Long-term liver-related outcomes and liver stiffness progression of statin usage in steatotic liver disease.

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score.

BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.

Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study.

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028).   Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: •  Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. • Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate.

Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis. Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD. Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE). Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests. Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group. Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

Cyclodextrins: Properties and Applications.

Cyclodextrins (CDs) are cyclic oligosaccharides that contain at least six d-(+)-glucopyranose units linked by α-(1, 4) glucosidic bonds [...].

Biosynthesis of Polyhydroalkanoates Doped with Silver Nanoparticles Using Pseudomonas putida and Pseudomonas aeruginosa for Antibacterial Polymer Applications.

In this study, the biosynthesis of polyhydroxyalkanoates (PHAs) was carried out using Pseudomonas putida and Pseudomonas aeruginosa. These PHAs were produced using reagent-grade glycerol and crude glycerol as the carbon sources. The objective was to compare the production of PHAs and to functionalize these polymers with silver nanoparticles to provide antibacterial properties for potential biomedical applications. The findings from the physical and chemical analyses confirmed the successful synthesis and extraction of PHAs, achieving comparable yields using both crude glycerol and reagent-grade glycerol as carbon sources across both strains. Approximately 16% higher PHAs production was obtained using Pseudomonas putida compared to Pseudomonas aeruginosa, and no significant difference was observed in the production rate of PHAs between the two carbon sources used, which means that crude glycerol could be utilized even though it has more impurities. Notably, PHAs functionalized with silver nanoparticles showed improved antibacterial effectiveness, especially those derived from reagent-grade glycerol and the Pseudomonas aeruginosa strain.

Body mass index implications in intrahepatic cholestasis of pregnancy and placental histopathological alterations.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. PATIENTS AND METHODS: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. RESULTS: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. CONCLUSION: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort.

OBJECTIVES: to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). METHODS: sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. RESULTS: the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. CONCLUSIONS: MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy. Histological inflammation and surrogate biomarkers of inflammation can overestimate liver stiffness, but only GGT was statistically significant in the multivariate analysis. Important features of NAFLD patients such as obesity, DM, or lipidic profile did not affect MRE accuracy.

Preliminary experience of the use of self-expanding nititol stent in refractory variceal bleeding: a real-world study.

BACKGROUND AND AIMS: The fully-covered self-expanding metal stent (SEMS) has a role in the management of refractory acute variceal haemorrhage. The aim of this study was to evaluate its effectiveness and complications in real-world practice. PATIENTS AND METHODS: An observational, descriptive, multicenter study was carried out. Eight patients with clinically significant portal hypertension who underwent a SEMS were included. RESULTS: SEMS placement controlled acute bleeding in 7 patients with technical success. Stents were removed after a median of 8 days. Rescue transjugular intrahepatic portosystemic shunt was performed around 48 hours after SEMS placement. Four patients survived after successful SEMS removal. The most common adverse event was stent loop in 2 patients. CONCLUSIONS: In our experience, SEMS was highly effective in controlling acute refractory variceal bleeding. Bleeding-related mortality rate was probably due to impossibility of TIPS implantation. Stent loop was a common limiting factor.

Clinical Evaluation of Serum Levels of SARS-CoV-2 Anti-Spike Protein IgG Antibodies in Infected Patients and Vaccinated Subjects.

BACKGROUND: The aim was clinical evaluation of immune response against SARS-CoV-2, analyzing serum levels of IgG antibodies against the SARS-CoV-2 protein S in infected and vaccinated patients, as well as in subjects with and without frequent comorbidities (arterial hypertension, diabetes mellitus, heart disease, and chronic respiratory disease). METHODS: Patients infected by SARS-CoV-2 confirmed by RT-PCR and subjects vaccinated with vaccines based on the mRNA encoding the SARS-CoV-2 protein S were studied. SARS-CoV-2 anti-S IgG serum levels were quantified by chemiluminescent microparticle immunoassay. RESULTS: There were 79 infected patients with a median age of 53.0 years; 35 women and 44 men; 42 patients with any comorbidities and 37 without comorbidities. The median of SARS-CoV-2 anti-S IgG serum level was 203.4 BAU/mL (11.6 - 5,620.6). The median antibody level in the infected patients with any comorbidities was higher than those without comorbidities. The group of vaccinated subjects included 96 subjects with a median age of 49.5 years; 77 women and 19 men; 31 subjects with any comorbidities and 65 without comorbidities. The median of SARS-CoV-2 anti-S IgG serum levels was 1,145.6 BAU/mL (138.3 - 4,828.1). No significant differences were found in terms of specific or global comorbidities in the vaccinated subjects. CONCLUSIONS: SARS-CoV-2 anti-S IgG serum levels were 5.6 times higher in vaccinated subjects than infected patients. The vaccination produces higher serum antibody levels than SARS-CoV-2 infection. This reinforces the indication for the vaccine in infected patients. These antibodies did not decrease significantly in patients with frequent comorbidities such as hypertension, diabetes, heart disease or chronic respiratory disease.