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1.
Medicine (Baltimore) ; 100(4): e23627, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530164

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common complication in the third trimester of pregnancy, which may result in premature delivery, fetal distress, stillbirth, and other adverse pregnancy outcomes. Ursodeoxycholic acid (UDCA) is a first-line treatment for ICP and has been controversial in improving adverse pregnancy outcomes. The purpose of this protocol is to systematically evaluate the effect of UDCA on pregnancy outcomes in patients with intrahepatic cholestasis during pregnancy. METHODS: To search the databases PubMed, Embase, Web of Science, the Cochrane Library, CNKI, WanFang, VIP, CBMDIsc by computer, then to include randomized controlled clinical studies on UDCA for treatment of intrahepatic cholestasis during pregnancy from the establishment of the database to October 1, 2020. Two researchers independently extract and evaluate the data of the included studies, and meta-analysis is conducted on the included literatures using RevMan5.3 software. RESULTS: This protocol evaluates the outcome of UDCA in improving ICP by incidence of postpartum hemorrhage in pregnant women preterm birth rates meconium contamination rate in amniotic fluid incidence of fetal distress scale of newborns scoring <7 in 5-min Apgar incidence of neonatal admission to neonatal intensive care unit. CONCLUSION: This protocol will provide an evidence-based basis for clinical use of UDCA in the treatment of intrahepatic cholestasis during pregnancy. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605 / OSF.IO / BE67H.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colestase Intra-Hepática/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez/epidemiologia , Cuidado Pré-Natal/métodos , Ácido Ursodesoxicólico/uso terapêutico , Feminino , Sofrimento Fetal/epidemiologia , Sofrimento Fetal/etiologia , Humanos , Incidência , Recém-Nascido , Metanálise como Assunto , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Projetos de Pesquisa , Natimorto/epidemiologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(34): e21698, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846787

RESUMO

Biliary dyspepsia presents as biliary colic in the absence of explanatory structural abnormalities. Causes include gallbladder dyskinesia, sphincter of Oddi dysfunction, biliary tract sensitivity, microscopic sludges, and duodenal hypersensitivity. However, no consensus treatment guideline exists for biliary dyspepsia. We investigated the effects of medical treatments on biliary dyspepsia.We retrospectively reviewed the electronic medical records of 414 patients who had biliary pain and underwent cholescintigraphy from 2008 to 2018. We enrolled patients who received litholytic agents and underwent follow-up scans after medical treatment. We divided the patients into the GD group (biliary dyspepsia with reduced gallbladder ejection fraction [GBEF]) and the NGD group (biliary dyspepsia with normal GBEF). We compared pre- and post-treatment GBEF and symptoms.Among 57 patients enrolled, 40 (70.2%) patients had significant GBEF improvement post-treatment, ranging from 34.4 ±â€Š22.6% to 53.8 ±â€Š26.8% (P < .001). In GD group (n = 35), 28 patients had GBEF improvement after medical treatment, and value of GBEF significantly improved from 19.5 ±â€Š11.0 to 47.9 ±â€Š27.3% (P < .001). In NGD group (n = 22), 12 patients had GBEF improvement after medical treatment, but value of GBEF did not have significant change. Most patients (97.1% in GD group and 81.8% in NGD group) had improved symptoms after medical treatment. No severe complication was reported during treatment period.Litholytic agents improved biliary colic in patients with biliary dyspepsia. Therefore, these agents present an alternative treatment modality for biliary dyspepsia with or without gallbladder dyskinesia. Notably, biliary colic in patients with gallbladder dyskinesia resolved after normalization of the GBEF. Further prospective and large-scale mechanistic studies are warranted.


Assuntos
Bile , Ácido Quenodesoxicólico/uso terapêutico , Dispepsia/tratamento farmacológico , Dispepsia/etiologia , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Feminino , Vesícula Biliar/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Brasília; s.n; 11 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117979

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ribavirina/uso terapêutico , Avaliação da Tecnologia Biomédica , Ácido Ursodesoxicólico/uso terapêutico , Imunoglobulinas/uso terapêutico , Prednisolona/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Cloroquina/uso terapêutico , Estudos Transversais , Estudos de Coortes , Interferon-alfa/uso terapêutico , Tacrolimo/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Ácido Fólico/uso terapêutico , Meropeném/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Ácido Micofenólico/uso terapêutico
4.
Med. clín (Ed. impr.) ; 155(4): 165-170, ago. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-195762

RESUMO

Background and AIM: To explore the efficacy treatment regimen in refractory PBC. METHODS: Triple treatment including ursodeoxycholic acid, prednisolone and immunosuppressant was prescribed to 47 refractory patients. Biochemistries, immune parameters, non-invasive liver fibrosis assessments were measured during follow-up. RESULTS: Triple therapy resulted in significant decrease in ALP, GGT, ALT, AST, TBIL, ALB, IgG, IgM, APRI, FIB-4 and S-INDEX. The biochemical cumulative normalization rates of ALP and other biochemical parameters were higher in long-term follow-up. Poor outcome was observed in patients with lower ALB, higher TBIL, PT, sp100 positivity and advanced liver pathology at baseline. Osteoporosis and bone fracture were observed in 15% patients. CONCLUSIONS: Triple therapy is associated with marked decrease and normalization of ALP and other parameters. ALB, TBIL, PT, sp100 and pathology were related with poor outcome. Osteoporosis should be closely monitored


ANTECEDENTES Y OBJETIVO: Explorar el régimen de tratamiento de eficacia en PBC refractario. MÉTODOS: Se prescribió un tratamiento triple que incluyó ácido ursodesoxicólico, prednisolona e inmunosupresor a 47 pacientes refractarios. Las bioquímicas, los parámetros inmunes, las evaluaciones no invasivas de fibrosis hepática se midieron durante el seguimiento. RESULTADOS: La triple terapia resultó en una disminución significativa de ALP, GGT, ALT, AST, TBIL, ALB, IgG, IgM, APRI, FIB-4 y S-INDEX. Las tasas de normalización bioquímica acumulada de ALP y otros parámetros bioquímicos fueron mayores en el seguimiento a largo plazo. Se observó un resultado deficiente en pacientes con ALB más bajo, TBIL más alto, PT, positivo de SP100 y enfermedad hepática avanzada al inicio del estudio. La osteoporosis y la fractura ósea se observaron en el 15% de los pacientes. CONCLUSIONES: La triple terapia se asocia con una marcada disminución y normalización de ALP y otros parámetros. ALB, TBIL, PT, SP100 y la enfermedad se relacionaron con un mal resultado. La osteoporosis debe estar bajo estrecha supervisión


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ácido Ursodesoxicólico/uso terapêutico , Prednisolona/uso terapêutico , Colangite/tratamento farmacológico , Cirrose Hepática Biliar/tratamento farmacológico , Resultado do Tratamento , Estudos de Coortes , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Biópsia
5.
Cochrane Database Syst Rev ; 7: CD000493, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32716060

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013. OBJECTIVES: To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy. DATA COLLECTION AND ANALYSIS: The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy. AUTHORS' CONCLUSIONS: When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).


Assuntos
Colestase/terapia , Complicações na Gravidez/terapia , Prurido/terapia , Carvão Vegetal/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Colestase/complicações , Resina de Colestiramina/uso terapêutico , Dexametasona/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Sofrimento Fetal/epidemiologia , Galactanos/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Mananas/uso terapêutico , Gomas Vegetais/uso terapêutico , Gravidez , Prurido/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , S-Adenosilmetionina/uso terapêutico , Natimorto/epidemiologia , Ácido Ursodesoxicólico/uso terapêutico
7.
Am J Gastroenterol ; 115(7): 1066-1074, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618657

RESUMO

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.


Assuntos
Fosfatase Alcalina/sangue , Bilirrubina/sangue , Colagogos e Coleréticos/uso terapêutico , Colangite/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Biomarcadores/sangue , Colangite/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Taxa de Sobrevida
9.
Int J Public Health ; 65(5): 683-691, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32500239

RESUMO

OBJECTIVE: To determine both the incidence and the prevalence of primary biliary cholangitis (PBC) in Eastern Slovakia and to describe its clinical course and the response to ursodeoxycholic acid (UDCA). METHODS: We recorded data of patients with PBC, who were followed up in gastroenterology and hepatology centers in Eastern Slovakia during the period from June 30, 1999, through June 30, 2019. RESULTS: The annual incidence of PBC varied from 0.7 to 1.5 cases per 100,000 inhabitants between 2014 and 2018. PBC prevalence steadily increased from initial 10.2 cases per 100,000 inhabitants in 2014 to 14.9 cases per 100,000 inhabitants in June 2019. The mean age at the time of diagnosis was 56.3 ± 10.9 years. 95.7% of patients were females, and female/male gender ratio was 22.3:1. In June 2019, prevalence in the female population was 28 cases per 100,000 women. At the time of diagnosis, three-quarters of patients were symptomatic and 10% of patients had liver cirrhosis. The mean follow-up was 7.3 ± 5.2 years. Response to UDCA was observed in 72.1% of patients. Patients with higher baseline alkaline phosphatase (ALP) levels, liver cirrhosis at entry or at the end of follow-up and women younger than 45 years responded worse to UDCA. One-quarter of patients had liver cirrhosis at the end of follow-up. During follow-up, 1.6% of patients underwent liver transplantation and 5.5% of patients died. Five-year and 10-year liver-related mortalities were 2.7% and 4.3%, respectively. CONCLUSION: PBC prevalence in Eastern Slovakia is increasing, and most of the patients respond to therapy with UDCA.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/epidemiologia , Cirrose Hepática Biliar/fisiopatologia , Ácido Ursodesoxicólico/uso terapêutico , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Eslováquia/epidemiologia
10.
Intern Med ; 59(11): 1401-1405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32475907

RESUMO

A 69-year-old man was referred to our department with acute hepatitis. He had been newly treated with benidipine hydrochloride for two months. His blood test results were as follows: aspartate aminotransferase, 1,614 IU/L; alanine aminotransferase, 1,091 IU/L and anti-smooth muscle antibody, ×80. Needle liver biopsy specimen showed interface hepatitis with mainly lymphocytic infiltration and bridging fibrosis in the periportal area. Immunohistochemistry revealed lymphocytic infiltration positive for IgG4. We diagnosed him with IgG4-related AIH with an etiology that was suspected of being drug-induced. Oral prednisolone was started and then tapered after achieving biochemical remission. Hepatitis recurred after the cessation of steroids; however, remission was achieved with ursodeoxycholic acid.


Assuntos
Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/etiologia , Hepatite Crônica/tratamento farmacológico , Imunoglobulina G/sangue , Nifedipino/efeitos adversos , Nifedipino/uso terapêutico , Prednisolona/uso terapêutico , Idoso , Anti-Inflamatórios/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Hepatite Autoimune/diagnóstico , Humanos , Japão , Masculino , Nifedipino/análogos & derivados , Resultado do Tratamento , Ácido Ursodesoxicólico/uso terapêutico
11.
Am J Gastroenterol ; 115(10): 1634-1641, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32467507

RESUMO

INTRODUCTION: Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) have been identified as potential biomarkers in primary biliary cholangitis (PBC), and this study assesses changes of these antibodies over time and if they are associated with clinical outcomes. METHODS: Two hundred fifty-four PBC patients (93.3% female, 51 ± 12.3 years old) were tested for anti-HK1 and anti-KLHL12, antimitochondrial (AMA), anti-gp210, and anti-sp100 antibodies. One hundred sixty-nine patients were tested twice and 49 three times within 4.2 (0.8-10.0) years. Biochemistry and clinical features at diagnosis, response to therapy, events of decompensation, and liver-related death or transplantation were evaluated. RESULTS: Anti-HK1 and anti-KLHL2 were detected in 46.1% and 22.8% patients, respectively. AMA were positive in 93.7%, anti-sp100 in 26.4%, and anti-gp210 in 21.3% of patients. Anti-HK1 and anti-KLHL12 positivity changed over time in 13.3% and 5.5% of patients, respectively. Anti-HK1 or anti-KLHL12 were present in 37.5% of AMA-negative patients, and in 40% of AMA, anti-gp210, and anti-sp100 negative. No significant differences were observed between those with or without HK1 and KLHL12 antibodies, but transplant-free survival and time to liver decompensation were significantly lower in patients anti-HK1 positive (P = 0.039; P = 0.04) and in those anti-sp100 positive (P = 0.01; P = 0.007). No changes in survival and events of liver decompensation were observed according to the positivity of AMA, anti-KLHL12, or anti-gp210 antibodies. DISCUSSION: HK1 and KLHL12 antibodies are present in 40% of PBC patients who are seronegative by the conventional PBC-specific antibodies. The novel antibodies remain rather steady during the course of the disease, and HK1 antibodies are associated with unfavourable outcomes.


Assuntos
Autoanticorpos/imunologia , Hexoquinase/imunologia , Cirrose Hepática Biliar/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Adulto , Antígenos Nucleares/imunologia , Autoantígenos/imunologia , Colagogos e Coleréticos/uso terapêutico , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática Biliar/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Prognóstico , Ácido Ursodesoxicólico/uso terapêutico
12.
Dtsch Med Wochenschr ; 145(5): 296-305, 2020 03.
Artigo em Alemão | MEDLINE | ID: mdl-32120404

RESUMO

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, autoimmune mediated cholestatic liver diseases. Other auto-immune diseases are often associated with PBC and PSC, and inflammatory bowel disease is present in the majority of PSC patients. In the course of disease, chronic inflammation in the liver leads to fibrotic restructuring and ultimately cirrhosis. The diagnosis of PBC is confirmed serologically and PSC is diagnosed via cholangiography, whereas MRCP is preferred over ERCP. For PBC, the first line therapy is ursodeoxycholic acid (UDCA). Prognosis is strongly dependent on the response to UDCA. The only approved second line therapy is obeticholic acid (OCA). Alternatively, Budesonide or Fibrates are often used off-label. In the management of PSC, prevention and adequate treatment of bacterial cholangitis play a major role. For both PBC and PSC novel treatments are currently being tested in clinical trials. Disease management should address compromising symptoms like pruritus and sicca as well as complications due to maldigestion and concomitant autoimmune diseases. The only curative treatment available is liver transplantation and should be considered at a MELD score of 15.


Assuntos
Doenças Autoimunes , Colangite Esclerosante , Cirrose Hepática Biliar , Colagogos e Coleréticos/uso terapêutico , Colangiografia , Ácidos Fíbricos/uso terapêutico , Humanos , Fígado/patologia , Fígado/fisiopatologia , Transplante de Fígado , Ácido Ursodesoxicólico/uso terapêutico
13.
Medicine (Baltimore) ; 99(3): e18855, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011505

RESUMO

RATIONALE: Prolonged cholestasis is a rare complication associated with endoscopic retrograde cholangiopancreatography (ERCP). PATIENT CONCERNS: A 68-year-old man who presented with worsening cholestasis after ERCP for the removal of a common bile duct stone. DIAGNOSIS: Total bilirubin increased up to 35.2 mg/dL after the 21st day post-ERCP. A percutaneous liver biopsy was performed and drug-related cholestasis was suspected as occurring as a result of the contrast agent. INTERVENTIONS: Oral ursodeoxycholic acid and cholestyramine were prescribed to the patient. OUTCOMES: By the 7th week post-ERCP, the patient's symptoms and markers of physiological health began to resolve. The bilirubin returned to normal levels on the 106th day post-ERCP. We reviewed the literature for studies of 9 patients with jaundice more than 30 days post-ERCP, the peak of total serum bilirubin occurred on 16th ±â€Š7th days and the recovery followed after mean time of 54th ±â€Š22th days. LESSONS: Although the cholestasis was prolonged, the outcome was favorable after medical therapy. There were no long-term consequences for the patient.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colestase/induzido quimicamente , Meios de Contraste/efeitos adversos , Idoso , Colagogos e Coleréticos/uso terapêutico , Colestase/tratamento farmacológico , Resina de Colestiramina/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Ácido Ursodesoxicólico/uso terapêutico
14.
Am J Gastroenterol ; 115(2): 262-270, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31985529

RESUMO

BACKGROUND: We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. METHODS: Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. RESULTS: Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. DISCUSSION: African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.


Assuntos
Afro-Americanos/estatística & dados numéricos , Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/terapia , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Americanos Asiáticos/estatística & dados numéricos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Modelos de Riscos Proporcionais , Taxa de Sobrevida
15.
Sci Rep ; 10(1): 977, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969665

RESUMO

As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-ß (PDGFR-ß clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Pericitos/efeitos dos fármacos , Vasos Retinianos/efeitos dos fármacos , Ácido Ursodesoxicólico/uso terapêutico , Animais , Quimiocina CCL2/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos , Pericitos/metabolismo , Pericitos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Ácido Ursodesoxicólico/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Dig Dis Sci ; 65(2): 470-479, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31377883

RESUMO

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear. METHODS: Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6 months of treatment with ursodeoxycholic acid (UDCA, 15 mg/kg d). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma's criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100 ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80. RESULTS: RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P < 0.05). High-RANK patients seemed to have better response to UDCA than low-RANK patients (88.9% vs. 40.9%, P < 0.05). The baseline biochemical parameters between the two groups were comparable. The decline percentages of ALP and GGT after UDCA treatment were more obvious in high-RANK patients than those in low-RANK patients (53.90% ± 9.82% vs. 23.93% ± 6.24%, P < 0.05; 74.11% ± 7.18% vs. 48.00% ± 8.17%, P < 0.05, respectively). HIBECs proliferation was significantly inhibited after treatment of RANKL or transfection with LV-RANK. Increased expression of IL-6 and E-cadherin was observed in HIBECs treated with RANKL or LV-RANK. CONCLUSION: The overall hepatic RANK expression was associated with disease severity and biochemical response in PBC patients. Activation of RANK/RANKL signaling pathway inhibited cholangiocytes proliferation in vitro. Our study suggested that RANK/RANKL pathway might be a potential target of immunotherapy of PBC based on its involvement in the occurrence and development of the disease.


Assuntos
Ductos Biliares Intra-Hepáticos/metabolismo , Células Epiteliais/metabolismo , Cirrose Hepática Biliar/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Adulto , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Aspartato Aminotransferases/metabolismo , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Ductos Biliares Intra-Hepáticos/citologia , Ductos Biliares Intra-Hepáticos/patologia , Caderinas/genética , Caderinas/metabolismo , Colagogos e Coleréticos/uso terapêutico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/genética , Masculino , Pessoa de Meia-Idade , Ligante RANK/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Receptor Ativador de Fator Nuclear kappa-B/genética , Índice de Gravidade de Doença , Transfecção , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ácido Ursodesoxicólico/uso terapêutico , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , gama-Glutamiltransferase/metabolismo
18.
Annu Rev Pharmacol Toxicol ; 60: 503-527, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31506007

RESUMO

Though ursodeoxycholic acid (UDCA) remains the baseline treatment for most cholestatic liver diseases, UDCA treatment leaves approximately one-third of patients with primary biliary cholangitis (PBC) and all patients with primary sclerosing cholangitis (PSC) at risk for disease progression. New anticholestatic agents, including nuclear receptor agonists, choleretics, and bile acid synthesis suppressors, will likely increase response rates to therapy in PBC and PSC. Strategies that target early immune-mediated injury have so far been disappointing, hampered by the lack of biomarkers to detect early disease states, which then could profit from immunomodulatory therapy. Future concepts need to personalize treatments according to disease stage, progression, and phase, and to combine multiple drugs to target different pathogenic pathways.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colestase/tratamento farmacológico , Animais , Colagogos e Coleréticos/farmacologia , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/fisiopatologia , Colestase/fisiopatologia , Doença Crônica , Progressão da Doença , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/fisiopatologia , Receptores Citoplasmáticos e Nucleares/agonistas , Ácido Ursodesoxicólico/uso terapêutico
20.
Life Sci ; 242: 117175, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31843528

RESUMO

AIMS: Ursodeoxycholic acid (UDCA) has been widely used in the treatment of primary biliary cholangitis (PBC) with chronic liver fibrosis, but its detailed mechanism remains unclear. This study was aimed to determine whether autophagic signaling is involved in the therapeutic effect of UDCA on liver fibrosis. METHODS: By using hepatic stellate cell (HSC) line LX2 and CCl4-induced fibrotic rat model, autophagy signaling was investigated by western blotting and mRFP-EGFP-LC3 tandem fluorescent tagged plasmid (ptfLC3) transfection technique. Anti-fibrotic profile was determined by western blotting, qRT-PCR, MTT assay, trypan blue, hydroxyproline assay and Masson staining. KEY FINDINGS: TGFß1 treatment decreased P62 accumulation and increased both autophagosomes and autolysosomes in LX2 cells, thereby elevated autophagic flux. Hydroxychloroquine (HCQ), antagonist of autophagy, was found to dramatically inhibit COL1A2 mRNA expression and cell proliferation in a dose-dependent manner. This coincides with the effect of UDCA intervention on collagen aggradation and cell viability. Meanwhile, UDCA inhibited TGFß1-induced autophagy flux. And rapamycin, agonist of autophagy, was found to impair the anti-fibrotic effect of UDCA. Moreover, study in vivo showed that UDCA alone or in combination with HCQ restored the CCl4-induced liver fibrosis in rodent models with autophagy inhibited profile. SIGNIFICANCE: Taken together, our study revealed that UDCA displays anti-fibrotic role by protecting HSC against production of collagen and inhibiting cellular viability involving autophagy inhibition and provide a new insight into the pharmacological basis of UDCA treatment for hepatic fibrosis.


Assuntos
Autofagia/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Animais , Western Blotting , Linhagem Celular , Modelos Animais de Doenças , Humanos , Hidroxicloroquina/farmacologia , Hidroxiprolina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/farmacologia
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