Determining the time to cholangiocarcinoma in pediatric-onset PSC-IBD.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. When a child is diagnosed with both PSC and inflammatory bowel disease (IBD), evidence-based information on counseling families and risk management of developing cholangiocarcinoma is limited. In this case series (PubMed/collaborators), we included patients with PSC-IBD who developed cholangiocarcinoma and contacted authors to determine an event curve specifying the time between the second diagnosis (IBD or PSC) and a diagnosis of cholangiocarcinoma.

Outcome in Caucasian patients with hepatitis B e antigen negative chronic infection: A long-term observational cohort study.

Sensitive polymerase chain reaction assays to measure hepatitis B virus (HBV) DNA became only available the last decade. Hence, the long-term outcome of Caucasian patients in Western Europe with hepatitis B e antigen (HBeAg)-negative chronic infection, especially with a baseline HBV DNA level ⩾2000 IU/mL, is still unclear. Out of a cohort of 1936 chronic HBV patients, 413 Caucasian individuals were identified with HBeAg-negative chronic infection, defined as persistently normal alanine aminotransferase (ALT) levels and HBV DNA levels <20 000 IU/mL.

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC.

Methods: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia.

Patients with large-duct primary sclerosing cholangitis and Crohn's disease have a better outcome than those with ulcerative colitis, or without IBD.

Background: Approximately 20% of primary sclerosing cholangitis (PSC) patients with concomitant inflammatory bowel disease (IBD) have Crohn's disease (CD).

Aim: To compare PSC/CD with other PSC patients.

Methods: Retrospective study of 240 PSC patients diagnosed between 1975 and 2012 (median follow-up 12 years).

Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function.

Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis.

Methods: Forty-four patients with NASH/ASH cirrhosis (decompensated n=29, compensated n=15) and nineteen controls undergoing endoscopy were recruited.

Primary sclerosing cholangitis, Crohn's disease and HLA-B27 in black South African women.

Crohn's disease is rare in South African black people and primary sclerosing cholangitis (PSC) is also rare in black patients with IBD, from South Africa. The presence of HLA-B27 is generally associated with seronegative spondylo-arthropathies and correlates with the occurrence of ankylosing spondylitis, recurrent mouth ulcers and uveitis, in patients with IBD. We describe two women with the combination of Crohn's disease, PSC and HLA-B27 from our cohort of the last 5 years of three black patients with Crohn's disease.

Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an observational case series study.

Background & Aims: Pruritus is a disabling complication of cholestatic liver disorders. Its management remains challenging. Ultraviolet B (UVB) phototherapy has been successfully used to treat pruritus in other indications.

Culture of mouse embryonic stem cells with serum but without exogenous growth factors is sufficient to generate functional hepatocyte-like cells.

Mouse embryonic stem cells (mESC) have been used to study lineage specification in vitro, including towards a hepatocyte-like fate, and such investigations guided lineage differentiation protocols for human (h)ESC. We recently described a four-step protocol to induce hepatocyte-like cells from hESC which also induced hepatocyte-like cell differentiation of mouse induced pluripotent stem cells. As ESC also spontaneously generate hepatocyte-like cells, we here tested whether the growth factors and serum used in this protocol are required to commit mESC and hESC to hepatocyte-like cells.

Malignancies and mortality in 200 patients with primary sclerosering cholangitis: a long-term single-centre study.

Background: The outcome of primary sclerosing cholangitis (PSC) has improved by liver transplantation (LT), but patients often develop malignancies. We analysed morbidity and mortality patterns to define strategies to prevent complications.

Methods: Two hundred consecutive patients diagnosed before October 2005 were studied.

Giant liver hemangioma: the role of female sex hormones and treatment.

Hepatic hemangiomas are the most common focal liver lesions and are especially prevalent in women. Giant hemangiomas are defined as hemangiomas of at least 4 cm in diameter and the majority remains stable in size over time. However, in some cases hemangiomas display growth and give rise to symptoms because of their space-occupying effect.

Primary sclerosing cholangitis complicated by amyloid A amyloidosis: complete regression of the nephrotic syndrome by liver transplantation.

Secondary amyloidosis may complicate chronic inflammatory conditions and mostly presents as a renal disease with nephrotic syndrome or renal insufficiency. Its prognosis is largely affected by control of the underlying disease. We report a patient with primary sclerosing cholangitis, who developed cirrhosis over a 4-year period.

Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells.

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes.

An update on cholangiocarcinoma associated with primary sclerosing cholangitis.

Purpose Of Review: Primary sclerosing cholangitis (PSC) is being diagnosed with increasing frequency. The most feared complication is the presence or development of cholangiocarcinoma (CCA). The present review summarizes recent data with regards to diagnosis, pathobiology and treatment.

Wilson's disease: long-term follow-up of a cohort of 24 patients treated with D-penicillamine.

Background And Study Aims: Detailed data on long-term effectiveness of various drug therapies in Wilson's disease (WD) are lacking. Therefore, we retrospectively reviewed our patient cohort treated with D-penicillamine.

Patients And Methods: This study reports on the clinical presentation, the diagnostic evaluation, and the disease course in 24 WD patients treated long-term (15+/-12 years, between 1969 and 2009) with D-penicillamine.

Quantitation of replication of the HCV genome in human livers with end-stage cirrhosis by strand-specific real-time RT-PCR assays: methods and clinical relevance.

HCV replicates in liver via an intermediate negative strand RNA. To study the relevance of HCV genome replication, quantitative strand-specific HCV real-time RT-PCR assays were developed and applied to livers explanted because of end-stage cirrhosis. The assays have broad ranges of determination and a high reproducibility and accuracy.

Cystic fibrosis transmembrane conductance regulator gene polymorphisms in patients with primary sclerosing cholangitis.

Background/aims: Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of bile ducts. The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC.

Porphyria cutanea tarda and liver disease. A retrospective analysis of 17 cases from a single centre and review of the literature.

Background/aims: Sporadic Porphyria Cutanea Tarda (sPCT) is associated with liver disease, e.g. HCV infection, haemochromatosis and especially alcoholic liver disease.

Increased serum phospholipase A2 activity after non-heart-beating donor liver transplantation and association with ischemia-reperfusion injury.

Background: Secretory phospholipase A(2) (sPLA(2)) degrades cell membrane phospholipids and plays an important role in the synthesis of pro-inflammatory lipid mediators (arachidonic acid and cytokines) during inflammatory events such as ischemia-reperfusion injury after liver transplantation (LTx). A role for sPLA(2) in LTx from non-heart-beating donors (NHBD) has never been demonstrated. Furthermore data on the natural sPLA(2) inhibition capacity are scarce.

Bilirubin in clinical practice: a review.

Bilirubin is an endogenous compound that can be toxic under certain conditions but, on the other hand, mild unconjugated hyperbilirubinaemia might protect against cardiovascular diseases and tumour development. Serum bilirubin levels are often enhanced under a variety of clinical conditions. These are discussed and the mechanisms are outlined.

Statins in hepatobiliary diseases: effects, indications and risks.

Background And Study Aims: Statins are among the most frequently used medications. Our aim was to study their indications or contraindications in hepatobiliary diseases.

Patient And Methods: This study was stimulated by a patient with PBC, marked hypercholesterolemia and cardiac problems.

Congenital veno-venous malformations of the liver: widely variable clinical presentations.

Background And Aim: Congenital portosystemic veno-venous malformations are rare abnomalities that often remain undiagnosed. Typically they are classified by their anatomical characteristics according to Morgan (extrahepatic, Abernethy malformations type Ia,b and II) and Park (intrahepatic, types 1-4). However, their clinical presentation is less dependent on the anatomical type.

Hepatitis C and insulin resistance: mutual interactions. A review.

Worldwide approximately 200 million people are chronically infected with hepatitis C virus (HCV). Chronic HCV infection represents the leading cause of liver cirrhosis and the main indication for liver transplantation in the western world. In addition, chronic HCV infection is associated with numerous clinical manifestations, including type 2 diabetes.

HBx or HCV core gene expression in HepG2 human liver cells results in a survival benefit against oxidative stress with possible implications for HCC development.

Hepatitis virus replication in the liver is often accompanied by inflammation resulting in the formation of reactive oxygen species (ROS) and nitric oxide (NO) and these may induce cell death. We investigated whether the expression of HBx or HCV core protein in HepG2 cells has an influence on the sensitivity of these cells for oxidative radicals. Our previous study, using the inducible HBV model of HepAD38, revealed that oxidative-stress-related genes are upregulated by virus replication.