Role of the IgG4-related cholangitis autoantigen annexin A11 in cholangiocyte protection.

BACKGROUND & AIMS: Annexin A11 was identified as autoantigen in IgG4-related cholangitis (IRC), a B-cell driven disease. Annexin A11 modulates calcium-dependent exocytosis, a crucial mechanism for insertion of proteins into their target membranes. Human cholangiocytes form an apical 'biliary bicarbonate umbrella' regarded as defense against harmful hydrophobic bile acid influx. The bicarbonate secretory machinery comprises the chloride/bicarbonate exchanger AE2 and the chloride channel ANO1. We aimed to investigate the expression and function of annexin A11 in human cholangiocytes and a potential role of IgG1/IgG4-mediated autoreactivity against annexin A11 in the pathogenesis of IRC. METHODS: Expression of annexin A11 in human liver was studied by immunohistochemistry and immunofluorescence. In human control and ANXA11 knockdown H69 cholangiocytes, intracellular pH, AE2 and ANO1 surface expression, and bile acid influx were examined using ratio microspectrofluorometry, cell surface biotinylation, and 22,23-3H-glycochenodeoxycholic acid permeation, respectively. The localization of annexin A11-mEmerald and ANO1-mCherry was investigated by live-cell microscopy in H69 cholangiocytes after incubation with IRC patient serum containing anti-annexin A11 IgG1/IgG4-autoantibodies or disease control serum. RESULTS: Annexin A11 was strongly expressed in human cholangiocytes, but not hepatocytes. Knockdown of ANXA11 led to reduced plasma membrane expression of ANO1, but not AE2, alkalization of intracellular pH and uncontrolled bile acid influx. High intracellular calcium conditions led to annexin A11 membrane shift and colocalization with ANO1. Incubation with IRC patient serum inhibited annexin A11 membrane shift and reduced ANO1 surface expression. CONCLUSION: Cholangiocellular annexin A11 mediates apical membrane abundance of the chloride channel ANO1, thereby supporting biliary bicarbonate secretion. Insertion is inhibited by IRC patient serum containing anti-annexin A11 IgG1/IgG4-autoantibodies. Anti-annexin A11 autoantibodies may contribute to the pathogenesis of IRC by weakening the 'biliary bicarbonate umbrella'. LAY SUMMARY: We previously identified annexin A11 as a specific autoantigen in immunoglobulin G4-related cholangitis (IRC), a B-cell driven disease affecting the bile ducts. Human cholangiocytes are protected against harmful hydrophobic bile acid influx by a defense mechanism referred to as the 'biliary bicarbonate umbrella'. We found that annexin A11 is required for the formation of a robust bicarbonate umbrella. Binding of patient-derived annexin A11 autoantibodies inhibits annexin A11 function, possibly contributing to bile duct damage by weakening the biliary bicarbonate umbrella in patients with IRC.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Primary biliary cholangitis.

Primary biliary cholangitis is an autoimmune liver disease that predominantly affects women. It is characterised by a chronic and destructive, small bile duct, granulomatous lymphocytic cholangitis, with typical seroreactivity for antimitochondrial antibodies. Patients have variable risks of progressive ductopenia, cholestasis, and biliary fibrosis. Considerations for the cause of this disease emphasise an interaction of chronic immune damage with biliary epithelial cell responses and encompass complex, poorly understood genetic risks and environmental triggers. Licensed disease-modifying treatment focuses on amelioration of cholestasis, with weight-dosed oral ursodeoxycholic acid. For patients who do not respond sufficiently, or patients with ursodeoxycholic acid intolerance, conditionally licensed add-on therapy is with the FXR (NR1H4) agonist, obeticholic acid. Off-label therapy is recognised as an alternative, notably with the pan-PPAR agonist bezafibrate; clinical trial agents are also under development. Baseline characteristics, such as young age, male sex, and advanced disease, and serum markers of liver injury, particularly bilirubin and ALP, are used to stratify risk and assess treatment responsiveness. Parallel attention to the burden of patient symptoms is paramount, including pruritus and fatigue.

S-adenosyl-L-methionine (SAMe) halts the autoimmune response in patients with primary biliary cholangitis (PBC) via antioxidant and S-glutathionylation processes in cholangiocytes.

S-adenosyl-L-methionine is an endogenous molecule with hepato-protective properties linked to redox regulation and methylation. Here, the potential therapeutic value of SAMe was tested in 17 patients with PBC, a cholestatic disease with autoimmune phenomena targeting small bile ducts. Nine patients responded to SAMe (SAMe responders) with increased serum protein S-glutathionylation. That posttranslational protein modification was associated with reduction of serum anti-mitochondrial autoantibodies (AMA-M2) titers and improvement of liver biochemistry. Clinically, SAMe responders were younger at diagnosis, had longer duration of the disease and lower level of serum S-glutathionylated proteins at entry. SAMe treatment was associated with negative correlation between protein S-glutathionylation and TNFα. Furthermore, AMA-M2 titers correlated positively with INFγ and FGF-19 while negatively with TGFß. Additionally, cirrhotic PBC livers showed reduced levels of glutathionylated proteins, glutaredoxine-1 (Grx-1) and GSH synthase (GS). The effect of SAMe was also analyzed in vitro. In human cholangiocytes overexpressing miR-506, which induces PBC-like features, SAMe increased total protein S-glutathionylation and the level of γ-glutamylcysteine ligase (GCLC), whereas reduced Grx-1 level. Moreover, SAMe protected primary human cholangiocytes against mitochondrial oxidative stress induced by tBHQ (tert-Butylhydroquinone) via raising the level of Nrf2 and HO-1. Finally, SAMe reduced apoptosis (cleaved-caspase3) and PDC-E2 (antigen responsible of the AMA-M2) induced experimentally by glycochenodeoxycholic acid (GCDC). These data suggest that SAMe may inhibit autoimmune events in patients with PBC via its antioxidant and S-glutathionylation properties. These findings provide new insights into the molecular events promoting progression of PBC and suggest potential therapeutic application of SAMe in PBC.

A Resected Case of Follicular Cholangitis That Was Positive on 18F-fluorodeoxyglucose-positron Emission Tomography.

We experienced a case of follicular cholangitis that was positive on fluorodeoxyglucose-positron emission tomography (18F-FDG-PET). A 70-year-old man was admitted for jaundice. Endoscopic retrograde cholangiography showed stenosis of the middle to upper choledocus. 18F-FDG-PET depicted a localized hot spot at the stenotic lesion (maximum standardized uptake value = 8.2). Although no malignant findings were found in the cytology or on a bile duct biopsy, malignancy could not be excluded, so surgical treatment was performed. Follicular cholangitis is a new, rare disease that causes severe biliary stricture. Only 11 cases of follicular cholangitis have been reported, including the present case.

Microbiology and clinical characteristics of acute cholangitis with their impact on mortality; a retrospective cross sectional study.

OBJECTIVE: To evaluate microbiological and clinical characteristics of acute cholangitis along with their impact on mortality, and to compare the role of early versus late biliary drainage in the management of cholangitis. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital Research Centre, Lahore, Pakistan, and comprised records of all patients presenting with acute cholangitis from June, 2012, to June, 2017. The risk factors, presence of bacteremia, resistance pattern of microbial pathogens and severity were assessed according to Tokyo guidelines in addition to associated mortality and recurrence at 3 months. Data was analysed using SPSS 20. RESULTS: Of the 230 patients, 137(59.6%) were male. The overall mean age was 56±13 years. The most common isolated organism was Escherichia coli 54(70.1%). Clinical severity (p=0.001), late biliary drainage (p=0.001) and use of multiple stents (p=0.03) were associated with increased mortality. However, in multivariable analysis, only high body mass index (p=0.01) and Tokyo severity grades II (p=0.04) and III (p=0.001) were significant factors associated with mortality. CONCLUSIONS: Early identification of risk factors, administration of appropriate antibiotics and establishing early biliary drainage were found to be the key management steps to reduce cholangitis-related mortality.

Monitoring of impaired phagocytic function of Kupffer cells in an obstructive cholangitis rat model using superparamagnetic iron oxide MRI and contrast-enhanced ultrasound.

BACKGROUND: Kupffer cells (KC) have an important role in the host defense in obstructive cholangitis. Non-invasive monitoring of phagocytic function of KC is pivotal. Several studies showed the possibility of non-invasive monitoring of phagocytic function of KC using superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) or contrast-enhanced ultrasound (CEUS). PURPOSE: To investigate the serial change of KC function using SPIO-MRI and CEUS and whether the SPIO-MRI parameter correlates with the CEUS parameter in obstructive cholangitis rat models. MATERIAL AND METHODS: With our institutional Animal Care and Use Committee approval, 19 rats (common bile duct ligation [CBDL]: n = 9; control: n = 10) underwent SPIO-MRI and CEUS at baseline, two, and four weeks after CBDL. The relative signal loss (RSL) of T2* value on SPIO-MRI and Kupffer phase parenchymal echogenicity (KPE) on CEUS were measured. The correlation between SPIO-MRI and CEUS parameters were compared with KC count. RESULTS: In CBDL group, RSL and KPE had significantly decreased (72.1% to 29.5%, 2.7 to 0.4) at four weeks compared with those in the control group (68.2% to 58.3%, 2.5 to 3.0, P < 0.05). During the follow-up period, RSL showed significantly positive correlations with KPE ( P = 0.007). In addition, at four weeks, we found RSL was positively correlated with KPE (ρ = 0.750, P = 0.002). KC count was negatively correlated to RSL and KPE at four weeks (ρ = -0.771, P = 0.001 and ρ = -0.644, P = 0.013). CONCLUSION: SPIO-MRI and CEUS may be equally useful for monitoring the serial changes of KC phagocytic function in vivo.

Coronary flow reserve in patients with primary biliary cholangitis.

BACKGROUND: It is still not clear whether primary biliary cholangitis (PBC) is associated with abnormalities of the cardiovascular system. We aimed to assess the relationship between PBC and coronary flow reserve (CFR). METHODS: Our inclusion criterion was a diagnosis of PBC with no clinical evidence of heart disease or metabolic syndrome. Coronary flow velocity in the left anterior descending coronary artery was measured using transthoracic Doppler echocardiography at rest (DFVr), and during adenosine infusion (DFVh). The corrected CFR (cCFR) was defined as the ratio of DFVh to DFVr corrected for cardiac workload (cDFVr). Microvascular resistance was also assessed in baseline (BMR) and hyperemic conditions (HMR). RESULTS: 37 PBC patients and 37 sex- and age-matched controls were considered. The cCFR was significantly lower in PBC patients (2.8 ±â€¯0.7 vs. 3.7 ±â€¯0.7, p < 0.0001), and abnormal (≤2.5) in 13 (35%) of them, but in none of the controls (p < 0.0001). The cDFVr was higher in patients with abnormal cCFR (29.0 ±â€¯6.0 vs. 20.4 ±â€¯4.5 cm/sec, p < 0.0001). The CFR and cCFR did not correlate with any characteristics of PBC, comorbidities or Framingham risk scores. The BMR and HMR correlated with time since PBC diagnosis and duration of symptoms. CONCLUSION: The CFR is reduced in PBC, apparently due to mechanisms correlating with the time since diagnosis. In particular, the higher cDFVr with a lower basal resistance in patients with cCFR ≤ 2.5 suggests a compensatory mechanism against any cardiomyocyte bioenergetics impairment.

Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model.

OBJECTIVE: To determine the diagnostic accuracy of Tokyo guidelines (TG) 2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis. METHODS: Retrospective 1-year study of consecutive hospital admissions for acute cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality. RESULTS: Of the 183 patients with acute cholangitis, diagnostic accuracy based on Charcot's triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p < .001), respectively. Regarding severity based on TG18/TG13, 30.6% of cases were severe. A poor prognosis was found in 10.9% of patients. After multivariate analysis, systolic blood pressure <90 mmHg (OR 11.010; p < .001), serum albumin <3 g/dL (OR 1.355; p = .006), active oncology disease (OR 3.818; p = .006) and malignant aetiology of obstructive jaundice (OR 2.224; p = .021) were independent predictors of poor prognosis. The discriminative ability of the model with these four variables was high (AUROC 0.842; p < .001), being superior to TG18/TG13 (AUROC 0.693; p = .005). CONCLUSIONS: TG18/TG13 showed high diagnostic accuracy in acute cholangitis. Compared with TG18/TG13, the simplified severity model ≥2 allows easy selection of patients who will benefit from admission to the intensive care unit and early biliary decompression.

A disclosed diagnosis for 24 year's unknown illness.

IgG4-related disease (IgG4-RD) is a newly described illness over the last several years. A 57-year-old man, who had been followed for chronic kidney disease (CKD), chronic pancreatitis and history of operated cholangitis, was admitted to our hospital for abdominal pain and worsening renal function. Serum levels of IgG and IgG4 were elevated. CT scan showed the characteristic findings of IgG4-related retroperitoneal fibrosis, pancreas and kidney disease. An endoscopic biopsy revealed the finding compatible with IgG4-RD. Steroid therapy led to the remission of his abdominal pain. Patients with CKD of unknown aetiology may have IgG4-RD.

Obstruction of the Biliary and Urinary System.

Biliary and urinary obstructions can be managed endoscopically or cystoscopically, surgically or by percutansous intervention or drainage. If the obtructed system is infected, emergent decompression is needed. Early recognition and treatment is paramount in both conditions. Acute cholangitis can present many different ways, from mild symptoms to fulminant sepsis. It is usually a result of ascending bacterial colonization and biliary obstruction resulting in bacterial overgrowth. Therefore, those patients with recent biliary instrumentation or previous biliary modification are at higher risk. Charcot's triad of fever, right upper quadrant abdominal pain, and jaundice is only seen in 50%-70% of patients. Fever is seen in over 90% of cases, pain is seen in 70% of cases, and jaundice is seen in 60% of cases. Altered mental status and hypotension are associated with severe cases. All 5 symptoms of fever, right upper quadrant abdominal pain, jaundice, altered mental status, and hypotension are referred to as Reynold's Pentad. Acute pyonephrosis can also present many different ways, from minimal symptoms to fulminant sepsis. Fever, chills, and flank pain are the classic symptoms, although some patients may be relatively asymptomatic. Pyonephrosis may present with a classic triad of fever, flank pain, and hydronephrosis, or simply hydronephrosis and sepsis. Pyonephrosis usually occurs as a result of urinary obstruction with either an ascending infection of the urinary tract or hematogenous spread of a bacterial pathogen as the culprit. Up to 75% of cases are related to urinary stone disease. Patients are at increased risk for pyonephrosis when they haven anatomic urinary tract obstruction, certain chronic diseases (diabetes meliitus and AIDS), or are immunosuppressed due to immunodeficiency or medications, (chronic steroid therapy).

Colangitis biliar primaria. Parte 1. Actualización: generalidades, epidemiología, factores involucrados, fisiopatología y manifestaciones clínicas / Primary biliary cholangitis. Part 1. State of the art, epidemiology, physiopathology and clinical manifestations

La colangitis biliar primaria (CBP), es una colangiopatía crónica caracterizada por la destrucción selectiva de las células epiteliales biliares de conductos hepáticos de pequeño y mediano calibre, que afecta principalmente a mujeres. Los principales síntomas son la fatiga y el prurito, sin embargo, gran porcentaje de los pacientes pueden ser asintomáticos. El diagnóstico se basa en anticuerpos antimitocondriales (AMA) con títulos >1:40, fosfatasa alcalina >1,5 veces del límite superior normal por más de 24 semanas e histología hepática compatible con la patología. Se asocia con múltiples enfermedades principalmente de carácter autoinmune extra hepáticas, enfermedades tiroideas, óseas, entre otras. El tratamiento de primera línea es el ácido ursodesoxicólico (AUDC) que a pesar que no cura la enfermedad, mejora las pruebas del perfil hepático, así como el retraso en la progresión a cirrosis. Actualmente se encuentran en estudio nuevos tratamientos y terapias adyuvantes. El propósito de esta revisión es ofrecer una actualización de este tema que se presenta en los servicios de medicina interna y gastroenterología; para su realización se conformó un equipo interdisciplinario que desarrolló una búsqueda en la base Medline a través de PubMed con las palabras claves correspondientes y se procedió a una lectura crítica y analítica de títulos, resúmenes y textos completos para el filtro, extracción y síntesis de la información encontrada

Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others. The first line treatment is ursodeoxycholic acid (UDCA), that improves liver function tests and delay the progression to cirrhosis. Currently, there are new treatments and adjuvant therapies on study. The purpose of this review is to offer an update in this topic, which is very important in gastroenterology and internal medicine. We formed an interdisciplinary team to search in the database Medline thorough PubMed with the key words describe below, we made a critical lecture of the titles and abstracts of each article to write this paper

Preoperative nutritional status and its impact on cholangitis after Kasai portoenterostomy in biliary atresia patients.

OBJECTIVE: To explore the preoperative nutrition status in patients with biliary atresia (BA) and its effect on the cholangitis of Kasai portoenterostomy (KPE). METHODS: 106 patients who had been diagnosed with BA type III and were undergoing KPE were divided into two groups according to the score obtained using STRONGkids. Preoperative and postoperative data were collected to compare general characteristics and postoperative outcomes between the different groups. RESULTS: Forty-nine (46.2%) patients were at moderate nutritional risk (MNR) and fifty-seven (53.8%) patients were at high nutritional risk (HNR) preoperatively. The MNR group had shorter postoperative hospitalization times than the HNR group (P = 0.023). The initial postoperative cholangitis occurred later (P = 0.002) and the incidence of early cholangitis was lower (P = 0.029) in patients at MNR than in those at HNR. The ratio of jaundice clearance (P = 0.02) and 2-year native liver survival (P = 0.0109) were significantly higher in MNR group than in HNR group. CONCLUSIONS: Patients with BA presented the greatest nutritional deficiencies and patients at HNR are more vulnerable to the early cholangitis and the rate of jaundice clearance is lower than those at MNR. The occurrence of initial postoperative cholangitis in MNR group was later than in HNR group.

Primary Biliary Cholangitis: advances in management and treatment of the disease.

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting.

[Primary biliary cholangitis. Part 1. State of the art, epidemiology, physiopathology and clinical manifestations]. / Colangitis biliar primaria. Parte 1. Actualización: generalidades,epidemiología, factores involucrados, fisiopatología y manifestaciones clínicas.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others. The first line treatment is ursodeoxycholic acid (UDCA), that improves liver function tests and delay the progression to cirrhosis. Currently, there are new treatments and adjuvant therapies on study. The purpose of this review is to offer an update in this topic, which is very important in gastroenterology and internal medicine. We formed an interdisciplinary team to search in the database Medline thorough PubMed with the key words describe below, we made a critical lecture of the titles and abstracts of each article to write this paper.

Procalcitonin is a useful biomarker to predict severe acute cholangitis: a single-center prospective study.

BACKGROUND: Procalcitonin is being increasingly used to diagnose and grade acute systemic bacterial infection at an early stage of disease onset. The aim of this prospective study was to evaluate the usefulness of procalcitonin for severity grading of acute cholangitis on patient admission. METHODS: Patients with acute cholangitis were prospectively enrolled. The severity of acute cholangitis was graded on the basis of the 2013 Tokyo guidelines (Japanese Society of Hepato-Biliary-Pancreatic Surgery, 2013). We compared the ability of procalcitonin level on admission to predict moderate/severe (vs mild) or severe (vs mild/moderate) acute cholangitis with the abilities of white blood cell (WBC) count and C-reactive protein (CRP) level. RESULTS: Two hundred thirteen patients were analyzed, and the severity of acute cholangitis was graded as mild, moderate, and severe in 108, 76, and 29 patients respectively. Procalcitonin level, WBC count, and CRP level all increased significantly according to the severity. In the receiver operating characteristic analyses, the area under the curve for procalcitonin for severe acute cholangitis was 0.90 [95% confidence interval (CI) 0.85-0.96] and was significantly greater than that for WBC (0.62; 95% CI 0.48-0.76) and that for CRP (0.70; 95% CI 0.60-0.80). The optimal cutoff value for procalcitonin for prediction of severe acute cholangitis was 2.2 ng/mL (sensitivity 0.97; specificity 0.73; accuracy 0.77). The areas under the curve for procalcitonin, WBC, and CRP for moderate/severe acute cholangitis were not significantly different. CONCLUSIONS: Procalcitonin predicted severe acute cholangitis better than conventional biomarkers. Severe cases for which urgent biliary drainage is indicated might be identified on admission on the basis of the cutoff values for procalcitonin suggested in this study.

SRIS y SDOM constructos asociados a sepsis / SRIS and SDOM constructs associated with sepsis

La sepsis es un síndrome de respuesta inflamatoria sistémica (SRIS) que se activa por infección. Por su parte, el síndrome de disfunción orgánica múltiple (SDOM) es el fallo de la función de órganos y sistemas críticos en pacientes que han desarrollado una SRIS. Debido a que SRIS y SDOM son consecuencias de una excesiva activación inflamatoria. El objetivo de este artículo es ofrecer una revisión sobre algunos aspectos fisiopatológicos del constructo SRIS / SDOM de origen infeccioso, utilizando a la colangitis aguda como un ejemplo de esta cadena de eventos.

Sepsis is a systemic inflammatory response syndrome (SIRS) that is triggered by infection. On the other hand, multiple organ dysfunction syndrome (MODS) is the failure of critical organ function in patients suffering from SIRS.Because SIRS and SDOM are consequences of excessive inflammatory activation. The aim of this article is to provide a review of some pathophysiological aspects of the SRIS / SDOM construct of infectious origin, using the acute cholangitis as an example of this chain of events.

[The value of volatile fatty acids, citrulline and malondialdehyde for diagnosis of suppurative cholangitis in obstructive jaundice and choosing of optimal surgical approach (with commentary)]. / Otsenka informativnosti pokazatelei letuchikh zhirnykh kislot, tsitrullina i malonovogo dial'degida dlya diagnostiki gnoinogo kholangita pri mekhanicheskoi zheltukhe i vybora optimal'noi khirurgicheskoi taktiki (s kommentariem).

AIM: To define the role of volatile fatty acids, citrulline and malondialdehyde for diagnosis of suppurative cholangitis in obstructive jaundice and to define optimal surgical approach. MATERIAL AND METHODS: We studied the results of examination and treatment of 87 patients with different hepatopancreatobiliary pathology complicated by obstructive jaundice. It was determined blood concentration and range of volatile fatty acids which are metabolites of facultative anaerobic and obligate anaerobic bacterial pathogens. RESULTS: In 39 patients the defined levels of acetic, propionic, butyric and isovaleric acids contributed to accurate diagnosis of suppurative cholangitis. Statistically significant threshold concentrations of volatile fatty acids were revealed. These values facilitate detection of anaerobic microflora in suppurative cholangitis. CONCLUSION: Research of contents of volatile fatty acids, citrulline and malondialdehyde contributes to early diagnosis of suppurative cholangitis in patients with obstructive jaundice and further objectifies an algorithm of surgical tactics.

Quantitation of the Rank-Rankl Axis in Primary Biliary Cholangitis.

There is substantial data that suggests an abnormality of innate immunity in patients with primary biliary cholangitis (PBC) which includes the transcription factor nuclear factor-kB (NF-kB) and well as downstream inflammatory signaling pathways. In addition, ImmunoChip analysis has identified a novel PBC-associated locus near the receptor activator of NF-kB ligand (RANKL) gene. Based on these observations, we investigated the role of the RANKL axis in the liver of patients with PBC compared to controls. We used immunohistochemistry to quantitate liver expression of RANKL, its receptor (RANK), and importantly the decoy receptor osteoprotegerin (OPG), including a total of 122 liver samples (PBC = 37, primary sclerosing cholangitis = 20, autoimmune hepatitis = 26, chronic hepatitis B = 32 and unaffected controls = 7). In addition, we studied RANKL-RANK-OPG co-localization in CD4 and CD8 T cells, B cells, dendritic cells, macrophages, NK, NKT cells, hepatocytes, and cholangiocytes. We report herein that RANK is constitutively expressed by cholangiocytes in both unaffected and diseased liver. However, cholangiocytes from PBC express significantly higher levers of RANK than either the unaffected controls or liver diseased controls. CD4, CD8 and CD19 cells with in the portal areas around bile ducts in PBC express significantly higher levels of RANKL compared to controls. Importantly, the overall hepatic RANKL level and the ratio of hepatic RANKL/OPG correlated with disease severity in PBC. In conclusion, our data indicate a role of RANK-RANKL axis in the innate immune activation in PBC and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL positive cells and ultimately the classic portal tract infiltrates.