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.

Giant stentolith: A rare complication of long-dwelling biliary endoprosthesis.

Endoscopic biliary stenting is performed for various indications in routine clinical practice. Plastic stents are indicated primarily for short-term biliary decompression and require removal or exchange after 12-16 weeks. However, patients who become asymptomatic after the procedure may not return for scheduled stent removal and subsequently present with severe complications. We herein present the case of a 57-year-old female who underwent biliary stenting after the endoscopic clearance of bile duct stones. Her symptoms resolved after the intervention, but she was lost to follow-up with the stent remaining in situ. Four years later, she presented with pain in the right hypochondrium and experienced recurrent episodes of cholangitis. Magnetic resonance cholangiopancreatography revealed a retained plastic stent in the proximal bile duct with a large stone cast around the stent-a stentolith. Owing to the large stone size and proximal migration of the retained biliary stent, the patient required open surgical exploration for stentolith removal. Patients with forgotten biliary stents presenting with serious complications are not uncommon in India. Unaware of the complications of long-dwelling biliary stents, patients ignore the advice for the timely removal of biliary stents. Detailed patient counselling, education and documentation are essential to avoid this condition.

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.

Síndrome de superposición: hepatitis autoinmune y colangitis biliar primaria. Resultados a largo plazo de una cohorte retrospectiva en un hospital universitario / Autoimmune hepatitis - primary biliary cholangitis overlap syndrome. Long-term outcomes of a retrospective cohort in a university hospital

INTRODUCCIÓN: La hepatitis autoinmune (HAI) con características de colangitis biliar primaria (CBP) es conocida como síndrome de superposición. Su prevalencia y pronóstico aún no han sido determinados comparativamente con aquellos con HAI. MÉTODOS: Se realizó un estudio de cohorte retrospectiva comparando pacientes con diagnóstico de HAI y síndrome de superposición por HAI-CBP, seguidos por 7años en un hospital universitario de Colombia, hasta el 31 de diciembre de 2016. RESULTADOS: Se incluyeron 210 pacientes (195 mujeres, edad media 48,5 años), de los cuales 32 (15,2%) tenían síndrome de superposición HAI-CBP. Al diagnóstico no se hallaron diferencias significativas por perfil demográfico, autoanticuerpos positivos (ANA, ASMA) excepto AMA (81,2% vs 3,9%; p < 0,001) y grado histológico de fibrosis. La presentación clínica más frecuente en HAI-CBP fueron síntomas inespecíficos y en HAI, hepatitis aguda. Aunque con diferencias no significativas, en HAI se presentó mayor respuesta bioquímica al manejo inmunosupresor (87,3% vs 74,2%; p = 0,061) y mayor número de recaídas en quienes lograron remisión parcial o completa durante tratamiento (12,4% vs 7,63%; p = 0,727). Los pacientes con HAI-CBP tuvieron mayor progresión a cirrosis (22,2% vs 13,1%; p = 0,038), incluso quienes lograron remisión bioquímica parcial o completa sin recaída, mayor indicación de TOH (p = 0,009), pero no retrasplante (p = 0,183); no hubo diferencias en la mortalidad. CONCLUSIÓN: El síndrome de superposición HAI-CBP constituye una proporción no despreciable entre aquellos con HAI, con mayor progresión a cirrosis, indicación de trasplante hepático y posiblemente retrasplante. Este mayor riesgo de desenlaces adversos sugiere seguimiento más estricto, probablemente con seguimiento hasta remisión histopatológica confirmada

BACKGROUND: Autoimmune hepatitis (AIH) with characteristics of primary biliary cholangitis (PBC) is known as overlap syndrome. Its prevalence and prognosis have not yet been determined comparatively with AIH. METHODS: A retrospective cohort study was conducted comparing patients diagnosed with AIH and AIH-PBC overlap syndrome, followed-up for seven years in a university hospital in Colombia, until 31 December 2016. RESULTS: A total of 210 patients were included (195 women, mean age 48.5 years). Of these, 32 (15.2%) had AIH-PBC overlap syndrome. At diagnosis, no significant differences were found by demographic profile, positive autoantibodies (ANA, ASMA), except AMA (81.2% vs 3.9%, P < .001), and histological grade of fibrosis. The most frequent clinical presentations were nonspecific symptoms in AIH-PBC and acute hepatitis in AIH. Although there were no significant differences, AIH showed a greater biochemical response to immunosuppressive management (87.3% vs 74.2%, P = .061) and a greater number of relapses in those who achieved partial or complete remission during treatment (12.4% vs 7.63%; P = .727). Patients with AIH-PBC had greater progression to cirrhosis (22.2% vs 13.1%, P = .038), even in those who achieved partial or complete biochemical remission without relapse, with greater indication of orthotopic liver transplantation (P = .009), but not retransplantation (P = .183); there were no differences in mortality. CONCLUSIONS: AIH-PBC overlap syndrome accounts for a significant proportion of patients with AIH, with greater progression to cirrhosis, indication of liver transplantation and possibly retransplantation. This higher risk of adverse outcomes suggests closer monitoring, probably with follow-up until confirmed histopathological remission

Cholangitis Lenta Causing Bile Cast Nephropathy: A Unique Model of Hepatorenal Failure in Sepsis.

INTRODUCTION: Inadequate perfusion and abnormal cellular metabolism are among the mechanisms of organ dysfunction in sepsis. Concomitant hepatorenal failure during the late phase of sepsis is poorly understood. CASE REPORT: The autopsy of a child who developed sepsis-induced hepatorenal failure revealed bile cast nephropathy, hepatic centrilobular necrosis and cholangitis lenta, a type of sepsis-induced cholestasis, with no biliary obstruction, fibrosis or cirrhosis. The liver and renal function declined at the same rate as procalcitonin increased. DISCUSSION: Failure of resolution and persistent inflammation in sepsis can result in ductular injury and stagnation of bile with subsequent cholemia. The kidney failure was associated with the formation of intratubular bile casts. CONCLUSION: This case illustrates how severe cholestasis in combination with bile cast nephropathy may be potential and unrecognized contributors to hepatorenal failure in sepsis. Whether bile toxicity causes renal failure in the context of cholangitis lenta should be further studied.

Disease Duration and Stage Influence Bone Microstructure in Patients With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro- and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex, and body mass index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the lumbar spine and hip, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess the geometric, volumetric, and microstructural changes of bone at the distal radius and tibia. Furthermore, serum analyses and measures of disease duration and stage including transient elastography were performed. Total, cortical, and trabecular volumetric BMD as well as geometric parameters were significantly reduced in PBC patients. Microstructural analysis revealed a significantly lower cortical thickness (p < 0.001) and bone volume per tissue volume (p < 0.001) in the radius and tibia but unchanged trabecular number in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression models pointed out that disease duration and stage are the primary factors that are independently associated with bone loss in PBC. A subgroup analysis of patients with additional autoimmune hepatitis (AIH) revealed no significant changes in bone structure compared with PBC only. Taken together, PBC patients demonstrate severe alterations in bone microstructure that are positively associated with disease duration and stage. By applying HR-pQCT in the distal radius and tibia, a combined bone loss syndrome expressed by a predominant decrease in BMD and cortical thickness could be detected. © 2018 American Society for Bone and Mineral Research.

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.

The Emergency Medicine-Focused Review of Cholangitis.

BACKGROUND: Cholangitis is a life-threatening infection of the biliary tract. Historically, the mortality secondary to cholangitis approached 100%. However, with early recognition, antibiotics, resuscitation, and surgical or endoscopic intervention, patient outcomes have significantly improved, although there is still progress to be made. OBJECTIVE OF REVIEW: The objective of this review is to provide an emergency medicine-centered approach to the risk factors, presentations, and various diagnostic and treatment modalities in cholangitis. DISCUSSION: Early recognition and treatment of cholangitis in the emergency department is instrumental in ensuring a favorable outcome for patients. Recognition of acute cholangitis can be challenging, as many patients do not present with the classic symptoms of Charcot's triad. This article reviews the risk factors in cholangitis, as well as the typical presentations and necessary diagnostic studies. Furthermore, once diagnosis is made, distinguishing those requiring emergent biliary decompression from those who may tolerate a delayed procedure can also be difficult. Scoring systems that attempt to identify patients who may tolerate a delayed approach have yet to be validated. This review discusses the appropriate antibiotic therapy based on most common pathogens, as well as the options for achieving biliary decompression. CONCLUSIONS: Cholangitis is a life-threatening infection that carries a high likelihood of poor outcomes if not treated early and aggressively in the emergency department. Appropriate recognition, early broad-spectrum antibiotics, and fluid resuscitation are paramount, and in patients with severe disease, early biliary decompression will significantly reduce mortality.

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).

Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia.

The prevalence of gallstones is 10% to 15% in adults. Individuals with acute cholecystitis present with right upper quadrant pain, fever, and leukocytosis. Management includes supportive care and cholecystectomy. The prevalence of choledocholithiasis is 10% to 20%, and serious complications include cholangitis and gallstone pancreatitis. The goal of management in individuals with choledocholithiasis consists of clearing common bile duct stones. Acute ascending cholangitis is a life-threatening condition involving acute inflammation and infection of the common bile duct. Treatment includes intravenous fluids, analgesia, intravenous antibiotics, and biliary drainage and decompression. Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones.

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