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3.
BMC Infect Dis ; 24(1): 180, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336644

RESUMO

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.


Assuntos
Bacteriemia , Colangite , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias , Pseudomonas , Bactérias Aeróbias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Colangite/tratamento farmacológico , Colangite/etiologia , Solo
4.
BMC Gastroenterol ; 24(1): 18, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178006

RESUMO

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.


Assuntos
Colangite , Cirrose Hepática Biliar , Humanos , Colagogos e Coleréticos/uso terapêutico , Colangite/tratamento farmacológico , Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico
5.
Medicina (B Aires) ; 84(1): 168-170, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38271946

RESUMO

Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is Escherichia coli. Candida sp acute cholangitis is a rare finding, which is more common in patients with immunosuppression, use of corticosteroids, prolonged antibiotic treatment or surgical procedures of the bile duct. We present the case of a 67-year-old woman with none of the above-mentioned history who consulted for fever, abdominal pain and jaundice. MRI of the abdomen revealed a lithiasic image in the common bile duct with dilation. It required endoscopic drainage of the biliary tract. Direct microscopic examination of the bile fluid revealed gram-negative bacilli and yeast, and in the culture of bile fluid Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL) and Candida glabrata were isolated. The patient completed the antibiotic treatment with piperacillin tazobactam and anidulafungin with good evolution. Bile duct infection by association of Gram-negative bacilli and Candida sp is a rare entity, more in patients without underlying diseases.


La colangitis aguda es una infección de la vía biliar, asociada a la obstrucción de esta. El cultivo de la bilis es positivo en la mayoría de los casos y el agente etiológico más frecuente es Escherichia coli. La colangitis aguda por Candida sp es un hallazgo poco común, que es más frecuente en pacientes con inmunocompromiso, uso de corticoides, tratamiento antibiótico prolongado o procedimientos quirúrgicos de la vía biliar. Presentamos el caso de una mujer de 67 años, que no presentaba ninguno de los antecedentes mencionados, y que consultó por fiebre, dolor abdominal e ictericia. En la resonancia magnética nuclear de abdomen se constató imagen litiásica en el colédoco con dilatación de la vía biliar. Requirió drenaje endoscópico del tracto biliar. En el examen microscópico directo del líquido biliar se evidenciaron levaduras y bacilos Gram negativos, y en el cultivo se aisló Klebsiella pneumoniae productora de betalactamasa de espectro extendido (BLEE) y Candida glabrata. La paciente completó el tratamiento antibiótico con piperacilina tazobactam y anidulafungina con buena evolución. La infección de la vía biliar por la asociación de bacilos Gram negativos y Candida sp es una entidad poco frecuente, más en pacientes sin enfermedades subyacentes.


Assuntos
Colangite , Klebsiella pneumoniae , Feminino , Humanos , Idoso , Candida glabrata , Colangite/tratamento farmacológico , Colangite/etiologia , Colangite/cirurgia , Antibacterianos/uso terapêutico , Bile , Bactérias Gram-Negativas , Escherichia coli
6.
Drugs ; 84(1): 1-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38082142

RESUMO

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that can progress to cirrhosis and hepatic failure if left untreated. Ursodeoxycholic acid (UDCA) was introduced as a first-line drug for PBC around 1990; it remarkably improved patient outcomes, leading to the nomenclature change of PBC in 2015, from primary biliary "cirrhosis" to primary biliary "cholangitis." Nevertheless, 20-30% of patients exhibit an incomplete response to UDCA, resulting in significantly worse outcomes compared to those with a complete response. Therefore, improving the long-term outcomes of patients with an incomplete response to UDCA has been recognized as an unmet need. In addition, patients with PBC often suffer from a variety of debilitating symptoms, such as pruritus, fatigue and sicca syndrome, which significantly impair their health-related quality of life. Thus, appropriate management of these symptoms is currently regarded as another unmet need for PBC treatment. In this review, several compounds and drugs under clinical trials that can potentially solve these unmet needs are comprehensively discussed, and future directions of treatment policy of PBC are proposed for significantly improving long-term outcome as well as health-related quality of life of patients.


Assuntos
Colangite , Colestase , Cirrose Hepática Biliar , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Colangite/tratamento farmacológico , Qualidade de Vida , Ácido Ursodesoxicólico/uso terapêutico , Colestase/tratamento farmacológico
8.
Am J Gastroenterol ; 119(1): 176-182, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37732816

RESUMO

INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.


Assuntos
Antibacterianos , Colangite , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Doença Aguda , Colangite/tratamento farmacológico , Colangite/etiologia
9.
J Infect Chemother ; 30(5): 423-428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37981024

RESUMO

INTRODUCTION: Cefmetazole (CMZ), an antibiotic with limited international distribution, is recommended by the Tokyo Guidelines 2018 (TG18) for non-severe cases of acute cholangitis (AC). However, the risk factors for CMZ-non-susceptible (CMZ-NS) bacteremia in AC remain unclear. Here, we aimed to investigate the risk factors for CMZ-NS bacteremia and evaluate mortality in patients with AC. METHODS: This single-center, retrospective, observational study included all patients diagnosed with definite bacteremic AC, based on TG18, from April 2019 to March 2023. Risk factors for CMZ-NS bacteremia were analyzed by univariate, and age- and sex-adjusted, logistic regression analyses. Mortality was compared by cause of obstruction, CMZ-susceptible/CMZ-NS bacteremia, and initial treatment. RESULTS: In total, 165 patients were enrolled. CMZ-NS bacteremia was diagnosed in 46 (27.9 %) patients. Histories of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy were identified as significant factors associated with the risk of CMZ-NS bacteremia. Thirteen patients died within 30 days of hospital admission. The mortality of patients with AC and malignant biliary obstruction was statistically higher than that of patients with bile duct stones. No patients with AC and bile duct stones died in the group with CMZ-NS bacteremia and inappropriate initial antibiotics. CONCLUSIONS: In AC, a history of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy are associated with an increased risk of CMZ-NS bacteremia. Therefore, the choice of empiric therapy for AC should be based on the etiology and patient background, rather than on the severity.


Assuntos
Colangite , Colestase , Diabetes Mellitus , Neoplasias Pancreáticas , Humanos , Antibacterianos/uso terapêutico , Cefmetazol , Colangite/complicações , Colangite/tratamento farmacológico , Neoplasias Pancreáticas/complicações , Estudos Retrospectivos , Fatores de Risco , Masculino , Feminino
10.
J Surg Res ; 293: 14-21, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37690382

RESUMO

INTRODUCTION: In acute cholangitis (AC), monitoring treatment response to antimicrobial therapy allows for making timely decisions on early biliary decompression. The aims of this study were to compare the discriminating powers of traditional blood inflammatory markers and propose new inflammatory markers that have a better ability to distinguish between patients with and without biliary tract infection. METHODS: This was a retrospective cohort study. Patients who underwent endoscopic retrograde cholangio-pancreaticography for AC and those without biliary tract inflammation were randomly selected in the 4:3 ratio of their hospital admissions from our hospital endoscopic retrograde cholangio-pancreaticography database. The exclusion criterion was the absence of C-reactive protein (CRP) measurements. RESULTS: The discriminating powers of the neutrophil count, lymphocytes, albumin, neutrophil-to-lymphocyte ratio, and CRP were superior to that of white blood cell (P1 < 0.005; P2 = 0.004; P3 < 0.0005; P4 < 0.0005; P5 < 0.0005). In monitoring treatment response in AC, lymphocyte count, albumin, neutrophil-to-lymphocyte ratio, and CRP were better than neutrophil count (P6 = 0.037, P7 < 0.005, P8, 9 < 0.0005). The area under the receiver operating characteristic curve (AUC) of CRP was higher than the AUC for lymphocytes, 96% (95% confidence interval [CI]: 94-98%) versus 81% (95% CI: 76-86%) (P < 0.0005), and larger than the AUC for albumin, 88% (95% CI: 84-92%) (P < 0.0005), indicating a greater discriminating power of CRP. However, the discriminating power of CRP-to-lymphocyte ratio (CLR) was more than that for CRP (P = 0.006) but equal to CRP-to-(lymphocytes∗albumin) ratio (CLAR) (P = 0.249). The AUCs of CLR and CLAR were both 98% (95% CI: 96-99%). CONCLUSIONS: CLR and CLAR have superior discriminating powers than traditional inflammatory markers used for monitoring treatment response in AC.


Assuntos
Proteína C-Reativa , Colangite , Humanos , Proteína C-Reativa/análise , Estudos Retrospectivos , Biomarcadores , Colangite/diagnóstico , Colangite/tratamento farmacológico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Albuminas , Curva ROC
12.
Medicine (Baltimore) ; 102(41): e35655, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37832080

RESUMO

RATIONALE: A chronic autoimmune liver disease known as primary biliary cholangitis (PBC) that selectively destructs small intrahepatic biliary epithelial cells and may result in biliary cirrhosis and eventually liver transplantation or death. PBC is associated with various other extrahepatic autoimmune diseases; however, the combination of PBC with ankylosing spondylitis has been rarely reported in the literature. Here, we reported a case of PBC with ankylosing spondylitis to improve our understanding of such coexistence and provide new ideas for the treatment of such patients. PATIENT CONCERNS: A 54-year-old man was presented to the Department of Rheumatology because of an abnormal liver function test for 7 years, chest and back pain for 1 year, and low back pain for 2 months. DIAGNOSES: Primary biliary cholangitis, ankylosing spondylitis, and old pulmonary tuberculosis. INTERVENTIONS: The patient refused to use nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, and biologic disease-modifying antirheumatic drugs; thus, he was treated with methylenediphosphonate (99Tc-MDP) and ursodeoxycholic acid (UDCA). OUTCOMES: The patient achieved remission with UDCA and 99Tc-MDP therapy. LESSONS: In the treatment of PBC combined with other disorders, the characteristics of different diseases should be considered. The patient reported herein was treated with 99Tc-MDP and UDCA, and his condition improved; thus, we consider 99Tc-MDP to be an effective treatment. Furthermore, in line with the current understanding of the pathogenesis of PBC and ankylosing spondylitis, we hypothesize that interleukin-17 inhibitor is an effective treatment for such patients.


Assuntos
Antirreumáticos , Doenças Autoimunes , Colangite , Cirrose Hepática Biliar , Espondilite Anquilosante , Masculino , Humanos , Pessoa de Meia-Idade , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Antirreumáticos/uso terapêutico , Colangite/complicações , Colangite/tratamento farmacológico , Colagogos e Coleréticos/uso terapêutico
13.
Int J Surg ; 109(12): 4009-4017, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678274

RESUMO

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.


Assuntos
Atresia Biliar , Colangite , Icterícia , Criança , Humanos , Lactente , Portoenterostomia Hepática/efeitos adversos , Estudos Prospectivos , Imunoglobulinas Intravenosas , Atresia Biliar/cirurgia , Atresia Biliar/complicações , Colangite/tratamento farmacológico , Colangite/etiologia , Icterícia/complicações , Antibacterianos/uso terapêutico , Meropeném , Estudos Retrospectivos , Resultado do Tratamento
14.
Cell Mol Gastroenterol Hepatol ; 16(6): 1011-1031, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37567385

RESUMO

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.


Assuntos
Colangite , Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Aminoácidos , Proteobactérias , Escherichia coli , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Alanina , Colangite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
15.
World J Gastroenterol ; 29(19): 3027-3039, 2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37274798

RESUMO

BACKGROUND: Acute cholangitis (AC) constitutes an infection with increased mortality rates in the past. Due to new diagnostic tools and therapeutic methods, the mortality of AC has been significantly reduced nowadays. The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection. However, the optimal duration of the antibiotic treatment of AC is still debatable. AIM: To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC. METHODS: This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence. The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Fifteen studies were included in the systematic review, and eight were eligible for meta-analysis. Due to heterogeneous duration cutoffs, three study-analysis groups were formed, with a cutoff of 2-3, 6-7, and 14 d. RESULTS: A total of 2763 patients were included in the systematic review, and 1313 were accounted for the meta-analysis. The mean age was 73.66 ± 14.67 years, and the male and female ratio was 1:08. No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d, compared to longer treatments (odds ratio = 0.78, 95% confidence interval: 0.23-2.67, I2 = 9%) and the recurrence rates and hospitalization length were also not different in all study groups. CONCLUSION: Short- and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC. Safe conclusions cannot be extracted concerning the hospitalization duration.


Assuntos
Antibacterianos , Colangite , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Colangite/tratamento farmacológico , Hospitalização
16.
Hepatol Commun ; 7(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37267215

RESUMO

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.


Assuntos
Colangite , Colestase , Cirrose Hepática Biliar , Masculino , Feminino , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/epidemiologia , Colangite/diagnóstico , Colangite/tratamento farmacológico , Colangite/epidemiologia , Prognóstico , Colestase/tratamento farmacológico
17.
Ann Hepatol ; 28(5): 101121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37302574

RESUMO

Anti-gp210 is the disease-specific anti-nuclear antibody (ANA) of primary biliary cholangitis (PBC). Anti-gp210-positive PBC patients have worse responses to ursodeoxycholic acid (UDCA) as compared with anti-gp210-negative patients. Moreover, anti-gp210-positive patients always present with more severe histopathologic features including lobular inflammation, interfacial hepatitis, and bile duct injury, and have a worse prognosis than their anti-gp210-negative counterparts. Previous studies have identified two antigenic epitopes recognized by anti-gp210. Although the pathogenetic mechanism of anti-gp210 production remains unclear, evidence suggests that the autoimmune response to anti-gp210 production might be due to molecular mimicry induced by bacteria or endogenous peptides. T cells and related cytokines play a critical role in the pathogenesis of PBC, however, the mechanism hasn't been fully understood. Thus, this review focuses on the clinicopathological characteristics of anti-gp210-positive PBC patients, the fundamental research of gp210 antigen, and the possible mechanism of anti-gp210 production to clarify the mechanism of anti-gp210-positive PBC and provide potential molecular targets for disease prevention and treatment in the future.


Assuntos
Colangite , Cirrose Hepática Biliar , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/tratamento farmacológico , Complexo de Proteínas Formadoras de Poros Nucleares , Ácido Ursodesoxicólico/uso terapêutico , Anticorpos Antinucleares , Prognóstico , Autoanticorpos , Colangite/diagnóstico , Colangite/tratamento farmacológico
18.
Front Immunol ; 14: 1184252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325634

RESUMO

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.


Assuntos
Colangite , Colestase , Cirrose Hepática Biliar , Animais , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/etiologia , Ácido Ursodesoxicólico/uso terapêutico , Colangite/tratamento farmacológico , Colangite/patologia , Colestase/tratamento farmacológico , Fibrose
19.
Zhonghua Gan Zang Bing Za Zhi ; 31(3): 247-251, 2023 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-37137849

RESUMO

There are limited drug options in the field of primary biliary cholangitis, so there is a great clinical need. In recent years, research and development of PBC treatment medications have been active domestically and internationally, and clinical trials have been conducted on multiple drugs with distinct targets. Therefore, on February 13, 2023, the State Drug Administration issued the "Technical Guidelines for Clinical Trials of Drugs for the Treatment of Primary Biliary Cholangitis" in order to guide and standardize the clinical trials of drugs for the treatment of PBC. This article briefly summarizes the key points of the guiding principles, focuses on the difficulties of clinical evaluation of drugs, discusses the key elements of clinical trials such as the selection of test populations and efficacy endpoints, and introduces the determination process through literature searches and expert discussion methods combined with reviewer experience and scientific considerations.


Assuntos
Colangite , Cirrose Hepática Biliar , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Colangite/tratamento farmacológico , Preparações Farmacêuticas
20.
Medicina (Kaunas) ; 59(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37109679

RESUMO

Background and Objectives: Acute cholangitis (AC) is still lethal if not treated promptly and effectively. Biliary drainage, also known as source control, has been acknowledged as the backbone treatment for patients with AC; nonetheless, antimicrobial therapy allows these patients to undergo non-emergent drainage procedures. This retrospective study aims to observe the bacterial species involved in AC and analyze the antimicrobial resistance patterns. Materials and Methods: Data were collected for four years, comparing patients with benign and malignant bile duct obstruction as an etiology for AC. A total of 262 patients were included in the study, with 124 cases of malignant obstruction and 138 cases of benign obstruction. Results: Positive bile culture was obtained in 192 (73.3%) patients with AC, with a higher rate among the benign group compared with malignant etiologies (55.7%.vs 44.3%). There was no significant difference between the Tokyo severity scores in the two study groups, identifying 34.7% cases of malignant obstruction with Tokyo Grade 1 (TG1) and 43.5% cases of TG1 among patients with benign obstruction. Similarly, there were no significant differences between the number of bacteria types identified in bile, most of them being monobacterial infections (19% in the TG1 group, 17% in the TG2 group, and 10% in the TG3 group). The most commonly identified microorganism in blood and bile cultures among both study groups was E. coli (46.7%), followed by Klebsiella spp. (36.0%) and Pseudomonas spp. (8.0%). Regarding antimicrobial resistance, it was observed that significantly more patients with malignant bile duct obstruction had a higher percentage of bacterial resistance for cefepime (33.3% vs. 11.7%, p-value = 0.0003), ceftazidime (36.5% vs. 14.5%, p-value = 0.0006), meropenem (15.4% vs. 3.6%, p-value = 0.0047), and imipenem (20.2% vs. 2.6%, p-value < 0.0001). Conclusions: The positive rate of biliary cultures is higher among patients with benign biliary obstruction, while the malignant etiology correlates with increased resistance to cefepime, ceftazidime, meropenem, and imipenem.


Assuntos
Anti-Infecciosos , Colangite , Colestase , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefepima , Ceftazidima , Meropeném , Escherichia coli , Estudos Retrospectivos , Farmacorresistência Bacteriana , Colestase/complicações , Colangite/complicações , Colangite/tratamento farmacológico , Imipenem
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