Bile acid diarrhea (BAD) is a condition in which excessive bile acids reach the colon, promoting water and electrolyte secretion and potentially causing diarrhea, and is known as one possible mechanism of post-cholecystectomy diarrhea. This case involved a 59-year-old man who had undergone cholecystectomy approximately 18 years earlier and had persistent loose stools and increased stool frequency. BAD was suspected by the treating physician, although it was not definitively confirmed by specific diagnostic testing. The patient was prescribed Questran powder 44.4% at 18 g/day. However, in Japan, the approved indications for Questran powder 44.4% include hypercholesterolemia, and its use for suspected BAD is off-label. The pharmacist was not involved in the diagnosis or treatment selection but reviewed domestic and overseas drug information as support for appropriate use after off-label prescribing. Based on the United Kingdom Summary of Product Characteristics, the pharmacist explained the administration method, the need to separate from concomitant medications, and the need for early follow-up. Before treatment, the patient-reported Bristol Stool Form Scale (BSFS) score was 5-6, and stool frequency was five to six times per day. On day 5, after treatment initiation, pharmacist follow-up showed improvement to a BSFS score of 4-5 and stool frequency of approximately two to three times per day. However, the patient reported difficulty taking the suspension because of its texture. Although the prescription instructed Questran powder 44.4% 18 g/day in two divided doses, the patient maintained the prescribed total daily amount of 18 g/day but took it in three divided administrations. The pharmacist provided the treating physician with information on symptom changes, administration difficulties, and discrepancies between the prescribed regimen and actual medication use via a tracing report. This single uncontrolled observation cannot establish the efficacy of cholestyramine or confirm BAD. Rather, this case illustrates the potential value of pharmacist-led follow-up after off-label prescribing, including early monitoring, identification of medication-use problems, and communication with the treating physician.

Cholestyramine is a nonabsorbable resin. Because it does not enter the mother's bloodstream, it will not reach the infant via breastmilk. It is acceptable for use during lactation.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder which is characterized by pruritus and elevated bile acids during pregnancy and is further coupled with higher maternal and fetal risks. We report a rare case of early-onset, refractory ICP with elevated liver enzymes in a 25-year-old primigravida with a monochorionic diamniotic twin gestation complicated by selective fetal growth restriction (sFGR). At 24 weeks of gestation, the patient presented with severe generalized pruritus, mainly on the palms and soles, impairing her quality of life. The patient with insignificant medical history of liver diseases, but has a significant family history of ICP. On examination, she was afebrile, hemodynamically stable, and without jaundice or rash. Laboratory findings revealed moderately raised bile acids (40.98 µmol/L) fulfilling criteria for moderate ICP but coupled with elevated liver enzymes. Viral hepatitis serologies, autoimmune profile, and abdominal ultrasound were all unremarkable. Treatment with ursodeoxycholic acid (UDCA) 500 mg twice daily was initiated. Given worsening biochemical (doubling of bile acids) and clinical findings, gastroenterologists were consulted after a week of treatment initiation, and their recommendation was to add cholestyramine 4 g once daily as an adjunctive. Afterwards, with persistently elevated bile acids, the UDCA dose increased to 500 mg three times daily, and cholestyramine was increased to 4 g twice daily. Phytonadione (vitamin K) 10 mg orally daily was added to reduce the risk of bleeding due to reduced absorption of fat-soluble vitamins caused by cholestyramine. At 32 weeks of gestation, she developed vomiting, coffee-ground emesis, vaginal spotting, and abdominal pain, progressing to preterm labor with non-reassuring fetal heart tracings. An emergency category 1 cesarean section was performed, delivering two viable female infants (1600 g and 1160 g), both admitted to the neonatal intensive care unit (NICU). Postnatally, the maternal condition was stable, and biochemical parameters normalized rapidly within 72 hours postpartum. Pruritus resolved completely, confirming the diagnosis of ICP.

Previous studies showed that exposure to long-acting anticoagulant rodenticides (LAARs) can induce neuropathology in adult rats. In the current study we tested if the potent LAAR brodifacoum similarly promoted neuropathology in adult rabbits which provide a better model of human LAAR poisoning. Adult male New Zealand White rabbits were administered by gavage a single administration of brodifacoum at its LD50 dose (200 μg/kg), followed by daily injections of vitamin K1 to prevent mortality due to anti-coagulation. After 3 weeks, examination of the cerebellum revealed an increase in glial cell activation, and a decrease in myelin content. A targeted lipidomics analysis was carried out to determine if brodifacoum altered the relative abundance of lipids enriched in myelin. We observed brodifacoum-dependent decreases in several sulfatides which were associated with an increase in expression of arylsulfatase A which degrades sulfatides. Daily treatment with the bile sequestrant cholestyramine, which accelerates LAAR clearance from the body, ameliorated brodifacoum -induced damage. These findings confirm that, despite daily vitamin K1 treatment, LAARs such as brodifacoum can induce neuropathology in adult animals and support the use of agents such as bile sequestrants to ameliorate those consequences.

Emerging evidence implicates bile acid-intestinal microbiota interactions in the pathogenesis of pruritus associated with primary biliary cholangitis (PBC). Cholestyramine, a bile acid sequestrant, is clinically recommended for pruritus alleviation. This study investigates its regulatory effects on gut microbiome composition and metabolite profiles. A prospective cohort of 54 pruritic PBC patients and 25 asymptomatic controls underwent longitudinal multi-omics profiling. Fecal 16S rRNA sequencing and untargeted metabolomics were performed pre-/post-4-week cholestyramine intervention (4 g twice daily). Serum autotaxin, as a biomarker for pruritus assessment, and liver function tests were completed simultaneously. Four important findings were listed as follows. (i) Pruritus phenotype characteristics: Pruritic patients exhibited elevated cholestasis indices (total bilirubin, alkaline phosphatase [ALP], and gamma-glutamyl transferase), higher ATX levels, and increased Gp210 antibody positivity compared to controls (all P < 0.01). Cholestyramine significantly reduced 5-D pruritus scores, ATX levels, and cholestasis markers (P < 0.01). (ii) Microbial dysbiosis: Gut microbiota diversity (Shannon/Simpson indices) was markedly decreased in pruritic patients, with taxonomic enrichment of Romboutsia, Stenotrophomonas, and Achromobacter, whereas Lachnospiraceae and Bacteroidaceae predominated in controls. (iii) Metabolomic perturbations: Metabolomic analysis identified diminished medium-chain fatty acids and indole derivatives (e.g., norharman) in pruritic patients. (iv) Therapeutic efficacy: Microbial-metabolite-clinical correlations revealed the pivotal role of the Romboutsia-norharman-ATX/ALP axis in the pathogenesis of pruritic PBC. Post-treatment, cholestyramine restored microbial diversity, normalized metabolite levels, and attenuated pruritus. Enterobacteriaceae/long-chain fatty acids have been identified as a significant marker for predicting the efficiency of the response to cholestyramine.IMPORTANCEPruritus in primary biliary cholangitis arises from synergistic cholestasis and gut microbiome-metabolite dysregulation. Cholestyramine mitigates symptoms by modulating the microbiome-metabolite-host axis, highlighting its therapeutic potential through microbiota remodeling and metabolic homeostasis restoration.

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate with survival outcomes for HCC patients. Gene signatures unique to the knockout females correspond with low-grade tumors and better survival. Ovariectomy blunts the metabolic changes and promotes liver tumorigenesis in females that, intriguingly, coincides with increased serum bile acid (BA) levels. Despite similar genetics, knockout male mice displayed higher serum BA concentrations, while female knockouts excreted more BAs. Decreasing enterohepatic BA recirculation using cholestyramine, an FDA-approved resin, dramatically reduced the liver cancer burden in male mice. Overall, we reveal that sex-specific BA metabolism leading to lower circulating BA concentration protects female livers from developing cancer. Thus, targeting BA excretion may be a promising therapeutic strategy against HCC.

The efficacy of 6 binders in sequestering perfluorooctane sulfonic acid (PFOS) under in vitro ruminal conditions was evaluated. Binders, including bentonite, montmorillonite aluminum pillared clay, chitosan, activated charcoal Norit, and cholestyramine resin (CHM), were tested at a dose of 1.8% (wt/wt; fresh basis). The PFOS (%) binding affinity of binders was calculated in relation to the control. A randomized complete block design (n = 4) was used to analyze the data. Only CHM, an anion-exchange resin, demonstrated strong potential to sequester PFOS (x_=52.5%) The binders did not affect the gas production kinetics and microbial fermentation profile parameters. Molecular dynamics simulations showed that PFOS molecules were strongly encapsulated within the CHM polymeric structure, primarily driven by interactions between the positively charged CHM and the negatively charged PFOS and stabilized by the hydrophobic interactions between the backbone of PFOS and CHM. Findings highlight the potential application of CHM in reducing PFOS contamination in livestock.