Search results for "Intrahepatic"
showing 10 items of 89 documents
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC …
2019
Drug-induced liver injury (DILI) is a matter of concern in the course of drug development and patient safety, often leading to discontinuation of drug-development programs or early withdrawal of drugs from market. Hepatocellular toxicity or impairment of bile acid (BA) metabolism, known as cholestasis, are the two clinical forms of DILI. Whole-body physiology-based modelling allows a mechanistic investigation of the physiological processes leading to cholestasis in man. Objectives of the present study were: (1) the development of a physiology-based model of the human BA metabolism, (2) population-based model validation and characterisation, and (3) the prediction and quantification of alter…
Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.
2021
Background & Aims Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. Methods A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Furth…
PBRM1 loss is a late event during the development of cholangiocarcinoma
2017
Aims: Somatic mutations in genes encoding chromatin remodellers have been reported recently in several cancer types, including approximately half of cholangiocarcinomas. One of the most commonly mutated chromatin remodellers in cholangiocarcinoma is the Polybromo-1 (PBRM1) gene located on chromosome 3p21, which encodes a subunit of the SWI/SNF complex. The aim of this study was to determine the timing of PBRM1 mutations in biliary carcinogenesis. Methods and results: In order to accomplish this goal, we used immunohistochemistry to assess PBRM1 protein expression in a series of precursor lesions and invasive biliary carcinomas. Previous studies have correlated loss of protein expression on …
Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset.
2017
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heter…
Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress.
2016
Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30days as evidenced by upregulation of liver enz…
Clinicopathological Significance of Syndecan-1 in Cholangiocarcinoma: A Study Based on Immunohistochemistry and Public Sequencing Data
2021
Background: Syndecan-1 (CD138
Circulatory response to volume expansion and transjugular intrahepatic portosystemic shunt in refractory ascites: Relationship with diastolic dysfunc…
2015
Abstract Background Cirrhotic cardiomyopathy may lead to heart failure in stressful circumstances, such as after transjugular intrahepatic portosystemic shunt (TIPS) placement. Aim To examine whether acute volume expansion predicts haemodynamic changes after TIPS and elicits signs of impending heart failure. Methods We prospectively evaluated refractory ascites patients (group A) and compensated cirrhotics (group B), who underwent echocardiography, NT-proBNP measurement, and heart catheterization before and after volume load; group A repeated measurements after TIPS. Results 15 patients in group A (80% male; 54 ± 12.4 years) and 8 in group B (100% male; 56 ± 6.2 years) were enrolled. Echoca…
Focal lesions in cirrhotic liver: what else beyond hepatocellular carcinoma?
2014
Detection and characterization of focal lesions in the cirrhotic liver may pose a diagnostic dilemma. Several benign and malignant lesions may be found in a cirrhotic liver along with hepatocellular carcinoma (HCC), and may exhibit typical or atypical imaging features. In this pictorial essay, we illustrate computed tomography and magnetic resonance imaging findings of lesions such as simple bile duct cysts, hemangioma, focal nodular hyperplasia-like nodules, peribiliary cysts, intrahepatic cholangiocarcinoma, lymphoma, and metastases, all of which occur in cirrhotic livers with varying prevalences. Pseudolesions, such as perfusion anomalies, focal confluent fibrosis, and segmental hyperpla…
Short- and long-term effects of the transjugular intrahepatic portosystemic shunt on portal vein thrombosis in patients with cirrhosis
2011
Background and aims Portal vein thrombosis (PVT) negatively impacts the prognosis in patients with cirrhosis. The aim of our study was to evaluate the effects of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis complicated by PVT. Methods Seventy consecutive cirrhotic patients with non-tumoural PVT treated with TIPS for portal hypertension complications from January 2003 to February 2010 in a tertiary-care centre were followed until last clinical evaluation, liver transplantation, or death. Results TIPS was successfully placed without major procedure-related complications. After TIPS, the portal venous system was completely recanalised in 57% of pati…
Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience.
2012
Abstract Aims The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC). Materials and methods 273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical ( n = 130), TACE ( n = 32), and systemic chemotherapy/best supportive care ( n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively. Results The 1-, 3-, and 5-year survival rates in patients after surgical resection were…