Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS).

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has proven clinical efficacy as rescue therapy for cirrhotic patients with acute portal hypertensive bleeding who fail endoscopic treatment.

Aims: To investigate predictive factors of 6-week and 1-year mortality in patients undergoing salvage TIPS for refractory portal hypertensive bleeding.

Methods: A total of 144 consecutive patients were retrospectively evaluated.

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity.

Objectives: We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis.

Methods: We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria.

Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate.

Unlabelled: Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis, leading to significant differences between "true" and calculated glomerular filtration rate (GFR). We compared the performance of the four-variable and six-variable Modification of Diet in Renal Disease and chronic kidney disease epidemiology with "true," or measured, GFR (mGFR) and the impact of this difference on Model for End-Stage Liver Disease (MELD) calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulae.

The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study.

Background & Aims: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Results: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients.

Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score.

Background: Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented.

Methods: The associations of nutritional status and sarcopenia with post-transplant infections, requirement for mechanical ventilation, intensive care (ICU) and hospital stay, and 1 year mortality were assessed in 232 consecutive transplant recipients. Nutritional status and sarcopenia were assessed using the Royal Free Hospital-Global Assessment (RFH-GA) tool and the L3-psoas muscle index (L3-PMI) on CT, respectively.

Elevated liver enzymes in inflammatory bowel disease: the role and safety of infliximab.

Background: Abnormal liver enzymes are frequently encountered in inflammatory bowel disease (IBD) patients. Infliximab has been implicated in inducing drug-induced liver injury, autoimmune hepatitis or reactivation of hepatitis B virus. We aimed to clarify the role of infliximab in liver impairment in an IBD cohort.

Hypothalamus-pituitary dysfunction is common in patients with stable cirrhosis and abnormal low dose synacthen test.

Background: Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics.

Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy.

Background & Aims: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC.

Methods: We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries.

The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis.

Unlabelled: The biochemical response to ursodeoxycholic acid (UDCA)--so-called "treatment response"--strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease.

Interobserver Agreement on Endoscopic Classification of Oesophageal Varices in Children.

Objectives: Data regarding agreement on endoscopic features of oesophageal varices in children with portal hypertension (PH) are scant. The aim of this study was to evaluate endoscopic visualisation and classification of oesophageal varices in children by several European clinicians, to build a rational basis for future multicentre trials.

Methods: Endoscopic pictures of the distal oesophagus of 100 children with a clinical diagnosis of PH were distributed to 10 endoscopists.

Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease.

Background: The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic fibrosis in people with liver diseases. Transient elastography is a non-invasive method for assessing and staging hepatic fibrosis.

Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study.

Objective: Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC.

Design: Risk factor analysis was performed in over 15 centres from North America and Europe spanning >40 years observation period using Cox proportional hazards assumptions, logistic regression, and Kaplan-Meier estimates.

Anti-tumour necrosis factor agent and liver injury: literature review, recommendations for management.

Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

Objectives: Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation.

Methods: Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection.

Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study.

Background & Aims: Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points.

Methods: We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies.

Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study.

Background And Aims: Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC.

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteria.

Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumor necrosis after transarterial embolization. 150 consecutive patients who underwent transplantation for HCC within the Milan criteria between 1996 and 2010 were included; data regarding inflammatory markers, patient and tumor characteristics were analyzed.

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C.

Unlabelled: The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model.

Liver transplantation for neuroendocrine tumour liver metastases.

Objective: Search and review of available literature were made to define the indications for and timing of liver transplantation for neuroendocrine tumour (NET) liver metastases.

Methods: Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were used for qualitative and quantitative synthesis of the systematic review.

Endogenous heparinoids detected by anti-Xa activity are present in blood during acute variceal bleeding in cirrhosis. A prospective study.

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.

Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 non-cirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).

Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleeding but was present in seven (23%) variceal bleeders (median levels: 0.

Future treatments of cirrhosis.

Cirrhosis can be sub-classified in clinical stages with distinct differences in prognosis and can even be reversed in some cases with successful etiological treatment. In this article, we review potential future therapies of cirrhosis, mainly focusing in the expansion of indications of currently licensed drugs. We strongly advocate that future therapies should focus on preventing the advent of complications and further progression of liver disease and should involve both primary and secondary care physicians.

The use of guideline images to improve histological estimation of hepatic steatosis.

Background & Aims: Guideline images of specific fat proportionate area (FPA) percentages have recently been published to aid the histological assessment of liver steatosis as subjective estimates of FPA are usually overestimated. To assess, (i) the effect of guideline images on accuracy and concordance of estimated FPA (eFPA), (ii) experience of steatosis grading systems on eFPA, (iii) the effect of magnification on assessment of FPA (iv) and produce a range of guideline images at x4 objective magnification (OM).

Methods: Two circulations of sample images (C1 and C2) were circulated to UK liver external quality assessment histopathology scheme members who were asked to independently evaluate steatosis.