scholarly journals Case Report: A Novel Homozygous Variant Identified in a Chinese Patient With Benign Recurrent Intrahepatic Cholestasis-Type 1

2021 ◽  
Vol 8 ◽  
Author(s):  
Huayu Chen ◽  
Dongbo Wu ◽  
Wei Jiang ◽  
Ting Lei ◽  
Changli Lu ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Liver Function Tests ◽  
Liver Disorder ◽  
Chinese Patient ◽  
The Novel ◽  
Homozygous Variant ◽  
Benign Recurrent Intrahepatic Cholestasis ◽  
Common Causes ◽  
Work Up

Benign recurrent intrahepatic cholestasis (BRIC) is a rare hereditary cholestatic liver disorder. Accurate diagnosis and timely interventions are important in determining outcomes. Besides clinical and pathologic diagnosis, genetic study of BRIC remains limited. Here, we report a young man enduring recurrent jaundice and severe pruritus for 15 years. The increased level of direct bilirubin was the main biochemical abnormality, and the work-up for common causes of jaundice were unremarkable. Liver biopsy showed extensive cholestasis of hepatocytes in zone 3. The novel homozygous variant including c.1817T > C and p.I606T was detected on his ATP8B1gene. The patient was finally diagnosed with BRIC-1. His symptoms were relieved, and liver function tests returned to normal after taking ursodeoxycholic acid. This case provides a different perspective to the methodology employed when dealing with cases of jaundice and helping diagnose rare diseases.

PROGRESSIVE FAMILY INTRAHEPATIC CHOLESTASIS: DIAGNOSTICS, TREATMENT (CLINICAL OBSERVATION)

2021 ◽  
Vol 19 (4) ◽  
pp. 462-467
Author(s):  
A. R. Obuhovich ◽  
◽  
N. N. Iaskevich ◽  
Keyword(s):  
Case Report ◽  
Intrahepatic Cholestasis ◽  
Clinical Observation ◽  
Gene Mutations ◽  
Literature Analysis ◽  
Genetic Progress ◽  
Benign Recurrent Intrahepatic Cholestasis

Jaundice is a manifestation of many diseases both benign and malignant. Genetic progress allowed to distinguish the group of unknown earlier rare cholestatic jaundices, which are resulted from gene mutations. There are no described algorithms of their diagnosis or treatment. In this article case report of the patient with benign recurrent intrahepatic cholestasis type 1 is presented. There is also literature analysis of this theme.

Fetal complications due to intrahepatic cholestasis of pregnancy

2015 ◽  
Vol 43 (2) ◽  
Author(s):  
Patrik Šimják ◽  
Antonín Pařízek ◽  
Libor Vítek ◽  
Andrej Černý ◽  
Karolína Adamcová ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Liver Function Tests ◽  
Liver Disorder ◽  
Intrauterine Fetal Death ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Management Options ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

AbstractIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

ATP8B1 and ATP11C: Two Lipid Flippases Important for Hepatocyte Function

2015 ◽  
Vol 33 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Jyoti Naik ◽  
Dirk R. de Waart ◽  
Karina Utsunomiya ◽  
Suzanne Duijst ◽  
Kam Ho Mok ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Bile Salts ◽  
Membrane Transporters ◽  
Cholestatic Liver Disease ◽  
Canalicular Membrane ◽  
Transport Vesicles ◽  
Benign Recurrent Intrahepatic Cholestasis ◽  
Conjugated Hyperbilirubinemia ◽  
Deficient Mice

P4 ATPases are lipid flippases and transport phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. Lipid flipping is important for the biogenesis of transport vesicles. Recently it was shown that loss of the P4 ATPases ATP8B1 and ATP11C are associated with severe Cholestatic liver disease. Mutation of ATP8B1 cause progressive familial Intrahepatic Cholestasis type 1 (PFIC1)and benign recurrent intrahepatic cholestasis type 1 (BRIC 1). From our observations we hypothesized that ATP8B1 deficiency causes a phospholipids randomization at the canalicular membrane, which results in extraction of cholesterol due to increase sensitivity of the canalicular membrane. Deficiency of ATP11C causes conjugated hyperbilirubinemia. In our preliminary result we observed accumulation of unconjugated bile salts in Atp11c deficient mice probably because of regulation in the expression or function of OATP1B2. Similar to ATP8B1, ATP11C have regulation on membrane transporters.

The Free Responsible Action of the Individual

2018 ◽  
Author(s):  
Michael P. DeJonge
Keyword(s):  
The Novel ◽  
Extreme Situation ◽  
The Third ◽  
Third Phase ◽  
Responsible Action ◽  
Action Type ◽  
Two Phases ◽  
The Individual ◽  
The Church

If, as Chapter 12 argues, much of Bonhoeffer’s resistance thinking remains stable even as he undertakes the novel conspiratorial resistance, what is new in his resistance thinking in the third phase? What receives new theological elaboration is the resistance activity of the individual, which in the first two phases was overshadowed by the resistance role played by the church. Indeed, as this chapter shows, Bonhoeffer’s conspiratorial activity is associated with what he calls free responsible action (type 6), and this is the action of the individual, not the church, in the exercise of vocation. As such, the conspiratorial activity is most closely related to the previously developed type 1 resistance, which includes individual vocational action in response to state injustice. But the conspiratorial activity differs from type 1 resistance as individual vocational action in the extreme situation.

575 Regression by hetIL-15 monotherapy in different mouse breast cancer models correlates with intratumoral infiltration of a novel population of dendritic cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A609-A609
Author(s):  
Sevasti Karaliota ◽  
Dimitris Stellas ◽  
Vasiliki Stravokefalou ◽  
Bethany Nagy ◽  
Cristina Bergamaschi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
Nk Cells ◽  
Flow Analysis ◽  
Laboratory Animals ◽  
Tumor Infiltration ◽  
The Novel ◽  
Phenotypic Profile ◽  
Conventional Type

BackgroundIL-15 is a cytokine which stimulates the proliferation and cytotoxic function of CD8+ T and NK cells. We have produced and applied the native heterodimeric IL-15 (hetIL-15) on several preclinical models, which have supported the anti-tumor activity of hetIL-15. Based on these results, hetIL-15 has advanced to clinical trials. The objectives of this study were to explore how hetIL-15 shapes the tumor microenviroment and to characterize the interactions between tumor-infiltrating lymphoid and myeloid cells.MethodsWe studied the efficacy of locoregional administration of heterodimeric IL-15 (hetIL-15) in two different orthotopic triple-negative breast cancer (TNBC) mouse models, syngeneic for C57BL/6 and Balb/c, respectively. The effects of hetIL-15 on immune cells were analyzed by flow cytometry, immunohistochemistry (IHC) and gene expression profiling. The profile of the novel infiltrated dendritic cell populations was further explored by bulk and single cell RNAseq.Results hetIL-15 resulted in tumor eradication in 40% of treated mice and reduction of metastasis. Subsequent rechallenges with the same cell line failed to generate tumor regrowth, suggesting the development of immunological memory in hetIL-15 treated mice. hetIL-15 promoted tumor accumulation of proliferating and cytotoxic CD8+ T and NK cells. Additionally, peritumoral hetIL-15 administration resulted in an increased tumor infiltration of both conventional type 1 dendritic cells (cDC1s) and of a novel DC population found only in the hetIL-15 treated animals. Phenotypic profile analysis confirmed the expression of several cDC1 specific markers, including CD103 and IRF8 on this DC population.Transcriptomics and flow analysis of intratumoral dendritic cells indicate that the new hetIL-15 induced cells reside preferentially in the tumors and are distinct from cDC1 and cDC2 populations. Both cDC1s and the novel DC population were inversely correlated with the tumor size.ConclusionsLocoregional administration of hetIL-15 results in complete eradication of EO771 and significant reduction of 4T1 primary breast cancer tumors, prolonged survival and long-lasting specific anti-tumor immunity. hetIL-15 increases the tumor infiltration of activated T and NK cells and intensifies the tumor infiltration of conventional type 1 dendritic cells (cDC1) and a new population of dendritic cells. We propose that the anti-cancer activity of hetIL-15 in primary EO771 tumors is orchestrated by the interplay of NK, CD8+T cells, cDC1 and a novel subset of DCs with a distinct phenotypic profile. These findings suggest a role for hetIL-15 in the treatment of breast cancer.Ethics ApprovalThe study was approved by the National Cancer Institute-Frederick Animal Care and Use Committee, approval number 19–324 and was conducted in accordance with the ACUC guidelines and the NIH Guide for the Care and Use of Laboratory Animals.

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