OBJECTIVE: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test.
METHODS: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results.
RESULTS: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result.
CONCLUSIONS: The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

The aim of this study was to investigate the effects of aflatoxin B1 (AFB1) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB1. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB1 group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB1 caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB1 upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB1 negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB1-induced cholestasis.

Amiodarone is a class 3 antiarrhythmic drug which may be associated with thyroid dysfunction. Amiodarone-induced thyrotoxicosis (AIT) is classified as type 1 (AIT 1; which may develop in the presence of latent autoimmune hyperthyroid condition) or type 2 (AIT 2; which develops in an apparently normal thyroid resulting from destructive thyroiditis). AIT 1 routinely requires treatment with thionamides, whereas AIT 2 is treated with steroids. Resistance to the conventional treatment of hyperthyroidism is not commonly found in clinical practice. This report discusses a case of AIT 2 resistant to conventional treatment. Despite being on high doses of carbimazole and steroids (prednisolone), the patient remained thyrotoxic. Cholestyramine, a bile salt sequestrant, was used as an adjunctive therapy resulting in significant clinical and biochemical improvement. The patient subsequently became euthyroid and is being followed up in endocrine clinic.

OBJECTIVE: Perinatal hypercholesterolemia exacerbates the development of atherosclerotic plaques in adult offspring. Here, we aimed to study the effect of maternal treatment with cholestyramine, a lipid-lowering drug, on atherosclerosis development in adult offspring of hypercholesterolemic ApoE-deficient (ApoE-/-) mice.
METHODS: ApoE-/- mice were treated with 3% cholestyramine (CTY) during gestation (G). After weaning, offspring (CTY-G) were fed control diet until sacrificed at 25weeks of age. Atherosclerosis development in the aortic root of offspring was assessed after oil-red-o staining, along with some of predefined atherosclerosis regulators such as LDL and HDL by high-performance liquid chromatography (HPLC), and bile acids (BA) and trimethylamine N-oxide (TMAO) by liquid chromatography-mass spectrometry (LC-MS/MS).
RESULTS: In pregnant dams, cholestyramine treatment resulted in significantly lower plasma total- and LDL-cholesterol as well as gallbladder total BA levels. In offspring, both males and females born to treated dams displayed reduced atherosclerotic plaques areas along with less lipid deposition in the aortic root. No significant change in plasma total cholesterol or triglycerides was measured in offspring, but CTY-G males had increased HDL-cholesterol and decreased apolipoproteins B100 to A-I ratio. This latter group also showed reduced gallbladder total and specifically tauro-conjugated bile acid pools, whereas for CTY-G females, hydrophilic plasma tauro-conjugated BA pool was significantly higher. They also benefited from lower plasma TMAO.
CONCLUSIONS: Prenatal cholestyramine treatment reduces atherosclerosis development in adult offspring of ApoE-/- mice along with modulating the plaques\' composition as well as some related biomarkers such as HDL-C, bile acids and TMAO.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
Chronic diarrhoea without an established cause is common.There are a small number of clinical trials, often with a limited number of patients or healthy volunteers.Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment.There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool.The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience.

BACKGROUND: Clostridioides difficile infection (CDI) is a common nosocomial infection. Risk factors for developing CDI include prior hospitalization, being older than 65 years old, antibiotic use, and chronic disease. It is linked with diarrhea and colitis and can vary in severity. It is a major cause of increased morbidity and mortality among hospitalized patients. However, community-acquired CDI is also increasing. Proper diagnosis and determination of severity are crucial for the treatment of CDI. Depending on how severe the CDI is, the patient may endorse different symptoms and physical exam findings. The severity of CDI will determine how aggressively it is treated. Management and treatment: Laboratory studies can be helpful in the diagnosis of CDI. In this regard, common labs include complete blood count, stool assays, and, in certain cases, radiography and endoscopy. Mild-to-moderate colitis is treated with antibiotics, but severe colitis requires a different approach, which may include surgery. Several alternative therapies for CDI exist and have shown promising results. This review will touch upon these therapies, which include fecal transplants, intravenous immunoglobulin, and the use of cholestyramine and tigecycline.
CONCLUSIONS: Prevention of CDI can be achieved by proper hygiene, vaccinations, and detecting the infection early. Proper hygiene is indeed noted to be one of the best ways to prevent CDI in the hospital setting. Overprescribing antibiotics is also another huge reason why CDI occurs. Proper prescription of antibiotics can also help reduce the chances of acquiring CDI.

A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB.
To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed.
Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination.
R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.

BACKGROUND: Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients.
METHODS: We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively.
RESULTS: Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three.
CONCLUSIONS: To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory.

Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.

Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low-density lipoprotein cholesterol (LDL-C) further exaggerated by the discontinuation of cholesterol-lowering therapy.
A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment.
Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K.
Pregnancy is associated with prolonged cessation of cholesterol-lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long-term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline-informed models of care covering family planning and pregnancy should be implemented for all women with FH.