Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Gender-specific development of experimental autoimmune cholangitis induced by double-stranded RNA.

Here we investigated the gender difference in murine cholangitis resembling human primary biliary cholangitis (PBC) caused by synthetic double-stranded RNA, and underlying hepatic innate immune responses. Female C57Bl/6 mice given repeated injections of polyinosinic-polycytidylic acid (poly I:C) for 24 weeks developed overt cholangitis with positive serum anti-mitochondria-M2 antibody, whereas male mice showed minimal pathological changes without induction in autoantibody. Poly I:C induced hepatic inflammatory cytokines and type-I interferons predominantly in females. Hepatic expression levels of toll-like receptor (TLR) 3 and melanoma differentiation-associated protein (MDA) 5 were equivalent in both genders; however, both mRNA and protein levels of retinoic acid-inducible gene (RIG)-I were nearly doubled in female livers. Following 4-week injections of poly I:C, not only hepatic RIG-I, but also TLR3 and MDA5 showed female-predominance. Moreover, hepatic RIG-I levels were 25% lower in ovariectomized mice, whereas supplementation of 17 ß-estradiol enhanced hepatic RIG-I expression, as well as cytokine induction. These results clearly indicate that hepatic RIG-I expression is potentiated by estrogen, and triggers gender-dependent hepatic innate immune response against double-stranded RNA, which most likely play a pivotal role in the pathogenesis of autoimmune cholangiopathies including PBC.

Dynamic Monitoring of sTREM-1 and Other Biomarkers in Acute Cholangitis.

BACKGROUND: Sepsis is a common complication of acute cholangitis (AC), which is associated with a high mortality rate. Our study is aimed at exploring the significance of white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), and temperature (T) alone or combined together in early identification and curative effect monitoring of AC with or without sepsis. METHODS: 65 consecutive cases with AC and 76 control cases were enrolled. They were divided into three groups: Group A (AC with sepsis), Group B (AC without sepsis), and Group C (inpatients without AC or other infections). The levels of WBC, CRP, PCT, sTREM-1, and temperature were measured dynamically. The study was carried out and reported according to STARD 2015 reporting guidelines. RESULTS: CRP had the highest AUC to identify AC from individuals without AC or other infections (AUC 1.000, sensitivity 100.0%, specificity 100.0%, positive predictive value 100.0%, and negative predictive value 100.0%). Among various single indexes, PCT performed best (AUC 0.785, sensitivity 75.8%, specificity 72.2%, positive predictive value 68.7%, and negative predictive value 78.8%) to distinguish sepsis with AC, while different combinations of indexes did not perform better. From day 1 to day 5 of hospitalization, the levels of sTREM-1 in Group A were the highest, followed by Groups B and C (P < 0.05); on day 8, sTREM-1 levels in Groups A and B declined back to normal. However, other index levels among three groups still had a significant difference on day 10. Both in Groups A and B, sTREM-1 levels declined fast between day 1 and day 2 (P < 0.05). CONCLUSIONS: CRP is the best biomarker to suggest infection here. PCT alone is sufficient enough to diagnose sepsis with AC. sTREM-1 is the best biomarker to monitor patients' response to antimicrobial therapy and biliary drainage.

Effects of Pristine C60 Fullerenes on Liver and Pancreas in α-Naphthylisothiocyanate-Induced Cholangitis.

BACKGROUND: A significant role in pathogenesis of cholangitis is attributed to excessive reactive oxygen species production and oxidative stress. Therefore, antioxidants could be promising therapeutics. AIMS: The effects of powerful free radical scavenger C60 fullerene on hepatic and pancreatic manifestations of acute and chronic cholangitis in rats were aimed to be discovered. METHODS: Acute (AC, 3 days) and chronic (CC, 28 days) cholangitis models were simulated by single (AC) and 4 weekly (CC) α-naphthylisothiocyanate per os administrations. Pristine C60 fullerene aqueous colloid solution (C60FAS, 0.15 mg/ml, size of aggregates 1.2-100 nm) was administered either per os or intraperitoneally at a dose of 0.5 mg/kg C60 fullerene daily (AC) and every other day (CC). Prednisolone was used as a reference. Liver and pancreas autopsies were analyzed, and blood serum biochemical markers were measured. Pan-cytokeratin expression in HepG2 cells was assessed after 48-h incubation with C60FAS. RESULTS: On AC, C60FAS normalized elevated bilirubin, alkaline phosphatase, and triglycerides, diminished fibrotic alterations in liver, and improved pancreas state when applied by both ways. Additionally, C60FAS per os significantly reduced the signs of inflammation in liver and pancreas. On CC, C60FAS also mitigated liver fibrosis and inflammation, improved pancreas state, and normalized alkaline phosphatase and triglycerides. The remedy effect of C60FAS was more expressed compared to that of prednisolone on both models. Furthermore, C60FAS inhibited pan-cytokeratin expression in HepG2 cells in a dose-dependent manner. CONCLUSION: Pristine C60 fullerene inhibits liver inflammation and fibrogenesis and partially improved liver and pancreas state under acute and chronic cholangitis.

Pembrolizumab-induced autoimmune haemolytic anaemia and cholangitis.

Increasing numbers of patients are now offered immunotherapy as part of their cancer treatment. These treatments, while often very effective, have a wide range of adverse effects that are distinct from those of traditional chemotherapy regimens. Thyroid disease, dermatological disease, colitis and pneumonitis are some of the most commonly reported immune side effects. We present a case of life-threatening de novo autoimmune haemolytic anaemia (AIHA) complicated by immune cholangitis induced by pembrolizumab. An 81-year-old woman with metastatic melanoma completed a two-year course of pembrolizumab in August 2018 and six weeks later presented to hospital with jaundice. Admission haemoglobin (Hb) was 91 g/L, rapidly decreasing to 31 g/L, at which point she required admission to the intensive care unit. AIHA is a rare but potentially life-threatening complication of checkpoint inhibitors and should be considered in patients presenting with anaemia during or after immunotherapy treatment.

A Simple Method for Measuring Adenosine Triphosphate in Acute Cholangitis Patients to Determine the Need for Emergency Biliary Drainage.

Objective Acute cholangitis is occasionally life-threatening and requires immediate treatment. For the management of acute cases, globally accepted diagnostic criteria and the use of severity grading, as defined in the Tokyo Guidelines 2018 (TG18), are recommended. This study was performed to explore the association between acute cholangitis and the level of adenosine 5'-triphosphate (ATP) in blood as determined with a simple measurement method. Methods Twenty-three consecutive patients admitted for acute cholangitis and 14 healthy individuals were enrolled. Based on the TG18, the patients were categorized according to the degree of severity as Grade I, II, or III. We measured the amount of ATP in blood samples using a bioluminescence meter and evaluated the correlation with the degree of severity. Results The ATP/total hemoglobin (tHgb) level showed a significant decline in association with an increase in severity, as that in the healthy controls was 236.60 ± 8.10 and in the Grade I, II, and III groups was 238.56 ± 6.98, 186.88 ± 7.62, and 154.60 ± 11.01, respectively (p<0.01). While no significant difference was observed between the healthy controls and Grade I patients (p=0.649), there was a statistically significant difference between Grade I and Grade II (p<0.01) in the ATP/tHgb level. According to a receiver operating characteristic analysis, the area under the curve for ATP/tHgb, used as an index for predicting the need for emergency biliary drainage (Grade II, III cases), was the highest among various examined factors. Conclusion The present novel measurement method was found to be simple to perform and useful for detecting acute cholangitis patients with a low ATP level who may require emergency biliary drainage.

Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis.

BACKGROUND: Pruritus is a common symptom seen in patients with chronic liver disease. However, frequency and severity of pruritus in patients with chronic liver disease is unclear. We investigated frequency, severity and predictive factors of pruritus in these patients from a large cohort. METHODS: A total of 2477 patients with chronic liver disease without allergies or skin diseases were investigated for itch frequency and severity. Itch severity was self-assessed using pruritus scores using the numerical rating scale (NRS). Multivariate regression analysis was performed to identify factors associated with pruritus. Serum autotaxin levels were measured in patients with primary biliary cholangitis (PBC), and the relationship to liver fibrosis and pruritus was analyzed. RESULTS: The frequency of pruritus in patients with chronic liver disease was significantly higher than in subjects without liver disease (29.8 and 16.2%, respectively, P < 0.001). NRS was high in patients with chronic liver disease, especially in those with PBC, as is generally expected. Multivariate analysis identified lower albumin, higher eosinophil count, and etiology of PBC as independent factors associated with severe pruritus (≥5 points of NRS). In patients with PBC, serum autotaxin levels were significantly correlated with liver fibrosis markers such as platelet count and liver stiffness, and hepatobiliary enzymes such as total bilirubin, aspartate aminotransferase and alkaline phosphatase. However, no significant correlations between serum autotaxin levels and frequency and severity of pruritus were observed in patients with PBC. CONCLUSION: The frequency of pruritus was high in patients with chronic liver disease. Reduction of liver function is associated with severe pruritus based on the large number of patients with chronic liver disease. Serum autotaxin is useful for assessing liver fibrosis and severity of cholangitis; however, it is not a predictive marker for severe pruritus in patients with PBC.

Mig chemokine in primary biliary cirrhosis.

Different studies investigated about the role of T-helper 1 cytokines and chemokines in primary biliary cirrhosis (PBC). Animal models with autoimmune cholangitis have been used to investigate the involvement of (C-X-C motif) receptor (CXCR)3 and its ligand (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) in the pathogenesis of PBC, suggesting a contribution of MIG in the development of PBC. In patients with PBC, in particular at the level of the portal areas of diseased livers, MIG expression and CXCR3+ cells have been found. MIG is positively associated with the severity of liver fibrosis. In PBC, circulating MIG levels and CXCR3+ cells are related with the progression of the disease; in fact, their expression increases significantly in PBC patients with respect to controls. Furthermore, it has been shown a significant reduction of these chemokines in the serum of PBC patients after treatment with ursodeoxycholic acid.

Pantoea dispersa bacteremia in an immunocompetent patient: a case report and review of the literature.

BACKGROUND: Pantoea is a Gram-negative, non-encapsulated, non-spore-forming, ubiquitous straight rod which can be isolated from geographical and ecological sources such as plant surfaces, buckwheat seeds, human feces, and the environment. The genus Pantoea is a rare pathogen in a clinical setting, and is divided into 20 different species such as Pantoea agglomerans, Pantoea ananatis, Pantoea deleyi, Pantoea dispersa, Pantoea septica, Pantoea stewartii or Pantoea rwandensis. Pantoea dispersa has been reported to cause other infections, including respiratory infections, neonatal sepsis, and bloodstream infections. We report a case of Pantoea dispersa bacteremia caused by acute cholangitis. This is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis as far as we had searched. CASE PRESENTATION: A 38-year-old Japanese woman suffered from acute cholangitis; a blood culture showed that Gram-negative rod was positive. The treatment was successful with intravenously administered meropenem, and it was switched to orally administered levofloxacin according to microbiological susceptibility. The organism was identified as Pantoea dispersa by both genetic investigation by 16S ribosomal RNA and additional biochemical tests. To the best of our knowledge, this is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis. CONCLUSION: The epidemiology and clinical features of Pantoea dispersa are still unknown. More cases of infections caused by Pantoea dispersa might be revealed with advancing technical methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16S ribosomal RNA analysis. Physicians must know that a variety of infections caused by Pantoea dispersa could occur in immunocompromised as well as immunocompetent patients.

Endoscopic Retrograde Cholangio-Pancreatography-Obtained Bile Culture Can Guide Antibiotic Therapy in Acute Cholangitis.

BACKGROUND: Only a small proportion of patients with biliary tree infection grow microorganisms in blood cultures. Antibiotics chosen or tailored based on organisms identified on blood cultures have a potential for under-treatment and unfavorable outcomes, including recurrent infection and early stent occlusion. In our current practice, we collect bile for culture if an Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is performed in patients with suspected cholangitis. In this study, we compare the microbial yield of blood cultures and ERCP-obtained bile cultures in patients with ascending cholangitis. METHODS: We reviewed medical records of all the patients treated for ascending cholangitis who had blood cultures and ERCP-obtained bile cultures at a tertiary care center between 2010 and 2016. Bile was collected for culture before injecting contrast, via a catheter after discarding the initial 3 mL. RESULTS: Ninety-three patients were included with mean age of 71 (±15) years. Out of 93 patients, 11 (12%) had prior sphincterotomy, 29 (31%) had an indwelling biliary stent, and malignant obstruction was the most common etiology (34%). ERCP-obtained bile cultures were positive in 90 out of 93 (97%) patients with monomicrobial growth in 34 out of 93 (39%) patients. Mixed intestinal flora was noted in 3 patients. Blood cultures were positive in only 30 out of 93 patients (32%) and 24 out of 93 (26%) patients had monomicrobial growth. Totally 26 out of 30 patients (87%) grew the same organism as the bile culture, 3 grew an organism different from bile cultures, and one had no growth in the bile culture. On multivariable analysis, the presence of an indwelling biliary stent was the lone factor associated with polymicrobial growth, 83 vs. 52%, p = 0.007. CONCLUSION: ERCP-obtained bile cultures are a reliable and feasible mechanism to evaluate patients with suspected biliary tree infection. This technique has a significantly higher yield when compared to blood culture. Selection and tailoring of antibiotics based on bile culture in the management of ascending cholangitis are advised.

Efficacy and Safety of Single-Session Endoscopic Stone Removal for Acute Cholangitis Associated with Choledocholithiasis.

Background/Aims: In early endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to choledocholithiasis, it is unclear that single-session stone removal can be safely performed. We examined the efficacy and safety of early single-session stone removal for mild-to-moderate acute cholangitis associated with choledocholithiasis. Methods: Among patients with mild-to-moderate acute cholangitis associated with choledocholithiasis who underwent early ERCP (n = 167), we retrospectively compared the removal group (patients who underwent single-session stone removal; n = 78) with the drainage group (patients who underwent biliary drainage alone; n = 89) and examined the effectiveness and safety of single-session stone removal by early ERCP. Results: The patients in the removal group had significantly fewer and smaller stones compared with those in the drainage group. The single-session complete stone removal rate was 85.9% in the removal group. The complication rate in early ERCP was 11.5% in the removal group and 10.1% in the drainage group, with no significant difference (P = 0.963). On comparing patients who underwent early endoscopic sphincterotomy (EST) with those who underwent elective EST after cholangitis had improved, the post-EST bleeding rates were 6.8% and 2.7%, respectively, with no significant difference (P = 0.600). The mean duration of hospitalization was 11.9 days for the removal group and 19.9 days for the drainage group, indicating a shorter stay for the removal group (P < 0.001). In multiple linear regression analysis, stone removal in early ERCP, number of stones, and C-reactive protein level were significant predictors of hospitalization period. Conclusions: Single-session stone removal for mild-to-moderate acute cholangitis can be safely performed. It is useful from the perspective of shorter hospital stay.

IgG4-related disease coexisting with autoimmune haemolytic anaemia.

An 85-year-old man presented with a pale appearance and generalised pruritic papules. Laboratory investigations disclosed eosinophilia, autoimmune haemolytic anaemia, mixed hyperbilirubinaemia, cholestasis and elevated serum IgG4 levels. Abdominal sonography and CT showed progressive dilatation of biliary trees, with diffuse pancreatic enlargement and a subtle capsule-like low-density rim around the pancreatic head and body. Endoscopic retrograde cholangiopancreatography found no stone-related biliary obstruction, while endoscopic transpapillary biopsy demonstrated chronic inflammation only. Nevertheless, the diagnosis of IgG4-related disease with coexisting autoimmune haemolytic anaemia was presumed. The clinical picture and laboratory abnormalities improved after administration of moderate dose of methylprednisolone.

Bile and circulating HMGB1 contributes to systemic inflammation in obstructive jaundice.

BACKGROUND: Obstructive jaundice (OJ) patients with cholangitis are prone to sepsis; however, the underlying mechanisms are still not clear and need to be clarified. METHODS: Analyzing all available published data related to the title of this article. RESULTS: OJ leads to absence of gut luminal bile and accumulation of hepatic and circulating bile acids. Absence of gut luminal bile deprives the gut from its antiinflammatory, endotoxin-binding, bacteriostatic, mucosal-trophic, epithelial tight-junction maintaining, and gut motility-regulating effects, leading to gut bacterial overgrowth, mucosal atrophy, mucosal tight-junction loss, and gut motility dysfunction. These alterations promote intestinal endotoxin and bacterial translocation (BT) into portal and systemic circulation. Gut BT triggers systemic inflammation, which can lead to multiple organ dysfunctions in OJ. The accumulation of hepatic and circulating bile acids kills/damages hepatocyte and Kupffer cells, and it also significantly decreases the number of liver natural killer T-cells in OJ. This results in impaired hepatic and systemic immune function, which facilitates BT. In addition, neutralizing bile HMGB1 can reverse endotoxemic bile-induced gut BT and mucosal injury in mice, suggesting that bile HMGB1 in OJ patients can be responsible for internal drainage-related clinical complications. Moreover, the elevated circulating HMGB1 level may contribute to multiple organ injuries, and it might also mediate gut BT in OJ. CONCLUSIONS: HMGB1 may significantly contribute to systemic inflammation and multiple organ dysfunctions in OJ.

Diagnostic inflammatory markers in acute cholangitis.

BACKGROUND: The 2018 Tokyo guidelines for acute cholangitis (AC) use white cell count (WCC) as one of the diagnostic criteria. However, the 2018 Tokyo guidelines grading does not provide guidance for AC patients with normal WCC. In this situation, other inflammatory biomarkers also can be used to diagnose AC and grade severity, but their diagnostic values are yet undetermined. The aims of this study were to evaluate the discriminative powers of common inflammatory markers compared with WCC for diagnosing AC and to determine their diagnostic cutoff levels. METHODS: This was a retrospective cohort study. Over 2 y, 96 patients who underwent endoscopic biliary decompression were identified from the Auckland City Hospital Radiology Department database. Only patients with a confirmed diagnosis of AC were included in the study. Thirty-four patients with AC and 18 controls met eligibility criteria. RESULTS: Comparing areas under the receiver operating characteristic curves, it was the lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP) that had the highest discriminative powers in diagnosing AC. Values of WCC for diagnosing AC were equal to or above 9.6 × 109/L, neutrophil count equal to or exceeding 4.9 × 109/L, lymphocyte count equal to or below 1.3 × 109/L, NLR 5.3 and above, albumin equal to or below 30.5 g/L, and CRP concentration 23.5 mg/L or above. CONCLUSIONS: Lymphocyte count, NLR, and CRP have superior discriminative powers to WCC, albumin, and neutrophil count and can be useful in the diagnosis of AC.

Red blood cell distribution width to platelet ratio levels in assessment of histologic severity in patients with primary biliary cholangitis.

We aimed to investigate the relationship between the histologic severity and red blood cell distribution width to platelet ratio (RPR) in patients with primary biliary cholangitis (PBC). One hundred and seven consecutive patients with liver biopsy-proven and as yet treatment-naïve PBC were enrolled as the primary and validation cohort. The histologic stages were divided into early stage (Scheuer's stage 1 & 2) and late stage (Scheuer's stage 3 & 4). The overall patient demographics, clinical manifestations, hematological tests and biochemical profile were retrospectively collected from our database. Both groups were compared in terms of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and AST/ALT ratio (AAR). Of the 77 patients in the primary cohort, a total of 24 (31.2%) had early stage PBC, whereas 53 (68.8%) represented late stage. Patients with late stage PBC showed significantly higher red blood cell distribution width (15.5 vs. 14.1%, p = .016), RPR (0.15 vs. 0.09, p < .001), direct bilirubin (32.4 vs. 12.9 µmol/L, p = .041), FIB-4 (3.41 vs. 6.34, p = .001) and significantly lower platelet (132.8 vs. 185.8 × 109/L, p = .002). The area under the curve, cut-off value, sensitivity, specificity, positive predictive value, negative predictive value for determining late stage were 0.74, 0.14, 49.1%, 95.8%, 96.3% and 46.0%, respectively. Additionally, high RPR may also serve as a prognostic indicator for 18-month mortality. In conclusion, RPR can be used as a non-invasive and effective predictor of histologic severity in patients with PBC.

The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines.

Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.

Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).

BACKGROUND AND AIMS: Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. METHODS: PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. RESULTS: 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. CONCLUSIONS: Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.

Procalcitonin as a Decision-Supporting Marker of Urgent Biliary Decompression in Acute Cholangitis.

BACKGROUND AND AIM: This study aimed to evaluate the association of serum procalcitonin (PCT) at hospital presentation with disease severity and clinical deterioration to septic shock in acute cholangitis. METHODS: This study included consecutive patients with a diagnosis of acute cholangitis who presented to the emergency department and underwent biliary drainage. PCT and blood culture tests were conducted at the time of initial presentation. Patients were categorized into three groups based on disease severity. White blood cell count, levels of C-reactive protein and PCT were compared regarding the following: cholangitis severity, blood culture positivity, and clinical deterioration to septic shock. RESULTS: A total of 204 consecutive patients were enrolled, with grade I severity in 39 (19.1%), grade II in 139 (68.1%), and grade III in 26 (12.7%). The numbers of patients with blood culture positivity and clinical deterioration were 6 (15.4%) and 1 (2.6%) in grade I, 45 (32.4%) and 4 (2.9%) in grade II, and 14 (53.8%) and 1 (5.6%) in grade III cholangitis, respectively. Only PCT was significantly associated with blood culture positivity (3.25 vs 0.62 ng/mL; P = 0.001) and clinical deterioration (9.11 vs 0.89 ng/mL; P = 0.040). The cutoff value of PCT for clinical deterioration to septic shock among patients with grade I and II was 3.77 ng/mL (sensitivity of 80.0% and specificity of 74.0%). CONCLUSION: PCT could be a promising marker of clinical deterioration to septic shock in acute cholangitis. Therefore, PCT might be used as a decision-supporting biomarker for urgent biliary decompression.

Platelet count to spleen thickness ratio is related to histologic severity of primary biliary cholangitis.

The aim of this study was to evaluate the ability of noninvasive markers to identify the histological severity of primary biliary cholangitis (PBC).Fifty-eight treatment-naïve PBC patients who had undergone liver biopsy were enrolled in our study. The patients' histological stages were based on the classifications of Ludwig and Scheuer. Aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), red blood cell distribution width to platelet ratio (RPR), and platelet count to spleen thickness (PC/ST) ratio were calculated. Using the area under the receiver operating characteristic curve (AUROC) to evaluate the accuracy of different markers for predicting the histological severity.Among the 58 treatment-naïve PBC patients, the patients of Scheuer stage I/II/III/IV were 17/25/11/5, respectively. PC/ST ratio (AUROC = 0.807) was superior to RPR (AUROC = 0.717), APRI (AUROC = 0.726), FIB-4 (AUROC = 0.722), and mean platelet volume (MPV) (AUROC = 0.671) in discriminating between stage I and stage ≥II. The AUROC of PC/ST ratio, RPR, APRI, FIB-4, and MPV were 0.939, 0.872, 0.816, 0.831 and 0.572, respectively, for Scheuer stage ≥III; 0.968, 0.795, 0.744, and 0.723, respectively for stage IV. The sensitivity and specificity of PC/ST ratio were 73.4%,79.1%; 81%,100%;88.7%,100% for detection of Scheuer stage ≥ II, Scheuer stage ≥ III and Scheuer stage IV, respectively.Our study findings indicated that compared with previous noninvasive test PRP, APRI, FIB-4 and MPV, PC/ST ratio shows the most accurate for distinguish the histologic severity of PBC patients.