Incidents and risk factors of biliary complications after orthotropic liver transplantation.

ABSTRACT: Biliary complications (BC) especially stenosis and strictures are the most common complications after orthotropic liver transplantation (OLT) procedure in adult recipients. The intention of this study was analyzed BC in 273 patients after OLT for the last 4 years in our department.Retrospective study of 273 patients underwent cadaveric donor liver transplantation between January 2014 and December 2017. Most of them (n = 268) have anastomosed bile duct in end to end, rest of them (n = 5) underwent hepaticojejunostomy. Statistical analysis was performed using Fischer exact test and Student t test. A P value <.05 was considered significant.BC were developed in 48/273 transplants (17.6%). The most frequent was biliary stricture (n = 42, 87.5%) followed by bile leak (n = 4, 8.3%) and choledocholitiasis (n = 2, 4.2%). Treatment was usually using endoscopic retrograde cholangiopancreatography. Recipients with hypotension during and after OLT treated by norepinephrine have a higher index of BC.Self-expanding metal stents implantation seems to be more effective than repeated balloon dilatation of anastomotic strictures with subsequent plastic biliary stent placement and associated with similar complication rate. Good fluid management against inotropic therapy may reduce risk of BC.

Choledochal cyst and aberrant biliary configuration along with situs inversus totalis: a case report.

Situs inversus totalis is the complete transpositioning of thoracoabdominal viscera into a mirror image of the normal configuration. Choledochal cyst is the congenital cystic dilation of the biliary tract. Both these conditions coexisting in a patient is extremely rare. We hereby present a case of type IC choledochal cyst in a patient with situs inversus totalis presenting with biliary sepsis secondary to choledocholithiasis. Also detailed are the management and operative strategies employed to deal with this rare entity.

Artificial intelligence in pancreaticobiliary endoscopy.

Artificial intelligence (AI) applications in health care have exponentially increased in recent years, and a few of these are related to pancreatobiliary disorders. AI-based methods were applied to extract information, in prognostication, to guide clinical treatment decisions and in pancreatobiliary endoscopy to characterize lesions. AI applications in endoscopy are expected to reduce inter-operator variability, improve the accuracy of diagnosis, and assist in therapeutic decision-making in real time. AI-based literature must however be interpreted with caution given the limited external validation. A multidisciplinary approach combining clinical and imaging or endoscopy data will better utilize AI-based technologies to further improve patient care.

Synergistic effects of cagA+ Helicobacter pylori co-infected with Opisthorchis viverrini on hepatobiliary pathology in hamsters.

Human liver fluke infection caused by Opisthorchis viverrini is associated with several biliary diseases including cholangiocarcinoma (CCA). Recently, it was discovered that the liver fluke is a reservoir of Helicobacter pylori, particularly the cagA-positive strain (cytotoxin-associated gene A) in its gut. Given that two carcinogenic pathogens are associated with CCA development, however, the role of cagA-positive H. pylori in opisthorchiasis has not been clarified. The present study was therefore aimed to investigate histopathological changes of the biliary system in hamsters co-infected with O. viverrini and cagA-positive H. pylori or O. viverrini and cagA-negative H. pylori, with controls of O. viverrini, cagA-positive H. pylori, or cagA-negative H. pylori alone, over time. Major histopathological changes were systematically investigated. All pathological features were quantified/semi-quantified and compared among the experimental groups. The results showed that O. viverrini infection groups (O. viverrini, cagA-positive H. pylori and cagA-negative H. pylori) showed a high degree of eosinophil and mononuclear cell infiltration, lymphoid aggregation and granuloma. Specifically, O. viverrini co-infected with cagA-positive H. pylori presented significantly higher inflammatory scores than O. viverrini and O. viverrini with cagA-positive H. pylori. Proliferation and adaptive lesions such as hyperplasia, goblet cell metaplasia and dysplasia were detected only in O. viverrini infection groups. Dysplasia, the precancerous lesion of CCA, was observed in the first-order bile ducts, especially where the inflammation existed and was found earlier and more severely in O. viverrini with cagA-positive H. pylori than other groups. Similarly, the BrdU (bromodeoxyuridine) proliferation index was significantly higher in O. viverrini co-infected with cagA-positive H. pylori than O. viverrini and O. viverrini with cagA-negative H. pylori groups. Periductal fibrosis was a prominent histopathologic feature in chronic infection in O. viverrini infection groups. Multiple logistic regression showed that O. viverrini co-infected with cagA-positive H. pylori and the duration of infection were the most important factors associated with periductal fibrosis (OR 3.02, 95% CI 1.02-9.29, p = 0.04 and OR 3.82, 95% CI 2.61-5.97, p<0.001). This study demonstrates that the liver fluke co-infected with cagA-positive H. pylori induces severe biliary pathology that may predispose to cholangiocarcinogenesis.

Cholangiopathy and Biliary Fibrosis in Cyp2c70-Deficient Mice Are Fully Reversed by Ursodeoxycholic Acid.

BACKGROUND AND AIMS: Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes. Cyp2c70-ablation in mice prevents synthesis of mouse/rat-specific muricholic acids (MCAs), but potential (patho)physiological consequences of their absence are unknown. We therefore assessed age- and gender-dependent effects of Cyp2c70-deficiency in mice. METHODS: The consequences of Cyp2c70-deficiency were assessed in male and female mice at different ages. RESULTS: Cyp2c70-/- mice were devoid of MCAs and showed high abundances of chenodeoxycholic and lithocholic acids. Cyp2c70-deficiency profoundly impacted microbiome composition. Bile flow and biliary BA secretion were normal in Cyp2c70-/- mice of both sexes. Yet, the pathophysiological consequences of Cyp2c70-deficiency differed considerably between sexes. Three-week old male Cyp2c70-/- mice showed high plasma BAs and transaminases, which spontaneously decreased thereafter to near-normal levels. Only mild ductular reactions were observed in male Cyp2c70-/- mice up to 8 months of age. In female Cyp2c70-/- mice, plasma BAs and transaminases remained substantially elevated with age, gut barrier function was impaired and bridging fibrosis was observed at advanced age. Addition of 0.1% ursodeoxycholic acid to the diet fully normalized hepatic and intestinal functions in female Cyp2c70-/- mice. CONCLUSION: Cyp2c70-/- mice show transient neonatal cholestasis and develop cholangiopathic features that progress to bridging fibrosis in females only. These consequences of Cyp2c70-deficiency are restored by treatment with UDCA, indicating a role of BA hydrophobicity in disease development.

Cholangiopancreatoscopy: Expanding the Diagnostic Indications of Endoscopic Retrograde Cholangiopancreatography.

Besides the adverse effects associated with endoscopic retrograde cholangiopancreatography (ERCP), indirect visualization of the biliopancreatic system through fluoroscopy has limited its diagnostic and therapeutic efficacy. Direct visualization through cholangiopancreatoscopy may overcome this limitation and allow the resolution of many dilemmas related to the diagnostic and therapeutic drawbacks of ERCP. Herein, we discuss the current indications of single-operator cholangioscopy (SOC) concerning the diagnostic interventions within the biliopancreatic system. The current role of SOC in the diagnosis of pancreatobiliary stenosis, primary sclerosing cholangitis, intraductal papillary mucinous neoplasm, and pre-surgical mapping of neoplastic lesions were reviewed. There is growing data in the literature supporting the early implementation of SOC in the diagnostic algorithm of pancreatobiliary diseases. In selected cases, this could prevent diagnostic delay and reduce the risks and costs related to repeated ERCPs. This potential characterizes SOC as safety and cost-effective.

Antenatally detected liver and biliary pathology.

Liver and biliary pathology in the neonate are rare and include a broad range of structural, neoplastic, infectious, genetic, and metabolic diseases. While most conditions present postnatally, antenatal detection is increasing given recent advances in antenatal imaging capabilities. In certain structural or obstructive liver diseases, antenatal detection now proves essential to help guide treatment and prevent morbidity. We review the epidemiology, pathophysiology, common antenatal diagnostic findings, and recommendations for surgical liver and biliary pathology in the neonate.

Fine-scale visualizing the hierarchical structure of mouse biliary tree with fluorescence microscopy method.

The liver is a vital organ and the hepatic lobule serves as the most basic structural and functional unit which is mainly assembled with parenchymal cells including hepatocytes and biliary epithelial cells. The continuous tubular arrangement of biliary cells which constitutes the biliary tracts is critical for liver function, however, the biliary tracts are often disrupted in many liver diseases such as cirrhosis and some congenital disorders. Visualization of the biliary tracts in fine-scale and three-dimension will help to understanding the structure basis of these liver diseases. In the present study, we established several biliary tract injury mouse models by diet feeding, surgery or genetic modification. The cytoplasm and nuclei of the parenchymal cells were marked by active uptake of fluorescent dyes Rhodamine B (red) and Hoechst (blue), respectively. After the removal of liver en bloc, the biliary tracts were retrogradely perfused with green fluorescent dye, fluorescein isothiocyanate (FITC). The liver was then observed under confocal microscopy. The fine-scale and three-dimensional (3D) structure of the whole biliary tree, particularly the network of the end-terminal bile canaliculi and neighboring hepatocytes were clearly visualized. The biliary tracts displayed clear distinct characteristics in normal liver and diseased liver models. Taken together, we have developed a simple and repeatable imaging method to visualize the fine-scale and hierarchical architecture of the biliary tracts spreading in the mouse liver.

[Obesity and Pancreatobiliary Disease].

Obesity has become a major medical and public health problem worldwide. Recent studies have shown that obesity is a chronic disease that is associated with many diseases, such as gallstone disease, acute pancreatitis, fatty liver, and digestive cancer. Obesity is also a risk factor for the formation of cholesterol gallstones. Clinical and epidemiological studies have suggested that obesity is positively associated with the risk of gallbladder cancer. Obesity may modulate the lipid and endogenous hormones metabolism, affect gallbladder motility, increase the risk of gallstones, and increased the risk of gallbladder cancer. In addition, obesity has been considered a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Obese patients develop systemic and local complications of acute pancreatitis more frequently. Several epidemiologic studies have suggested an association of pancreatic cancer with high body mass and lack of physical activity. This study reviewed the literature on obesity and pancreatobiliary disease in terms of epidemiology and mechanism.

Efficacy and Safety of Short-type Single Balloon Enteroscopy-assisted Peroral Direct Cholangioscopy Using an Ultra-slim Endoscope in Patients With Surgically Altered Anatomy.

BACKGROUND: The efficacy and safety of peroral direct cholangioscopy (PDCS) in patients with surgically altered anatomy (SAA) are unclear. The present study aimed to evaluate the efficacy and safety of short-type single balloon enteroscope (s-SBE)-assisted PDCS using an ultra-slim endoscope in patients with SAA. MATERIALS AND METHODS: We retrospectively analyzed 12 sessions of PDCS performed in 8 patients with surgically altered gastrointestinal or pancreatobiliary anatomy between November 2017 and September 2019 at our institution. Endoscopic retrograde cholangiopancreatography using s-SBE was initially performed. Subsequently, the s-SBE was exchanged for an ultra-slim endoscope through an overtube with an inflated balloon to perform PDCS. We analyzed the success rates and adverse events resulting from the procedure. RESULTS: Six patients had biliary stones and 2 had biliary strictures. The types of reconstruction were Roux-en-Y choledochojejunostomy (n=5), Billroth II gastrectomy (n=2), and Roux-en-Y gastrectomy (n=1). Biliary insertion of the ultra-slim endoscope was successful in all 12 sessions. Biliary interventions included electronic hydraulic lithotripsy in 5 sessions, stone removal using basket catheter in 3 sessions, biopsy in 2 sessions, and diagnosis of no residual stones in 2 sessions. Complete stone removal was finally achieved in all 6 patients with biliary stones. Biliary strictures in 2 patients were diagnosed as adenocarcinoma following a biopsy. The adverse events were cholangitis of mild severity in 3 sessions. CONCLUSION: S-SBE-assisted PDCS using an ultra-slim endoscope was useful and safe in patients with SAA, although care should be taken to avoid adverse events.

Donor hepatectomy time influences ischemia-reperfusion injury of the biliary tree in donation after circulatory death liver transplantation.

BACKGROUND: Donor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. METHODS: First, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportional-hazards regression analyses were used to assess the influence of hepatectomy time on the development of non-anastomotic biliary strictures. RESULTS: Livers with severe histological bile duct injury had a higher median hepatectomy time (P = .03). During normothermic machine perfusion, livers with a hepatectomy time >50 minutes had lower biliary bicarbonate and bile pH levels. In the nationwide retrospective study, donor hepatectomy time was an independent risk factor for non-anastomotic biliary strictures after donation after circulatory death liver transplantation (Hazard Ratio 1.18 per 10 minutes increase, 95% Confidence Interval 1.06-1.30, P value = .002). CONCLUSION: Donor hepatectomy time negatively influences histological bile duct injury before normothermic machine perfusion and bile composition during normothermic machine perfusion. Additionally, hepatectomy time is a significant independent risk factor for the development of non-anastomotic biliary strictures after donation after circulatory death liver transplantation.

Pancreatic and biliary tract involvement in IgG4-related disease.

The diagnosis and treatment of pancreatic and biliary tract involvement in IgG4 disease can be challenging for physicians. A French series shows that the pancreas is the most frequently involved organ in systemic IgG4 disease. Pancreatitis may be found in more than 50% of patients with IgG4 disease and the biliary tract is involved in one third. Pancreatic or biliary involvement may be isolated, metachronous or synchronous of other IgG4-related organ injuries. Pancreatitis related to IgG4 disease is called autoimmune pancreatitis (AIP) type 1. The diagnosis is mainly suspected in the presence of symptoms and morphological features. Changes observed on conventional imaging are not typical and are usually similar to lesions observed in autoimmune pancreatitis type 2. AIP type 1 can also sometimes have a clinical or morphological presentation that mimics pancreatic cancer, especially pseudo-tumoral forms, associated with obstructive jaundice, weight loss and fatigue. Thus, the first challenge is to confirm the diagnosis of autoimmune pancreatitis and to exclude cancer. The AIP type must then be determined to decide on the most appropriate treatment.

Brush Cytology Performance for the Assessment of Biliopancreatic Strictures.

INTRODUCTION: Brush cytology is commonly used during endoscopic retrograde cholangiopancreatography for the diagnostic evaluation of biliopancreatic strictures. However, since the overall sensitivity of brush cytology is poor, the exclusion of malignancy is difficult. Recognition of factors related to the patient, technique or lesion may help improve the diagnostic yield of brush cytology. The objective of this study was to evaluate the diagnostic yield of brush cytology in the assessment of biliopancreatic strictures and identify predictive factors associated with a positive diagnosis of malignancy. METHODS: Retrospective study that evaluated all consecutive patients that underwent brush cytology for the investigation of biliopancreatic strictures in a tertiary center, between January 2012 and January 2018. RESULTS: One hundred and sixty-five patients that underwent 182 procedures were included. A diagnosis of malignancy was confirmed in 110 patients (66.7%), of whom 62 had positive brush cytology (sensitivity 53.7%, specificity 98.5%, accuracy 69.8%). On the multivariate analysis, age ≥68 years (OR 4.83, 95% CI 1.04-22.37) and lesions suspicious of metastasis on cross-sectional imaging (OR 8.58, 95% CI 1.70-43.38) were independently associated with a positive result. Subanalysis of the patients presenting with these two factors (n = 26) revealed an increase in the diagnostic yield (sensitivity 80.8%). CONCLUSION: Age ≥68 years and lesions suspicious of metastasis on cross-sectional imaging are independent factors associated with a positive result. Patient selection taking these factors into account may increase the diagnostic yield of brush cytology.

Prospective randomized trial of a new multibending versus conventional ultra-slim endoscope for peroral cholangioscopy without device or endoscope assistance (with video).

BACKGROUND AND AIMS: Currently available peroral cholangioscopy (POC) is a duodenoscopy-assisted procedure that does not involve directly inserting an endoscope into the biliary tree. A prototype multibending (MB) ultra-slim endoscope has been developed as a dedicated cholangioscope to overcome the technical difficulties of direct POC. In this study, we evaluated the efficacy of the new MB ultra-slim endoscope compared with a conventional ultra-slim endoscope for free-hand insertion of an endoscope into the bile duct for direct POC without the assistance of accessories. METHODS: Ninety-two patients with biliary disease requiring diagnostic and/or therapeutic direct POC were assigned randomly to groups examined using an MB ultra-slim endoscope (MB group, n=46) versus a conventional ultra-slim endoscope (conventional group, n=46). The primary outcome was the technical success of free-hand insertion of the endoscope during direct POC, defined as successful insertion of the endoscope through the ampulla of Vater and advancement of the endoscope up to the bifurcation or to the obstructed segment of the biliary tree without any accessories within 15 minutes. RESULTS: Free-hand biliary insertion of the endoscope for direct POC was technically successful in 41 patients (89.1%) in the MB group, which was significantly higher than the rate (14 patients, 30.4%) in the conventional group (P < .001). The procedure time (mean ± standard deviation) of direct POC using free-hand biliary insertion of the endoscope was significantly shorter in the MB group than in the conventional group (3.2 ± 1.8 vs 6.0 ± 3.0 minutes, P = .004). Adverse events were observed in 3 patients (6.5%) in the MB group and 2 patients (4.3%) in the conventional group (P = .500), all of whom were treated conservatively. The technical success rates of the diagnostic or therapeutic intervention were not significantly different between the 2 groups in patients undergoing successful direct POC. CONCLUSIONS: Free-hand biliary insertion of the MB ultra-slim endoscope showed a high technical success rate without severe adverse events and effectively decreased procedure time compared with a conventional ultra-slim endoscope. Direct POC using the MB ultra-slim endoscope can be used for novel diagnostic and therapeutic procedures of the biliary tree without the assistance of another endoscope or accessory. (Clinical trial registration number: NCT02189421.).

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

Association of Arterial Hypertension with Hepatobiliary Pathology: The Occurrence of Comorbidity and Features of Metabolic Processes.

Comorbidity of hypertension and hepatobiliary pathology has negative medical and social consequences, including an increase in the indicators of hospital admissions, disability and mortality. OBJECTIVE: The aim was to study the occurrence of hypertension combined with hepatobiliary diseases depending on social status, gender and age in 2003-2017 and their influence on indicators of metabolic processes in patients with a therapeutic profile. METHODS: A cross-sectional study using the inpatients' medical record database of the clinic of Federal Research Centre for Basic and Translational Medicine (Novosibirsk, Russia), which collects demographics, diagnoses (using ICD-10 codes), procedures and examinations of all inpatients from 2003-2017 was conducted. The incidence of comorbidity of hypertension and hepatobiliary pathology depending on age, gender and social status, based on the analysis of 13496 medical records was examined. A comparative analysis of biochemical parameters characterizing the main types of metabolism (lipid, protein, carbohydrate and purine) was carried out in 3 groups of patients: with hypertension; with hepatobiliary pathology, and with a combined pathology. RESULTS: During the years 2003-2005, there was the greatest frequency of this comorbidity in workers, in women, in the age group 60 years and older. In 2009-2017, the highest incidence was observed in the male administrative staff. In patients with this comorbidity, more pronounced changes in carbohydrate, protein, lipid and purine metabolism were found in comparison with groups of patients with isolated diseases. CONCLUSION: The results highlight the need to improve the system of prevention and treatment of comorbidity taking into account sex, age, occupation and features of metabolism.

Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.

Primary biliary cholangitis (PBC) primarily targets cholangiocytes and is characterized by liver fibrosis and biliary proliferation. Activation of the secretin (Sct)/secretin receptor (SR) axis, expressed only by cholangiocytes, increases biliary proliferation, liver fibrosis, and bicarbonate secretion. We evaluated the effectiveness of SR antagonist treatment for early-stage PBC. Male and female dominant-negative TGF-ß receptor II (dnTGF-ßRII) (model of PBC) and wild-type mice at 12 wk of age were treated with saline or the SR antagonist, Sec 5-27, for 1 wk. dnTGF-ßRII mice expressed features of early-stage PBC along with enhanced Sct/SR axis activation and Sct secretion. dnTGF-ßRII mice had increased biliary proliferation or senescence, inflammation, and liver fibrosis. In dnTGF-ßRII mice, there was increased microRNA-125b/TGF-ß1/TGF-ß receptor 1/VEGF-A signaling. Human early-stage PBC patients had an increase in hepatobiliary Sct and SR expression and serum Sct levels. Increased biliary Sct/SR signaling promotes biliary and hepatic damage during early-stage PBC.-Kennedy, L., Francis, H., Invernizzi, P., Venter, J., Wu, N., Carbone, M., Gershwin, M. E., Bernuzzi, F., Franchitto, A., Alvaro, D., Marzioni, M., Onori, P., Gaudio, E., Sybenga, A., Fabris, L., Meng, F., Glaser, S., Alpini, G. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis.

[Hepatobiliary Manifestation of Inflammatory Bowel Disease].

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Spontaneous Cholangiofibrosis in a Wistar Rat.

In a 2-year carcinogenicity study, we identified a spontaneous cholangiofibrosis in a control male Wistar rat. This lesion has long been considered as a compound-related change, with no spontaneous cases reported in the Wistar rat. In addition to routine hematoxylin and eosin stains evaluation, we applied Masson's trichrome staining, Alcian blue-periodic acid-Schiff staining, and OV-6 immunohistochemistry staining. The special staining demonstrated the fibrous component in the interstitium and intestinal metaplasia of the epithelium (presence of goblet cells), while the positive anti-OV-6 reaction indicated the bile duct origin of the epithelium. These results help to confirm the diagnosis of cholangiofibrosis in this case. We report this rare case to alert pathologists that spontaneous cholangiofibrosis does occur in Wistar rats.