Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disorder caused by biallelic mutations in the ABCB4 gene, leading to multidrug resistance protein 3 (MDR3) deficiency. PFIC3 often presents with clinical and biochemical features that overlap with Wilson's disease (WD), including hepatic copper accumulation and elevated urinary copper excretion. These similarities contribute to frequent misdiagnosis, resulting in inappropriate chelation therapy and delayed appropriate management. This systematic review examines reported cases of PFIC3 initially misdiagnosed as WD to highlight diagnostic challenges and assess patient outcomes. A comprehensive search across PubMed, ScienceDirect and Google Scholar identified 11 eligible studies involving 16 patients. Most cases were first treated as WD, receiving chelation therapy without clinical improvement. Diagnosis was later revised to PFIC3 following negative ATP7B mutation testing and identification of ABCB4 variants, often via whole-genome sequencing. Upon switching to ursodeoxycholic acid (UDCA), most patients experienced clinical stabilization. The findings underscore the need for heightened awareness of PFIC3 as a differential diagnosis in atypical WD cases, especially when ceruloplasmin is normal and Kayser-Fleischer (KF) rings are absent. Early genetic testing is essential to avoid mismanagement. Further observational studies are warranted to estimate misdiagnosis frequency and guide diagnostic protocols.

Sarcopenia, characterized by progressive skeletal muscle loss, is associated with poor outcomes in various diseases. Traditional methods for assessing muscle cross-sectional area using computed tomography (CT) scans are manual, time-consuming and prone to variability. This study comprehensively validates a deep-learning (DL) pipeline for accurate and reproducible sarcopenia detection on computed tomography across diverse disease abdominal conditions and imaging protocols. We utilized the publicly available Sparsely Annotated Region and Organ Segmentation (SAROS) CT dataset (n = 550 CT scans, 6516 slices) for model training. Testing was conducted on 601 CT scans from public (SAROS, Cancer Imaging Archive [TCIA], WAW-TACE) and in-house multi-center datasets representing varied clinical conditions (acute pancreatitis, inflammatory bowel disease, gallbladder cancer and distal bile duct obstruction). The implemented pipeline integrated TotalSegmentator for L3 vertebral segmentation, automated L3 slice extraction and skeletal muscle segmentation using nnU-Net. Performance evaluation included expert qualitative scoring, Dice scores, intersection over union (IoU) and diagnostic accuracy metrics for sarcopenia detection. The DL pipeline demonstrated consistent segmentation accuracy across diverse datasets, with mean Dice scores ranging from 0.9287 to 0.9701 and mean IoU values up to 0.9423. Expert evaluation confirmed reliable L3 vertebral segmentation (78%-85% rated as complete) and skeletal muscle segmentation (90%-92.6% rated as excellent). Sarcopenia detection was consistent across varied patient populations, with sensitivity (0.94-0.97), specificity (0.84-0.97) and AUC values up to 0.92. Importantly, sub-group analysis confirmed comparable performance across varying disease conditions, CT protocols, contrast usage and radiation doses. This study demonstrates that a deep-learning pipeline can achieve consistent and reliable performance for skeletal muscle segmentation and sarcopenia detection across heterogeneous abdominal CT protocols and diverse clinical conditions.

To define standardised outcomes, the Core Outcome Set (COS) for reporting in studies of Intrahepatic Cholestasis of Pregnancy (ICP). e-Delphi survey and consensus process. International. 155 individuals from Asia, Europe, Oceania, North and South America: 31 patients (20%), 121 clinicians (78%), and 3 researchers (2%). Maternal and perinatal outcomes reported in studies of ICP were collated. Stakeholders in ICP research and clinical care scored the importance of each outcome using a 9-point Likert scale over three rounds; short-listed outcomes were ranked during face-to-face consensus meetings. The final COS was agreed by the Study Steering Committee. The study was registered prospectively with Core Outcome Measures in Effectiveness Trials. Ethical approval was granted by the King's College London Research Ethics Committee (KCL MRA-23/24-39574). From 54 manuscripts, 97 individual clinical outcomes were attributed to ICP. Twenty three outcomes were shortlisted by the e-Delphi surveys, the ranking of which enabled selection of 10 core outcomes. Maternal core outcomes comprise: total maternal bile acid (BA) concentration (maximum), gestational age at peak BA concentration, and itch impact on maternal wellbeing. Birth core outcomes comprise: stillbirth, gestational age at birth, and spontaneous preterm birth versus induced preterm birth. Neonatal core outcomes comprise: perinatal death within 7 days of birth, perinatal asphyxia, neonatal unit admission, and mechanical ventilation. Given the heterogeneity of reported outcomes, we have confirmed the need for a COS in ICP, standardising the minimum reported outcomes to reduce outcome reporting bias and research wastage.

Background:Intrahepatic cholestasis of pregnancy (ICP) is a multifactorial liver disorder associated with adverse pregnancy outcomes. Chronic hepatitis B (CHB) has been reported with increased risk of ICP, while the clinical characteristics and outcomes of isolated ICP compared with ICP involving CHB remain poorly understood.Methods:ICP involving CHB was defined as the co-concurrence of ICP with CHB, categorized into immune-tolerant CHB (n=44), inactive CHB (n=86), immune-active CHB (n=127), and grey zone CHB (n=89). Isolated ICP (n=826) was defined as ICP without viral hepatitis, while immune-active CHB with normal elevated total bile acid (TBA) (n=87) serves as controls.Results:Women with ICP involving immune-active CHB experienced the most severe biochemical abnormalities and adverse outcomes, whereas other CHB subgroups exhibited biochemical profiles and outcomes comparable to isolated ICP cases. Assisted reproductive technology (aOR, 1.24), TBA levels (40–99.9 µmol/L-aOR, 1.27, ≥100 µmol/L-aOR, 1.60), and immune-active CHB (aOR, 1.12) were associated with increased risks of composite adverse outcomes. Stratified analysis revealed that TBA ≥40 µmol/L significantly correlated with increased risks of total and iatrogenic preterm birth and neonatal intensive care unit admission (p<0.05); while TBA ≥100 µmol/L was further associated with elevated risks of meconium-stained amniotic fluid and lower Apgar scores (p<0.05). Immune-active CHB women with normal TBA demonstrated relatively higher levels of transaminase but achieved the most favorable pregnancy outcomes.Conclusions:ICP involving immune-active CHB demonstrated the most severe biochemical abnormalities and adverse pregnancy outcomes, while ICP involving other CHB immune phases showed transient mild biochemical changes and outcomes comparable to isolated ICP. The findings underscore the need to tailor diagnostic, monitoring, and management strategies based on TBA levels and the immune status of CHB.

Combined clinical and genomic analysis uncovers neonatal-onset Wilson disease in two siblings with idiopathic cholestasis.

Background: Several genes encoding proteins essential for normal bile production have been associated with progressive familial intrahepatic cholestasis in children, but there are few studies evaluating the frequency of variants in these genes among adults with chronic cholestatic disease. The aim of this study was to assess frequency of variants in progressive familial intrahepatic cholestasis–associated genes in adults with idiopathic or episodic cholestatic chronic liver disease (cCLD). Methods: Patients with cCLD of unknown cause followed in 4 different reference centers in Brazil were genotyped for ABCB11 , ABCB4 , ABCC2 , ATP8B1 , CFTR , JAG1 , KIF12 , LSR , MYO5B , NR1H4 , PPM1F , SERPINA1 , TJP2 , USP53 , VIPAS39 , VPS33B , PEX26 , and WDR83OS gene variants using Illumina platforms. Primary biliary cholangitis, primary sclerosing cholangitis, and other causes of cCLD were excluded. Results: Sixty-five patients (40 females; mean±SD age at disease onset, 26.8±13.4 y) were included. Most (65%) had either a family history of cholestatic liver disease or previous signs and symptoms of intrahepatic cholestasis of pregnancy or low phospholipid–associated cholelithiasis. Fifty-seven (88%) had cCLD, whereas 8 (12%) reported recurrent episodic cholestasis. Some had evidence at diagnosis of cirrhosis (n=20) or hepatocellular carcinoma (n=2) or had undergone liver transplantation (n=10). Sequencing revealed 28 variants in ABCB4 (n=25) and ABCB11 (n=3) genes in 42 patients [65%; heterozygous (n=31), homozygous (n=4), and compound heterozygous (n=7)]. Only 17 (61%) were previously reported. Most variants (57%) were classified as pathogenic or likely pathogenic. Conclusions: More than half of the patients with cCLD of unknown cause exhibited pathogenic or likely pathogenic variants in bile transporter genes, particularly ABCB4 . Genotyping may identify most of those patients as late-onset patients with multidrug resistance protein 3 deficiency.

To describe the long-term clinical significance of hepatolithiasis identified in dogs undergoing cholecystectomy. 14 dogs that underwent cholecystectomy at a single university and had evidence of mineralizations or stones within the intrahepatic ducts on preoperative ultrasound between January 1, 2014, and May 31, 2024, were included. Dogs diagnosed with gallbladder disease requiring cholecystectomy and hepatolithiasis on preoperative ultrasound with or without intrahepatic duct dilation. Of 183 dogs undergoing cholecystectomy in 10 years, 14 (8%) were diagnosed with hepatolithiasis on preoperative diagnostic imaging. The median age and weight at the time of surgery were 11 years old (range, 3 to 13 years) and 7.3 kg (range, 1.63 to 30.0 kg), respectively. Gallbladder culture results were available for 12 of 14 dogs, showing no growth in 7 of 12 (58%), unimicrobial growth in 3 of 12 (25%), and polymicrobial growth in 2 of 12 (16.7%). Liver biopsies most commonly revealed hepatitis or cholangiohepatitis (9 of 14 [64%]). None of the dogs had any hepatoliths addressed during the cholecystectomy procedure. Perioperative mortality occurred in 2 of 14 (14%). No dogs surviving the perioperative period required follow-up surgical intervention due to progression or migration of hepatoliths into the common bile duct or other intrahepatic biliary obstruction within a median follow-up of 538.5 days (range, 147 to 3,316 days). Hepatolithiasis did not pose long-term complications in this population of dogs undergoing cholecystectomy. Dogs did not require secondary surgeries or long-term medical management for hepatolithiasis; therefore, the prognosis did not appear to be worse in dogs undergoing cholecystectomy.

This multicenter retrospective study aimed to compare surgery-related adverse events (AEs) of percutaneous transhepatic biliary drainage (PTBD) with those of endoscopic ultrasound-guided biliary drainage (EUS-BD) for preoperative management of malignant distal bile duct obstruction (MDBO). We reviewed data from 15 centers in Japan between 2012 and 2021. Patients with MDBO who underwent PTBD or EUS-BD after failed endoscopic retrograde cholangiopancreatography (ERCP) and later underwent pancreaticoduodenectomy (PD) were included. The primary outcome was surgery-related AEs. Secondary outcomes included drainage-related outcomes, surgery-related outcomes, disease-free survival (DFS), and overall survival (OS). Risk factors associated with surgery-related AEs were also evaluated. In total, 2350 patients received biliary drainage before PD. Of the 73 patients in whom ERCP failed, 65 underwent PTBD and 11 underwent EUS-BD. EUS-BD showed a significantly higher internalization rate (100% vs. 28%, p < 0.001), fewer sessions (median 1 vs. 2, p = 0.006), and shorter hospital stay (10 vs. 22 days, p = 0.002). Surgery-related AEs were similar between groups. In the multivariate analysis, age ≥ 71 years and ASA-PS ≥ 2 were identified as significant risk factors for surgery-related AEs, whereas the drainage method was not a significant factor. No significant differences were observed in DFS or OS between the groups. Surgical-related outcomes, DFS, and OS after EUS-BD were comparable to those after PTBD; however, EUS-BD allowed a higher internalization rate, fewer sessions, and a shorter hospital stay, making it the preferred option for preoperative biliary drainage after failed ERCP.

Alagille Syndrome (ALGS) is a rare multisystem disorder of autosomal dominant type which is primarily caused due to mutations in the JAG1 gene and, less commonly, NOTCH2, both integral to Notch signalling. Clinically, ALGS is further characterised by cholestatic liver disease because of intrahepatic bile duct paucity, along with some cardiac and skeletal abnormalities, ocular defects, renal involvement, and distinct facial features. Diagnosis of ALGS depends upon the presence of at least three of five main clinical features, which are later supported through liver biopsy, genetic testing, and imaging. Differential diagnosis of ALGS includes biliary atresia, Progressive Familial Intrahepatic Cholestasis (PFIC), neonatal hepatitis, and syndromes with overlapping phenotypes such as Noonan and Kabuki syndromes. Management in such cases is largely supportive, which mainly focuses on relieving cholestasis and pruritus, along with proper nutritional adequacy, and addressing systemic complications. Liver transplant is reserved only for end-stage disease or intractable symptoms. A multidisciplinary approach is an essential aspect of treatment to improve patient outcomes, along with quality of life.

Clinical and biological characteristics of dengue in pregnant women in Reunion Island: A nested case-control analysis in the EPIDENGUE cohort study.

BackgroundLiver health is critical in pregnancy due to this organ adapting to meet gestational metabolic demands. Although overall function typically remains normal, hormonal and metabolic shifts can alter hepatic structure and complicate assessment. Conventional liver tests and imaging (e.g., ultrasonography and biochemical markers) have limited ability to distinguish physiological changes from pathologies such as intrahepatic cholestasis of pregnancy, steatosis, or fibrosis. Ultrasound-derived fat fraction (UDFF) and automated point shear-wave elastography (Auto-pSWE) provide noninvasive, quantitative measures of hepatic fat and stiffness. These techniques are well established in nonpregnant populations, but their applicability for pregnancy-related liver changes remains underexplored. This descriptive pilot study aimed to establish trimester-specific reference values for UDFF and Auto-pSWE in healthy singleton pregnancies and to determine their correlations with clinical and biochemical parameters, thereby providing novel quantitative benchmarks for hepatic assessment during gestation.MethodsThirty normotensive women with singleton pregnancies underwent liver ultrasonography and biochemical evaluations during the first (11–13⁶⁄₇ weeks), second (20–24 weeks), and third (32–36 weeks) trimesters. Measurements included UDFF, liver stiffness (Young modulus in kilopascals) and shear-wave velocity (SWV; in meters per second), maternal anthropometric and serum biomarkers [alanine aminotransferase (ALT), total bile acids, and albumin]. Statistical analyses comprised Kruskal-Wallis tests for comparing trimesters and Spearman correlation coefficients for assessing associations between variables.ResultsMaternal body mass index (BMI) increased significantly across trimesters, from 20.68±1.79 to 23.77±1.82 kg/m2 (P<0.001). UDFF values rose markedly, from 1.92%±0.30% in the first trimester to 4.58%±1.48% in the third trimester (P<0.001), corresponding to an approximate 139% increase. Liver stiffness parameters also increased significantly with gestational age: elasticity rose from 4.33±0.19 kPa to 5.80±1.43 kPa, while SWV increased from 1.26±0.03 to 1.45±0.05 m/s (both P values <0.001). Strong positive correlations were observed between UDFF and SWV (r=0.81), BMI (r=0.78), and ALT (r=0.77) (all P values <0.01), indicating an association between hepatic fat accumulation, tissue stiffness, and maternal metabolic status. Elasticity showed a significant association with total bile acids (P<0.05), indicating a potential link to hepatic functional changes. No significant correlations were found with albumin, total bilirubin, or coagulation indices.ConclusionsIn this cohort, UDFF and liver stiffness increased across trimesters, reflecting physiological weight gain. These quantitative ultrasound biomarkers appear promising as noninvasive tools for monitoring early liver health, helping distinguish normal pregnancy-related hepatic changes from pathological conditions. The reference values reported in this paper may aid in improving prenatal liver assessment and guide timely interventions for optimizing maternal and fetal outcomes. However, these preliminary findings remain to be validated in larger multicenter cohorts with postpartum follow-up.

ObjectiveThis study conducted a retrospective matched analysis to explore the differences and potential associations in perinatal complications between pregnancies achieved through in-vitro fertilization-embryo transfer (IVF-ET) and natural conception.MethodsA total of 806 pregnant women who delivered at the Department of Obstetrics, First Hospital of Lanzhou University, China, from January 2019 to August 2024 were included, with 403 cases in the experimental group and 403 matched controls (natural conception) based on admission month and gestational age (±7 days).ResultsAnalysis revealed that the experimental group exhibited significantly higher incidences of multiple gestations, anemia, postpartum hemorrhage, gestational hypertension, gestational diabetes mellitus, and intrahepatic cholestasis of pregnancy compared to the control group. In singleton pregnancy analysis, these differences persisted except for pelvic inflammation. The findings suggest that ART pregnancies may increase perinatal risks through factors such as embryo manipulation, hormonal interventions, and underlying maternal pathologies.ConclusionThis matched retrospective study highlights that IVF-ET pregnancies are associated with significantly higher risks of multiple gestations and obstetric complications, independent of multifetal pregnancies. The findings underscore the necessity of optimizing embryo transfer strategies, such as promoting single embryo transfer and implementing enhanced monitoring protocols for high-risk complications in resource-limited settings like Northwest China. This study provides regional evidence to support the development of tailored ART guidelines.

This study aimed to develop and validate a prediction model for preterm birth in patients with intrahepatic cholestasis of pregnancy. A retrospective analysis was conducted using demographic and clinical data from 370 patients with intrahepatic cholestasis of pregnancy. Multivariate logistic regression was used to screen predictive factors and construct the prediction model. The model’s discriminative ability, calibration, and clinical utility were evaluated. Six relevant independent predictors were identified: employment status, placental grading, pharmacotherapy status, lymphocyte count, neutrophil count, and serum total bile acid level. The constructed model demonstrated excellent discriminative ability and calibration in the training set, with an area under the curve of 0.85 (95% CI: 0.78–0.91) and a P value of 0.147 in the Hosmer-Lemeshow test. Decision curve analysis in the training set showed that the model provided clinical net benefit across a risk threshold range of 4% to 45%. This study established the first preterm birth prediction tool for intrahepatic cholestasis of pregnancy integrating multidimensional indicators. It provides an objective basis for early clinical identification of high-risk patients and has significant clinical value.

The purpose of this case report is to evaluate the outcomes of cholecystoenterostomy surgery following the diagnosis of bile duct obstruction in a cat based on clinical, ultrasonographic, and laboratory findings. The subject of this study was an 8-month-old Blue Point cat. The cat was brought Animal Hospital with complaints of vomiting 7-8 times a day, anorexia, and lethargy. A physical examination, ultrasonographic examination, and blood analysis were performed. Leukopenia, neutropenia hypokalemia, and hyperlactatemia and metabolic acidosis were diagnosed. Feline Panleukopenia Virus (FPV) antigen test for diagnosis of panleukopenia was also confirmed as positive. Ultrasonographic examination revealed dilatation of the gallbladder and thickening of its wall. There was a decrease in intestinal transport from the proximal part of the duodenum. Fluid electrolyte and supportive treatment was started for panleukopenia. The common bile duct (ductus choledochus) was incised, and a cholecystoenterostomy 1.0 catheter was placed to relieve the obstruction. The duct was sutured with 4/0 multifilament absorbable suture material. The patient was discharged after staying for one week. One week later, the cat was called for a follow-up to remove the sutures. No complications were observed, and the general condition of the patient was found to be good. The prognosis has been monitored for three month, with the patient's condition being assessed through monthly follow-up visits. This case demonstrates that cholecystoenterostomy can be a successful surgical option for the treatment of biliary obstruction in cats when appropriate case selection and careful postoperative monitoring are performed.

Rare genetic diseases (RGDs) affect individuals, families, and healthcare systems worldwide. Population-scale genomic data remain largely restricted to Western cohorts with an estimated 10,000 RGDs. South Asian populations remain underrepresented in molecular, clinical, and genomic databases. This study presents the first preliminary molecular genetic characterization of RGDs in the Punjabi population of Pakistan. Data were collected from the provincial RGD registry at the Punjab Thalassemia and Other Genetic Disorders Prevention and Research Institute (PTGDPRI), Lahore. Families diagnosed using next-generation sequencing (NGS) between 2021 and 2023 were enrolled. Structured questionnaires captured clinical, demographic, and socioeconomic information, and statistical and genetic analyses were performed to assess allele frequencies, and disease distribution. The registry included 167 families with 72 distinct RGDs, with a mean burden of 0.81 ± 0.24 affected children per family. Niemann–Pick disease (NP), progressive familial intrahepatic cholestasis (PFIC), and mucopolysaccharidosis (MPS) were the most common diseases. Consanguinity was observed in 89% of families, 77% of which involved first-cousin marriages, and was significantly associated with RGD incidence. Most families belonged to low-income groups despite high literacy rates, underscoring inequity in healthcare. The primary and secondary variants included 131 variants, including copy number variants (CNVs) and single nucleotide variants (SNVs), annotated as pathogenic, likely pathogenic, or variants of unknown significance (VUS) across 109 genes, including 24 South Asian-enriched variants. This study provides the first genomic and epidemiological overview of RGDs in the Punjabi population. The findings reveal how genetic, socioeconomic, and cultural factors converge to amplify the RGD burden and highlight the need for affordable molecular diagnostics, inclusive genomic databases, and regional genomic surveillance initiatives in South Asia.

Cholestatic liver disease disproportionately affects South Asians, yet they remain underrepresented in genomic studies. This recall study aimed to recall volunteers from a British South Asian genetic cohort that were considered to be at high risk of cholestatic liver disease based on their genotype or phenotype. Cases were defined as participants with rare (minor allele frequency <1%) heterozygous loss of function (LoF) variants in ABCB4 and ABCB11 (genotype re-call) or with a previous intrahepatic cholestasis of pregnancy (ICP) diagnosis (ICD10 O26.6). Cases were matched 1:1 to controls. A detailed medical and family history was taken along with fasting anthropometric and transient elastography (TE) measurements and blood samples. Out of 22 eligible volunteers, 9 (41%) participate in the recall (8/9 genotype and 1/9 phenotype recall). Among the recalled cases there are 5 ABCB4 LoF, 3 ABCB11 LoF, and 1 ICP phenotype. Of these, 5/9 (55.6%) exhibit findings suggestive of liver involvement (genotype re-call). Specifically, 2/5 (50%) have increased liver stiffness on TE with one also demonstrating abnormal liver blood tests. 2/5(40%) report at least 2 cholestatic symptoms and an additional 1/5 (20%) demonstrates abnormal liver blood tests without increased liver stiffness. This study shows findings suggestive of liver involvement in 55.6% of volunteers, underscoring the potential of rare heterozygous ABCB4/11 variants as markers for identifying individuals at high risk of developing cholestatic liver disease. Consequently, individuals at higher genetic risk benefit from monitoring, personalised treatment and prevention strategies for cholestatic liver disease.

Introduction: Hepatitis B virus (HBV) infection remains a major global health problem, presenting with diverse clinical manifestations. The cholestatic form of acute HBV is rare and may indicate underlying comorbidities or coinfections. Human immunodeficiency virus (HIV) coinfection can profoundly alter the clinical course of HBV, leading to more severe and prolonged disease. Case Presentation: We report a 39-year-old man who presented with fatigue, anorexia, jaundice, and dark urine. Laboratory evaluation revealed markedly elevated bilirubin and transaminase levels, confirming acute HBV infection (HBsAg+, anti-HBc IgM+, HBeAg+). Initial virological assessment demonstrated HBV DNA 257,000 IU/mL, HIV RNA 77,800 copies/mL, and a CD4+ T-cell count of 374/mm3 at presentation. Antiretroviral therapy (ART) (bictegravir/emtricitabine/tenofovir alafenamide) was initiated but temporarily withheld when total bilirubin peaked at 29 mg/dL on day 19. Ursodeoxycholic acid was also withdrawn due to its potential contribution to cholestasis. The patient experienced persistent hyperbilirubinemia lasting 95 days, which gradually resolved with supportive therapy. The ART was successfully reintroduced without recurrent hepatotoxicity or immune reconstitution inflammatory syndrome (IRIS). At the third month of therapy, the HIV RNA level had declined markedly, and CD4+ counts had improved. Conclusions: This case highlights that prolonged cholestatic acute HBV may serve as the initial clinical clue to underlying HIV infection, reinforcing the importance of routine HIV screening in atypical HBV presentations and careful evaluation for viral versus drug-induced liver injury during ART initiation.

Gallbladder amyloidosis is an exceptionally rare condition that may clinically mimic extrahepatic cholestasis. An 81-year-old man presented with persistent cholestatic jaundice and recurrent right upper quadrant pain. Laboratory evaluation showed conjugated hyperbilirubinemia and elevated cholestatic liver enzymes without signs of inflammation. Imaging studies, including ultrasound, MRCP, and CT, demonstrated gallstones and gallbladder wall thickening but no bile duct dilation or obstruction. Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound were unremarkable. Because of ongoing pain and cholestasis, laparoscopic cholecystectomy was performed. Histopathological examination revealed chronic fibrosing cholecystitis with marked submucosal and vascular deposition of amorphous eosinophilic material, showing apple-green birefringence under polarized light after Congo red staining, consistent with amyloid. Immunohistochemistry favored transthyretin (ATTR) amyloid deposition. Postoperatively, the patient recovered uneventfully with resolution of pruritus and normalization of bilirubin. Extensive systemic evaluation excluded generalized amyloidosis, indicating a localized form of gallbladder amyloidosis. This case underscores the importance of considering infiltrative diseases such as amyloidosis in the differential diagnosis of unexplained cholestatic jaundice, particularly when imaging fails to show mechanical obstruction. Recognition of this entity may prevent unnecessary invasive interventions and emphasizes the diagnostic value of histopathological confirmation following cholecystectomy.

An unusual case of Kippel-Trenaunay syndrome complicated with intrahepatic cholestasis of pregnancy and disseminated intravascular coagulation.

IntroductionAzathioprine (AZA) is an immunosuppressant approved for renal transplant rejection and rheumatoid arthritis. Recent FDA alerts have raised concerns about its link to intrahepatic cholestasis of pregnancy (ICP), a condition with serious maternal and fetal risks. This study used disproportionality analysis as a hypothesis-generating approach to evaluate the reporting association between AZA and ICP during pregnancy and to compare AZA with other drugs previously implicated in ICP.MethodsA retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) reports from 1968 to Q2 2024. Disproportionality analysis was performed using reporting odds ratios (RORs), with statistical significance defined as a lower limit of the 95% confidence interval (CI) >1 and at least three unique cases. Subgroup analyses were conducted by pregnancy status and underlying autoimmune indications, and comparative analyses were performed against drugs previously reported to induce ICP.ResultsAmong 35,576 AZA-related reports, 67 specifically documented ICP. A strong signal was detected for ICP ROR025 = 153.0; IC025 = 5.8; EBGM05 = 144.37), ranking among the highest AZA-associated adverse events. In pregnant women, ICP also showed a significant signal (ROR025 = 5.46; IC025 = 1.93; EBGM05 = 5.31). Subgroup analyses by indication revealed elevated risks in Crohn’s disease (ROR025 = 66.99; IC025 = 4.8; EBGM05 = 64.73), and Colitis ulcerative (ROR025 = 9.01; IC025 = 1.95; EBGM05 = 9.95). Comparative analyses demonstrated that AZA had a higher proportion of ICP cases than other drugs reported to induce ICP.ConclusionThis pharmacovigilance analysis identifies a disproportionality signal suggesting a possible association between AZA and intrahepatic cholestasis of pregnancy. These hypothesis-generating findings underscore the importance of cautious use and clinical vigilance when prescribing AZA to women of reproductive age.