Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

BACKGROUND & AIMS: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions. METHODS: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported. RESULTS: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%. CONCLUSIONS: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Partitioning and in vitro bioaccessibility of apple polyphenols during mechanical and physiological extraction: A hierarchical clustering analysis with LC-ESI-QTOF-MS/MS.

Polyphenol partitioning during mechanical (cold-pressing) and physiological (digestion) extraction at the individual polyphenol and subclass level was investigated. UHPLC-ESI-QTOF-MS/MS analysis yielded a comprehensive identification of 45 polyphenols whose semi-quantification revealed a hierarchical clustering strongly determined by polyphenol structure and their location within the apple tissue. For instance, pomace retained most flavonols and flavanols (degree of polymerization DP 5-7), which were highly hydrophobic, hydroxylated, or large (>434 Da), and more abundant in peel. In vitro digestion UHPLC-ESI-QTOF-MS/MS analysis of whole apple (and its corresponding matrix-free extract) clustered polyphenols into five main groups according to their interaction with plant cell walls (PCWs) during each digestion phase. This grouping was not reproduced in pomace, which exhibited a greater matrix effect than whole apple during oral and gastric digestion. Nevertheless, the interaction between most polyphenol groups, including dihydrochalcones, flavanols (DP 1-4) and hydroxycinnamic acid derivatives, and pomace PCWs was lost during intestinal digestion.

Guidance document: risk assessment of patients with cirrhosis prior to elective non-hepatic surgery.

As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment. Well-recognised risks include those of general anaesthesia, bleeding, infections, impaired wound healing, acute kidney injury and cardiovascular compromise. Intra-abdominal or cardiothoracic surgery are particularly high-risk interventions. Clinical assessment supplemented by blood tests, imaging, liver stiffness measurement, endoscopy and assessment of portal pressure (derived from the hepatic venous pressure gradient) can facilitate risk stratification. Traditional prognostic scoring systems including the Child-Turcotte-Pugh and Model for End-stage Liver Disease are helpful but may overestimate surgical risk. Specific prognostic scores like Mayo Risk Score, VOCAL-Penn and ADOPT-LC can add precision to risk assessment. Measures to mitigate risk include careful management of varices, nutritional optimisation and where possible addressing any ongoing aetiological drivers such as alcohol consumption. The role of portal decompression such as transjugular intrahepatic portosystemic shunting can be considered in selected high-risk patients, but further prospective study of this approach is required. It is of paramount importance that patients are discussed in a multidisciplinary forum, and that patients are carefully counselled about potential risks and benefits.

Analysis of Migrant Cyclic PET Oligomers in Olive Oil and Food Simulants Using UHPLC-qTOF-MS.

Oligomers are a particular category of non-intentionally added substances (NIAS) that may be present in food contact materials (FCMs), such as polyethylene terephthalate (PET), and consequently migrate into foods. Here, an ultra-high-pressure liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-qTOF-MS) method was developed for the analysis of 1st series cyclic PET oligomers in virgin olive oil (VOO) following a QuEChERS clean-up protocol. Oligomer migration was evaluated with two different migration experiments using bottles from virgin and recycled PET: one with VOO samples stored in household conditions for a year and one using the food simulant D2 (95% v/v ethanol in water) at 60 °C for 10 days. Calibration curves were constructed with fortified VOO samples, with the LOQs ranging from 10 to 50 µg L-1 and the recoveries ranging from 86.6 to 113.0%. Results showed no migration of PET oligomers in VOO. However, in the simulated study, significant amounts of all oligomers were detected, with the migration of cyclic PET trimers from recycled bottles being the most abundant. Additional substances were tentatively identified as linear derivatives of PET oligomers. Again, open trimer structures in recycled bottles gave the most significant signals.

Systematic review and meta-analysis: impact of anti-viral therapy on portal hypertensive complications in HBV patients with advanced chronic liver disease.

BACKGROUND: The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. METHODS: MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. RESULTS: Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37-0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26-0.74) and ascites (RR, 0.10; 95% CI: 0.01-1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30-0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25-0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75-0.97 and RR, 0.85; 95% CI: 0.73-0.99, respectively). CONCLUSION: NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death.

Safety assessment of the process LOGIFRUIT, used to recycle high-density polyethylene and polypropylene crates for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process LOGIFRUIT (EU register number RECYC260). The input consists of pre-washed high-density polyethylene (HDPE) or polypropylene (PP) crates from closed and controlled food distribution loops. The process separates crates by material type. Crates are ground to flakes, possibly extruded to pellets and used by companies approved to be in the loop to manufacture new crates. The Panel considered that the quality management system (QAS) put in place to ensure compliance of the origin of the input with Commission Regulation (EC) No 282/2008 and to provide full traceability is critical. The Panel concluded that, when run under the conditions described, the input of the process LOGIFRUIT exclusively originates from product loops which are in closed and controlled chains. The process is designed to ensure that only crates intended for food contact are used and that contamination other than by food can be ruled out. Therefore, the recycling process LOGIFRUIT to produce HDPE and PP crates to be used in contact with fruits and vegetables, and packed meat and fish, dairy, bakery and pastry products is not of safety concern.

Safety assessment of the process Cajas y Palets en una Economia Circular (CAPEC), used to recycle high-density polyethylene and polypropylene crates for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Cajas y Palets en una Economia Circular (CAPEC) (EU register number RECYC242). The input consists of crates made of high-density polyethylene (HDPE) or polypropylene (PP) originating from closed and controlled product loops for the packaging of whole fruits and vegetables. Flakes or pellets are produced that will be used by manufacturers of new crates for food contact. The Panel considered that the management system put in place to ensure compliance of the origin of the input with Commission Regulation (EC) No 282/2008 and to provide full traceability from input to final product is the critical process step. It concluded that the input of the process CAPEC originates from product loops which are in closed and controlled chains designed to ensure that only materials and articles that have been intended for food contact are used and that contamination can be ruled out when run under the conditions described by the applicant. The recycling process CAPEC is therefore suitable to produce recycled HDPE and PP crates intended to be used in contact with fruits and vegetables.

Development, Validation and Application of an Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) Method after QuEChERS Cleanup for Selected Dichloroanilines and Phthalates in Rice Samples.

Dichloroanilines and phthalic acid esters (phthalates) are food contaminants, stable in solution even at high temperatures, which exhibit considerable toxic effects, while acting as endocrine disruptors. In the present study, a quick and easy UHPLC-MS/MS method for simultaneously analyzing two dichloroanilines (3,4-DCA and 3,5-DCA) and six phthalates (DMP, DnBP, BBP, DnOP, DEHP, and mBP) in commercial rice samples was developed, validated, and applied. For the cleanup process, the methodology of quick, easy, cheap, effective, rugged, and safe (QuEChERS) was applied, whereas different dispersants (GCB, C18, and PSA) were tested. What was developed and presented had limits of detection ranging from 0.017 up to 0.12 mg/kg, recoveries (trueness) below 120%, and relative standard deviations (RSD; precision) <15% for all target analytes, whilst no significant matrix effects occurred for all analytes. It was determined that the rice samples analyzed using this developed technique did not contain any of the two dichloroaniline compounds (3,4-DCA and 3,5-DCA) nor two of the six phthalate (DMP and mBP) compounds analyzed, while the levels of other phthalates (DEHP, BBP, DnBP and DnOP) were within the legal limits. The current method ensures a fast and easy approach for the high-throughput quantification of the selected food contaminants in rice.

Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria.

BACKGROUND: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. METHOD: Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. RESULTS: Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77-2.67). The median follow-up period was 5.1 95% CI [4.7-5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51-10.59], P < 0.001) and body mass index (0.74 95% CI [0.59-0.89], P < 0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 - 1.94], P = 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96-0.99], P = 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P = 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 - 2.05], P = 0.036) and SMI were (HR 0.98 95% CI [0.95-0.99], P = 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. CONCLUSIONS: Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.

Increased Body Mass Index and Type 2 Diabetes Are the Main Predictors of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Liver Biopsies of Patients With Human Immunodeficiency Virus Monoinfection.

BACKGROUND: Liver disease is an important cause of morbidity and mortality in people living with human immunodeficiency virus (PLWH), of which nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause. There are limited data investigating NAFLD in HIV monoinfection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD, and nonalcoholic steatohepatitis (NASH) among PLWH and explore the diagnostic accuracy of noninvasive markers of fibrosis. METHODS: This was a retrospective, cross-sectional, international, multicenter study including patients with HIV monoinfection, without chronic viral hepatitis or other known causes of chronic liver disease, who underwent liver biopsy for abnormal liver biochemistry and/or clinical suspicion of liver fibrosis. RESULTS: A total of 116 patients from 5 centers were included. Sixty-three (54%) had NAFLD, of whom 57 (92%) had NASH. Overall, 36 (31%) had advanced fibrosis (≥F3) and 3 (3%) had cirrhosis. Of the 53 cases without NAFLD, 15 (28%) had advanced fibrosis. Collagen proportionate area was similar between cases with and without NAFLD (3% vs 2%). Body mass index was independently associated with NAFLD (aOR, 1.2; 95% CI, 1.08-1.34), and type 2 diabetes was independently associated with advanced fibrosis (aOR, 3.42; 95% CI, 1.00-11.71). The area under the curve for advanced fibrosis was 0.65 and 0.66 for both NAFLD Fibrosis Score (NFS) and FIB-4. Cutoff values of -1.455 (NFS) and 1.3 (FIB-4) have negative-predictive values of 0.80 and 0.82, respectively. CONCLUSIONS: Advanced fibrosis is strongly associated with type 2 diabetes in PLWH. Serological markers require further optimization.

Analysis of PBT and PET cyclic oligomers in extracts of coffee capsules and food simulants by a HPLC-UV/FLD method.

A HPLC-UV/FLD method was validated for the quantification of six polyethylene terephthalate (PET) and four polybutylene terephthalate (PBT) oligomers. PBT oligomers are EU regulated, while the PET ones are considered non-intentionally added substances (NIAS). LOQs were higher than 0.4 and 3.5 µg kg-1 for the simulants and in the polymer extracts, respectively. Recoveries ranged from 95 to 114 % with RSDs below 12%. Migration testing of PBT and polypropylene coffee capsules were performed with H2O and simulant C, and extracts were obtained with accelerated solvent extraction (ASE). For the latter legislative limits weren't surpassed. As no migration limits are existing for the analytes, both EFSA's toxicological threshold of concern (TTC) and sum of oligomers approaches were applied. The majority of oligomers were below the TTC (90 µg/person/day), but the limit value of 50 µg/kg food was surpassed for some capsules, which indicates a significant intake in both single and multiple consumption.

Development and validation of a fast gas chromatography mass spectrometry method for the quantification of selected non-intentionally added substances and polystyrene/polyurethane oligomers in liquid food simulants.

A simple, fast, sensitive and reliable method was developed for the simultaneous determination of 13 food contact materials (FCM) regulated substances and non-intentionally added substances (NIAS) migrating into official food simulants. The method has been optimized to quantify the monomers styrene and α-methyl styrene, selected polystyrene oligomers (dimers, trimers) and polyester urethane-based oligomers (PU) cyclic oligomers, as well as cyclic NIAS originating from food packaging such as 2,6-Di-tert-butylbenzoquinone and 7,9-Di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione. The method employs liquid-liquid extraction of aqueous ethanol food simulants with dichloromethane, and analysis with gas chromatography coupled to mass spectrometry (GC-MS) with a total analysis time of less than 16 min, with limits of detections ranging from 0.32 ng mL-1 (1,1-diphenyl-ethylene) to 14.8 ng mL-1 for 7,9-di-tert-butyl-1-oxaspiro[4.5]deca-6,9-diene-2,8-dione and respective limits of quantification from 1.0 ng mL-1 to 41.7 ng mL-1, for the same analytes. Accuracy and precision results showed that the method is sufficiently accurate for all target analytes, with recoveries ranging between 80 and 110% and relative standard deviations (RSDs) smaller than 16% at the three selected concentration levels. The method has been successfully applied to seven FCM. Results indicated that significant amounts of polystyrene monomers, dimers and trimers are migrating into food simulants; this is also the case for polyester urethane-based oligomers (PU). Exposure assessment estimation was performed using EFSA's approach on the total sum of migrating oligomers. In certain cases, amounts of PS and PU oligomers found to be in some cases higher than the respective limits, for the sum of oligomers with a MW lower than 1000 Da.

Influence of pre-heating of food contact polypropylene cups on its physical structure and on the migration of additives.

Laboratories unexpectedly carried out pre-heating of polypropylene beverage cups prior to performing a migration test in a proficiency test. Principal component analysis of the data collected showed that the preheating temperature of the cups contributed to an increased variance of the data and distinguishing pre-heating and non-pre-heating groups. This triggered to study the effect of applying such pre-heating on the physical structure of the material and on the migration of additives to food simulant D1 (ethanol 50% v/v). Several cups were pre-heated at selected temperatures and either analyzed with differential scanning calorimetry to establish the degree of crystallinity or used for the migration test. Six target additives from Regulation (EU) No 10/2011 were quantified in the food simulant using HPLC-FLD and LC-MS. Results show that pre-heating of the beverage cups led to a significant change in the degree of crystallinity, resulting in a change of analyte migration in comparison to the migration results from non-pre-heated cups.

Determination of selected dichloroanilines and phthalates in lyophilised mussels samples with ultra-high performance liquid chromatography-tandem mass spectrometry after QuEChERS clean-up.

Mussels, a marine filter organism, constitute a food product and an established sentinel organism for marine pollution. An analytical method following a QuEChERS extraction and clean-up protocol has been developed for the determination of phthalic acid esters (PAE), including di-n-octyl phthalate (DnOP), di-(2-ethyl hexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), di-methyl phthalate (DMP) and di-n-butyl phthalate (DnBP), as well as 3,4-dichloroaniline and 3,5-dichloroaniline in lyophilised mussels samples. A gradient elution program starting from 40% A (methanol-0.1% formic acid) - 60% B (H2O-0.1% formic acid) up to 100% A was applied, with a total duration of 15 min, at a flow rate of 200 µL min-1 using a 1.8 µm particle size C18 analytical column. All target analytes were detected with a triple quadrupole MS, using electrospray ionisation (ESI) in positive ionisation mode, in SRM mode under optimised conditions. Sample preparation consisted of lyophilisation of the mussels sample and grinding, followed by a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) protocol. Among the different dispersants evaluated for sample clean-up effectiveness, primary secondary amine (PSA) was found to be the most efficient. Results indicated good chromatographic separation, fast sample preparation procedure, low LODs and LOQs, good trueness expressed as recovery and good precision as evaluated by RSD. In the mussels samples examined DEHP was the most abundant PAE, reaching a maximal concentration of 280 µg/kg of lyophilised weight whereas the levels of DnBP were at approximately 36% of the legal migration limit in foods determined by the EU.

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurement (LSMs) in assessing steatosis and fibrosis in patients with suspected nonalcoholic liver disease (NAFLD). METHODS: We collected data from 450 consecutive adults who underwent liver biopsy analysis for suspected NAFLD at 7 centers in the United Kingdom from March 2014 through January 2017. FibroScan examinations with M or XL probe were completed within the 2 weeks of the biopsy analysis (404 had a valid examination). The biopsies were scored by 2 blinded expert pathologists according to nonalcoholic steatohepatitis clinical research network criteria. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for the categories of steatosis and fibrosis. We assessed effects of disease prevalence on positive and negative predictive values. For LSM, the effects of histological parameters and probe type were appraised using multivariable analysis. RESULTS: Using biopsy analysis as the reference standard, we found that CAP identified patients with steatosis with an AUROC of 0.87 (95% confidence interval [CI] 0.82-0.92) for S≥S1, 0.77 (95% CI 0.71-0.82) for S≥S2, and 0.70 (95% CI 0.64-0.75) for S=S3. Youden cutoff values for S≥S1, S≥S2, and S≥S3 were 302 dB/m, 331 dB/m, and 337 dB/m, respectively. LSM identified patients with fibrosis with AUROCs of 0.77 (95% CI 0.72-0.82) for F≥F2, 0.80 (95% CI 0.75-0.84) for F≥F3, and 0.89 (95% CI 0.84-0.93) for F=F4. Youden cutoff values for F≥F2, F≥F3, and F=F4 were 8.2 kPa, 9.7 kPa, and 13.6 kPa, respectively. Applying the optimal cutoff values, determined from this cohort, to populations of lower fibrosis prevalence increased negative predictive values and reduced positive predictive values. Multivariable analysis found that the only parameter that significantly affected LSMs was fibrosis stage (P<10-16); we found no association with steatosis or probe type. CONCLUSIONS: In a prospective analysis of patients with NAFLD, we found CAP and LSM by FibroScan to assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.70 to 0.89. Probe type and steatosis did not affect LSM. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT01985009.

Investigation and management of a raised serum ferritin.

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.

Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey.

OBJECTIVE: Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. DESIGN: An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. RESULTS: 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). CONCLUSIONS: The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions.

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer.

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).

A hydrophilic interaction chromatography-tandem mass spectrometry method for amino acid profiling in mussels.

A UHPLC-HILIC-tandem MS method has been developed and validated for the quantification of 21 amino acids (20 protein amino acids and cystine) in their free form (FAA) and as protein constituents (total amino acids, TAA) in a rich protein food matrix such as lyophilized mussels (Mytilus galloprovincialis) samples. FAA were analyzed after suspending the samples in the presence of trichloroacetic acid in order to prevent dissolving the proteins, while TAA were determined after acid hydrolysis with 6M HCl in the presence of 4% v/v thioglycolic acid as a reducing agent. In hydrolysed samples 17 amino acids could be determined since tryptophan, cysteine, cystine and asparagine were degraded during acid hydrolysis. Linear regression coefficients (R2) were above 0.99 for all amino acids. Accuracy and precision, expressed as recovery (%) and relative standard deviation (RSD, %) were in acceptable levels, ranging from 78.2 to 123.3% and below 15%, respectively for both FAA and TAA. Uncertainty was also below 12% for FAA and below 22% for TAA. Sensitivity of the method was high with LOD values ranging from 0.003 to 0.034g/100g for FAA and 0.001 to 0.004g/100g for TAA, while LOQ ranged from 0.009 to 0.104g/100g for FAA and 0.002 to 0.011g/100g for TAA. The method proved to be a fast and reliable tool for acquiring information on free and total amino acids profile in high protein content foodstuffs such as mussels.

The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC).

SUMMARY: Adipose tissue secretes adipokines with proinflammatory and anti-inflammatory properties. Our aim was to assess the role of adipose tissue in generalized inflammatory state of advanced NSCLC patients and the possible use of leptin, adiponectin and resistin as diagnostic and prognostic markers. Correlation of adipose tissue with weight loss in advanced NSCLC patients was also studied. Fasting serum levels of leptin, adiponectin and resistin were determined in 101 advanced NSCLC patients (76 without weight loss and 25 with weight loss) and 51 healthy volunteers using commercially available ELISA. Adipokine serum levels were determined at diagnosis, at the end of first-line chemotherapy and at the time of disease progression for those who responded to treatment. Epidemiological, anthropometrical and laboratory data were assessed. Serum leptin and adiponectin levels presented no differences. Serum resistin levels were significantly increased in NSCLC patients after adjustment for age, sex and BMI. Multivariate analysis showed that these adipokines at diagnosis could not be used as predictive factors for overall survival or time to progression. Only serum resistin levels were associated with weight loss. Despite no direct involvement of leptin and adiponectin, resistin as a proinflammatory cytokine may play a role in the pathogenesis of weight loss in NSCLC patients.