Search

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis., Objectives: ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP., Methods: The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded., Results: Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241-2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415-9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates., Conclusion: ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: There have been strong suggestions that acute inflammation promotes tumour growth, and has a tendency for increased invasiveness, leading to poor survival after surgery. When cholangitis coexists with ampulla of vater cancer, the patient's prognosis may be influenced by the acute inflammatory status of the bile duct. We evaluated the relationship between the severity of acute cholangitis, preoperative CRP levels and survival., Methods: We retrospectively analysed 154 patients who underwent surgical resection for AOV cancer between January 2003 and November 2018. Cholangitis was graded according to Tokyo Guidelines 2018. Patients were categorised into two groups based on their CRP levels: CRP > 1 mg/L and CRP ≤ 1 mg/L. Relationship of cholangitis grade and CRP >1 mg/L with survival was assessed., Results: The mean age of the patients was 65.8 years. Preoperative cholangitis was present in 40 (25.9%) patients, of which 28 (18.2%) had mild cholangitis, 11 (7.1%) had moderate cholangitis, and one (0.6%) had severe cholangitis. CRP was elevated preoperatively in 56 (36.4%) patients. The median follow-up period was 33.5 months. Severity of cholangitis significantly affected the overall survival (P < 0.001) and disease-free survival (P < 0.001). Patients with mild cholangitis had a median overall survival of 43 months compared to 14 months in those with moderate cholangitis. A preoperative CRP level of >1 mg/L was significantly associated with poor overall survival (P = 0.023) but not with disease-free survival (P = 0.128), although it was associated with a trend towards poorer survival. The survival rate of patients with CRP ≤1 mg/L was 77.4%, whereas that of patients with CRP >1 mg/L was 56.7%. In multivariable analysis, age >65 years (P = 0.015), cholangitis grade (P = 0.050), CRP > 1 mg/L (P = 0.045), venous invasion (P = 0.005), and perineural invasion (P = 0.034) were independent prognostic factors for overall survival while cholangitis grade (P = 0.049) and perineural invasion (P = 0.004) were independent prognostic factors for disease-free survival., Conclusion: Acute inflammation when associated with cancer can have a negative effect on patient's survival. Patients with higher grades of cholangitis should be adequately treated to improve the inflammatory status., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: There is a lack of literature on postendoscopic retrograde cholangiopancreatography (ERCP) complications in predominantly black urban populations of low socioeconomic status. The aim of this study was to determine the incidence and predictors of post-ERCP complications in this patient population., Design: Retrospective review of ERCP cases performed at two hospitals from 2007 to 2017 was performed. The categories of complications evaluated were overall complications, severe or fatal complications, pancreatitis, bleeding, infection, perforation and cardiopulmonary events. Predictors of complications were determined by univariate analysis., Results: A total of 1079 ERCP procedures were reviewed. There were 106 complications (9.8%). Twenty-one were severe (1.9%) and 20 were fatal (1.9%). Both post-ERCP pancreatitis (PEP) and post-ERCP bleeding occurred in 18 patients (1.7%) each. Risk factors for overall complications were male sex (OR 1.54), ASA grade IV or V (OR 2.19), prior history of PEP (OR 6.98) and pancreatic duct stent placement (OR 2.75). Those who were ASA grade III or lower (OR 0.4) or who underwent biliary stone extraction (OR 0.62) had fewer complications. PEP was more likely in those with a prior history of PEP (OR 37.6). Those with a suspected or known biliary duct stone had less frequent pancreatitis (OR 0.32). Post-ERCP bleeding was more likely in the presence of cholangitis (OR 8.72)., Conclusion: Outcomes of ERCP in a predominantly black urban population demonstrate a lower incidence of PEP and all-cause mortality compared with historical data reported in the general population. Potential risk factors for post-ERCP complications were identified but require larger studies for validation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical findings with triaditis and individual disease components overlap and may include hyporexia, weight loss, lethargy, vomiting, diarrhea, dehydration, icterus, abdominal pain, thickened bowel loops, pyrexia, dyspnea, and shock. A definitive diagnosis of triaditis requires histologic confirmation of inflammation in each organ, but this may not be possible because of financial or patient-related constraints. Evidence-based data indicate that histologic lesions of triaditis are present in 30% to 50% of cats diagnosed with pancreatitis and cholangitis/inflammatory liver disease. Treatment of triaditis is based on the overall health status of the patient and the type and severity of disease in component organs., Competing Interests: Disclosure The authors have no disclosures to report nor was funding required for production of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The anti-DIC biological agent, recombinant human soluble thrombomodulin (rhTM), is being used clinically for DIC treatment in Japan. Patients with acute cholangitis associated with DIC are severe and require improved treatment. In addition, although clinical efficacy of rhTM in patients with acute cholangitis and DIC is expected, its efficacy is controversial. Thus, it is useful to evaluate rhTM in patients with acute cholangitis with DIC. This study aimed to validate the hypothesis that rhTM use improves in-hospital mortality in patients with acute cholangitis with DIC. A propensity score-matching analysis using a nationwide administrative database, the Japanese Diagnosis Procedure Combination Inpatient Database from April 2012 to March 2018, was performed. This database includes administrative claims data for all inpatients discharged from more than 1,000 participating hospitals, covering 92% of all tertiary-care emergency hospitals in Japan. Eligible patients (n = 2,865) were categorized into the rhTM (n = 1,636) or control groups (n = 1,229). Propensity score-matching created a matched cohort of 910 pairs with and without rhTM. In-hospital mortality between the groups in the unmatched analysis showed no significant difference (rhTM vs. control; 10.8% vs. 12.2%; p = 0.227). However, in-hospital mortality between the groups in the propensity score-matched analysis showed a significant difference (rhTM vs. control; 9.5% vs. 12.9%; p = 0.021). These results demonstrated that the rhTM group had significantly lower in-hospital mortality for patients with acute cholangitis with DIC. We propose that rhTM should be used for the treatment of patients with acute cholangitis with DIC.

Rationale: Intermittent combined pancreaticobiliary obstruction may lead to multiple episodes of ascending cholangitis and pancreatitis, usually due to choledocholithiasis or periampullary mass. However, one of the rare causes is periampullary or juxtapapillary duodenal diverticulum. Although duodenal diverticula are relatively common in the general population, the overwhelming majority are asymptomatic. Duodenal diverticula can cause combined pancreaticobiliary obstruction through multiple mechanisms such as stasis-induced primary choledocholithiasis, stasis-induced intradiverticular enterolith, or longstanding diverticulitis, causing stenosing fibrosing papillitis or a combination of more than one of these mechanisms. Herein, I report a case of Lemmel syndrome due to a combination of multiple mechanisms and review the available literature on the epidemiology, pathogenesis, clinical presentation, diagnostic work-up, and management of juxtapapillary duodenal diverticulum., Patient Concerns: Multiple episodes of abdominal pain, jaundice, anorexia, fever, and significant unintentional weight loss., Diagnoses and Interventions: Primary choledocholithiasis, recurrent ascending cholangitis, recurrent acute pancreatitis, and pancreatic atrophy due to giant juxtapapillary duodenal diverticulum, with unsuccessful endoscopic retrograde cholangiopancreatography that was completely resolved after open transduodenal sphincteroplasty and septoplasty, transampullary and transcystic common bile duct exploration and stone extraction, and duodenal diverticular inversion., Outcome: Complete resolution of combined pancreaticobiliary obstruction without recurrence for 2 years after surgery., Lessons: Surgeons should be aware of such rare syndromes to avoid misdiagnosis and delayed or inappropriate management. Furthermore, they should understand the different available operative options for cases that are refractory to endoscopic approach.

The aim of the study was to develop a new early noninvasive diagnostic model for primary biliary cholangitis (PBC).A total of 118 PBC patients who had undergone a liver biopsy were enrolled in the study, and were randomized into a model group (78 patients) and a validation group (40 patients). The patients' histological stages were based on the classifications of the Scheuer's stage. All common parameters and liver pathological results were analyzed. And total bile acid to platelet ratio, aspartate aminotransferase to platelet ratio index, fibrosis index based on 4 factors and red cell distribution width to platelet ratio were calculated.There were 106 (89.8%) women and 12 men in this study, and the number of patients in Scheuer stage I, II, III, and IV hepatic fibrosis was 52 (44.1%), 36 (30.5%), 26 (22.0%), and 4 (3.4%), respectively. The areas under the receiver operating characteristic curves of the total bile acid to platelet ratio (TPR), the aspartate aminotransferase to platelet ratio index, the fibrosis index based on 4 factors , and the red cell distribution width to platelet ratio for predicting advanced liver fibrosis were 0.771, 0.715, 0.618, and 0.517 respectively. The areas under the receiver operating characteristic curves of the TPR was higher than other non-invasive serological models.As a simple, inexpensive and easily accessible non-invasive liver fibrosis diagnostic model, the TPR may be a new noninvasive marker for predicting histologic severity of PBC.

Acute biliary conditions include cholangitis, obstruction, and biliary leakage. All these conditions may lead to severe biliary sepsis, which can be life threatening. Infected obstructed cholangitis is a medical emergency that requires active medical therapy and early biliary decompression is recommended. This article provides an overview of the clinical presentations and management of biliary sepsis. The technique, clinical applications, and outcomes of percutaneous transhepatic biliary drainage and those related to gall bladder drainage are highlighted. Future alternatives to conventional biliary drainage are discussed., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Aims: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near-infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral oxygen saturation (StO 2 ) and altered patterns of microvascular cerebral blood perfusion and whether these alterations were associated with clinical phenotype. This observational case-control study was conducted at a tertiary hospital clinic (University of Calgary Liver Unit)., Approach and Results: Thirteen female patients with noncirrhotic PBC, seven female patients with cirrhotic PBC, and 11 healthy female controls were recruited by physician referral and word of mouth, respectively. NIRS was used to measure cerebral hemoglobin and oxygen saturation. A wavelet phase coherence method was used to estimate the coherent frequency coupling of temporal changes in cerebral hemodynamics. The PBC group demonstrated significantly reduced cerebral StO 2 (P = 0.01, d = 0.84), indicating cerebral hypoxia, significantly increased cerebral deoxygenated hemoglobin concentration (P < 0.01, d = 0.86), and significantly reduced hemodynamic coherence in the low-frequency band (0.08-0.15 Hz) for oxygenated hemoglobin concentration (P = 0.02, d = 0.99) and total hemoglobin (tHb) concentration (P = 0.02, d = 0.50), indicating alterations in cerebrovascular activity. Complete biochemical response to ursodeoxycholic acid (UDCA) therapy in early patients with PBC was associated with increased cerebral tHb concentration and decreased hemodynamic coherence., Conclusions: Using NIRS, patients with PBC were found to have hypoxia, increased cerebral hemoglobin concentration, and altered cerebrovascular activity, which were reversed in part in UDCA responders. In addition, symptoms and quality-of-life measures did not correlate with brain hypoxia or cerebrovascular dysregulation in patients with PBC., (© 2019 by the American Association for the Study of Liver Diseases.)

Background & Aims: Inflammation plays an important role in the pathogenesis of cholestatic liver injury, but it is unclear whether the inflammasome is involved and is the objective of this study., Methods: Gene expression was analyzed in the livers of patients with primary biliary cholangitis (n = 15) and primary sclerosing cholangitis (n = 15). Bile duct ligation (BDL) or sham operation was performed in wild-type (WT) and Caspase-1 -/- (Casp1 -/- ) mice for 7 days. Mouse hepatocytes and macrophages were treated with bile acids., Results: Caspase-1, NLRP1, NLRP3 and IL-1β were significantly increased in the livers of cholestatic patients when compared to healthy control subjects (n = 9). Significantly higher levels of plasma IL-1β (826 vs 345 pg/ml), ALT (674 vs 482 U/L) and ALP (900 vs 622 U/L) were seen in WT BDL mice compared to Casp1 -/- BDL mice. Caspase-1 cleavage was found only in WT BDL livers. Assessment of liver histology indicated more fibrosis in Casp1 -/- BDL mice than in WT BDL mice, confirmed by analyses of liver hydroxyproline content and the expression of fibrotic genes. Profiling of immune cells revealed that there were more macrophages in Casp1 -/- BDL livers than in WT BDL livers. Further macrophage phenotype characterization indicated that Casp1 -/- BDL livers had more M2 anti-inflammatory macrophages evidenced by more CD206 positive cells and higher expression of IL-4, CD163, Fizz1 and IL-33. When mouse hepatocytes and peritoneal macrophages were exposed to cholestatic levels of major endogenous bile acids (300μM TCA), neither IL-1β induction nor procaspase-1 cleavage were detected., Conclusions: The inflammasome exacerbates cholestatic liver injury, but bile acids do not directly activate the inflammasome., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute cholangitis (AC) complicated by septic shock is associated with 40% mortality. The best screening method for diagnosing sepsis in patients with AC is unknown. In this study, we aimed to compare the discriminative powers of systemic inflammatory response syndrome criteria (SIRS test) and the 2018 Tokyo Guidelines for moderate cholangitis (TG18 test) in screening AC patients for sepsis and to estimate their predictive abilities., Methods: This was a retrospective diagnostic accuracy study in which the TG18 and SIRS tests were applied to two groups of patients; 52 patients with 70 hospital admissions had AC with shock index ≥0.7 and 46 patients with 57 hospital admissions had AC with shock index <0.7, uncomplicated choledocholithiasis, obstructive jaundice and biliary stent removal., Results: The sensitivity and specificity for the TG18 test in identifying AC patients with sepsis were 69% and 68%, respectively. The SIRS test applied to the same patient cohort yielded 93% sensitivity and 79% specificity. The SIRS test had a larger area under the receiver operating characteristic curve, 86% and 69%, respectively (P = 0.0004). With a sepsis prevalence of 23% in patients with biliary tract infections, the positive predictive value (PPV) for the SIRS test was 57% (95% confidence interval (CI) 44-69%) and the negative predictive value was 97% (95% CI 94-99%). The PPV and negative predictive value for the TG18 criteria were 39% (95% CI 30-50%) and 88% (95% CI 83-92%), respectively., Conclusion: The SIRS test had better discriminative power in identifying AC patients with sepsis than the TG18 criteria, but had a low PPV., (© 2019 Royal Australasian College of Surgeons.)

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.

Background and Aims: Sporadic hepatitis E is an emerging indigenous disease in Europe induced by genotype 3 of the virus. While the disease takes an acute self-limited course in immunocompetent individuals, under immunocompromised conditions chronic hepatitis E might develop. The histology of chronic hepatitis E has not been described in detail systematically., Methods: Liver biopsies from 19 immunosuppressed patients with chronic hepatitis E were collected: 17 were organ transplant recipients, one had a CD4-deficiency and one had received steroid therapy because of ulcerative colitis. Biopsies were processed with standard stains. Evaluation of histologic activity and fibrosis was performed according to Ishak. Additionally, immunohistochemistry with antibodies directed against open reading frame 2 and 3 of the virus was performed and liver biopsies were tested for hepatitis E virus RNA., Results: Biochemical data showed an increase in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase and total bilirubin. Histopathology displayed typical features of chronic hepatitis with mild to moderate activity. The number of polymorphonuclear leucocytes was considerably increased and all patients had a florid cholangitis that presented as a destructive form in five of them. Hepatocytes and bile duct epithelia stained positive for hepatitis E virus by immunohistochemistry., Conclusions: Chronic hepatitis E in immunocompromised individuals runs a similar course as hepatitis B and C and shows similar histopathology. However, the presence of destructive cholangitis in some cases accompanied by an increased number of polymorphonuclear leucocytes is markedly different. Immunohistochemically the virus is present in bile duct epithelia, seemingly the cause for cholangitis., (© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.)

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events( RR =1.56, P =0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups( RR =1.01, P =0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients( RR =0.63, P =0.03);however,there was no significant difference in the risk of stroke( RR =1.11, P =0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

Background & Aims: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC., Methods: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW)., Results: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1-81.2) among UDCA-treated patients and 60.7% (95% CI 58.2-63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40-0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45-0.69; p <0.001)., Conclusion: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC., Lay Summary: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Fatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions., Methods: A comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class., Results: We identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69-1.08, p = 0.19, I 2  = 56.2%). While liver transplantation did reduce degree of fatigue (SMD - 0.57, 95% CI - 0.89 to - 0.24, p = 0.001, I 2  = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed., Conclusions: While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.

Background: We investigated the effect of Shenfu injection (SFI) in Wistar rats with acute obstructive cholangitis (AOC) and considered the possible molecular mechanisms of the effects. Methods: The 96 rats were divided randomly into three groups. In one group, the common bile duct was subjected to ligation (BDL), and 0.2 mL of saline was injected into the proximal bile ducts. To create AOC, again, the common bile duct was ligated, and 0.2 mL of lipopolysaccharide (LPS)) (2 mg/mL) was injected into the proximal ducts. In the Shenfu injection (SFI) group, the material (10 mg/kg) was injected into the tail vein 2 hours before induction of AOC. The hepatic histopathologic changes were observed under a light microscope. The endotoxin, tumor necrosis factor-α (TNF-α), alanine transaminase (ALT), and total bilirubin (TB) concentrations in the serum were measured at different time points (0, 4, 8, and 16 hours) after ligation. The expression of nuclear transcription factor-κB (NF-κB) and CD14 in Kupffer cells also was analyzed at different times by Western blotting. Results: The TNF-α, ALT, and TB concentrations in the serum and the expression of CD14 and NF-κB in Kupffer cells were significantly higher in the SFI group than in the BDL group, but all were significantly lower than in the AOC group. Compared with the AOC group, the edema of cholangiocytes was alleviated in the SFI group, and the infiltration of inflammatory cells around cholangiocytes was reduced. Conclusion: Shenfu injection significantly alleviated bile duct injury. The potential mechanism may be associated with inhibition of CD14 expression and prevention of NF-κB activation in Kupffer cells.

Gap junctions (GJs) and tight junctions (TJs) are essential to maintain the function of hepatocytes. Changes in biliary tract pressure and the effect of lipopolysaccharide (LPS) may lead to acute obstructive cholangitis (AOC) and cause liver injury via GJ and TJ dysfunction. Hydrogen has been confirmed to have a protective role in various organs during pathological conditions and inflammation. The present study investigated the function of junction proteins and the potential application of H2 in AOC‑induced liver injury. An AOC rat model was established by LPS injection through a bile duct catheter, while the distal bile duct was closed. The catheter sealing caps were removed and bile was allowed to flow out from the catheters at 12 h after LPS infusion. The potential application of H2 was studied in the AOC rat model with biliary drainage. It was observed that AOC induced the disruption of junction proteins of both GJs and TJs. H2 administration reversed AOC‑induced disruption of GJs and TJs after biliary drainage. The mechanism of this phenomenon suggests that H2 may have effectively attenuated AOC‑induced inflammatory and oxidative damage, and decreased matrix metalloproteinase activity. H2 may accelerate the reversal of AOC‑induced liver dysfunction, and this phenomenon may depend on reversing the inhibition of GJs and TJs.

Background and Aims: Little is known about the prevalence or treatment of pruritus associated with primary biliary cholangitis (PBC). We analyzed data from patients with PBC recruited from all clinical centers in the United Kingdom (UK) to characterize the prevalence, severity, progression, and treatment of pruritus., Methods: We performed cross-sectional and longitudinal studies of patients in the UK-PBC cohort to assess trajectories of pruritus. Data on pruritus frequency, severity, and therapy were collected via paper questionnaires completed by 2194 patients at their initial assessment in 2011 and then again in 2014 and 2017. Self-reported treatment data were validated against the prescription record of PBC cohort in the Clinical Practice Research Datalink, a primary care database. We defined persistent pruritus as itch that occurs frequently or all the time and severe pruritus as PBC-40 pruritus domain scores of 12 or more, throughout their disease course. Latent class mixed models were used to study pruritus trajectories and identify factors associated with high pruritus., Results: At initial assessment, 1613 (73.5%) patients had experienced pruritus at some point since their development of PBC-persistent pruritus was reported by 34.5% of the patients and severe pruritus by 11.7%. Only 37.4% of patients with persistent pruritus and 50% with severe pruritus reported ever receiving cholestyramine. Frequencies of rifampicin use were 11% in patients with persistent pruritus and 23% in patients with severe pruritus. Comparison of 2011 and 2014 surveys (comprising 1423 patients) showed consistent self-reported data on pruritus. Proportions of patients in the UK-PBC cohort treated with cholestyramine or naltrexone (37.4% and 4.4%) did not differ significantly from proportions treated in the Clinical Practice Research Datalink cohort (30.4% and 4.4%) (P = .07 for cholestyramine and P = .32 for naltrexone). Latent class mixed models (n = 1753) identified 3 different groups of pruritus. Multivariable analysis identified younger age at diagnosis and higher level of alkaline phosphatase at 12 months after diagnosis as factors significantly associated with persistent high pruritus., Conclusions: In a large national cohort study of patients with PBC, we found a high prevalence of pruritus and inadequate guideline-recommended therapy. Patient-reported data used to determine pruritus prevalence and treatment are reliable. Younger age and levels of higher alkaline phosphatase were associated with persistent pruritus. We need to increase awareness and management of pruritus in PBC in the UK., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA., Methods: From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Cox’s proportional hazard regression model., Results: Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023)., Conclusions: In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.

Objective The efficacy and safety of concomitant use of antithrombin (AT) with recombinant human soluble thrombomodulin (rTM) for acute cholangitis-induced disseminated intravascular coagulation (AC-induced DIC) remains unclear. This study was conducted to investigate the efficacy of AT combined with rTM as anticoagulant therapy for AC-induced DIC. Methods One hundred patients with AC-induced DIC received anticoagulant therapy using rTM from April 2010 to December 2017. Of the 83 patients treated with rTM immediately after the diagnosis of DIC, excluding those who had not undergone biliary drainage or who had malignancies or a serum AT III level >70%, 56 patients were studied. Outcomes and adverse events (AEs) were retrospectively compared between the 16 patients treated with rTM alone (rTM group) and the 40 patients treated with rTM and AT (rTM+AT group). Results Patients' background characteristics did not differ markedly, except for a significantly higher serum D-dimer level in the rTM group than in the rTM+AT group (p=0.038). The DIC resolution rates on day 9 were 100% and 95.1% in the rTM and rTM+AT groups, respectively (p=0.909). The mean DIC scores were significantly lower in the rTM group than in the rTM+AT group on days 3 (p=0.012), 5 (p<0.001), 7 (p=0.033), and 9 (p=0.007). The incidence of AEs was 6.3% and 10.0% (p=0.941), and the in-hospital mortality rates was 0% and 5.0% (p=0.909) in the rTM and rTM+AT groups, respectively. Conclusion The concomitant use of AT with anticoagulant therapy using rTM for AC-induced DIC may not help improve the treatment outcome.

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 ± 0.7 vs. 3.7 ± 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 ± 6.0 vs. 20.4 ± 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., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the etiology, clinical features and outcomes of bacteremia in older patients with solid tumors., Methods: All episodes of bacteremia in hospitalized patients with solid tumors were prospectively collected. Patients aged ≥70 years were compared to patients aged <70 years. Risk factors for case-fatality rates in older patients were identified., Results: We compared 217 episodes of bacteremia involving older patients and 525 occurring in younger patients. Older patients had more frequently other comorbidities, but were less commonly neutropenic and carried less frequently central venous catheters. Bacteremia from an abdominal source was more common in patients ≥70, whereas an endogenous source and catheter-related infection were less frequently observed. Streptococcus bovis group (3.7% vs. 0.8%, p = .01) and Listeria monocytogenes (4.6% vs. 1.9%, p = .04) were more common in older patients, whereas coagulase-negative staphylococci were less frequently found (1.4% vs. 5.3% p = .01). Infection due to multi-drug resistant (MDR) strains was significantly higher in older patients (17.1% vs. 10.9%, p = .02), who in addition, presented higher overall mortality (35.4% vs 27.7%, p = .04). In older patients, lung tumor, neutropenia, and low grade fever were associated with early mortality, whereas comorbidities, corticosteroids, septic shock and inadequate empirical antibiotic therapy were associated with overall mortality., Conclusions: We identified remarkable differences in the etiology and sources of bacteremia between older and younger cancer patients with bacteremia. Older patients had more frequent infection due to MDR organisms and presented a higher overall mortality. Corticosteroids and inadequate empirical antibiotic therapy are modifiable factors associated with mortality., (Copyright © 2018. Published by Elsevier Ltd.)

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.

Background: Post-hepatectomy liver failure (PHLF) is a serious complication after major hepatectomy with extrahepatic bile duct resection (Hx with EBDR) that may cause severe morbidity and even death. The purpose of this study was to compare several criteria systems as predictors of PHLF-related mortality following Hx with EBDR for perihilar cholangiocarcinoma (PHCC)., Methods: The study cohort consisted of 222 patients who underwent Hx with EBDR for PHCC. We compared several criteria systems, including previously established criteria (the International Study Group of Liver Surgery (ISGLS) criterion; and the "50-50" criterion), and our institution's novel systems "Max T-Bili" defined as total bilirubin (T-Bili) >7.3 mg/dL during post-operative days (POD) 1-7, and the "3-4-50" criterion, defined as total bilirubin >4 mg/dL and prothrombin time <50% on POD #3., Results: Thirteen patients (5.8%) died from PHLF-related causes. The 3-4-50 criterion showed high positive predictive values (39.1%), the 3-4-50, Max T-Bili, and 50-50 criterion showed high accuracies (91.7, 86.9, and 90.5%, respectively) and varying sensitivities (69.2, 69.2, and 38.5% respectively)., Conclusions: The 3-4-50, Max T-Bili, and 50-50 criterion were all useful for predicting PHLF-related mortality after Hx with EBDR for PHCC., (© 2018 S. Karger AG, Basel.)

Primary biliary cholangitis is a chronic liver disorder characterized by progressive cholestasis that may evolve to liver cirrhosis. While ursodeoxycholic acid is the treatment of choice, around 30% of patients do not respond to this therapy. These patients have a poorer prognosis, hence should be identified early in order to be offered therapy options. Along these lines, improved understanding of the condition's pathophysiology has allowed the development of newer drugs, including obeticholic acid and fibrates. This review offers a perspective on risk stratification and treatment for these patients, from ursodeoxycholic acid to second-line treatments.

An 87-year-old man was admitted to our hospital due to fever and elevated liver enzymes. Computed tomography (CT) scan revealed bile duct stones with a dilated biliary system, which confirmed the diagnosis of cholangitis. A 12-cm simple hepatic cyst was also seen in the right liver, which had been detected on CT scan 5 years before, and did not change in size. Fever did not subside even after endoscopic biliary drainage and a repeated CT scan showed an enlarged cyst up to 14 cm, suggesting cyst infection. An enlarged hepatic cyst collapsed after percutaneous transhepatic drainage, along with resolution of fever. Simple hepatic cysts are common and most of them are asymptomatic. Infection of simple hepatic cysts is a rare condition and the major entry route is considered as the biliary tract as communication between the biliary tract and cysts is reportedly observed in those cases. However, in our case, no communication was seen on cholangiogram or cystogram on fluoroscopy and bilirubin level of the cyst aspirate was low. Given the fact that patients with cholangitis are rarely complicated by hepatic cyst infection, other routes of bacterial entry to simple hepatic cysts should also be considered.

Background: Recurrent pyogenic cholangitis (RPC) is a known risk factor for intrahepatic cholangiocarcinoma (ICC), whether it represents a poor prognostic factor remains controversial. The aim of this study was to investigate the post-hepatectomy oncological outcomes of patients with ICC and coexisting RPC., Method: A retrospective analysis with propensity score matching (PSM) was performed for comparison between ICC patient with and without RPC., Results: There were 143 patients with ICC with a median follow-up of 21 months. RPC was diagnosed in 18% of patients. The time from RPC diagnosis to ICC diagnosis was 137(47-481) months. The 3-year disease-free (DFS) and overall survival for the whole population was 34% and 43% respectively. Preoperative child score, elevated carcinoembryonic antigen, presence of microvascular invasion, multiple tumours, presence of postoperative complications and RPC were independent factors for DFS and OS. After PSM, 60 ICC patients who did not have RPC were compared with 20 ICC patients with RPC. Patients with RPC had significantly worse median DFS (10 vs 23 months, P = 0.020) and OS (15 vs 45 months, P = 0.004) when compared to the patients without RPC., Conclusion: RPC represents a poor prognostic factor affecting outcomes after hepatectomy for patients with ICC., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective This study was performed to assess the effectiveness and safety of percutaneous cholecystostomy (PC) for biliary decompression. Methods We retrospectively analyzed our institution's PC database from March 2015 to August 2017 and selected patients with biliary obstruction. The primary outcomes were the technical and clinical success rates. As secondary outcomes, adverse events and pain after PC were compared with those of patients who underwent PC for acute cholecystitis during the same period. Results Twenty patients underwent PC for biliary obstruction (cholangitis, 19; pancreatitis, 1). The technical and clinical success rates were 100%. The median serum total bilirubin level decreased considerably from 4.5 to 1.4 mg/dL after PC. An adverse event (catheter migration) occurred in 1 patient, and 17 patients developed pain after PC. During the same period, 104 patients underwent PC for cholecystitis. Adverse events occurred in 7 patients, and 62 developed pain. There was no significant difference in the adverse event rate between the cholangitis/pancreatitis and cholecystitis groups (5.0% vs. 6.7%, respectively), but pain occurred considerably more frequently in the cholangitis/pancreatitis group (94.4% vs. 63.9%, respectively). Conclusions PC is an effective and safe method for biliary decompression in selected patients. However, attention should be paid to postoperative pain.

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.

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with multiple debilitating complications. Osteoporosis is a common complication of PBC resulting in frequent fractures and leading to significant morbidity in this population, yet evidence for effective therapy is lacking. We sought to summarize our current understanding of the pathophysiology of osteoporosis in PBC, as well as current and emerging therapies in order to guide future research directions. A complete search with a comprehensive literature review was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, and the Countway Library. Osteoporosis in PBC is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Despite this fundamental difference, current treatment recommendations are based primarily on experience with postmenopausal osteoporosis. Trials specific to PBC-related osteoporosis are small and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in PBC relies on the mitigation of risk factors such as smoking and alcohol use, as well as encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in PBC remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in PBC and summarizes current and emerging therapies., Competing Interests: Conflict-of-interest statement: There are no other financial disclosures or conflicts of interest in the production of this manuscript.

The therapy of primary biliary cholangitis (PBC) has lagged behind other autoimmune diseases despite significant improvements in our understanding of both immunological and molecular events that lead to loss of tolerance to the E2 component of pyruvate dehydrogenase, the immunodominant autoepitope of PBC. It is well known that Ly6C hi monocytes are innate immune cells infiltrating inflammatory sites that are dependent on the expression of C-C motif chemokine receptor 2 (CCR2) for emigration from bone marrow. Importantly, humans with PBC have a circulating monocyte pro-inflammatory phenotype with macrophage accumulation in portal tracts. We have taken advantage of an inducible chemical xenobiotic model of PBC and recapitulated the massive infiltration of monocytes to portal areas. To determine the clinical significance, we immunized both CCR2-deficient mice and controls with 2OA-BSA and noted that CCR2 deficiency is protective for the development of autoimmune cholangitis. Importantly, because of the therapeutic potential, we focused on inhibiting monocyte infiltration through the use of cenicriviroc (CVC), a dual chemokine receptor CCR2/CCR5 antagonist shown to be safe in human trials. Importantly, treatment with CVC resulted in amelioration of all aspects of disease severity including serum total bile acids, histological severity score, and fibrosis stage. In conclusion, our results indicate a major role for Ly6C hi monocytes and for CCR2 in PBC pathogenesis and suggest that inhibition of this axis by CVC should be explored in humans through the use of clinical trials.

Background: The aim of this study was to compare the clinical outcomes between patients with preoperative cholangitis and noncholangitis patients to determine whether the preoperative cholangitis would be able to serve as an independent predictive factor on hilar cholangiocarcinoma (HCC) outcomes., Methods: A systematic literature search for reported preoperative cholangitis in patients with hilar cholangiocarcinoma was performed in 4 databases: PubMed, Web of Science, Embase, and the Cochrane Library, published from 1979 to 2017., Results: In total, the initial search identified 1228 articles. Of these studies only 9 studies met the inclusion criteria and were included in this analysis. Differences between preoperative cholangitis existing and noncholangitis patients were observed in terms of mortality (RR = 2.29; 95% CI = 1.48-3.52; P = .0002), overall morbidity (RR = 1.15;95% CI = 1.00-1.32; P = .04), Liver failure (RR = 1.15;95% CI = 1.00-1.32; P = .04), Infection (RR = 1.52;95% CI = 1.16-2.00; P = .003), sepsis (RR = 2.40;95% CI = 1.25-4.5; P = .008)., Conclusions: The results lend support to the notion that in hilar cholangiocarcinoma patients, the existence of preoperative cholangitis is statistically associated with the higher postoperative mortality and morbidity. Also that it increases the risk of liver failure and infection. therefore, it is very important to properly control the preoperative cholangitis before surgery.

Background/aims: Recently, recombinant human soluble thrombomodulin (rTM) has been developed as a new drug for disseminated intravascular coagulation (DIC). This study aims to evaluate the clinical benefit of rTM in patients with sepsis-induced DIC caused by acute cholangitis who underwent biliary drainage., Methods: Patients were divided into two groups: the rTM therapy group and the non-rTM therapy group. The primary outcome was the DIC resolution rate at 7 days, and the secondary outcome was 28-day mortality rate., Results: Thirty-five patients were treated by rTM, and 36 patients were treated without rTM for DIC. The rate of resolution of DIC at day 7 was significantly higher in the rTM group than in the non-rTM group (82.9% vs 55.6%, p=0.0012). Compared with the non-rTM group, the 28-day survival rate of the r-TM group was significantly higher (rTM vs non-rTM, 91.4% vs 69.4%, p=0.014). According to multivariate analysis, non-rTM (hazard ratio [HR], 2.681) and CRP (HR, 2.370) were factors related to decreased survival., Conclusions: rTM treatment may have a positive impact on improving DIC and survival rates in patients with severe acute cholangitis.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Chronic Hepatitis C Virus (HCV) infection has been commonly linked to the development of autoimmunity, in part through activation of B cells. B cells are also postulated to play a pathogenic role in the autoimmune liver disease Primary Biliary Cholangitis (PBC). Patients with concurrent PBC and HCV infection carry an increased risk of more progressive disease, although the mechanism underlying this effect is poorly understood. Utilizing a case series of patients with concurrent PBC and HCV, the aim of this study was to evaluate for the potential impact of HCV eradication upon autoimmunity/autoantibody production., Case Presentation: A case series evaluating three patients with co-existing PBC-HCV infection receiving non-interferon based HCV treatments with direct-acting antivirals (DAA). One of three patient received Ursodeoxycholic acid (UDCA; 13 mg/kg/day) during the treatment period. Sustained virological response (SVR) to DAA's was assessed using a HCV Quantitative Nucleic Acid Test (Abbott). Autoantibodies associated with autoimmune liver diseases (including PBC) and liver biochemistry, were measured before, during and after DAA treatment (Mitogen Advanced Diagnostics Laboratory, Calgary, Canada). All patients achieved an SVR, as determined by negative HCV RNA test 12 weeks post-DAA therapy. Titres of anti-mitochondrial antibodies (AMA-M2), anti- branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate dehydrogenase complex (anti-3E-BPO), and anti- tripartite motif-containing protein 21 (TRIM21/Ro52) remained unchanged, despite successful HCV eradication. Two of the three patients exhibited a transient decrease in some autoantibody titres during DAA treatment, but these returned to baseline levels post-DAA therapy., Conclusions: Within the limitations of a case series, our results suggest that HCV co-infection may not be a significant driver of PBC-related autoimmunity/autoantibody production. However, a larger n-value is required to truly assess for the effect of HCV eradication on autoantibody production.