Review

Authors: Kamil Rutkowski, Karina Udrycka, Barbara Włodarczyk...

The aim of this paper is to raise awareness of MC as a clinically significant condition and to highlight its under-recognition, risk factors, diagnosis, management, and complications. This paper underlines the diagnostic and therapeutic challenges associated with the often nonspecific symptoms of MC. In order to create this article, we reviewed available articles found in the PubMed database and searched for articles using the Google Scholar platform. Microscopic colitis (MC) is a chronic inflammatory bowel disease, classified into three types: lymphocytic, collagenous, and unspecified. The average age of onset of MC is around 62-65 years and the disease is more common in women than men (nine times more common). The main symptom of MC is watery diarrhoea without blood, other symptoms include defecatory urgency, faecal incontinence, abdominal pain, nocturnal bowel movements, and weight loss. Once considered a rare disease, MC is now being diagnosed with increasing frequency, but diagnosis remains difficult. To date, a number of causative factors for MC have been identified, including smoking, alcohol consumption, medications (including NSAIDs, PPIs, SSRIs, and ICPIs), genetic factors, autoimmune diseases, bile acid malabsorption, obesity, appendicitis, and intestinal dysbiosis. It may be difficult to recognize and should be differentiated from inflammatory bowel diseases (Crohn's disease and ulcerative colitis), irritable bowel syndrome (IBS), coeliac disease, infectious bowel disease, and others. Diagnosis involves biopsy at colonoscopy and histopathological evaluation of the samples. Treatment consists of budesonide oral (the gold standard) or enema. Alternatives include bile acid sequestrants (cholestyramine, colesevelam, and colestipol), biologics (infliximab, adalimumab, and vedolizumab), thiopurines, methotrexate, and rarely, surgery.

PubMed: 39407743
DOI: 10.3390/jcm13195683

Review

Authors: Magdalena-Cristina Stanciu, Marieta Nichifor, Carmen-Alice Teacă...

Bile acid sequestrants (BASs) are non-systemic therapeutic agents used for the management of hypercholesterolemia. They are generally safe and not associated with serious systemic adverse effects. Usually, BASs are cationic polymeric gels that have the ability to bind bile salts in the small intestine and eliminate them by excretion of the non-absorbable polymer-bile salt complex. This review gives a general presentation of bile acids and the characteristics and mechanisms of action of BASs. The chemical structures and methods of synthesis are shown for commercial BASs of first- (cholestyramine, colextran, and colestipol) and second-generation (colesevelam and colestilan) and potential BASs. The latter are based on either synthetic polymers such as poly((meth)acrylates/acrylamides), poly(alkylamines), poly(allylamines) and vinyl benzyl amino polymers or biopolymers, such as cellulose, dextran, pullulan, methylan, and poly(cyclodextrins). A separate section is dedicated to molecular imprinting polymers (MIPs) because of their great selectivity and affinity for the template molecules used in the imprinting technique. Focus is given to the understanding of the relationships between the chemical structure of these cross-linked polymers and their potential to bind bile salts. The synthetic pathways used in obtaining BASs and their in vitro and in vivo hypolipidemic activities are also introduced.

PubMed: 37367171
DOI: 10.3390/gels9060500

Meta-Analysis Review

Authors: Alpo Vuorio, Jaana Kuoppala, Petri T Kovanen...

BACKGROUND

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.

OBJECTIVES

To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.

SEARCH METHODS

Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017.

SELECTION CRITERIA

Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.

DATA COLLECTION AND ANALYSIS

Two authors independently assessed studies for inclusion and extracted data.

MAIN RESULTS

We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence).

AUTHORS' CONCLUSIONS

Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Brachial Artery; Carotid Intima-Media Thickness; Child; Child, Preschool; Cholesterol, LDL; Creatine Kinase; Female; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Puberty; Randomized Controlled Trials as Topic; Vasodilation

PubMed: 28685504
DOI: 10.1002/14651858.CD006401.pub4

Meta-Analysis

Authors: Alpo Vuorio, Jaana Kuoppala, Petri T Kovanen...

BACKGROUND

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.

OBJECTIVES

To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.

SEARCH METHODS

Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019.

SELECTION CRITERIA

Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.

DATA COLLECTION AND ANALYSIS

Two authors independently assessed studies for inclusion and extracted data.

MAIN RESULTS

We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.

AUTHORS' CONCLUSIONS

Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Topics: Adolescent; Adult; Child; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Randomized Controlled Trials as Topic; Young Adult

PubMed: 31696945
DOI: 10.1002/14651858.CD006401.pub5

Review

Authors: Michael Camilleri, Priya Vijayvargiya

Bile acids (BAs) are the central signals in enterohepatic communication, and they also integrate microbiota-derived signals into enterohepatic signaling. The tissue distribution and signaling pathways activated by BAs through natural receptors, farsenoid X receptor and G protein-coupled BA receptor 1 (GPBAR1, also known as Takeda G-coupled receptor 5), have led to a greater understanding of the mechanisms and potential therapeutic agents. BA diarrhea is most commonly encountered in ileal resection or disease, in idiopathic disorders (with presentation similar to functional diarrhea or irritable bowel syndrome with diarrhea), and in association with malabsorption such as chronic pancreatitis or celiac disease. Diagnosis of BA diarrhea is based on Se-homocholic acid taurine retention, 48-hour fecal BA excretion, or serum 7αC4; the latter being a marker of hepatic BA synthesis. BA diarrhea tends to be associated with higher body mass index, increased stool weight and stool fat, and acceleration of colonic transit. Biochemical markers of increased BA synthesis or excretion are available through reference laboratories. Current treatment of BA diarrhea is based on BA sequestrants, and, in the future, it is anticipated that farsenoid X receptor agonists may also be effective. The optimal conditions for an empiric trial with BA sequestrants as a diagnostic test are still unclear. However, such therapeutic trials are widely used in clinical practice. Some national guidelines recommend definitive diagnosis of BA diarrhea over empirical trial.

Topics: Benzothiazoles; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestenones; Cholestyramine Resin; Chronic Disease; Colesevelam Hydrochloride; Colestipol; Diarrhea; Diet, Fat-Restricted; Feces; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Isoxazoles; Liver; Malabsorption Syndromes; Receptors, Cytoplasmic and Nuclear; Sequestering Agents; Taurocholic Acid

PubMed: 32558690
DOI: 10.14309/ajg.0000000000000696