FXR agonist obeticholic acid induces liver growth but exacerbates biliary injury in rats with obstructive cholestasis.

Cholestasis impairs liver regeneration following partial liver resection (PHx). Bile acid receptor farnesoid X-receptor (FXR) is a key mediator of liver regeneration. The effects of FXR agonist obeticholic acid (OCA) on liver (re)growth were therefore studied in cholestatic rats.

Whither systems medicine?

New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails.

The portal-drained viscera release fibroblast growth factor 19 in humans.

Fibroblast growth factor 19 (FGF19) is an ileum-derived endrocrine factor that is produced in response to transepithelial bile salt flux. FGF19 represses bile salt synthesis in the liver. Despite the general assumption that FGF19 signals to the liver via portal blood, no human data are available to support this notion.

The ascending pathophysiology of cholestatic liver disease.

In this review we develop the argument that cholestatic liver diseases, particularly primary biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in "downstream" bile ducts. This eventually leads to cholestasis, and this causes bile salt (BS)-mediated toxic injury of the "upstream" liver parenchyma.

Prolonged fibroblast growth factor 19 response in patients with primary sclerosing cholangitis after an oral chenodeoxycholic acid challenge.

Background: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients.

Cholic acid therapy in Zellweger spectrum disorders.

Introduction: Zellweger spectrum disorders (ZSDs) are characterized by a failure in peroxisome formation, caused by autosomal recessive mutations in different PEX genes. At least some of the progressive and irreversible clinical abnormalities in patients with a ZSD, particularly liver dysfunction, are likely caused by the accumulation of toxic bile acid intermediates. We investigated whether cholic acid supplementation can suppress bile acid synthesis, reduce accumulation of toxic bile acid intermediates and improve liver function in these patients.

Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: potential implications for pathogenesis.

Objective: The risk of hepatocellular carcinoma (HCC) is increased in patients with metabolic syndrome (MS), possibly related to nonalcoholic fatty liver disease (NAFLD). As histological features of NAFLD may regress in cirrhosis, we compared steatosis versus steatohepatitis in the nontumoral liver of noncirrhotic HCC patients.

Patients And Methods: A retrospective clinicopathological analysis was carried out in 91 noncirrhotic HCC patients.

The role of bile salts in liver regeneration.

A growing body of evidence has demonstrated that bile salts are important for liver regeneration following partial hepatectomy. The relative bile salt overload after partial liver resection causes activation of bile salt receptors in non-parenchymal (viz. the plasma membrane receptor TGR5) and parenchymal (viz.

Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis.

Background & Aims: To better understand the pathogenesis of primary sclerosing cholangitis, anti- and pro-inflammatory factors were studied in bile.

Methods: Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation.

Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers: results from a large cohort in the Netherlands.

Objectives: Hepatocellular carcinoma (HCC) usually occurs in patients with cirrhosis, but can also develop in noncirrhotic livers. In the present study we explored associated risk factors for HCC without cirrhosis and compared patient and tumor characteristics and outcomes in HCC patients with and without underlying cirrhosis.

Methods: Patients with HCC diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated.

Surveillance for hepatocellular carcinoma is associated with increased survival: Results from a large cohort in the Netherlands.

Background & Aims: Effectiveness of surveillance for hepatocellular carcinoma is controversial. We here explore its effects in "real life" clinical practice.

Methods: Patients with hepatocellular carcinoma diagnosed in the period 2005-2012 in five Dutch academic centers were evaluated.

The gut microbiota of nonalcoholic fatty liver disease: current methods and their interpretation.

The role of intestinal bacteria in the pathogenesis of nonalcoholic fatty liver disease is increasingly acknowledged. Recently developed microbial profiling techniques are beginning to shed light on the nature of gut microbiota alterations in nonalcoholic fatty liver disease. In this review, we summarize the gut microbiota composition changes that have been reported during different stages of human nonalcoholic fatty liver disease, and highlight the relation between bile acids and gut bacteria in this context.

Monitoring of Total and Regional Liver Function after SIRT.

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function.

Characterization and treatment of persistent hepatocellular secretory failure.

Background & Aims: Hepatocellular secretory failure induced by drugs, toxins or transient biliary obstruction may sometimes persist for months after removal of the initiating factor and may then be fatal without liver transplantation. We characterized patients with severe persistent hepatocellular secretory failure (PHSF) and treated them with the pregnane X receptor (PXR) agonist, rifampicin. We also studied the effect of rifampicin on PXR-dependent expression of genes involved in biotransformation and secretion in vitro.

Calorie restriction and Roux-en-Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects.

Objective: To study the effect of different weight loss strategies on levels of the metabolic regulator FGF21 in morbidly obese females with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM).

Design: Observational intervention trial.

Patients And Measurements: Weight reduction was achieved by Gastric Banding (GB, n = 11) or Roux-en-Y Gastric Bypass (RYGB, n = 16) in subjects with NGT, and by RYGB (n = 15) or a very-low-calorie diet (VLCD, n = 12) in type 2 diabetics.

MicroRNAs: role and therapeutic targets in viral hepatitis.

MicroRNAs regulate gene expression by binding to the 3'-untranslated region (UTR) of target messenger RNAs (mRNAs). The importance of microRNAs has been shown for several liver diseases, for example, viral hepatitis. MicroRNA-122 is highly abundant in the liver and is involved in the regulation of lipid metabolism.

Comparison of interobserver agreement of magnetic resonance elastography with histopathological staging of liver fibrosis.

Purpose: MR elastography (MRE) can serve as an accurate surrogate marker of liver fibrosis. For any diagnostic test that is to replace the current reference standard, interobserver agreement should be at least as good and preferably better. The objective of this study was to perform a head-to-head comparison of the interobserver agreements of MRE and liver fibrosis staging on biopsy in a single cohort of hepatitis patients.

[Bariatric surgery: part of a systematic approach to obesity].

Bariatric surgery is becoming popular as treatment of morbid obesity. With this popularity there is a danger that it surpasses or even replaces conservative medical therapy. Instead, bariatric surgery should be part of a systematic approach in the treatment of obesity.

Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C.

Objective: To compare the diagnostic accuracy of TE and MRE and establish cutoff levels and diagnostic strategies for both techniques, enabling selection of patients for liver biopsy.

Methods: One hundred three patients with chronic hepatitis B or C and liver biopsy were prospectively included. Areas under curves (AUROC) were compared for TE and MRE for METAVIR fibrosis grade ≥ F2 and ≥F3.