The prospective validation of a scoring system to assess mucosal cleanliness during EGD.

BACKGROUND AND AIMS: Cleanliness of the mucosa of the upper GI (UGI) tract is critical for performing a high-quality EGD. The aim of this study was to validate a recently developed UGI cleanliness scale (the Polprep: Effective Assessment of Cleanliness in Esophagogastroduodenoscopy [PEACE] system) in the detection of clinically significant lesions (CSLs) in the UGI tract. METHODS: Patients who underwent a complete diagnostic EGD were prospectively enrolled from August 2021 to October 2022. The UGI tract (esophagus, stomach, and duodenum) cleanliness was scored from 0 to 3 for each segment. The primary outcomes were the detection of CSLs and PEACE scores. RESULTS: Of 995 patients enrolled from 5 centers, adequate cleanliness (AQ; all scores ≥2) was found in 929 patients. In multivariate regression analysis, AQ was associated with the number of diagnosed CSLs (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.06-3.01; P = .03). Other factors related to CSL detection were duration of EGD (OR, 1.29, 95% CI, 1.23-1.35, P < .001), male sex (OR, 1.33, 95% CI, 1.04-1.71; P = .025), and EGD indication (dyspepsia, alarm symptoms, gastritis surveillance, other indications vs GERD) (OR, 0.43 [95% CI, 0.31-0.6, P < .001], OR, 0.44 [95% CI, 0.28-0.67, P < .001], OR, 0.44 [95% CI, 0.25-0.76; P = .004], and OR, 0.44 [95% CI, 0.31-0.62; P < .001], respectively). Twenty-seven patients were diagnosed with UGI neoplasia, all in patients with adequate cleanliness of the UGI tract. CONCLUSIONS: Adequate cleanliness of the UGI tract as assessed with the PEACE system was associated with a significantly higher detection rate of CSLs during EGD. The relationship of this scale with UGI neoplasia detection warrants further investigation.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Heterotopic Gastric Mucosa in the Proximal Esophagus: Prospective Study and Systematic Review on Relationships with Endoscopic Findings and Clinical Data.

Cervical inlet patches (CIP) are common endoscopic findings with uncertain pathogenesis and clinical significance. We aimed to perform a systematic review and prospective study of clinical data and endoscopic findings related to CIP. It was a prospective single-center study conducted between 10/01/2017 and 9/01/2018. Forty patients with histopathologically confirmed CIP were compared with 222 individuals in the reference group. The systematic review was executed in accordance with the PRISMA guideline. Alcohol consumption tended to be higher among patients with CIP (3.0 ± 4.6 vs. 1.9 ± 5.0 standard drinks/week CIP patients and reference group, respectively; p < 0.001). Dysphagia was more frequent among patients with CIP (25% vs. 1.4%, CIP patients and reference group, respectively; p < 0.001), and sore throat and hoarseness were less frequent in patients with CIP (17.5% vs. 26.6% CIP patients and reference group, respectively; p < 0.01). In the multivariate regression analysis, the only risk factor of CIP occurrence was dysphagia (OR 21.9, 95%CI 4.9-98.6; p < 0.001). Sore throat and hoarseness were a reverse-risk factor of CIP diagnosis (OR 0.3, 95%CI 0.1-0.93; p = 0.04). Clinical data and coexisting endoscopic findings were not related to CIP. In the presented study, dysphagia was related to CIP occurrence, and sore throat and hoarseness tended to be less frequent among patients with CIP.

Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis.

BACKGROUND: Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. METHODS: We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. RESULTS: In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.

Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale.

BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

Influence of COVID-19 Pandemic on Endoscopic Procedures in Two European Large-Capacity Endoscopy Units: "Keep Calm, Keep Safe and Scope on?"

BACKGROUND: The COVID-19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. OBJECTIVE: The aim of this was to analyze the influence of the early SARS-CoV2-pandemic on endoscopic care and work flow in 2 European tertiary endoscopy units. METHODS: Data from 2 tertiary endoscopy units (Katowice and Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. RESULTS: During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent endoscopic retrograde cholangiopancreatography or interventional endoscopic ultrasound procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. CONCLUSIONS: The SARS-CoV2-pandemic halved the endoscopy service of 2 tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.

Analysis of Point Shear Wave Elastography and Biochemical Markers for the Detection of Liver Fibrosis.

Background and Objectives: This work focuses on the possibility of using the point shear wave elastography (pSWE) method for detecting biochemical markers in diffuse liver diseases. Additionally, this study addresses the issue of the influence of ultrasound factors on the pSWE quality indicators of the obtained measurements. Materials and Methods: A pSWE examination was performed on 139 patients (69 female and 70 male) diagnosed with diffuse liver disease. The average age for all patients was 50.7 ± 15.0 years (female: 52.7 ± 15.2 years; male: 48.8 ± 14.6 years). Of these 139 patients, 65 met the inclusion criteria regarding biochemical parameters. The pSWE quality indicators were related to abnormalities found in B-mode ultrasound. Results: A strong positive correlation was found between the results of the pSWE and all biochemical indexes analysed, with the exception of age/platelet count (PLT), for which an average correlation was obtained. The greatest correlation was observed between the elastography and King's Score index. There was no correlation observed between elastography and any of the analysed parameters or biochemical indexes considered. The pSWE measurements were impaired by factors such as thick soft tissue, uneven hepatic surface, hepatomegaly and female gender. No statistically significant difference in pSWE quality indicators parameters was found between disease entities. Conclusions: pSWE seems to be a complementary method for detecting biochemical indexes, but its results can be influenced by numerous factors.

A Rare Mutation in The APOB Gene Associated with Neurological Manifestations in Familial Hypobetalipoproteinemia.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants-c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)-in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

Mucosal miR-3677 is over-expressed in cirrhotic patients with gastric antral vascular ectasia (GAVE).

INTRODUCTION: Gastric antral vascular ectasia (GAVE) is a rare vasculopathy that associates several diseases, most commonly liver cirrhosis. It usually presents as an occult gastrointestinal bleeding leading to profound iron deficiency anemia. We hypothesized that GAVE is local mucosal pathology dependent on genetic mechanisms, and the purpose of the study was to characterize miRNAs expression in gastric tissue of patients with cirrhosis and GAVE. MATERIALS AND METHODS: Thirteen patients with GAVE and cirrhosis and 35 healthy subjects were recruited. Microarray analysis and comparative microRNA study was done by quantitative polymerase chain reaction (qPCR). The microarray scores were grouped with use of the hierarchical clusterization analysis and miRNA target prediction was done with TargetScan 6.2 algorithm and Gene Ontology analysis (DIANA-miRPath). RESULTS: Concentration of miR-3677 in GAVE-affected mucosa was higher by 72% in comparison with GAVE-free mucosa of patients with cirrhosis (33.7 vs. 35.6 PCR cycles; p < .001) and by 45% in comparison with normal mucosa (33.7 vs. 34.9 PCR cycles; p < .05). According to Gene Ontology analysis miR-3677 was related to angiopoietin-like protein 4 (ANGPTL4) gene. CONCLUSION: GAVE in liver cirrhosis is associated with increased expression of miR-3667 that may be linked with ANGPTL4 gene.

Non-alcoholic fatty liver and advanced fibrosis in the elderly: Results from a community-based Polish survey.

BACKGROUND & AIMS: Development of non-alcoholic fatty liver (NAFL) is dependent on metabolic factors occurring at an increased frequency with advancing age. Until now, few studies have explored the prevalence of NAFL in aged populations. Our study aimed to determine the prevalence of NAFL and advanced fibrosis in the elderly population participating in a national survey of a community-based elderly cohort. METHODS: A total of 3003 participants (mean age 79.6 years, 46.8% male) were enrolled in the study, after applying the following exclusion criteria: individuals younger than 65 years old (n=829) and those with positive serological biomarkers of HBV or HCV infection (n=391), chronic alcohol ingestion (n=727) or incomplete data records (n=745). Based on the fatty liver index (FLI), the participants were classified into three categories: FLI<30 (no NAFL), 30≤FLI<60 (borderline) and FLI≥60 (NAFL). According to the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), the participants were divided into three advanced fibrosis risk categories: NFS<-1.455 (low risk), -1.455≤NFS≤0.676 (intermediate risk) and NFS>0.676 (high risk). RESULTS: The prevalence of NAFL in the general population was 37.2%; the prevalence reached 51.4% in participants 65-70 years of age and decreased with advancing age (P<.0001). The prevalence of advanced fibrosis was 7.79% (14.8% in the NAFL population) and increased with advancing age (P<.005). CONCLUSIONS: The prevalence of NAFL and metabolically driven advanced fibrosis are relatively common in the elderly population, and these hepatic conditions run in adverse directions with advancing age.

Hepatic chemerin mRNA in morbidly obese patients with nonalcoholic fatty liver disease.

The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI < 40 kg/m2 and ≥ 40 kg/m2. Serum chemerin concentration tended to be higher in patients with hepatocyte ballooning, greater extent of steatosis, and definite nonalcoholic steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.

Vaspin mRNA levels in the liver of morbidly obese women with nonalcoholic fatty liver disease.

The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships with metabolic and histopathological features. The study included 56 severely obese women who underwent intraoperative wedge liver biopsy during bariatric surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin mRNA found in all included patients was markedly higher in patients with body mass index (BMI) ≥ 40 kg/m2 (4.59 ±3.09 vs. 0.44 ±0.33; p = 0.05). An evident but statistically insignificant difference in vaspin mRNA levels was observed between patients with and without hepatocyte ballooning (4.77 ±4.23 vs. 0.45 ±0.29, respectively), with and without steatosis (4.80 ±4.20 vs. 0.41 ±0.29, respectively), without and with fibrosis (0.25 ±0.80 vs. 6.23 ±7.2, respectively), and those without and with lobular inflammation (0.27 ±1.0 vs. 5.55 ±10.1, respectively). There was marked difference in vaspin mRNA between patients with simple steatosis/borderline nonalcoholic steatohepatitis (NASH) compared to those with definite NASH (0.24 ±0.96 vs. 10.5 ±10.4). Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic vaspin mRNA seems to be markedly elevated in morbidly obese patients with more advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear mRNA levels within the NAFLD spectrum and an evident increase in patients with fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded.

Justified granulation aided noninvasive liver fibrosis classification system.

BACKGROUND: According to the World Health Organization 130-150 million (according to WHO) of people globally are chronically infected with hepatitis C virus. The virus is responsible for chronic hepatitis that ultimately may cause liver cirrhosis and death. The disease is progressive, however antiviral treatment may slow down or stop its development. Therefore, it is important to estimate the severity of liver fibrosis for diagnostic, therapeutic and prognostic purposes. Liver biopsy provides a high accuracy diagnosis, however it is painful and invasive procedure. Recently, we witness an outburst of non-invasive tests (biological and physical ones) aiming to define severity of liver fibrosis, but commonly used FibroTest®, according to an independent research, in some cases may have accuracy lower than 50 %. In this paper a data mining and classification technique is proposed to determine the stage of liver fibrosis using easily accessible laboratory data. METHODS: Research was carried out on archival records of routine laboratory blood tests (morphology, coagulation, biochemistry, protein electrophoresis) and histopathology records of liver biopsy as a reference value. As a result, the granular model was proposed, that contains a series of intervals representing influence of separate blood attributes on liver fibrosis stage. The model determines final diagnosis for a patient using aggregation method and voting procedure. The proposed solution is robust to missing or corrupted data. RESULTS: The results were obtained on data from 290 patients with hepatitis C virus collected over 6 years. The model has been validated using training and test data. The overall accuracy of the solution is equal to 67.9 %. The intermediate liver fibrosis stages are hard to distinguish, due to effectiveness of biopsy itself. Additionally, the method was verified against dataset obtained from 365 patients with liver disease of various etiologies. The model proved to be robust to new data. What is worth mentioning, the error rate in misclassification of the first stage and the last stage is below 6.5 % for all analyzed datasets. CONCLUSIONS: The proposed system supports the physician and defines the stage of liver fibrosis in chronic hepatitis C. The biggest advantage of the solution is a human-centric approach using intervals, which can be verified by a specialist, before giving the final decision. Moreover, it is robust to missing data. The system can be used as a powerful support tool for diagnosis in real treatment.

Omentin serum concentration and hepatic expression in chronic hepatitis C patients - together or apart?

Chronic hepatitis C (CHC) is accompanied by numerous metabolic disorders, partially associated with altered adipokine system regulation. Omentin (intelectin-1) is a novel adipokine known to play a pivotal role in metabolic regulation in CHC. In a group of 63 CHC patients (29 men/34 women) infected with genotype 1b, aged 6.6 ± 14.6 years, serum omentin levels and its gene expression in liver tissue were examined and their association with metabolic and histopathological features was assessed. Serum omentin levels were significantly higher in CHC patients compared to controls (p < 0.001), regardless of sex, body mass index (BMI), insulin sensitivity and lipid concentrations. There was no correlation between serum omentin and omentin hepatic expression. Neither parameter was associated with any histological features. Serum omentin in non-obese CHC patients seems not to be related to metabolic disorders or liver pathology. Omentin hepatic expression shows no relationship with either serum omentin levels or histopathological features. This suggests different mechanisms regulating circulating omentin concentration and omentin hepatic expression in CHC.

A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.

BACKGROUND & AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. METHODS: Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. RESULTS: We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS: We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5-year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.

Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. METHODS: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire-metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. DISCUSSION: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. TRIAL REGISTRATION: European Union Clinical Trials Register, EudraCT, 2021-006069-39. Registered on March 13, 2022.

Performance of biliary stents in malignant biliary strictures.

INTRODUCTION: Endoscopic stenting is a commonly applied method of treatment in patients with malignant biliary strictures. It involves the use of self­expandable metal stents (SEMSs) or plastic stents (PSs). OBJECTIVES: The aim of the study was to compare the effectiveness of SEMSs and PSs in the endoscopic drainage of malignant strictures of the biliary tree and its sequels for future optimalization of this treatment method. PATIENTS AND METHODS: Data on 618 consecutive patients with malignant biliary stricture, in whom 1271endoscopic retrograde cholangiopancreatography procedures with biliary stenting have been performed in the years 2012-2017 with at least 3­year follow­up,  were retrospectively derived from a hospital database. RESULTS: The main indications for stenting were pancreatic cancer (37%) and cholangiocarcinoma (34%). The use of SEMSs resulted in a greater decline of serum bilirubin as compared with PSs (37% vs 32% of baseline concentration; P = 0.01). Consequently, hospital stay was shorter by more than 2 days (mean [SD], 9.5 [5.6] vs 11.8 [7.9] days; P <0.001). The median (interquartile range) patency time of SEMSs was more than 2 times longer than for PSs (118 [56-232] days vs 46 [18-97] days; P <0.001), and procedure­related complications were less frequent (19.3% vs 12.9%, respectively in the SEMS and PS group; P = 0.001). SEMSs proved also to be more cost­effective; the hospital profit was 1375 USD for a single hospitalization with SEMS insertion. CONCLUSIONS: In patients with malignant strictures of the biliary tree SEMSs outperform PSs. SEMSs should be used as a treatment of choice for biliary drainage in that group of patients.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis.

BACKGROUND & AIMS: In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress. METHODS: Eighty-two participants with type 1 AIH who had undergone liver biopsy were included (44 in training and 38 in validation sets). Liver histology was assessed according to the histologic activity index (HAI; score 0-18) and Ishak's histologic fibrosis index (HFI; score 0-6). High inflammation was defined as HAI>4, and advanced fibrosis was defined as HFI>2. Routine laboratory test findings and stepwise linear regression were used to develop the best models predicting HAI and HFI. The best cut-off value to predict high inflammation and advanced fibrosis for these formulas was then calculated based on receiver-operating characteristic analysis. RESULTS: The cut-off value for a model predicting high inflammation was ≥3.57 (AUROC = 0.93; 95% CI: 0.86-1.00), with 100% sensitivity and 85% specificity. High inflammation was confirmed with an 81% positive predictive value and excluded with a 100% negative predictive value. In the validation set, the sensitivity, specificity, positive predictive value and negative predictive values were 100, 56, 88 and 100% respectively. The diagnostic yield of the fibrosis score was unsatisfactory. CONCLUSIONS: The noninvasive inflammatory score based on four routine laboratory parameters discriminated patients with and without significant hepatic inflammation and may facilitate follow-up of type 1 AIH patients.