Treatment Options and Continuity of Care in Metabolic-associated Fatty Liver Disease: A Multidisciplinary Approach.

The terms non-alcoholic fatty liver disease and non-alcoholic steatohepatitis have some limitations as they use exclusionary confounder terms and the use of potentially stigmatising language. Recently, a study with content experts and patients has been set to change this nomenclature. The term chosen to replace non-alcoholic fatty liver disease was metabolic dysfunction-associated steatotic liver disease (MASLD), which avoids stigmatising and helps improve awareness and patient identification. MASLD is the most common cause of chronic liver disease with an increasing prevalence, accounting for 25% of the global population. It is considered the hepatic manifestation of the metabolic syndrome with lifestyle playing a fundamental role in its physiopathology. Diet change and physical activity are the cornerstones of treatment, encompassing weight loss and healthier behaviours and a holistic approach. In Europe, there is no approved drug for MASLD to date and there is a substantial unmet medical need for effective treatments for patients with MASLD. This review not only provides an update on advances in evidence for nutrition and physical activity interventions but also explores the different therapeutic options that are being investigated and whose development focuses on the restitution of metabolic derangements and halting inflammatory and fibrogenic pathways.

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.

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.

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.

Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease.

Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47-3.41) and large (HR 3.86, 95% CI 2.34-6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39-5.05) and large (HR 4.90, 95% CI 2.49-9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16-6.74) or large (HR 5.29, 95% CI 1.96-14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

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.

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 (AU)

Emerging pharmacological treatment options for MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) prevalence and incidence is rising globally. It is associated with metabolic comorbidities, obesity, overweight, type 2 diabetes mellitus, and at least two metabolic risk factors, such as hypertension, hypertriglyceridemia, hypercholesterolemia, insulin resistance, and cardiovascular risk, increasing the risk of mortality. The excessive accumulation of fat comprises apoptosis, necrosis, inflammation and ballooning degeneration progressing to fibrosis, cirrhosis, and liver decompensations including hepatocellular carcinoma development. The limitation of approved drugs to prevent MAFLD progression is a paradigm. This review focuses on recent pathways and targets with evidence results in phase II/III clinical trials.

Prevalence of non-alcoholic fatty liver disease (NAFLD) in a cohort of patients with type 2 diabetes: the PHIGNA-DM2 study.

Introduction: Background: type 2 diabetes (T2D) is a risk factor for nonalcoholic fatty liver disease (NAFLD). Objective: to evaluate the prevalence of NAFLD in a cohort of patients with T2D. Methods: an observational, descriptive study performed between May 2018 and December 2019 at the Endocrinology and Nutrition Unit. The χ² test was performed for qualitative variables and a non-parametric test for the comparison of medians of quantitative variables. Steatosis degree was defined by the coefficient attenuated parameter (CAP): (S0: < 248 dB/m; S1: 248-268 dB/m; S2: 268-288 dB/m; S3: > 288 dB/m) or stiffness: F0-F1: < 8 kPa; F2: 8-10 kPa; F3: 10-15 kPa; F4: > 15 kPa, using transient elastography (TE) (FibroScan®). A univariate analysis was performed and subsequently a multivariate analysis with statistically significant variables used to study the predictive factors of intense steatosis and advanced fibrosis. Results: n = 104 patients with T2D; 84 (80.7 %) were obese. TE demonstrated advanced fibrosis in 20 % and intense steatosis (S3) in more than 50 %. Lower total bilirubin (OR: 0.028; 95 % CI: (0.002-0.337); p = 0.005) was found to be an independent factor for S3 steatosis in the multivariate analysis. BMI ((OR: 1.497; 95 % CI: (1.102-2.034); p = 0.01)) was a predictive factor for advanced fibrosis in a multivariate analysis. Conclusions: NAFLD-associated intense steatosis and NAFLD-associated fibrosis were commonly found in patients with T2DM and obesity. Diabetic patients should be screened for liver disease as one more target organ.

Introducción: Antecedentes: la diabetes de tipo 2 (DM2) es un factor de riesgo para la enfermedad del hígado graso no alcohólico (EHGNA). Objetivo: evaluar la prevalencia de la EHGNA en una cohorte de pacientes con DM2. Métodos: estudio descriptivo observacional realizado entre mayo de 2018 y diciembre de 2019 en la Unidad de Endocrinología y Nutrición. Se realizó una prueba de χ² para las variables cualitativas y una prueba no paramétrica para la comparación de medianas de variables cuantitativas. El grado de esteatosis se definió mediante el parámetro coeficiente atenuado (CAP): (S0: < 248 dB/m; S1: 248-288 dB/m; S2: 268-288 dB/m; S3: > 288 dB/m) o rigidez: F0-F1: < 8 kPa; F2: 8-10 kPa; F3: 10-15 kPa; F4: > 15 kPa, usando la elastografía transitoria (TE) (FibroScan®). Se realizó un análisis univariante y posteriormente un análisis multivariante con las variables estadísticamente significativas para estudiar los factores predictivos de esteatosis intensa y fibrosis avanzada. Resultados: n = 104 pacientes con DM2; 84 (80,7 %) eran obesos. La TE demostró fibrosis avanzada en el 20 % y esteatosis intensa (S3) en más del 50 %. Los niveles disminuidos de bilirrubina total (OR: 0.028; 95 % CI: (0.002-0.337); p = 0.005) se encontraron como factores independientes para la esteatosis S3 en el analisis multivariable. El IMC (OR: 1.497; 95 % CI: (1.102-2.034); p = 0.01) fue un factor predictivo de fibrosis avanzada. Conclusiones: la esteatosis intensa asociada a EHGNA y la fibrosis asociada a EHGNA se encontraron comúnmente en pacientes con DM2 y obesidad. Los pacientes diabéticos deben someterse a pruebas de detección de enfermedad hepática como un órgano diana más.

Prevalence of non-alcoholic fatty liver disease (NAFLD) in a cohort of patients with type 2 diabetes: the PHIGNA-DM2 study / Prevalencia de la hepatopatía grasa no alcohólica (HGNA) en una cohorte de pacientes con diabetes de tipo 2: el estudio PHIGNA-DM2

Background: type 2 diabetes (T2D) is a risk factor for nonalcoholic fatty liver disease (NAFLD). Objective: to evaluate the prevalence of NAFLD in a cohort of patients with T2D. Methods: an observational, descriptive study performed between May 2018 and December 2019 at the Endocrinology and Nutrition Unit. The χ² test was performed for qualitative variables and a non-parametric test for the comparison of medians of quantitative variables. Steatosis degree was defined by the coefficient attenuated parameter (CAP): (S0: < 248 dB/m; S1: 248-268 dB/m; S2: 268-288 dB/m; S3: > 288 dB/m) or stiffness: F0-F1: < 8 kPa; F2: 8-10 kPa; F3: 10-15 kPa; F4: > 15 kPa, using transient elastography (TE) (FibroScan®). A univariate analysis was performed and subsequently a multivariate analysis with statistically significant variables used to study the predictive factors of intense steatosis and advanced fibrosis. Results: n = 104 patients with T2D; 84 (80.7 %) were obese. TE demonstrated advanced fibrosis in 20 % and intense steatosis (S3) in more than 50 %. Lower total bilirubin (OR: 0.028; 95 % CI: [0.002-0.337]; p = 0.005) was found to be an independent factor for S3 steatosis in the multivariate analysis. BMI (OR: 1.497; 95 % CI: [1.102-2.034]; p = 0.01) was a predictive factor for advanced fibrosis in a multivariate analysis. Conclusions: NAFLD-associated intense steatosis and NAFLD-associated fibrosis were commonly found in patients with T2DM and obesity. Diabetic patients should be screened for liver disease as one more target organ. (AU)

Antecedentes: la diabetes de tipo 2 (DM2) es un factor de riesgo para la enfermedad del hígado graso no alcohólico (EHGNA). Objetivo: evaluar la prevalencia de la EHGNA en una cohorte de pacientes con DM2. Métodos: estudio descriptivo observacional realizado entre mayo de 2018 y diciembre de 2019 en la Unidad de Endocrinología y Nutrición. Se realizó una prueba de χ² para las variables cualitativas y una prueba no paramétrica para la comparación de medianas de variables cuantitativas. El grado de esteatosis se definió mediante el parámetro coeficiente atenuado (CAP): (S0: < 248 dB/m; S1: 248-288 dB/m; S2: 268-288 dB/m; S3: > 288 dB/m) o rigidez: F0-F1: < 8 kPa; F2: 8-10 kPa; F3: 10-15 kPa; F4: > 15 kPa, usando la elastografía transitoria (TE) (FibroScan®). Se realizó un análisis univariante y posteriormente un análisis multivariante con las variables estadísticamente significativas para estudiar los factores predictivos de esteatosis intensa y fibrosis avanzada. Resultados: n = 104 pacientes con DM2; 84 (80,7 %) eran obesos. La TE demostró fibrosis avanzada en el 20 % y esteatosis intensa (S3) en más del 50 %. Los niveles disminuidos de bilirrubina total (OR: 0.028; 95 % CI: (0.002-0.337); p = 0.005) se encontraron como factores independientes para la esteatosis S3 en el analisis multivariable. El IMC (OR: 1.497; 95 % CI: (1.102-2.034); p = 0.01) fue un factor predictivo de fibrosis avanzada. Conclusiones: la esteatosis intensa asociada a EHGNA y la fibrosis asociada a EHGNA se encontraron comúnmente en pacientes con DM2 y obesidad. Los pacientes diabéticos deben someterse a pruebas de detección de enfermedad hepática como un órgano diana más. (AU)

Better recurrence-free survival after stent bridge to surgery compared to emergency surgery for obstructive left-sided colonic cancer in patients with stage III status of the American Joint Committee on Cancer (AJCC): a bicentric retrospective study.

PURPOSE: Stenting as a bridge to surgery (SBTS) can transform an emergency surgery (ES) into an elective surgery in patients with symptomatic left-sided malignant colonic obstruction. Concerns have been raised regarding short-term morbidity and long-term oncologic outcomes, with contrasting results reported in the literature. Our main aim is to evaluate not only long-term oncologic outcomes but also short-term postoperative outcomes of stented patients who underwent elective surgery compared to those who had ES. METHODS: From January 2006 to May 2012, we retrospectively identified patients with confirmed left-sided colorectal cancer obstruction. This was done in two centers of reference of colorectal diseases in southern Spain with patients who were treated with curative intent either with ES or SBTS. The short- and long-term results were compared between both groups. RESULTS: There were 71 patients in the stenting group and 66 in the emergency surgery group, with similar demographic data. Initial stoma creation rates were lower in the SBTS group (16.9% vs. 54.5%, p < 0.005) and the primary anastomosis rate was higher in the same group (83.1% vs. 45.5%, p < 0.005). Five-year recurrence-free survival (RFS) rates were comparable between groups (75.3 vs. 59.8%, p = 0.220), but RFS rates at 5 years for AJCC pathologic stage III were higher in the stenting group (69.7% vs 30%, p = 0.004). Both groups were comparable regarding overall and cancer-specific survival outcomes. CONCLUSIONS: The use of SBTS reduces ostomy rates in patients with obstructive colon malignancies. Long-term survival results are similar. Patients in the SBTS group with stage III AJCC status showed a higher 5-year recurrence-free survival rate than those in the ES group.

Presentation of a malignant peritoneal mesothelioma in the forma of rough hepatic calcifications.

We present 2 radiological pictures of a malignant peritoneal mesothelioma with hepatic infiltration, in the form of impressive rough calcifications.

Calcificaciones groseras hepáticas como forma de presentación de un mesotelioma maligno peritoneal / Presentation of a malignant peritoneal mesothelioma in the forma of rough hepatic calcifications

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Complicaciones colónicas agudas en paciente con enfermedad de Chagas / Acute colonic complications in a patient with Chagas disease

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Acute colonic complications in a patient with Chagas disease.

We present the case of a young bolivian woman who suffered two acute and impressive colonic complications due to a Chagasic megacolon.