Antimicrobial therapy for acute cholangitis: Tokyo Guidelines

Antimicrobial agents should be administered to all patients with suspected acute cholangitis as a priority as soon as possible. Bile cultures should be performed at the earliest opportunity. The important factors which should be considered in selecting antimicrobial therapy include the agent’s activity against potentially infecting bacteria, the severity of the cholangitis, the presence or absence of renal and hepatic diseases, the patient’s recent history of antimicrobial therapy, and any recent culture results, if available. Biliary penetration of the microbial agents should also be considered in the selection of antimicrobials, but activity against the infecting isolates is of greatest importance. If the causative organisms are identified, empirically chosen antimicrobial drugs should be replaced by narrower-spectrum antimicrobial agents, the most appropriate for the species and the site of the infection

ALBI and PALBI grades are associated with the outcome of patients with stable decompensated cirrhosis

Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC. Aim. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality / liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases. Material and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome. Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p < 0.001 and HR: 2.06, 95%CI [1.47, 2.9], p < 0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621, 0.744], respectively). ALBI and PALBI performed better than CTP score (p = 0.0044 and p = 0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complications. Conclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosis. © 2019, Fundacion Clinica Medica Sur. All rights reserved

Galectin-3 is associated with glomerular filtration rate and outcome in patients with stable decompensated cirrhosis

Background: Newly introduced galectin-3 (gal-3) has been associated to impaired renal function. Gal-3 may become prognostic biomarker in hepatic diseases. Aim: To investigate the association of gal-3 with prognosis and renal function in patients with stable decompensated cirrhosis. Method: We studied prospectively 100 stable decompensated patients in our Department between 2010 and 2017. We measured gal-3 in serum samples. Patients’ renal function was assessed using 51Chromium-EDTA (“true GFR”). Results: Seventy patients (70%) survived and 30 died (n = 16) or underwent LT (n = 14). Twenty nine patients (29%) had normal gal-3, 71 (71%) had ≥11.7 ng/mL; they differed significantly regarding mean “true”-GFR: 90 ± 20 mL/min vs. 76 ± 26 mL/min, p = 0.03 and mean creatinine: 0.83 ± 0.14 mg/dL vs. 0.97 ± 0.4 mg/dL, p = 0.05. Median gal-3 levels were 17.5 ng/mL (range 4.9–76.5 ng/mL); 49 patients with gal-3 ≥17.5 ng/mL had significantly higher MELD score, (15 ± 5 vs. 13 ± 4, p = 0.02) and worse “true” GFR (74 vs. 85 mL/min, p = 0.04). Gal-3 had good performance in predicting “true”-GFR < 60 mL/min; AUC: 0.71, 95%CI [0.58–0.85], best cut off value 17.5 ng/mL. Kaplan–Meier analysis, using median gal-3 (17.5 ng/mL) revealed different survival time for our patients (log-rank p = 0.04). Conclusion: Gal-3 proved trustworthy marker of established chronic kidney disease, with predictive ability in stable decompensated cirrhosis. Gal-3 came also a significant factor for our patients’ outcome. © 2019 Editrice Gastroenterologica Italiana S.r.l

Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment

Spondyloarthropathies (SpA) include many different forms of inflammatory arthritis and can affect the spine (axial SpA) and/or peripheral joints (peripheral SpA) with Ankylosing spondylitis (AS) being the prototype of the former. Extraarticular manifestations, like uveitis, psoriasis and inflammatory bowel disease (IBD) are frequently observed in the setting of SpA and are, in fact, part of the SpA classification criteria. Bowel involvement seems to be the most common of these manifestations. Clinically evident IBD is observed in 6%-14% of AS patients, which is significantly more frequent compared to the general population. Besides, it seems that silent microscopic gut inflammation, is evident in around 60% in AS patients. Interestingly, occurrence of IBD has been associated with AS disease activity. For peripheral SpA, two different forms have been proposed with diverse characteristics. Of note, SpA (axial or peripheral) is more commonly observed in Crohn's disease than in ulcerative colitis. The common pathogenetic mechanisms that explain the link between IBD and SpA are still ill-defined. The role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint ("gut-joint" axis) has been recognized, in the context of a genetic background including associations with alleles inside or outside the human leukocyte antigen system. Various therapeutic modalities are available with monoclonal antibodies against tumour necrosis factor, interleukin-23 and interleukin-17, being the most effective. Both gastroenterologists and rheumatologists should be alert to identify the coexistence of these conditions and ideally follow-up these patients in combined clinics. © 2019 Baishideng Publishing Group Inc. All rights reserved

Trough Levels of Everolimus Are Associated With Recurrence Rates of Hepatocellular Carcinoma After Liver Transplantation

Purpose: Everolimus, a mammalian target of rapamycin inhibitor, may have a protective role on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but data regarding the impact of its trough serum levels on HCC recurrence are missing. Methods: Fifty-five patients (43 men, age 55 ± 8 years) who underwent LT for HCC were evaluated. Several demographic and clinical variables were recorded, including radiological and histological characteristics of HCC as well as dosages and trough levels of immunosuppressive regimens. Results: HCC recurrence occurred in 11 (20%) patients: 5 (25%) of 20 patients under calcineurin inhibitors and 6 (17%) of the 35 patients under everolimus (P =.48). The patients with HCC recurrence (n = 11, group 1), compared to those without recurrence (n = 44, group 2), had significantly more frequent HCC in the explant: outside Milan criteria (P =.001), microvascular invasion (P <.001), and higher number of nodules (P =.001). In multivariate analysis, microvascular invasion was the only independent factor significantly associated with HCC recurrence (OR: 2.3, 95% CI: 1.4–10.5, P =.03). Among the patients who received everolimus-based immunosuppression, the recipients with HCC recurrence, compared to those without HCC recurrence, had significantly lower mean trough levels of everolimus at 7–12 months post-LT (3.9 vs 5.9 ng/mL, P =.001), while the patients with mean trough levels of everolimus >6 ng/mL had decreased HCC recurrence rates (log rank: 2.3, P =.007). Conclusions: We found for the first time mean concentrations of everolimus between 7–12 months post-LT as the only modifiable variable related with HCC recurrence in LT recipients. However, larger studies are needed for final conclusions. © 2019 Elsevier Inc