ß7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD. METHODS: We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n = 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes. RESULTS: In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P = .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P = .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation. CONCLUSIONS: In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Integrinas/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colangite Esclerosante/sangue , Colangite Esclerosante/complicações , Colangite Esclerosante/imunologia , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/imunologia , Integrinas/imunologia , Testes de Função Hepática , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Curr Hepatol Rep ; 18(1): 115-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31008013

RESUMO

PURPOSE OF REVIEW: Biologics are well established in the treatment of many immuno-inflammatory diseases including inflammatory bowel disease (IBD). However, although primary sclerosing cholangitis (PSC) is closely associated with IBD, the role of biologics in PSC remains uncertain. Many new biologics are becoming available to treat IBD, and this review aims to use the experience of biologics in PSC so far to guide more effective evaluation of emerging therapies in the future. RECENT FINDINGS: Antibodies to TNF-α were the first biologics used in IBD, and retrospective analysis suggests that they may have some benefit in PSC, even though an early randomised controlled trial (RCT) showed no effect. Mechanistic studies suggest that TNF-α may have a pathogenic role in PSC. An antibody to integrin α4ß7 is effective in IBD, and there are emerging data on its effects in PSC, although no RCT data are available. Mechanistic studies suggest that interrupting the migration of lymphocytes is relevant in PSC. Two biologics, targeting vascular adhesion protein-1 (VAP-1), and lysyl oxidase-like 2 (LOXL2) have been tested in RCTs. The trial of anti-VAP1 is ongoing, whilst the anti-LOXL2 trial was negative. SUMMARY: Anti-TNF antibodies may benefit PSC when used to treat concomitant IBD, and this may be a direct effect on the liver in a subgroup of patients, or may be an indirect effect of treating IBD. Similarly, anti-integrin therapy may benefit a subset of patients with IBD and PSC. RCTs could decide the role of emerging biologics in PSC, although future trials should be guided by biomarkers that could predict response to the pathway being targeted.

12.
Hepatology ; 69(5): 2120-2135, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30566748

RESUMO

We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation.


Assuntos
Colangite Esclerosante/mortalidade , Fosfatase Alcalina/sangue , Colangite Esclerosante/sangue , Colangite Esclerosante/genética , Colangite Esclerosante/cirurgia , Feminino , Antígenos HLA/genética , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Medição de Risco , Reino Unido/epidemiologia
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