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1.
Hepatol Commun ; 8(2)2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38285883

RESUMO

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.


Assuntos
Colangite Esclerosante , Doença Hepática Terminal , Doenças Inflamatórias Intestinais , Humanos , Estudos Retrospectivos , Colangite Esclerosante/diagnóstico , Negro ou Afro-Americano , Diagnóstico Tardio , Índice de Gravidade de Doença , Doenças Inflamatórias Intestinais/complicações
4.
Am J Transplant ; 22(9): 2195-2202, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35486028

RESUMO

"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.


Assuntos
Neoplasias Hepáticas , Transplante de Fígado , Sarcopenia , Adulto , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Masculino , Músculo Esquelético/patologia , Obesidade/complicações , Obesidade Abdominal/complicações , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações
5.
Hepatology ; 76(4): 1150-1163, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35332569

RESUMO

BACKGROUND AND AIMS: The NASH Clinical Research Network histologic scoring system, the gold-standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). APPROACH AND RESULTS: Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80-0.85) and interrater (0.60-0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68-0.79), including those extending scores from 0-2 to 0-4. Steatosis measures (interrater ICCs, 0.72-0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory-Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70-0.87. CONCLUSIONS: After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Biópsia , Fibrose , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
6.
Hepatol Commun ; 6(7): 1589-1597, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35238498

RESUMO

The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single-arm open-label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per-protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug-related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.


Assuntos
Compostos de Bifenilo , Colangite Esclerosante , Ácidos Dicarboxílicos , Compostos de Bifenilo/efeitos adversos , Colangite Esclerosante/tratamento farmacológico , Ácidos Dicarboxílicos/efeitos adversos , Humanos , Projetos Piloto
7.
Hepatology ; 75(6): 1368-1369, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34953148

Assuntos
Aptidão Física
9.
J Clin Gastroenterol ; 55(5): 449-457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32976197

RESUMO

GOALS: We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). BACKGROUND: The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. MATERIALS AND METHODS: Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. RESULTS: The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). CONCLUSION: LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.


Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática Biliar , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico por imagem , Cirrose Hepática Biliar/patologia , Espectroscopia de Ressonância Magnética , Curva ROC
10.
Dig Dis Sci ; 66(5): 1715-1719, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32436124

RESUMO

BACKGROUND: Standard of care treatment for AIH includes prednisone monotherapy or dual therapy prednisone-azathioprine. However, many hepatologists alternatively use azathioprine monotherapy to avoid side effects of long-term corticosteroids. AIMS: To determine whether azathioprine monotherapy is comparable to dual prednisone-azathioprine for maintenance of remission in AIH. METHODS: A retrospective chart review of 260 individuals with AIH from a single institution was performed; 45 individuals were included. Exclusion criteria included concomitant PBC or PSC, use of alternative treatment regimen, and/or failure to reach remission. Treatment regimen received was guided by clinician standard of practice, not patients' clinical factors. Initial remission was defined as normalization of serum ALT for at least two consecutive blood draws. Data were analyzed for 5 years post-remission, recording outcome and dose of prednisone and/or azathioprine. RESULTS: 83% of individuals were female, and average age was 65 years. Median dose of prednisone and azathioprine for the dual-therapy group was 5 mg and 100 mg, respectively, while median azathioprine dose for the monotherapy group was 75 mg. Considering overall outcome, 93% of all patients maintained remission. 80% of the dual-therapy group, and 95% of the azathioprine monotherapy group maintained remission. Using Chi-square analysis to compare the maintenance of remission between dual therapy and azathioprine monotherapy, a p value of 0.28 was calculated. CONCLUSIONS: AASLD guidelines recommend dual prednisone-azathioprine as standard of care for maintenance of remission in AIH. Our results suggest that azathioprine monotherapy is equivalent to prednisone-azathioprine. Azathioprine monotherapy offers a significant advantage in mitigating risks of long-term corticosteroid therapy.


Assuntos
Azatioprina/uso terapêutico , Glucocorticoides/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Prednisona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Azatioprina/efeitos adversos , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Hepatology ; 74(1): 281-295, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33226645

RESUMO

BACKGROUND AND AIMS: Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. APPROACH AND RESULTS: Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5-year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary-to-secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary-to-secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine-learning model, PSC-BA profile score (concordance statistic [C-statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C-statistic, 0.86). CONCLUSIONS: Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.


Assuntos
Ascite/epidemiologia , Ácidos e Sais Biliares/sangue , Colangite Esclerosante/complicações , Varizes Esofágicas e Gástricas/epidemiologia , Encefalopatia Hepática/epidemiologia , Adulto , Idoso , Ascite/etiologia , Estudos de Casos e Controles , Colangite Esclerosante/sangue , Colangite Esclerosante/fisiopatologia , Varizes Esofágicas e Gástricas/etiologia , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Encefalopatia Hepática/etiologia , Humanos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos
12.
J Gastroenterol ; 55(11): 1087-1097, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32770464

RESUMO

BACKGROUND: The long-term outcomes of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are not well known. METHODS: The outcomes of patients with IgG4-SC at Mayo Clinic (1999-2018) were compared to an age- and gender-matched (1:1 ratio) group of patients with primary sclerosing cholangitis (PSC). RESULTS: We identified 89 patients with IgG4-SC; median age at diagnosis was 67 years, 81% were males, and the median follow-up was 5.7 years. Seventy-eight patients received prednisone for induction of remission, and 53 received at least one other immunosuppressive agent for maintenance of remission. Of the IgG4-SC group, 10 died (median time from diagnosis until death was 6.5 years): 2 due to cirrhosis, 3 due to cholangiocarcinoma (CCA), and 5 due to non-hepatobiliary causes. Eleven patients in the PSC group underwent liver transplantation, while none did in the IgG4-SC group. The incidence of a hepatobiliary adverse event (cirrhosis or CCA) was 3.4 times greater in the PSC compared to the IgG4-SC group (events per 1000 person-years: 52.6; 95% CI 38-73; vs. 15.6; 95% CI 7-32). The probability of development of a hepatobiliary adverse event within 10 years was 11% in the IgG4-SC compared to 45% in the PSC group (P = 0.0001). The overall survival tended to be higher in the IgG4-SC compared to the PSC group (10-year: 79% vs. 68%, respectively; P = 0.11). CONCLUSIONS: In a cohort of IgG4-SC patients, 88% of whom were treated with immunosuppressive drugs, the risk of cirrhosis and CCA was significantly lower compared to an age- and gender-matched group with PSC.


Assuntos
Colangite Esclerosante/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunossupressores/administração & dosagem , Prednisona/administração & dosagem , Idoso , Neoplasias dos Ductos Biliares/epidemiologia , Colangiocarcinoma/epidemiologia , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/imunologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Scand J Gastroenterol ; 55(8): 941-950, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32633158

RESUMO

BACKGROUND: Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV. METHODS: Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50 mg/kg/day in 3 divided doses if weight <30kg, and 500 mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline. RESULTS: 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n = 59; median age was 13.5 years [range, 1.5-44 years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7 years (range, 0.2-14 years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6 months of OV treatment. One patient underwent liver transplantation 8 years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events. CONCLUSION: In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.


Assuntos
Antibacterianos , Colangite Esclerosante , Vancomicina , Adolescente , Adulto , Alanina Transaminase , Antibacterianos/uso terapêutico , Criança , Colangite Esclerosante/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos , Vancomicina/uso terapêutico , gama-Glutamiltransferase
14.
Dig Dis Sci ; 65(10): 3014-3022, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31897896

RESUMO

BACKGROUND: Studies suggest that gender differences in academic medicine exist. Men frequently have better measures of performance such as number of publications, number of citations, remuneration, and funding. AIMS: To evaluate whether a gender disparity in authorship exists. METHODS: We recorded the gender of first and senior authors of original papers, editorials/reviews from liver-related manuscripts in Gastroenterology, Hepatology, Transplantation, American Journal of Gastroenterology, and Liver Transplantation from January 2014 to 2016. RESULTS: Of 2424 articles reviewed, we excluded 232 (10%) due to inability to determine gender. Among papers analyzed, 72.0% were original and 28.1% reviews/editorials with 65.1% of first authors being male and 34.9% female. Only 20.3% of papers with multiple authors had a female senior author. The proportion of male first and senior authorship between original papers and reviews/editorials was comparable. 72% of original papers had a male as first or senior author, but only 28% females. 71% of review/editorial papers had a male as first or senior author, but only 29% females. When the senior author of an original paper was female, 47.1% of first authors were male and 52.9% female. When the senior author was male, 67.1% of first authors were male and 32.9% female (p < 0.00001). CONCLUSIONS: A significant gender difference exists in Hepatology publications. Female authorship mirrors the percentage of female AASLD membership; however, female senior authorship remains disproportionate. In general, funding for male authors is greater. Fewer women are first authors when the senior author is male, highlighting the importance of female mentorship in Hepatology.


Assuntos
Autoria , Pesquisa Biomédica/tendências , Gastroenterologia/tendências , Publicações Periódicas como Assunto/tendências , Pesquisadores/tendências , Bibliometria , Feminino , Humanos , Masculino , Fatores Sexuais
15.
Hepatology ; 70(5): 1816-1829, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31220351

RESUMO

Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut-off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best-studied technique for assessing sarcopenia in patients with cirrhosis. Cut-off values for sarcopenia, defined as SMI < 50 cm2 /m2 in male and < 39 cm2 /m2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.


Assuntos
Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado , Sarcopenia/complicações , Sarcopenia/diagnóstico , Canadá , Tomada de Decisão Clínica , Prova Pericial , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios , Sarcopenia/terapia , Estados Unidos
16.
Am J Gastroenterol ; 114(10): 1593-1605, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31169523

RESUMO

Cholestatic liver diseases encompass a broad spectrum of pathologies, with the core injury occurring at the level of cholangiocytes and progressing to hepatic fibrosis and liver dysfunction. Primary biliary cholangitis and primary sclerosing cholangitis are the most significant progressive cholangiopathies in adults. Although rare, they commonly evolve to liver failure and need for liver transplantation. Despite recent advances in the basic knowledge of these cholangiopathies, the pathogenesis is still elusive. Targeted treatments to prevent disease progression and to preclude malignancy are not yet available. This review will address the general clinical features of both diseases, analyze their commonalities and differences, and provide a state-of-the art overview of the currently available therapeutics.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Colestase/tratamento farmacológico , Doença Hepática Terminal/prevenção & controle , Fatores Imunológicos/uso terapêutico , Adulto , Sistema Biliar/patologia , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapêutico , Colangite Esclerosante/complicações , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/patologia , Colestase/epidemiologia , Colestase/etiologia , Colestase/patologia , Ensaios Clínicos como Assunto , Progressão da Doença , Quimioterapia Combinada , Doença Hepática Terminal/epidemiologia , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/patologia , Humanos , Expectativa de Vida , Prevalência , Prognóstico , Resultado do Tratamento , Ácido Ursodesoxicólico/uso terapêutico
17.
Scand J Gastroenterol ; 54(5): 633-639, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131678

RESUMO

Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC). Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC. Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750 mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires. Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n = 98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10-4.32) to 2.46 (1.89-4.41), p = .36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported. Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC. Abbreviations PSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colangite Esclerosante/tratamento farmacológico , Curcumina/administração & dosagem , Adulto , Fosfatase Alcalina/sangue , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Colangite Esclerosante/sangue , Curcumina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Transplantation ; 103(11): 2312-2317, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30985575

RESUMO

BACKGROUND: We examined the association between sarcopenia and post-transplant mortality in acutely ill inpatients with cirrhosis who underwent urgent liver transplantation. METHODS: Included were inpatients at 4 centers who were urgently listed as nonstatus 1 and transplanted from 2005 to 2017 with an abdominal computed tomography scan <90 days before transplantation. Skeletal muscle index (SMI) = total skeletal muscle cross-sectional area at the L3 vertebral level, normalized to height. Cox regression associated SMI with post-transplant mortality. Optimal search identified SMI cutoffs to detect survival. RESULTS: Of 126 inpatients, 63% were male patients, model for end-stage liver disease (MELDNa) was 32, and follow up was 5.1 years. Among men, 23% died. Median SMI was lower in men who died versus survived (45 versus 51 cm/m). SMI was associated with post-transplant mortality (hazard ratio [HR] = 0.96 per cm/m, 95% CI 0.92-0.99). Patients with SMI ≤ 48 cm/m versus >48 cm/m experienced higher rates of death at 1 year (86% versus 95%) and 3 years (73% versus 95%) (Log-rank P = 0.01). In MELD-adjusted analysis, sarcopenia was strongly associated with post-transplant mortality (HR = 4.39, 95% CI 1.49-12.97). Among women, 35% died. Median SMI was similar in women who died versus survived (45 versus 44 cm/m). SMI was not associated with post-transplant mortality (HR = 1.02, 95% CI 0.96-1.09). Optimal search did not identify any SMI cutoff that predicted post-transplant mortality. CONCLUSIONS: Among patients who underwent urgent inpatient evaluation and liver transplantation, we identified an SMI cutoff value of 48 cm/m to predict post-transplant mortality in men. Our data support the use of SMI as a tool to capture the impact of muscle depletion on post-transplant mortality in acutely ill men with cirrhosis undergoing urgent liver transplantation.


Assuntos
Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Músculo Esquelético/patologia , Sarcopenia/etiologia , Doença Aguda , Adulto , Estado Terminal , Feminino , Humanos , Pacientes Internados , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
19.
Am J Transplant ; 19(7): 1896-1906, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30980701

RESUMO

Frailty has emerged as a powerful predictor of outcomes in patients with cirrhosis and has inevitably made its way into decision making within liver transplantation. In an effort to harmonize integration of the concept of frailty among transplant centers, the AST and ASTS supported the efforts of our working group to develop this statement from experts in the field. Frailty is a multidimensional construct that represents the end-manifestation of derangements of multiple physiologic systems leading to decreased physiologic reserve and increased vulnerability to health stressors. In hepatology/liver transplantation, investigation of frailty has largely focused on physical frailty, which subsumes the concepts of functional performance, functional capacity, and disability. There was consensus that every liver transplant candidate should be assessed at baseline and longitudinally using a standardized frailty tool, which should guide the intensity and type of nutritional and physical therapy in individual liver transplant candidates. The working group agreed that frailty should not be used as the sole criterion for delisting a patient for liver transplantation, but rather should be considered one of many criteria when evaluating transplant candidacy and suitability. A road map to advance frailty in the clinical and research settings of liver transplantation is presented here.


Assuntos
Fragilidade , Intestinos/transplante , Transplante de Fígado , Sociedades Médicas , Atividades Cotidianas , Adulto , Algoritmos , Criança , Humanos , Padrões de Prática Médica
20.
Am J Transplant ; 19(9): 2517-2524, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30811848

RESUMO

Solid organ transplant recipients who contract coccidioidomycosis are at risk for complicated, protracted, disseminated, and severe disease. To date, no studies have described outcomes for patients who develop coccidioidomycosis only after the first posttransplant year. This study was a joint project of Mayo Clinic Hospital, Phoenix, Arizona, and the University of Arizona/Banner University Medical Center, Tucson, Arizona. We retrospectively reviewed electronic health records for patients with a history of solid organ transplant between January 1, 1998, and October 11, 2014, who developed coccidioidomycosis after the first transplant year. We identified 91 patients. Of those, 37/91 (40.7%) had pulmonary coccidioidomycosis (29/37 [78.4%] were symptomatic); and 5/91 (5.5%) had extrapulmonary disease (all were symptomatic). One patient (1.1%) died. Coccidioidomycosis was evident in 2/91 (2.2%) patients within 3 months of antirejection treatment. Many of the patients (51/91 [56.0%]) had asymptomatic coccidioidomycosis, 27 (27.9%) of whom were followed up closely but did not receive antifungal medication and had no sequelae. Although solid organ recipients taking low-level immunosuppression after the first posttransplant year appeared to have less symptomatic, disseminated, or fatal coccidioidal infection than historical cohorts, this remains an important infection with morbidity and mortality even after the first posttransplant year.


Assuntos
Coccidioidomicose/complicações , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Antifúngicos/uso terapêutico , Arizona/epidemiologia , Coccidioidomicose/epidemiologia , Registros Eletrônicos de Saúde , Doenças Endêmicas , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Risco , Transplantados , Resultado do Tratamento , Adulto Jovem
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