Oral Lipid-Lowering Treatments Beyond Statins: Too Old and Outdated or Still Useful?

Purpose of Review For many years, the lipid-lowering armamentarium consisted of statins and/or ezetimibe and/or bile acid sequestrants and/or fibrates. Now, with the availability of new drugs mostly injectables, the field has changed and the role of oral non-statin drugs (including bempedoic acid) must be reevaluated. Recent Findings Ezetimibe remains a very important combination partner for statins with continuously increasing treatment numbers. Bempedoic acid is another interesting combination partner for statin/ezetimibe or ezetimibe alone but lacks in contrast to ezetimibe evidence from outcome trials. The role of fibrates is less clear as they have shown disappointing results in outcome trials but may still be used in selected, high-risk patients with combined dyslipidemia. Bile acid sequestrants are now rarely used as there are stronger, better tolerable ways to lower LDL-cholesterol. Summary With the introduction of new injectable lipid-lowering drugs, some oral drugs such as ezetimibe and bempedoic acid still have an important spot in our treatment algorithm others such as fibrates have a less clear role while again others are now rarely used.

TP1.2.1SeHCAT scan as an investigation for chronic diarrhoea; a single trust experience

Introduction: Recent published (British Society of Gastroenterology) guidelines strongly recommended investigating unexplained chronic loose stools with SeHCAT scans when available rather than empirical treatment. SeHCAT scan was introduced at our trust in 2015. We aimed to audit this locally. Methods All SeHCAT scans that were done at our trust trust from Jan 2015 to March 2020 were included. Patient demographics along with risk factors and duration of symptoms were documented as well as the referred speciality. Results 55 patients were identified. Average age at time of diagnosis was 50y (18-70y). M:F was 1:3.2 . Most scans were requested by the oncology team as part of the “pelvic radiotherapy late effects service” (n = 25), followed by the gastroenterology team (n = 22) and general surgery team (n = 8). The mean duration of symptoms was 4 years. 73% of the scans showed evidence of bile acid malabsorption (BAM) (n = 40) with bile retention <15%, with the majority of them (n = 30) having severe BAM (retention <5%). 60% of the patients had at least one lower GI endoscopy as part of their workup. The majority of patients were found to have type 3 BAM (n = 37). 60% of patients had symptom improvement on either diet alone or with bile-acid sequestrants (n = 23) and were discharged. Conclusion: SeHCAT scan is a useful test to investigate unexplained chronic diarrhoea. It is important to identify patients at risk of developing bile acid malabsorption. It is currently underutilized by our trust, which might be because of funding issues and awareness among clinicians.

Treatment of Dyslipidaemia in Children

Childhood dyslipidaemia is one of the main traditional cardiovascular risk factors that initiate and exacerbate the atherosclerotic process. Healthcare providers may play a key role in the management of children with lipid abnormalities; however, they have to properly evaluate the normal lipid values and know the available treatment options in children and adolescents. Current guidelines recommend healthy behaviours as the first-line treatment for childhood dyslipidaemia. The therapeutic lifestyle changes should focus on dietary modifications, daily physical activity, reduction in body weight and tobacco smoking cessation. Parents play a key role in promoting their children’s healthy habits. In children with more severe forms of lipid abnormalities and in those who do not benefit from healthy behaviours, pharmacological therapy should be considered. Safe and effective medications are already available for children and adolescents. Statins represent the first-line pharmacological option, while ezetimibe and bile acid sequestrants are usually used as second-line drugs. Despite their limited use in children, other lipid-lowering agents (already approved for adults) are currently available or under study for certain categories of paediatric patients (e.g., familial hypercholesterolemia). Further studies are needed to evaluate the long-term efficacy, safety and tolerability of novel lipid-lowering drugs, especially in children.

Hyperlipidemia Condition and Novel-Drug Therapies: A Overall Study

Hyperlipidaemia is an condition that increases the chance of coronary heart disease (CHD) and atherosclerotic disease (ASHD) in blood vessels. Hyperlipidaemia occurs in response to smoking, obesity, sedentary lifestyle, and other risk factors to extend CHD. Cardiovascular disease (CVD) is the reason for death. Hyperlipidaemia is divided into two broad classifications: Primary (familial) and Secondary (acquired). Primary hyperlipidemia has been generated by hereditary defects and climatic factors or by undisclosed mechanisms. Secondary hyperlipidemia concern to the metabolic disorders linked with the diabetes mellitus, liver complication, thyroid, and kidney complications. Hyperlipidemia also refers to as elevated levels of lipids within the blood. Circulating lipid are carried in lipoproteins that transport the lipids to varied tissues for energy use, lipid deposition, hormone production, and steroid formation. The lipoprotein consists of esterified and unesterified cholesterol, triglycerides, phospholipids, and protein. The general public who have hyperlipidemia experience no symptoms. Hyperlipidemia is most oftenly correlated with high-fat diets, a stationary lifestyle, obesity and diabetes mellitus. Four different classes of cholesterol-lowering drugs namely, statins, niacin, resins, and fibrates are available to treat hyperlipidemia; however, statins are now considered to be the first line therapy. The preventable causes of hyperlipidemia can include: Smoking, Being overweight, Physical inactivity, Steroid use, Alcohol consumption & Diet high in saturated fat, & cholesterol such as cheese, meat, fried & processed foods and egg yolk. The treatment of hyperlipidemia includes statins, bile acid sequestrants, fibric acids, niacin, and cholesterol absorption inhibitors. There are some of the novel drugs which are selected for the treatment of hyperlipidemia which includes: Evolocumab, Alirocumab, Bempedoic acid, Lomitapide, Evinacumab, and Sebelipase alfa.

A CASE REPORT ON WILSON’S DISEASE: A RARE CLINICAL CONDITION OF COPPER DEPOSITION IN LIVER

Wilson’s disease is a rare inherited disorder and is characterized by the accumulation of copper in various tissues and also in organs like the liver, brain, kidneys and cornea. Symptoms in paediatrics characteristically appear with hepatic involvement. In this case we have discussed about an eleven-year-old male child, who was presented to the Paediatric department in a tertiary care hospital with chief complaints of yellowish discoloration of eyes, dark coloured urine and high grade fever. Due to the accumulation of copper there were decreased levels of ceruloplasmin and there was an increased 24 hour urinary copper, which confirms the Wilson’s disease in this child. Child was treated with Cephalosporin antibiotics, vitamins, laxative, and bile acid sequestrants. Child showed gradual improvement in clinical symptoms and got discharged without any further event. Quality of evidence was assessed according to the GRADE system. Early diagnosis and management helped to prevent serious complications.

Role of antispasmodics in the treatment of irritable bowel syndrome

Introduction. IBS is a functional bowel disorder that has a significant impact on patients and society, especially in terms of quality of life and medical costs.Pathogenesis. It is believed that the pathogenesis of IBS consists of several mechanisms: the syndrome of intersection of functional disorders (gut-brain), stress, visceral hypersensitivity and changes in motor skills.Visceral hypersensitivity. Changes in visceral sensitivity in IBS are characterized by central abnormalities in areas of the cerebral cortex. Motility impairment in IBS manifests itself as abnormal myoelectric activity in the colon, resulting in repetitive contractions of the small intestine and colon, which appear to cause pain.Intestinal microflora. FODMAPs are found in high amounts in some fruits, artificial sweeteners, legumes, and green vegetables and are poorly absorbed by all people. FODMAPs have enzymatic and osmotic effects that may contribute to the onset of symptoms in some patients.The principles of IBS therapy. Treatment for IBS should be based on the type and severity of symptoms. For the treatment of IBS, drugs of various pharmacological groups are used, depending on the prevailing symptoms. These include opioid receptor agonists, bile acid sequestrants, guanylate cyclase agonists, chlorine channel activators, as well as antibiotics, probiotics, antidepressants, 5-HT3 receptor antagonists, and antispasmodics.Myotropic antispasmodics. Drugs with antispasmodic activity are used to treat functional and organic diseases of the gastrointestinal tract as a basic therapy or «on demand». Mebeverine quickly and effectively relieves spasm, pain and the entire complex of intestinal symptoms, in addition, the drug reduces visceral hypersensitivity due to a local anesthetic effect. The drug has a high safety profile and has a number of advantages over drugs of the same pharmacological group.Conclusion. Myotropic antispasmodics have been shown to be highly effective in the treatment of IBS. Mebeverine occupies a special place among myotropic antispasmodics. Its combined action provides a pronounced antispasmodic activity along with a high safety profile.

Early Prevention of Atherosclerosis: Detection and Management of Hypercholesterolaemia in Children and Adolescents

Coronary heart disease (CHD) is the main cause of death and morbidity in the world. There is a strong evidence that the atherosclerotic process begins in childhood and that hypercholesterolaemia is a CHD major risk factor. Hypercholesterolaemia is a modifiable CHD risk factor and there is a tracking of hypercholesterolaemia from birth to adulthood. Familial hypercholesterolaemia (FH) is the most common primitive cause of hypercholesterolaemia, affecting 1:200–250 individuals. Early detection and treatment of hypercholesterolaemia in childhood can literally “save decades of life”, as stated in the European Atherosclerosis Society Consensus. Multiple screening strategies have been proposed. In 2008, the American Academy of Pediatrics published the criteria for targeted screening, while some expert panels recommend universal screening particularly in the young, although cost effectiveness has not been fully analysed. Blood lipid profile evaluation [total cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C) and triglycerides] is the first step. It has to be ideally performed between two and ten years of age. Hypercholesterolaemia has to be confirmed with a second sample and followed by the detection of family history for premature (before 55 years in men and 60 years in women) or subsequent cardio-vascular events and/or hypercholesterolaemia in 1st and 2nd degree relatives. The management of hypercholesterolaemia in childhood primarily involves healthy lifestyle and a prudent low-fat diet, emphasising the benefits of the Mediterranean diet. Statins are the cornerstone of the drug therapy approved in USA and in Europe for use in children. Ezetimibe or bile acid sequestrants may be required to attain LDL-C goal in some patients. Early identification of children with severe hypercholesterolaemia or with FH is important to prevent atherosclerosis at the earliest stage of development, when maximum benefit can still be obtained via lifestyle adaptations and therapy. The purpose of our review is to highlight the importance of prevention and treatment of hypercholesterolaemia starting from the earliest stages of life.

Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

Active Enterohepatic Cycling is Not Required for the Choleretic Actions of 24-norUrsodeoxycholic Acid in Mice

The superior ability of norursodeoxycholic acid (norUDCA) to induce a bicarbonate-rich hypercholeresis has been attributed to its ability to undergo cholehepatic shunting and norUDCA is currently being evaluated as a therapeutic for forms of liver disease. The goal of this study was to use mouse models to investigate contributions of bile acid transporters to the choleretic actions of norUDCA. Here, we show that the apical sodium-dependent bile acid transporter (ASBT) and Organic solute transporter-alpha (OSTα) are dispensable for norUDCA-stimulation of bile flow and biliary bicarbonate secretion in mice. Analysis of the liver transcriptome revealed that norUDCA induced hepatic expression of a limited number of transporter genes, particularly organic anion transporting polypeptide 1a4 (Oatp1a4). However, norUDCA potently stimulated a bicarbonate-rich hypercholeresis in Oatp1a/1b-deficient mice. Blocking intestinal bile acid reabsorption by co-administration of an ASBT inhibitor or bile acid sequestrant did not impact the ability of norUDCA to induce bile flow in wildtype mice. The results support the concept that these major bile acid transporters are not directly involved in the absorption, cholehepatic shunting, or choleretic actions of norUDCA. Additionally, the findings support further investigation of the therapeutic synergy between norUDCA and ASBT inhibitors or bile acid sequestrants for cholestatic liver disease.

New Kids on the Block: A Review of the Latest Iatrogenic Foreign Materials Seen in Gastrointestinal Specimens

Context.— With the increasing development and use of iatrogenic agents, pathologists are encountering more novel foreign materials in retrieved gastrointestinal specimens. These colorful and unusual-appearing foreign materials can pose a diagnostic dilemma to those unaware of their morphology, especially if the relevant clinical history is lacking. Objective.— To discuss the histopathologic features, clinical scenarios and significance, and differential diagnosis of relatively recently described, yet quickly expanding, family of iatrogenic agents that can present as foreign materials in gastrointestinal specimens—pharmaceutical fillers (crospovidone and microcrystalline cellulose), submucosal lifting agents (Eleview and ORISE), lanthanum carbonate, hydrophilic polymers, OsmoPrep, yttrium 90 microspheres (SIR-Sphere and TheraSphere), and resins (sodium polystyrene sulfonate, sevelamer, and bile acid sequestrants). Data sources.— We collate the findings of published literature, including recently published research papers and authors' personal experiences from clinical sign-out and consult cases. Conclusions.— Correct identification of these iatrogenic agents is important because the presence of some novel agents can explain the histopathologic findings seen in the background specimen, and specific novel agents can serve as diagnostic clues to prompt the pathologist to consider other important and related diagnoses. Awareness of even biologically inert agents is important for accurate diagnosis and to avoid unnecessary and expensive diagnostic studies.