OBJECTIVE: This study addressed the challenge of detecting and classifying the severity of ductopenia in parotid glands, a structural abnormality characterized by a reduced number of salivary ducts, previously shown to be associated with salivary gland impairment. The aim of the study was to develop an automatic algorithm designed to improve diagnostic accuracy and efficiency in analyzing ductopenic parotid glands using sialo cone-beam CT (sialo-CBCT) images.
METHODS: We developed an end-to-end automatic pipeline consisting of three main steps: (1) region of interest (ROI) computation, (2) parotid gland segmentation using the Frangi filter, and (3) ductopenia case classification with a residual neural network (RNN) augmented by multidirectional maximum intensity projection (MIP) images. To explore the impact of the first two steps, the RNN was trained on three datasets: (1) original MIP images, (2) MIP images with predefined ROIs, and (3) MIP images after segmentation.
RESULTS: Evaluation was conducted on 126 parotid sialo-CBCT scans of normal, moderate, and severe ductopenic cases, yielding a high performance of 100% for the ROI computation and 89% for the gland segmentation. Improvements in accuracy and F1 score were noted among the original MIP images (accuracy: 0.73, F1 score: 0.53), ROI-predefined images (accuracy: 0.78, F1 score: 0.56), and segmented images (accuracy: 0.95, F1 score: 0.90). Notably, ductopenic detection sensitivity was 0.99 in the segmented dataset, highlighting the capabilities of the algorithm in detecting ductopenic cases.
CONCLUSIONS: Our method, which combines classical image processing and deep learning techniques, offers a promising solution for automatic detection of parotid glands ductopenia in sialo-CBCT scans. This may be used for further research aimed at understanding the role of presence and severity of ductopenia in salivary gland dysfunction.

Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management.

Intrahepatic cholestasis of pregnancy (ICP) typically presents in the second half of pregnancy. Severe ICP is associated with increased risk of stillbirth. Little is known regarding elevated bile acids in the first trimester. We present a case of severely elevated bile acids in the first trimester, resistant to conservative management, in a patient with pre-existing cholestatic liver disease and aortic valve disease requiring anticoagulation. Therapeutic plasma exchange was used. In those with pre-existing cholestatic disease, early bile acid elevation is likely distinct from ICP, and conservative strategies may not be useful. In addition, therapeutic enoxaparin appears safe in therapeutic plasma exchange.

Vanishing bile duct syndrome (VBDS) has been postulated that may be related to Hodgkin\'s lymphoma (HL). In the present study, we present a 75-year-old male patient with HL who received chemotherapy but has not received any radiotherapy. The patient\'s condition worsened in further days, and he died with the diagnosis of cirrhosis and hepatic failure.

Vanishing bile duct syndrome is a rare, acquired disease that has been described in different pathologic conditions\' including adverse drug reactions, autoimmune diseases, graft vs host disease, and neoplasms. It is a condition characterized by progressive loss of intrahepatic bile ducts leading to ductopenia and cholestasis. Here we report a 27-year-old female who presented with jaundice and cholestatic hepatitis and was finally diagnosed with vanishing Bile duct syndrome secondary to Hodgkin lymphoma. Physicians need to consider a range of differential diagnoses, especially malignancies, in suspected cases of vanishing bile duct syndrome.

About 15% to 28% of patients treated with thiopurines experienced adverse drug reactions, such as haematological and hepatic toxicities. Some of these related to the polymorphic activity of the thiopurine S-methyltransferase (TPMT), the key detoxifying enzyme of thiopurine metabolism. We report here a case of thiopurine-induced ductopenia with a comprehensive pharmacological analysis on thiopurine metabolism. A 34-year-old woman, with a medical history of severe systemic lupus erythematosus with recent introduction of azathioprine therapy, presented with mild fluctuating transaminase blood levels consistent with a hepatocellular pattern, which evolved to a cholestatic pattern over the next weeks. A blood thiopurine metabolite assay revealed low 6-thioguanine nucleotides (6-TGN) level and a dramatically increased 6-methylmercaptopurine ribonucleotides (6-MMPN) level, together with an unfavourable [6-MMPN:6-TGN] metabolite ratio and a high TPMT activity. After a total of about 6 months of thiopurine therapy, a transjugular liver biopsy revealed a ductopenia, and azathioprine discontinuation led to further clinical improvement. In line with previous reports from the literature, our case supports the fact that ductopenia is a rare adverse drug reaction of azathioprine. The mechanism of reaction is unknown but may involve high 6-MMPN blood level, due to unusual thiopurine metabolism (switched metabolism). Early therapeutic drug monitoring with measurement of 6-TGN and 6-MMPN blood levels may help physicians to identify patients at risk of similar duct injury.

Vanishing bile duct syndrome (VBDS) is a rare condition characterized by progressive loss, destruction, and disappearance of the intra-hepatic bile ducts, leading to cholestasis and ductopenia. The exact mechanism of development of VDBS has not been established yet. Diagnosis of VBDS mainly relies on clinical and disease related presentations, but liver biopsy is compulsory for diagnosis. Due to the low incidence reported in the literature, a standardized treatment of VDBS has not been established; hence, this rare condition must be managed at a tertiary liver referral center. Here, we report the management and treatment of VBDS of an 81-year-old woman without any history of exposure to antibiotics, neoplasms, etc.

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One aetiology is drug-induced liver injury. Cloxacillin, an antistaphylococcal penicillin, typically causes \"bland\" cholestasis. We present the first case of cloxacillin-induced acute ductopenia or VBDS and a review of published cloxacillin-induced liver injuries. A 66-year-old woman with no prior liver disease, but known penicillin allergy, was treated for postcarotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a 2-week history of weakness and jaundice. Laboratory work-up showed elevated liver enzymes with a cholestatic pattern, hyperbilirubinemia and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation and ductopenia with epithelial injury, but no ductular reaction. Two months later she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure 4 months later. Four additional articles were found with histopathologic descriptions of cloxacillin-related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10-60 days. Cloxacillin-induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described \"bland\" cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.

Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood.
We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined.
Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed.
Two novel pathogenic ABCB4 variants were identified: c.620 T > G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis.
Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.

BACKGROUND: Hepatic dysfunction in patients with classical Hodgkin lymphoma (cHL) is of multifactorial aetiology. Prompt evaluation with laboratory tests and imaging methods is sufficient for diagnosis in most cases. Intrahepatic cholestasis and vanishing bile duct syndrome (VBDS) may complicate cHL as rare paraneoplastic phenomena. Liver biopsy provides crucial evidence of cholestasis, and ductopenia, if present, confirms the diagnosis of VBDS.
METHODS: We report on a cHL patient that presented with jaundice and bulky mediastinal disease and unfold the therapeutic dilemmas we confronted. Marked hyperbilirubinemia was successfully reversed with brentuximab vedotin (BV) at a dose of 1.2 mg/kg and the patient was subsequently treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) at full doses, achieving complete metabolic response. A literature review of intrahepatic cholestasis in cHL is also presented based on currently available data with focus on treatment options and clinicopathologic associations.
CONCLUSIONS: VBDS and intrahepatic cholestasis are rare and potentially fatal complications of cHL. Their prompt recognition and appropriate treatment can dramatically affect cHL patients\' outcome. BV, used at a reduced dose as a bridging therapy, should be considered as a high-priority treatment plan in these challenging cases.