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Journal of Hepatology Nov 2023Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by...
BACKGROUND & AIMS
Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.
METHODS
Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).
RESULTS
A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).
CONCLUSION
Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.
IMPACT AND IMPLICATIONS
Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.
Topics: Humans; Aged; Cardiovascular Diseases; Metabolic Syndrome; Biological Specimen Banks; Glycated Hemoglobin; UK Biobank; Risk Factors; Liver Diseases; Digestive System Diseases; Biomarkers; Iron
PubMed: 37348789
DOI: 10.1016/j.jhep.2023.05.046 -
Revista Espanola de Enfermedades... Nov 2023A 76-year-old man with multiple cardiovascular risk factors (hypertension, DM2, LD, smoker) and severe peripheral arterial disease (iliofemoral bypass, supracondylar...
A 76-year-old man with multiple cardiovascular risk factors (hypertension, DM2, LD, smoker) and severe peripheral arterial disease (iliofemoral bypass, supracondylar amputation) came to the emergency with coffee ground emesis and mild anemia. Urgent gastroscopy showed diffuse circumferential black mucosa covered by fibrin affecting the middle and distal esophageal third. Acute esophageal necrosis is a rare cause of gastrointestinal bleeding that should be suspected in patients with cardiovascular risk factors with an image of a black esophagus that is abruptly interrupted at the EGJ.
Topics: Male; Humans; Aged; Necrosis; Esophageal Diseases; Hematemesis; Gastrointestinal Hemorrhage; Acute Disease
PubMed: 36205331
DOI: 10.17235/reed.2022.9217/2022 -
Gastroenterology Jun 2024Celiac disease (CeD) is a chronic immune-mediated condition triggered by gluten consumption in genetically predisposed individuals. Approximately 1% of the general... (Review)
Review
Celiac disease (CeD) is a chronic immune-mediated condition triggered by gluten consumption in genetically predisposed individuals. Approximately 1% of the general population is affected by the disorder. Disease presentation is heterogeneous and, despite growing awareness among physicians and the public, it continues to be underestimated. The most effective strategy for identifying undiagnosed CeD is proactive case finding through serologic testing in high-risk groups. We reviewed the most recent evidence on the association between CeD and more than 20 conditions. In light of this review, CeD screening is recommended in individuals with (1) autoimmune disease and accompanying symptoms suggestive of CeD; (2) diseases that may mimic CeD (eg, irritable bowel syndrome [IBS], inflammatory bowel disease [IBD], and microscopic colitis); and (3) among patients with conditions with a high CeD prevalence: first-degree relatives, idiopathic pancreatitis, unexplained liver enzyme abnormalities, autoimmune hepatitis, primary biliary cholangitis, hyposplenism or functional asplenia with severe bacterial infection, type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease, Sjögren's syndrome, dermatitis herpetiformis, recurrent aphthous syndrome and enamel defects, unexplained ataxia, peripheral neuropathy, delayed menarche or premature menopause, Down syndrome, Turner syndrome, Williams syndrome, chronic fatigue syndrome, IgA nephropathy, and IgA deficiency. CeD serology should be the initial step in the screening process. However, for patients with any of the aforementioned disorders who are undergoing upper endoscopy, biopsies should be performed to rule out CeD.
Topics: Humans; Celiac Disease; Autoimmune Diseases; Diagnosis, Differential; Inflammatory Bowel Diseases; Serologic Tests; Risk Factors; Prevalence; Genetic Predisposition to Disease
PubMed: 38460606
DOI: 10.1053/j.gastro.2024.02.044 -
Best Practice & Research. Clinical... Dec 2023Autoimmune liver diseases (AILDs) are complex diseases with unknown causes and immune-mediated pathophysiology. In primary biliary cholangitis (PBC) and autoimmune... (Review)
Review
Autoimmune liver diseases (AILDs) are complex diseases with unknown causes and immune-mediated pathophysiology. In primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) disease modifying drugs are available which improve patient quality and quantity of life. In primary sclerosing cholangitis (PSC) no medical therapy is available and the only accepted treatment is liver transplantation (LT). PBC, PSC and AIH possess features that describe the archetype of patients within each disorder. On the other hand, the classical disorders are not homogeneous, and patients within each diagnosis may present with a range of clinical, biochemical, serological, and histological findings. Singularly, they are considered rare diseases, but together, they account for approximately 20% of LTs in Europe and USA. Management of these patients is complex, as AILDs are relatively uncommon in clinical practice with challenges in developing expertise, disease presentation can be sneaky, clinical phenotypes and disease course are heterogeneous. Prognostic models are key tools for clinicians to assess patients' risk and to provide personalized care to patients. Aim of this review is to discuss challenges of the management of AILDs and how the available prognostic models can help. We will discuss the prognostic models developed in AILDs, with a special focus on the prognostic models that can support the clinical management of patients with AILDs: in PBC models based on ursodeoxycholic acid (UDCA) response and markers of liver fibrosis; in PSC several markers including biochemistry, disease stage and radiological semiquantitative markers; and finally in AIH, markers of disease stage and disease activity.
Topics: Humans; Prognosis; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Liver Diseases; Autoimmune Diseases; Hepatitis, Autoimmune
PubMed: 38103932
DOI: 10.1016/j.bpg.2023.101878 -
Organogenesis Dec 2023Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic...
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, and hepatotoxicity. The mechanisms by which hepatocytes respond to and cope with CLD remain largely unexplored. This study includes the characterization of hepatocytes isolated from explanted livers of patients with PBC and PSC. We examined the expression of hepatocyte-specific genes, intracellular bile acid (BA) levels, and oxidative stress in primary-human-hepatocytes (PHHs) isolated from explanted livers of patients with PBC and PSC and compared them with control normal human hepatocytes. Our findings provide valuable initial insights into the hepatocellular response to cholestasis in CLD and help support the use of PHHs as an experimental tool for these diseases.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Cholestasis; Bile Acids and Salts
PubMed: 37598346
DOI: 10.1080/15476278.2023.2247576 -
Digestion 2024Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions,... (Review)
Review
BACKGROUND
Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD.
SUMMARY
HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird's beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction.
KEY MESSAGE
Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment.
Topics: Humans; Esophageal Achalasia; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Sphincter, Lower; Manometry; Endoscopy, Gastrointestinal; Esophagogastric Junction
PubMed: 37634495
DOI: 10.1159/000533347 -
The Lancet. Gastroenterology &... Aug 2023Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate... (Meta-Analysis)
Meta-Analysis
Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis.
BACKGROUND
Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.
METHODS
This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.
FINDINGS
Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.
INTERPRETATION
Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
FUNDING
Innovative Medicines Initiative 2.
Topics: Humans; Female; Middle Aged; Male; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Liver Cirrhosis; Fibrosis
PubMed: 37290471
DOI: 10.1016/S2468-1253(23)00141-3 -
Marine Drugs Nov 2023Diseases such as obesity; cardiovascular diseases such as high blood pressure, myocardial infarction and stroke; digestive diseases such as celiac disease; certain types... (Review)
Review
Diseases such as obesity; cardiovascular diseases such as high blood pressure, myocardial infarction and stroke; digestive diseases such as celiac disease; certain types of cancer and osteoporosis are related to food. On the other hand, as the world's population increases, the ability of the current food production system to produce food consistently is at risk. As a result, intensive agriculture has contributed to climate change and a major environmental impact. Research is, therefore, needed to find new sustainable food sources. One of the most promising sources of sustainable food raw materials is macroalgae. Algae are crucial to solving this nutritional deficiency because they are abundant in bioactive substances that have been shown to combat diseases such as hyperglycemia, diabetes, obesity, metabolic disorders, neurodegenerative diseases and cardiovascular diseases. Examples of these substances include polysaccharides such as alginate, fucoidan, agar and carrageenan; proteins such as phycobiliproteins; carotenoids such as β-carotene and fucoxanthin; phenolic compounds; vitamins and minerals. Seaweed is already considered a nutraceutical food since it has higher protein values than legumes and soy and is, therefore, becoming increasingly common. On the other hand, compounds such as polysaccharides extracted from seaweed are already used in the food industry as thickening agents and stabilizers to improve the quality of the final product and to extend its shelf life; they have also demonstrated antidiabetic effects. Among the other bioactive compounds present in macroalgae, phenolic compounds, pigments, carotenoids and fatty acids stand out due to their different bioactive properties, such as antidiabetics, antimicrobials and antioxidants, which are important in the treatment or control of diseases such as diabetes, cholesterol, hyperglycemia and cardiovascular diseases. That said, there have already been some studies in which macroalgae (red, green and brown) have been incorporated into certain foods, but studies on gluten-free products are still scarce, as only the potential use of macroalgae for this type of product is considered. Considering the aforementioned issues, this review aims to analyze how macroalgae can be incorporated into foods or used as a food supplement, as well as to describe the bioactive compounds they contain, which have beneficial properties for human health. In this way, the potential of macroalgae-based products in eminent diseases, such as celiac disease, or in more common diseases, such as diabetes and cholesterol complications, can be seen.
Topics: Humans; Cardiovascular Diseases; Celiac Disease; Polysaccharides; Dietary Supplements; Seaweed; Proteins; Carotenoids; Phenols; Obesity; Diabetes Mellitus; Delivery of Health Care; Cholesterol; Hyperglycemia
PubMed: 37999402
DOI: 10.3390/md21110578 -
Frontiers in Immunology 2023During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to... (Review)
Review
During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.
Topics: Humans; Carcinoma, Hepatocellular; Esophageal and Gastric Varices; Liver Neoplasms; Gastrointestinal Hemorrhage; Liver Cirrhosis; Macrophages; Fibrosis
PubMed: 38116017
DOI: 10.3389/fimmu.2023.1277808 -
Diagnostics (Basel, Switzerland) Aug 2023Endoscopic ultrasound (EUS) has emerged as a widely utilized tool in the diagnosis of digestive diseases. In recent years, the potential of artificial intelligence (AI)... (Review)
Review
Endoscopic ultrasound (EUS) has emerged as a widely utilized tool in the diagnosis of digestive diseases. In recent years, the potential of artificial intelligence (AI) in healthcare has been gradually recognized, and its superiority in the field of EUS is becoming apparent. Machine learning (ML) and deep learning (DL) are the two main AI algorithms. This paper aims to outline the applications and prospects of artificial intelligence-assisted endoscopic ultrasound (EUS-AI) in digestive diseases over the past decade. The results demonstrated that EUS-AI has shown superiority or at least equivalence to traditional methods in the diagnosis, prognosis, and quality control of subepithelial lesions, early esophageal cancer, early gastric cancer, and pancreatic diseases including pancreatic cystic lesions, autoimmune pancreatitis, and pancreatic cancer. The implementation of EUS-AI has opened up new avenues for individualized precision medicine and has introduced novel diagnostic and treatment approaches for digestive diseases.
PubMed: 37685350
DOI: 10.3390/diagnostics13172815