Intrahepatic Biliary Cystadenoma With Colonic Adenomatous Polyps in a Patient With Chronic Hepatitis B: A Case Report and Literature Review

Background: Biliary cystadenomas are rare cystic tumors of the bile duct system that are mostly benign but also have the possibility of malignant transformation. Biliary cystadenomas mostly occur in the intrahepatic bile ducts and are more common in middle-aged women. Due to non-specific radiology, preoperative diagnosis is difficult and is usually performed by postoperative pathology. Complete resection is the best treatment option, and the postoperative prognosis is good.Case Description: This study reports a case of a patient with biliary cystadenoma who was diagnosed with simultaneous chronic hepatitis B and colon (hepatic flexure) adenomatous polyps. The patient presented to the doctor because of abdominal pain, and a blood test showed hepatitis B. Computed tomography revealed both right liver and colonic lesions. Colonoscopy revealed polyps, and the postoperative pathological diagnosis was adenomatous polyps. Laparoscopic resection of the right liver tumor was performed, and it was diagnosed as hepatobiliary cystadenoma by postoperative pathological analysis combined with immunohistochemistry.Conclusion: In patients with chronic hepatitis, the shape of biliary cystadenoma may not be very typical, and it is necessary to combine this with immunohistochemistry for diagnosis. When multiple lesions are detected in the painful area, the diagnosis of each lesion and its treatment sequence are worthy of consideration. Under normal circumstances, the prognosis of biliary cystadenoma is good; however, in patients with chronic hepatitis B, more cases need to be observed for verification.

Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency

Background Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. Methods To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. Results BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. Conclusion These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.

Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts.

Three-dimensional scaffolds decellularized from native organs are a promising technique to establish engineered liver grafts and overcome the current shortage of donor organs. However, limited sources of bile duct cells and inappropriate cell distribution in bioengineered liver grafts have hindered their practical application. Organoid technology is anticipated to be an excellent tool for the advancement of regenerative medicine. In the present study, we reconstructed intrahepatic bile ducts in a rat decellularized liver graft by recellularization with liver ductal organoids. Using an ex vivo perfusion culture system, we demonstrated the biliary characteristics of repopulated mouse liver organoids, which maintained bile duct markers and reconstructed biliary tree-like networks with luminal structures. We also established a method for the co-recellularization with engineered bile ducts and primary hepatocytes, revealing the appropriate cell distribution to mimic the native liver. We then utilized this model in human organoids to demonstrate the reconstructed bile ducts. Our results show that liver ductal organoids are a potential cell source for bile ducts from bioengineered liver grafts using three-dimensional scaffolds.

Corona again? SSC after a severe COVID-disease

Secondary sclerosing cholangitis (SSC) is a severe complication of intensive care treatment in critically ill patients. It is characterized by rapid onset and severe chlolestasis with elevation of gGT. In contrast to primary sclerosing cholangitis, SSC-CIP has a distinct and timely well defined trigger and can have a rapid progress to cirrhosis and liver failure. In context of the COVID-19-pandemic, there are reports about patients, who developed SSC after a severe COVID-infection and intensive care treatment.We report on a 62-year old patient without any relevant pre-existing illnesses, who suffered from severe COVID-19 pneumonia with the need for long term ventilation. In the course of the disease he developed a critical-illness-polyneuropathy a pronounced cholestasis. After recovery from COVID-pneumonia, the PNP regressed but the cholestasis progressed. MRCP showed only irregular intrahepatic bile ducts, while EUS showed echogenic intraductal longitudinal structures characteristic for intraductal casts and for SSC-CIP. This was confirmed with ERC, where the complete necrotic bile ducts could be extracted and retrieved for histological and molecular analysis.The patient was included in a scheduled ERC-program to prevent a progress of SSC and the concomitant cirrhosis.SSC is an often missed diagnosis, which obviously can also occur in COVID-patients. In case of elevated liver function tests with cholestasis, EUS might be the key diagnostic method to characterize intraductal casts and identify those patients who should undergo ERC.

Caroli's disease (clinical observation)

In their medical practice doctors deal with rare diseases which present difficulties in making a clinical diagnosis, in this case additional diagnostic methods are required. One of these diseases is Caroli's disease (syndrome), characterized by cystic enlargement of the intrahepatic bile ducts with frequent formation of intrahepatic stones. Taking into account the difficulties of early diagnosis, we present our own observation.

Secondary sclerosing cholangitis: a lesser known side effect of pembrolizumab therapy

Introduction/Objective Immune check-point inhibitors have increasingly taken hold as mainstays of various cancer treatments, revolutionizing outcomes for individuals diagnosed with terminal malignancy. Hepatotoxicity is reported to occur in 2-10% patients, predominantly manifesting as a mixed cholestatic hepatitis pattern of injury. Cholangitis is a rare immune-mediated adverse event (irAE). We present a case of pembrolizumab-induced secondary sclerosing cholangitis presenting with multiple biliary strictures. Early recognition is crucial as these cases are resistant to treatment with steroids. Methods/Case Report 82-year-old woman with recurrent, metastatic, high grade urothelial carcinoma status post cystectomy and neoadjuvant chemotherapy, presented with new onset obstructive jaundice (alkaline phosphatase 958 U/L, aspartate aminotransferase of 331 U/L, alanine aminotransferase of 422 U/L, and total bilirubin of 19.8 mg/dL) following two weeks of pembrolizumab therapy. MRCP suggested intrahepatic biliary ductal dilation. ERCP showed multiple strictures involving hepatic bifurcation, left, right and intrahepatic ducts with beaded intrahepatic bile ducts. Liver biopsy showed expanded portal tracts with mixed inflammatory infiltrate, extensive bile duct injury, neutrophilic cholangitis, ductular proliferation, and perivenular cholestasis (10% dropout) concerning for mechanical obstruction. CK7 did not show ductopenia and immunostain IgG4 was negative. All autoimmune work-up was negative. Liver enzymes continued to rise despite multiple therapeutic stents, drains, high-dose corticosteroids, ursodiol and mycophenolate mofetil. The patient died five months later. Results (if a Case Study enter NA) NA Conclusion Pemrolizumab-induced secondary sclerosing cholangitis is a rare, hence under-recognized, adverse effect of check point inhibitor-mediated hepatotoxicity. It is important to recognize this association, as it has limited benefit from steroid therapy. Our finding of pembrolizumab-related SC adds to the growing body of literature of immune check-point inhibitor-related hepatobiliary injury and calls for further characterization of PD-1/PD-L1 inhibitor SC and its clinical implications.

Congenital hepatic fibrosis and its mimics: a clinicopathologic study of 19 cases at a single institution

Background Congenital hepatic fibrosis (CHF) is a rare inherited form of ductal plate malformation associated with polycystic kidney disease. The diagnosis requires histopathologic confirmation, but can be challenging to distinguish from other undefined fibrocystic liver diseases. We aimed to describe the clinicopathologic features of congenital hepatic fibrosis (CHF), with comparisons to other entities that may clinically and/or histologically mimic CHF. Methods Nineteen cases that carried a clinical and/or histologic impression of CHF were identified at our institution, of which the histology was reassessed and reappraised into two categories: CHF (n=13) and mimics (n=6). The clinicopathologic features between the two groups were analyzed and compared. Results The CHF group was further sub-classified into those with clinical suspicion (CHF-c, n=8) and those as incidental histology findings (CHF-i, n=5). Patients of CHF-i were much older than CHF-c or mimics (P<0.05). Male and female were equally affected. Six of 8 CHF-c (66.7%) had concurrent kidney diseases, including 5 polycystic kidney diseases. Five of 6 mimics (83.3%) had various kidney diseases, including nephronophthisis, Alport syndrome, renal agenesis, and nephrolithiasis. None of the CHF-i patients had kidney disease, but 3 were associated with hepatic carcinomas. Histology analysis demonstrated characteristic triads (bile duct abnormalities, portal vein hypoplasia, and fibrosis) in all CHF cases. One mimic had paucity of intrahepatic bile ducts, while the other 5 mimics showed abnormal portal veins and nodular regenerative hyperplasia consistent with hepatoportal sclerosis (HPS). Conclusions Our study demonstrates classic histology triad of CHF despite a wide spectrum of clinical presentations. HPS is unexpectedly a clinical mimicker of CHF, which can be distinguished histologically.

Multi-Organ Involvement of Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition of unknown etiology, with presumed autoimmune mechanisms. It is characterized by high levels of IgG4 and variable clinical manifestations. It can involve one or multiple organs. Herein, we reported the case of a 62-year-old man with three organs involvement. He initially presented with recurrent jaundice. Laboratory analysis revealed cholestasis, high gamma-globulin levels, renal failure, and proteinuria. Abdominal Magnetic Resonance Imaging (MRI) showed segmental strictures of the left intrahepatic bile ducts and the wirsung duct with an increased volume of the pancreas and diffuse bilateral enlargement of the kidneys. Laboratory tests revealed high IgG4 levels (770 mg/dL). Based on the biological and radiological findings, we have suggested the diagnosis of systemic IgG4-related disease involving bile ducts, the pancreas, and probably the kidneys. Renal biopsy revealed lymphoplasmacytic infiltrate and fibrosis, but no IgG4-positive cell. The patient received corticosteroid therapy with a complete resolution of all symptoms and a rapid normalization of all blood tests. The present case underlines the complexity of IgG4-RD because of its variable clinical presentation. The diagnosis is challenging and should be carefully assessed for possible multi-organ involvement.

Prevention of structural changes in liver in patients with chronic acalculous cholecystitis

Chronic acalculous cholecystitis is the cause of violations of the functional state of the liver in the form of stagnation in the intrahepatic bile ducts and a decrease in the activity of hepatocytes and is considered within the framework of a single pathology of the hepatobiliary tract. Complex therapy with the inclusion of the drug ademetionine, which in addition to the hepatoprotective effect affects the outflow of intrahepatic bile, contributes to the restoration of the detected violations.