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Find video protocols related to scientific articles indexed in Pubmed.
Histological Changes in Nontumoral Liver Secondary to Radioembolization of Hepatocellular Carcinoma with Yttrium 90-impregnated Microspheres: Report of Two Cases.
Semin. Liver Dis.
PUBLISHED: 11-04-2014
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Transarterial radioembolization (TARE) with yttrium-90 is a minimally invasive locoregional therapy for hepatocellular carcinoma (HCC), and involves selective delivery of glass or resin microspheres impregnated with radioactive yttrium-90 into small arteries preferentially supplying the tumor for tumoricidal effect thus sparing the nontumoral liver, or into lobar artery to induce atrophy and contralateral hypertrophy. Clinically, post-TARE a small proportion of cases develop radioembolization-induced liver disease. Histological changes of TARE on nontumoral liver parenchyma have not been well characterized. Herein, we report two cases of liver resections for HCC post-TARE, and describe the histological changes in nontumoral liver parenchyma.
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Inhibition of the CXCL12/CXCR4 chemokine axis with AMD3100, a CXCR4 small molecule inhibitor, worsens murine hepatic injury.
Hepatol. Res.
PUBLISHED: 08-28-2014
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Activation of hepatic stellate cells and development of chronic inflammation are two key features in the progression of hepatic fibrosis. We have shown that in vitro activated stellate cells increase their expression of CXCL12 as well as the receptor CXCR4 and that receptor engagement promotes a profibrogenic phenotype. Furthermore, injury promotes increased hepatic expression of CXCL12 and a massive infiltration of CXCR4-expressing leukocytes, granulocytes and myeloid cells. The primary site of inflammatory cell accumulation is around the CXCL12-rich portal tracts and within fibrotic septae, indicating a role for CXCR4 during injury. In order to characterize the relevance of the CXCR4/CXCL12 chemokine axis during hepatic injury we inhibited the axis using AMD3100, a CXCR4 small molecule inhibitor, in models of chronic and acute liver injury.
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A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration.
Gut
PUBLISHED: 08-20-2014
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The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression.
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Update on the new classification of hepatic adenomas: clinical, molecular, and pathologic characteristics.
Arch. Pathol. Lab. Med.
PUBLISHED: 07-31-2014
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Hepatic adenoma is an uncommon, benign, hepatic neoplasm that typically occurs in women of child-bearing age, often with a history of long-term use of oral contraceptive drugs. This is usually detected as an incidental mass lesion in a noncirrhotic liver during imaging studies. Pathologic evaluation by needle core biopsy remains the gold standard for diagnosis. Molecular studies have revealed that hepatic adenomas involve unique molecular pathways that are distinct from hepatocellular carcinoma. Based on these studies, a French collaborative group has recently proposed a molecular-pathologic classification for hepatic adenomas. In addition, advances in molecular studies have led to reclassification of the "telangiectatic variant of focal nodular hyperplasia" as "hepatic adenoma, inflammatory subtype."
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DCE-MRI of the liver: effect of linear and nonlinear conversions on hepatic perfusion quantification and reproducibility.
J Magn Reson Imaging
PUBLISHED: 06-14-2014
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To evaluate the effect of different methods to convert magnetic resonance (MR) signal intensity (SI) to gadolinium concentration ([Gd]) on estimation and reproducibility of model-free and modeled hepatic perfusion parameters measured with dynamic contrast-enhanced (DCE)-MRI.
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High mobility group box-1 (HMGB1) participates in the pathogenesis of alcoholic liver disease (ALD).
J. Biol. Chem.
PUBLISHED: 06-13-2014
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Growing clinical and experimental evidence suggests that sterile inflammation contributes to alcoholic liver disease (ALD). High mobility group box-1 (HMGB1) is highly induced during liver injury; however, a link between this alarmin and ALD has not been established. Thus, the aim of this work was to determine whether HMGB1 contributes to the pathogenesis of ALD. Liver biopsies from patients with ALD showed a robust increase in HMGB1 expression and translocation, which correlated with disease stage, compared with healthy explants. Similar findings were observed in chronic ethanol-fed wild-type (WT) mice. Using primary cell culture, we validated the ability of hepatocytes from ethanol-fed mice to secrete a large amount of HMGB1. Secretion was time- and dose-dependent and responsive to prooxidants and antioxidants. Selective ablation of Hmgb1 in hepatocytes protected mice from alcohol-induced liver injury due to increased carnitine palmitoyltransferase-1, phosphorylated 5'AMP-activated protein kinase-?, and phosphorylated peroxisome proliferator-activated receptor-? expression along with elevated LDL plus VLDL export. Native and post-translationally modified HMGB1 were detected in humans and mice with ALD. In liver and serum from control mice and in serum from healthy volunteers, the lysine residues within the peptides containing nuclear localization signals (NLSs) 1 and 2 were non-acetylated, and all cysteine residues were reduced. However, in livers from ethanol-fed mice, in addition to all thiol/non-acetylated isoforms of HMGB1, we observed acetylated NLS1 and NLS2, a unique phosphorylation site in serine 35, and an increase in oxidation of HMGB1 to the disulfide isoform. In serum from ethanol-fed mice and from patients with ALD, there was disulfide-bonded hyperacetylated HMGB1, disulfide-bonded non-acetylated HMGB1, and HMGB1 phosphorylated in serine 35. Hepatocytes appeared to be a major source of these HMGB1 isoforms. Thus, hepatocyte HMGB1 participates in the pathogenesis of ALD and undergoes post-translational modifications (PTMs) that could condition its toxic effects.
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NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity.
Nat Commun
PUBLISHED: 03-25-2014
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The Beclin 1-Vps34 complex, the core component of the class III phosphatidylinositol-3 kinase (PI3K-III), binds Atg14L or UVRAG to control different steps of autophagy. However, the mechanism underlying the control of PI3K-III activity remains elusive. Here we report the identification of NRBF2 as a component in the specific PI3K-III complex and a modulator of PI3K-III activity. Through its microtubule interaction and trafficking (MIT) domain, NRBF2 binds Atg14L directly and enhances Atg14L-linked Vps34 kinase activity and autophagy induction. NRBF2-deficient cells exhibit enhanced vulnerability to endoplasmic reticulum (ER) stress that is reversed by re-introducing exogenous NRBF2. NRBF2-deficient mice develop focal liver necrosis and ductular reaction, accompanied by impaired Atg14L-linked Vps34 activity and autophagy, although the mice show no increased mortality. Our data reveal a key role for NRBF2 in the assembly of the specific Atg14L-Beclin 1-Vps34-Vps15 complex for autophagy induction. Thus, NRBF2 modulates autophagy via regulation of PI3K-III and prevents ER stress-mediated cytotoxicity and liver injury.
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Osteopontin induces ductular reaction contributing to liver fibrosis.
Gut
PUBLISHED: 02-04-2014
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In human chronic liver disease, there is association between ductular reaction (DR) and fibrosis; yet, the mechanism triggering its onset and its role in scar formation remains unknown. Since we previously showed that osteopontin (OPN) is highly induced during drug-induced liver fibrosis, we hypothesised that OPN could drive oval cells (OC) expansion and DR and signal to hepatic stellate cells (HSC) to promote scarring.
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Pancreatic recurrence of intrahepatic cholangiocarcinoma: Case report and review of the literature.
World J Gastrointest Surg
PUBLISHED: 01-15-2014
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Intrahepatic cholangiocarcinomas (ICC) are malignant tumors arising from the intrahepatic bile ducts that frequently recur after resection. The main sites of recurrence are the remnant liver, lymph nodes and lungs. Metastasis to the pancreas has never been reported. This case describes a 24-year-old woman who underwent a hepatic lobectomy in 2008 for an ICC. Almost 4 years after her surgery she presented with a pancreatic mass and lung nodules. An endoscopic ultrasound guided fine needle aspiration of the pancreatic mass and a video-assisted thoracoscopic surgery resection for the lung nodules were performed for diagnostic purposes. Pathological analyses of specimens revealed recurrence of her primary ICC in both pancreas and lungs. Subsequently, the patient received systemic chemotherapy. The patient is currently off chemotherapy and remains well. Moreover, she is pregnant. This is the first report of an ICC with pancreatic metastasis.
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UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma.
Cancer Cell
PUBLISHED: 01-06-2014
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Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an essential regulator of DNA methylation that is highly expressed in many cancers. Here, we use transgenic zebrafish, cultured cells, and human tumors to demonstrate that UHRF1 is an oncogene. UHRF1 overexpression in zebrafish hepatocytes destabilizes and delocalizes Dnmt1 and causes DNA hypomethylation and Tp53-mediated senescence. Hepatocellular carcinoma (HCC) emerges when senescence is bypassed. tp53 mutation both alleviates senescence and accelerates tumor onset. Human HCCs recapitulate this paradigm, as UHRF1 overexpression defines a subclass of aggressive HCCs characterized by genomic instability, TP53 mutation, and abrogation of the TP53-mediated senescence program. We propose that UHRF1 overexpression is a mechanism underlying DNA hypomethylation in cancer cells and that senescence is a primary means of restricting tumorigenesis due to epigenetic disruption.
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Lamivudine resistance leading to de novo hepatitis B infection in recipients of hepatitis B core antibody positive liver allografts.
Hepatol. Res.
PUBLISHED: 09-05-2013
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Most studies have shown that lamivudine (LAM) prophylaxis is sufficient to prevent hepatitis B virus (HBV) transmission in recipients of hepatitis B core antibody positive (HBcAb(+) ) allografts. However, de novo hepatitis B (DNHB) is known to occur in this patient population. Herein, we report a case series of four liver transplant recipients who developed DNHB after receiving HBcAb(+) allografts due to acquisition of LAM resistance mutations, suggesting that LAM prophylaxis may be suboptimal. A retrospective chart review was performed of all adult liver transplants performed at Mount Sinai from 2001 to 2010. A total of 79 patients received HBcAb(+) allografts for non-hepatitis B-related liver disease. Of these 79 recipients, four patients developed DNHB and were found to have documented LAM resistance. With the increasing use of HBcAb(+) donor livers, we suspect that there will also be a growing number of cases of DNHB due to acquisition of LAM resistance. We suggest that other agents, such as entecavir or tenofovir, be considered for use as prophylaxis in this patient population to decrease this risk.
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Clinical Factors That Predict Noncirrhotic Portal Hypertension in HIV-Infected Patients: A Proposed Diagnostic Algorithm.
J. Infect. Dis.
PUBLISHED: 08-02-2013
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Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.
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Recurrent hepatitis C virus infection and outcome after living-donor liver transplant.
Exp Clin Transplant
PUBLISHED: 07-30-2013
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In living-donor liver transplant recipients with hepatitis C virus infection, outcomes of recurrent hepatitis C virus infection and fibrosis progression are not well documented. We evaluated fibrosis progression, response to pegylated interferon treatment, and long-term graft survival in living-donor liver transplant recipients who had hepatitis C virus infection.
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Mucosal addressin cell adhesion molecule (MAdCAM-1) expression is upregulated in the cirrhotic liver and immunolocalises to the peribiliary plexus and lymphoid aggregates.
Dig. Dis. Sci.
PUBLISHED: 06-12-2013
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Enhanced cell expression of MAdCAM-1 is critical in tissue recruitment of lymphocytes in response to stimuli expressing the ?4?7 integrin. MAdCAM-1 is well characterized in gut mucosa with emerging evidence of hepatic expression.
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Medullary thymic epithelial cell depletion leads to autoimmune hepatitis.
J. Clin. Invest.
PUBLISHED: 05-17-2013
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TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6?TEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6?TEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6?TEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6?TEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease.
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Hepatoportal sclerosis (obliterative portal venopathy) and nodular regenerative hyperplasia in a patient with myasthenia gravis: A case report and review of the published work.
Hepatol. Res.
PUBLISHED: 05-15-2013
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Nodular regenerative hyperplasia (NRH) and hepatoportal sclerosis, also known as obliterative portal venopathy (OPV), are two causes of non-cirrhotic portal hypertension (NCPH). NCPH is an increasingly recognized entity that can be seen in association with collagen vascular diseases and with the use of medications such as azathioprine and didanosine, but oftentimes the etiology remains unidentified. We herein report a case of NCPH occurring due to OPV and NRH in a 64-year-old woman with myasthenia gravis (MG), status post-thymectomy. Portal hypertension was diagnosed incidentally on computed tomography in the absence of predisposing factors. Extensive work-up to determine the etiology of any underlying liver disease was unrevealing. NRH and OPV were identified on liver biopsy. Subsequently, the patient had variceal bleeding that necessitated transjugular intrahepatic portosystemic shunt placement. A few similar cases of NCPH occurring in the setting of MG have been previously reported, suggesting that the immunological mechanisms involved in the pathogenesis of myasthenia may also have contributed to the development of NCPH.
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Increased thickness of abdominal subcutaneous adipose tissue occurs more frequently in steatohepatitis than in simple steatosis.
Arch. Pathol. Lab. Med.
PUBLISHED: 05-01-2013
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The incidence of obesity is increasing and contributes to the rising incidence of fatty liver. Body mass index (BMI) is used to assess the degree of obesity but does not take into account the pattern of body fat distribution.
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Impact of intrahepatic hepatitis B DNA and covalently closed circular DNA on survival after hepatectomy in HBV-associated hepatocellular carcinoma patients.
Ann. Surg. Oncol.
PUBLISHED: 01-11-2013
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Chronic hepatitis B virus (HBV) infection induces persistent but ineffective immune activation that contributes to necroinflammation, fibrosis, and risk of hepatocellular carcinoma (HCC). This study aims to determine the relationship of intrahepatic total HBV (ih HBV) DNA and covalently closed circular DNA (cccDNA) with necroinflammation and fibrosis, and their impact on prognosis after resection in HBV HCC patients.
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Obliterative portal venopathy: a clinical and histopathological review.
Dig. Dis. Sci.
PUBLISHED: 01-09-2013
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Non-cirrhotic portal hypertension (NCPH) is characterized by the elevation of the portal pressure in the absence of cirrhosis. Obliterative portal venopathy (OPV) as a cause of NCPH is being increasingly diagnosed, especially after recent reports of its occurrence in patients with HIV using didanosine. Patients usually present with episodes of variceal hemorrhage and other features of portal hypertension including jaundice, ascites, encephalopathy and hepatopulmonary syndrome. Hepatic synthetic function is typically well preserved and the laboratory evaluation in OPV patients typically reveals only mild nonspecific hematological abnormalities chiefly related to hypersplenism. Its diagnosis remains a challenge and patients are often mistakenly diagnosed as having cirrhosis. Despite the increasing recognition of OPV, its etiology and pathogenesis are still unclear. A number of etiologies have been proposed including genetic predisposition, recurrent bacterial infections, HIV infection and highly active antiretroviral therapy, an altered immune response, hypercoagulability, and exposure to chemicals and certain medications. Histopathological evaluation remains critical in excluding cirrhosis and other causes of portal hypertension, and is the only way of definitively establishing the diagnosis of OPV. Clinicians should have a high index of suspicion for OPV in patients who present with variceal bleeding and splenomegaly and who do not have other features of cirrhosis. The purpose of this review is to summarize the known etiologies for OPV and its associated clinical aspects and correlations, and to also provide ample histophotomicrographs of OPV to aid in the diagnosis. It will also help raise awareness of this entity amongst pathologists and clinicians alike.
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Post-transcriptional activation of PPAR alpha by KLF6 in hepatic steatosis.
J. Hepatol.
PUBLISHED: 01-06-2013
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Dysregulated glucose homeostasis and lipid accumulation characterize non-alcoholic fatty liver disease (NAFLD), but underlying mechanisms are obscure. We report here that Krüppel-like factor 6 (KLF6), a ubiquitous transcription factor that promotes adipocyte differentiation, also provokes the metabolic abnormalities of NAFLD by post-transcriptionally activating PPAR?-signaling.
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Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease.
PLoS ONE
PUBLISHED: 01-01-2013
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Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA) and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan). In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis.
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Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer.
PLoS ONE
PUBLISHED: 01-01-2013
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Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the third leading cause of cancer death worldwide. The only approved systemic treatment for unresectable HCC is the oral kinase inhibitor, sorafenib. Recombinant human acid sphingomyelinase (rhASM), which hydrolyzes sphingomyelin to ceramide, is an orphan drug under development for the treatment of Type B Niemann-Pick disease (NPD). Due to the hepatotropic nature of rhASM and its ability to generate pro-apoptotic ceramide, this study evaluated the use of rhASM as an adjuvant treatment with sorafenib in experimental models of HCC.
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Rapid regression of atherosclerosis with MTP inhibitor treatment.
Atherosclerosis
PUBLISHED: 01-01-2013
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Regression of atherosclerosis is a vital treatment goal of atherosclerotic vascular disease. Inhibitors of the microsomal triglyceride transfer protein (MTP) have been shown to reduce apolipoprotein B (apoB)-containing lipoproteins in animals and humans effectively. Therefore, the major aim of our study is to evaluate the effect of MTP inhibition on atherosclerotic plaque regression.
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Acute cellular rejection resulting in sinusoidal obstruction syndrome and ascites postliver transplantation.
Transplantation
PUBLISHED: 10-14-2011
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The cause of ascites formation postliver transplantation (LT) is multifactorial. Sinusoidal obstruction syndrome (SOS) is a rare cause of ascites post-LT and has been reported to occur as a sequela of acute cellular rejection (ACR). We sought to examine the histologic features of patients developing ascites in the setting of ACR.
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Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring.
J Immunotoxicol
PUBLISHED: 06-30-2011
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Maternal environmental exposures during pregnancy are known to affect disease onset in adult offspring. For example, maternal asthma exacerbations during pregnancy can worsen adult asthma in the offspring. Cigarette smoking during pregnancy is associated with future onset of cardiovascular disease, obesity and diabetes. However, little is known about the effect of maternal environmental exposures on offspring susceptibility to liver disease. This pilot study examined the long-term effect of maternal allergen challenge and/or cigarette smoking during pregnancy on hepatic inflammation and fibrosis in adult mouse offspring. Ovalbumin (OVA) or phosphate-buffered saline (PBS)-sensitized/challenged CD-1 dams were exposed to mainstream cigarette smoke (MCS) or filtered air from gestational day 4 until parturition. Eight weeks postnatally, offspring were sacrificed for comparison of hepatic histology and mRNA expression. Adult male offspring of OVA-sensitized/challenged dams exposed to MCS (OSM) displayed significantly increased liver fibrosis (9.2% collagen content vs. <4% for all other treatment groups). These mice also had 1.8-fold greater collagen 1A1 mRNA levels. From the results here, we concluded that maternal allergen challenge in combination with cigarette smoke exposure during pregnancy may be an important risk factor for liver disease in adult male offspring.
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Fibromodulin, an oxidative stress-sensitive proteoglycan, regulates the fibrogenic response to liver injury in mice.
Gastroenterology
PUBLISHED: 06-23-2011
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Collagen I deposition contributes to liver fibrosis, yet little is known about other factors that mediate this process. Fibromodulin is a liver proteoglycan that regulates extracellular matrix organization and is induced by fibrogenic stimuli. We propose that fibromodulin contributes to the pathogenesis of fibrosis by regulating the fibrogenic phenotype of hepatic stellate cells (HSCs).
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Hepatocellular carcinoma arising in a pigmented telangiectatic adenoma with nuclear ?-catenin and glutamine synthetase positivity: case report and review of the literature.
Am. J. Surg. Pathol.
PUBLISHED: 05-17-2011
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Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of hepatocellular adenoma that is often underrecognized by pathologists. We report a case of hepatocellular carcinoma arising within a pigmented telangiectatic hepatocellular adenoma in a noncirrhotic man with diffuse glutamine synthetase and nuclear ?-catenin positivity. This case highlights malignant transformation of telangiectatic adenomas, and describes a previously unreported association between pigment deposition and telangiectatic adenoma. Radiology, gross pathology, and histopathology are shown. Review of the literature with attention to ?-catenin and glutamine synthetase staining, malignant transformation, patient characteristics, the presence of Dubin-Johnson-like pigment, and genetic characteristics of telangiectatic adenomas are discussed.
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Clinical characterization of patients developing histologically-proven fibrosing cholestatic hepatitis C post-liver transplantation.
Hepatol. Res.
PUBLISHED: 03-24-2011
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Aim:? Fibrosing cholestatic hepatitis C (FCH) post-liver transplantation (LT) is an uncommon disorder with extremely poor outcome. Using stringent histological criteria, we sought to identify cases of FCH to better characterize its incidence, clinical features and outcomes. Methods:? From January 1991 to December 2007, 973 LT for hepatitis C virus (HCV) were performed at our center. Using the pathology database, 51 cases with a provisional diagnosis of FCH were identified. FCH was diagnosed histologically by cholestasis accompanied by thin periportal fibrous septa, ductular reaction and mild inflammation. Results:? FCH was reconfirmed in 24 recipients; seven had concurrent biliary problems. Twenty-seven cases were excluded; biopsy was unavailable in nine cases, 15 did not meet the histological criteria of FCH and three had missing clinical information. All received deceased donors at a mean age of 64.4?years (15/17 aged >50?years). Mean time from LT to FCH was 7.6?months with 16 of 17 diagnosed within 1?year of LT. At diagnosis, mean viral load was 14.4?million IU/mL, bilirubin 16.2?mg/dL, aspartate aminotransferase 262?IU/mL, alanine aminotransferase 192?IU/mL and alkaline phosphatase 299?IU/mL. All 17 patients died or required re-LT a mean of 7.8?months after the FCH diagnosis. Conclusion:? FCH occurs infrequently and is typified by hyperbilirubinemia, donor age of more than 50?years, extremely high HCV RNA and specific histological changes occurring within the first several months post-LT with extremely poor patient and graft survival. Histology alone is not reliable for the diagnosis of FCH, especially in the setting of recurrent HCV with concurrent biliary problems.
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Cholangiolocellular carcinoma: an innocent-looking malignant liver tumor mimicking ductular reaction.
Semin. Liver Dis.
PUBLISHED: 02-22-2011
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The authors present an interesting case of a 60-year-old man who underwent right hepatectomy for a diagnosis of hepatocellular carcinoma (HCC) on a background of noncirrhotic chronic hepatitis C. Pathologic examination confirmed the presence of HCC near the porta hepatis, which invaded the right portal vein branch. In addition, a well-demarcated 13.5 × 7.8 × 4.0 cm yellow and firm area upstream of the HCC was noted. This yellow area corresponded to a tumoral ductular proliferation, which cytologically was extremely bland, but invaded portal tracts and the adjacent liver parenchyma. This tumoral proliferation mimicked ductular reaction, except that it had more anastomosing structures and was associated with abundant hyalinized fibrotic stroma. Cytologically, the tumor cells had round to oval nuclei with fine chromatin, indistinct nucleoli, and scant cytoplasm. They exhibited immunohistochemical features of hepatic progenitor cells, i.e., expressing CK7, CK19, and N-CAM; and their malignancy was supported by the p53 and Ki67 immunoreactivity. The authors concluded that the patient had cholangiolocellular carcinoma with an aggressive hepatocellular carcinoma component. Cholangiolocellular carcinoma has been reported to be associated with chronic hepatitis C viral infection and to derive from hepatic progenitor cells, which explains why hepatocellular carcinoma and/or cholangiocarcinoma component may be present.
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Intrahepatic cholangiocarcinoma: new insights in pathology.
Semin. Liver Dis.
PUBLISHED: 02-22-2011
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Cholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis. This review focuses on ICC, which is rising in incidence with the emergence of hepatitis C virus (HCV) infection as a risk factor. The authors examined 73 ICC, which were resected at The Mount Sinai Medical Center in New York City, and reviewed the literature. The tumors were categorized into classical and nonclassical ICCs based on histopathology. Classical ICCs (54.8%) were characterized by a tubular, glandular, or nested pattern of growth, were significantly associated with tumor size of more than 5 cm and the absence of underlying liver disease and/or advanced fibrosis. Nonclassical ICCs (45.2%) consisted of tumors with trabecular architecture, tumors that exhibited features of extrahepatic carcinomas, and carcinomas considered to be derived from hepatic progenitor cells, i.e., combined hepatocellular/cholangiocarcinomas and cholangiolocellular carcinomas (ductular type of ICC). They were smaller and often arose in chronic liver disease, mostly HCV infection, and/or with significant fibrosis. The role of immunohistochemistry in the diagnosis of ICC and the importance of the new American Joint Committee on Cancer Staging System for ICC are also discussed.
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Increasing hepatic arteriole wall thickness and decreased luminal diameter occur with increasing age in normal livers.
J. Hepatol.
PUBLISHED: 01-12-2011
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There is no data to suggest that the size of bile ducts, portal venules, and hepatic arterioles varies according to age in the normal human liver. We sought to examine whether hepatic arteriolar size, wall thickness, and luminal diameter change with increasing age.
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Pathology of chronic hepatitis B and chronic hepatitis C.
Clin Liver Dis
PUBLISHED: 11-09-2010
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Histologic evaluation of the liver is a major component in the medical management and treatment algorithm of patients with chronic hepatitis B (HBV) and chronic hepatitis C (HCV). Liver biopsy in these patients remains the gold standard, and decisions on treatment are often predicated on the degree of damage and stage of fibrosis. This article outlines the clinical course and serologic diagnosis of HBV and HCV for the clinician and the pathologist, who together have a close working relationship in managing patients with acute and chronic liver disease. The salient histologic features are elucidated in an attempt to provide the clinician with an understanding of the basic histopathology underlying chronic HCV and HBV.
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The development of hepatoportal sclerosis and portal hypertension due to didanosine use in HIV.
Virchows Arch.
PUBLISHED: 08-06-2010
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Hepatoportal sclerosis (HPS) is one of several entities known to cause noncirrhotic portal hypertension. To date, its etiology is unknown. There have been increasing reports of HPS occurring in patients with human immunodeficiency virus (HIV), and the US Food and Drug Administration (FDA) recently issued an advisory regarding the development of noncirrhotic portal hypertension in association with didanosine (ddI) use. We report on a patient with HIV who had taken ddI for 4 years and who developed portal hypertension. Histopathological review of paired liver biopsies showed an initial drug hepatotoxicity, microvascular liver injury, and the presence of HPS. Despite cessation of ddI, the latter biopsy showed resolution of the drug-induced injury, but it also showed progression of the HPS. The patients portal hypertension also progressed suggestive of an unremitting vascular injury. This case demonstrates the development of HPS resulting from a drug-induced microvascular injury. The paired biopsies demonstrate that the initial vascular injury may disappear but that the portal hypertension and HPS progress.
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Insulin resistance predicts re-treatment failure in an efficacy study of peginterferon-?-2a and ribavirin in HIV/HCV co-infected patients.
J. Hepatol.
PUBLISHED: 02-19-2010
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Few studies evaluated the efficacy of HCV re-treatment and the predictors of response in HIV/HCV co-infected patients. The role of insulin resistance as a predictor of response in this population is unknown. The aim of this study is to evaluate the safety and efficacy of pegylated interferon-?-2a and ribavirin in re-treatment of HIV/HCV co-infected patients, predictors of sustained virological response, including insulin resistance, and the relationship between insulin resistance and liver histology.
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Plasma cell hepatitis in hepatitis C virus patients post-liver transplantation: case-control study showing poor outcome and predictive features in the liver explant.
Liver Transpl.
PUBLISHED: 11-26-2009
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Plasma cell hepatitis (PCH) is characterized by plasma cell infiltration seen in allografts of patients who underwent liver transplantation (LT) for conditions other than autoimmune hepatitis. We identified 40 PCH patients who underwent LT for hepatitis C virus (HCV) by searching our pathology database (1994-2006) for the keywords liver allograft, lymphoplasmacytic, and plasma cell(s). We selected 2 control patients who received LT for HCV for each PCH case. The control patients were matched according to date of LT and availability of biopsy material at the time interval to development of PCH in PCH patients. Explant and post-LT biopsy slides were blindly reviewed by 2 liver pathologists and the severity of the plasma cell infiltrate was scored. A score of 3 (plasma cells composing >30% of the infiltrate) defined PCH in allograft biopsies. Five random areas of dense inflammation were also examined in explant livers and the highest score was used. Poor outcome was defined as death or advanced fibrosis (stage >or= 4 of 6). We found that PCH patients were more likely to have worse outcomes than control patients (65% versus 40%, P < 0.01), including increased mortality (50% versus 30%, P < 0.05). Kaplan-Meier survival analysis showed significantly worse survival for PCH patients from 4 to 10 years post-LT (P < 0.05). Explants from 40% of PCH patients had a score of 3 compared to 18% of control patients (P < 0.01). We found that the development of PCH is associated with poor outcome in patients undergoing LT for HCV. The association of significant plasma cell infiltrates in native livers of HCV patients developing PCH suggests that some patients may have a predisposition to developing PCH.
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Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.
J Immunotoxicol
PUBLISHED: 11-14-2009
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Owing to increased obesity, non-alcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the United States. NAFLD is considered a component of metabolic syndrome, a cluster of disorders that also includes diabetes mellitus, dyslipidemia, arteriosclerosis, and hypertension. Exposure to ambient air particulate matter with aerodynamic diameters < 2.5 microm (PM(2.5)) is a risk factor for arteriosclerosis and lung disease, but its effect on NAFLD is unknown. PM(2.5) induces pulmonary dysfunction via Toll-like receptor (TLR) activation on alveolar macrophages. TLR activation of Kupffer cells, resident hepatic macrophages, and subsequent pro-inflammatory cytokine production have been shown to play a key role in NAFLD progression. We hypothesized that PM(2.5) exposure is a significant risk factor for the progression of NAFLD. Thus, following exposure of male C57BL/6 mice fed high fat chow (HFC) to concentrated air particulate matter (CAPs) or filtered air for 6 weeks, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed HFC, the hepatic inflammatory grade (3.00 +/- 0.00 vs. 1.50 +/- 0.71, P < 0.001) and fibrosis stage (1.00 +/- 0.00 vs. 0.60 +/- 0.52, P = 0.023) were both significantly higher in mice exposed to CAPs versus filtered air, respectively. Increased numbers of Kupffer cells contained PM in CAPs-exposed mice scores of (2.00 +/- 0.94 vs. 0.20 +/- 0.42, respectively, P < 0.001). PM exposure increased IL-6 secretion up to seven-fold in a dose-dependent manner by isolated wild-type but not TLR4(-/-) Kupffer cells (P < 0.050). In conclusion, ambient PM(2.5) exposure may be a significant risk factor for NAFLD progression.
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Drug-induced steatohepatitis leading to cirrhosis: long-term toxicity of amiodarone use.
Semin. Liver Dis.
PUBLISHED: 10-13-2009
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Nonalcoholic steatosis/steatohepatitis is the most common cause for abnormal liver chemistries. Apart from metabolic syndrome, drugs may also lead to development of steatohepatitis that may, rarely, progress to cirrhosis and portal hypertension. We discuss a case of amiodarone-induced steatohepatitis with advanced fibrosis, presenting with hepatic decompensation and portal hypertension manifesting as ascites and recurrent esophageal variceal hemorrhage. Amiodarone is a lipophilic drug that concentrates in the liver and usually, over a period of time, leads to toxicity related to drug accumulation. There is marked histological similarity between amiodarone-induced liver disease and alcoholic and nonalcoholic steatohepatitis. The clinical manifestations of amiodarone-induced hepatotoxicity and the mechanism of toxicity are also discussed.
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Human CD34+ cells are capable of generating normal and JAK2V617F positive endothelial like cells in vivo.
Blood Cells Mol. Dis.
PUBLISHED: 08-10-2009
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Endothelial like cells (ELCs) are thought to originate from either a hierarchy of endothelial progenitor cells (EPC), monocytes or monocyte derived multipotent progenitor cells (MOMCs). In this report, the ability of CD34(+) cells to generate ELC in vivo was examined using an immunodeficient mouse transplant assay system. The Philadelphia chromosome negative (Ph(-)) myeloproliferative neoplasms (MPN) are associated with the acquired mutation, JAK2V617F. In order to further examine the ability of cord blood and JAK2V617F positive MPN CD34(+) cells to generate ELC, CD34(+) cells were transplanted into NOD/SCID mice. Cells within the livers and lungs of recipient mice had phenotypic and molecular properties of human ELC as examined using RT-PCR, flow cytometric analysis and fluorescence microscopy. These cells possessed either human wild type JAK2 or JAK2V617F indicating that they were derived from the transplanted human cells and that a fraction of such cells were involved by the malignant process. Furthermore, human CD144(+) cells isolated from the livers of recipient mice formed clusters in vitro composed of ELC, which contained either wild type JAK2 or JAK2V617F suggesting that these cells are derived from either MOMC or EPC that have an extensive proliferative capacity as well as some degree of self renewal capacity. These studies indicate that adult CD34(+) cells can be affected by JAK2V617F and that they can generate ELC which might play a role in the development of thrombosis in patients with MPN.
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Graft rejection occurring in post-liver transplant patients receiving cytotoxic chemotherapy: a case series.
Liver Transpl.
PUBLISHED: 05-30-2009
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Liver transplant recipients are known to be at increased risk for the development of de novo neoplasms or the recurrence of preexisting malignancies, and this is possibly related to the use of immunosuppressive medication. Little is known about the effects of cytotoxic chemotherapy on graft function after transplantation. A retrospective chart and pathology database review was undertaken to identify post-liver transplant patients developing rejection during chemotherapy. All liver biopsies were reviewed by a hepatopathologist. Three patients were identified. All patients were diagnosed with cancer within 7 years of liver transplantation; two-thirds died soon after the diagnosis of malignancy. Rejection occurred soon after chemotherapy was started. All patients were receiving prednisone and tacrolimus (trough levels: 2.1-4.8 ng/mL). One patient developed plasma cell hepatitis (de novo autoimmune hepatitis). There was no histologic evidence of hepatotoxicity due to the chemotherapeutic agents. Cytotoxic chemotherapy should be used in liver transplant recipients with caution, and immunosuppressant doses should be maintained at therapeutic levels, as patients may be at risk for allograft rejection. Treatment of rejection or plasma cell hepatitis in this setting should be undertaken in a timely and aggressive fashion to prevent chronic ductopenic rejection.
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Hepatic stellate cells express functional CXCR4: role in stromal cell-derived factor-1alpha-mediated stellate cell activation.
Hepatology
PUBLISHED: 05-13-2009
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Chemokine interactions with their receptors have been implicated in hepatic stellate cell (HSC) activation. The hepatic expression of CXCR4 messenger RNA is increased in hepatitis C cirrhotic livers and plasma levels of its endogenous ligand, stromal cell-derived factor-1alpha (SDF-1alpha), correlate with increased fibrosis in these patients. The expression of CXCR4 by HSCs has not been reported. We therefore examined whether HSCs express CXCR4 in vivo and in vitro and explored whether SDF-1alpha/CXCR4 receptor engagement promotes HSC activation, fibrogenesis, and proliferation. The hepatic protein expression of both CXCR4 and SDF-1alpha is increased in hepatitis C cirrhotic livers and immunoflourescent and immunohistochemical staining confirms that HSCs express CXCR4 in vivo. Immortalized human stellate cells as well as primary human HSCs express CXCR4, and cell surface receptor expression increases with progressive culture-induced activation. Treatment of stellate cells with recombinant SDF-1alpha increases expression of alpha-smooth muscle actin and collagen I and stimulates a dose-dependent increase in HSC proliferation. Inhibitor studies suggest that SDF-1alpha/CXCR4-dependent extracellular signal-regulated kinase 1/2 and Akt phosphorylation mediate effects on collagen I expression and stellate cell proliferation.
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The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome.
Blood
PUBLISHED: 03-17-2009
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Patients with myeloproliferative disorders are at a high risk of developing thrombotic events. Several investigators have hypothesized that endothelial cell (EC) abnormalities might contribute to this prothrombotic state. Budd-Chiari syndrome (BCS) and portal vein thrombosis have been reported to be associated with JAK2V617F-positive hematopoiesis. We explored whether JAK2V617F was present in ECs in the vessels of polycythemia vera (PV) patients with BCS using laser capture microdissection followed by nested polymerase chain reaction or reverse-transcribed polymerase chain reaction. The ECs of the 2 BCS patients with PV were homozygous for the JAK2V617F and were shown to express transcripts characteristic of ECs but not hematopoietic cells. ECs of the other BCS patient with PV and 2 patients with hepatoportal sclerosis without PV contained exclusively wild-type JAK2. The presence of JAK2V617F in both ECs and hematopoietic cells belonging to BCS patients with PV indicate that ECs in PV are involved by the malignant process and that in a subpopulation of the patients the disease might originate from a common cell of origin for hematopoietic and ECs.
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Rapid reversal of parenteral-nutrition-associated cirrhosis following isolated intestinal transplantation.
J. Gastrointest. Surg.
PUBLISHED: 03-06-2009
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Liver disease and the development of hepatic fibrosis are complications associated with total parenteral nutrition (TPN). Patients developing cirrhosis and portal hypertension in the setting of intestinal failure have a high mortality and may require combined liver and intestinal transplantation which carries much higher morbidity and mortality than isolated intestinal transplantation.
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A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma.
Gastroenterology
PUBLISHED: 02-13-2009
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Hepatocellular carcinoma (HCC) recurs in approximately 70% of cases after resection. Vascular invasion by tumor cells can be classified as gross or microscopic (microvascular invasion [mVI]) and is a risk factor for recurrence. We examined a large cohort of patients with HCC who were treated by resection to identify features of mVI that correlated with recurrence and survival.
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Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo.
J. Hepatol.
PUBLISHED: 02-04-2009
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The success of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC) has focused interest on the role of Ras signaling in this malignancy. We investigated the molecular alterations of the Ras pathway in HCC and the antineoplastic effects of sorafenib in combination with rapamycin, an inhibitor of mTOR pathway, in experimental models.
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Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection.
Clin. Infect. Dis.
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We and others have shown that primary hepatitis C (HCV) infection in men infected with human immunodeficiency virus (HIV) causes early-onset liver fibrosis; however, little is known about the long-term natural history of the liver disease in these HIV-infected men.
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Fulminant hepatic failure attributed to ackee fruit ingestion in a patient with sickle cell trait.
Case Rep Transplant
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We report a case of fulminant liver failure resulting in emergent liver transplantation following 3 weeks of nausea, vomiting, and malaise from Jamaican Vomiting Sickness. Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks. It is characterized by acute gastrointestinal illness and hypoglycemia. In severe cases, central nervous system depression can occur. In previous studies, histologic sections taken from patients with Jamaican Vomiting Sickness have shown hepatotoxicity similar to that seen in Reye syndrome and/or acetaminophen toxicity. We highlight macroscopic and microscopic changes in the liver secondary to hepatoxicity of Ackee fruit versus those caused by a previously unknown sickle cell trait. We discuss the clinical variables and the synergistic hepatotoxic effect of Ackee fruit and ischemic injury from sickled red blood cells, causing massive hepatic necrosis in this patient.
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Diffusion-weighted imaging of the liver with multiple b values: effect of diffusion gradient polarity and breathing acquisition on image quality and intravoxel incoherent motion parameters--a pilot study.
Radiology
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To optimize intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging by estimating the effects of diffusion gradient polarity and breathing acquisition scheme on image quality, signal-to-noise ratio (SNR), IVIM parameters, and parameter reproducibility, as well as to investigate the potential of IVIM in the detection of hepatic fibrosis.
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Antifibrotic activity of sorafenib in experimental hepatic fibrosis: refinement of inhibitory targets, dosing, and window of efficacy in vivo.
Dig. Dis. Sci.
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Sorafenib, which is approved for treatment of HCC, has also shown promising antifibrotic activity, and therefore refinement of its dosing requirements and window of efficacy are important goals prior to antifibrotic clinical trials.
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Hepatocellular carcinoma in a noncirrhotic patient with HIV: a case report and review of the literature.
Semin. Liver Dis.
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A 59-year-old man with human immunodeficiency virus (HIV) was referred for persistently elevated liver enzyme activities. His HIV was well controlled on antiretroviral therapy and his viral load was undetectable. He had no history of chronic liver disease and had minimal alcohol intake. He was asymptomatic and his physical exam was unremarkable without any stigmata of liver disease. Beyond the elevations in alkaline phosphatase and gamma-glutamyl transferase, the rest of his laboratory work, including viral hepatitis serologies and serum ?-fetoprotein, was within normal limits. A computed tomography (CT) scan revealed a mildly nodular liver but hepatic mass or ascites was not seen. He was subsequently followed every 3 to 6 months without any change in his clinical symptoms, laboratory values, or imaging tests. Two years after the original visit, the patient presented with acute onset of abdominal pain, an AFP of 15.8 ng/mL, and a 9-cm hepatic mass on imaging. Given his preserved liver function, he underwent right hepatic lobectomy. Histologic examination of the resected tissue was consistent with hepatocellular carcinoma (HCC). The uninvolved liver was noncirrhotic and unremarkable except for mild portal inflammation. As the vast majority of HIV patients who develop HCC have established chronic liver diseases such as hepatitis B and/or C along with cirrhosis, this case of HCC in an HIV patient without cirrhosis or viral hepatitis is rare. Although current screening guidelines recommend imaging only for patients with HIV and hepatitis B/C cirrhosis, closer monitoring may be important in HIV patients with even subtle liver dysfunction.
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Plasma cell hepatitis (de-novo autoimmune hepatitis) developing post liver transplantation.
Curr Opin Organ Transplant
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Cases of de-novo autoimmune hepatitis/plasma cell hepatitis (PCH) are increasingly being diagnosed by liver transplant centers. Its pathogenesis is poorly understood but this entity appears to be a variant of rejection. Herein, we review recent clinical reports of patients developing PCH.
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Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.
Gastroenterology
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Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection.
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Hepatoportal sclerosis: CT and MRI appearance with histopathologic correlation.
AJR Am J Roentgenol
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The purposes of this study were to describe the spectrum of cross-sectional imaging findings of pathologically proven hepatoportal sclerosis and to compare the features of advanced and nonadvanced hepatoportal sclerosis.
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Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues.
Gastroenterology
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The pathogenesis of liver fibrosis involves activation of hepatic stellate cells, which is associated with depletion of intracellular lipid droplets. When hepatocytes undergo autophagy, intracellular lipids are degraded in lysosomes. We investigated whether autophagy also promotes loss of lipids in hepatic stellate cells to provide energy for their activation and extended these findings to other fibrogenic cells.
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Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal.
Ann. Surg. Oncol.
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Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.
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Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-? and prevents early alcohol-induced liver injury in mice.
Hepatology
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Rationale: Although osteopontin (OPN) is induced in alcoholic patients, its role in the pathophysiology of alcoholic liver disease (ALD) remains unclear. Increased translocation of lipopolysaccharide (LPS) from the gut is key for the onset of ALD since it promotes macrophage infiltration and activation, tumor necrosis factor-? (TNF?) production and liver injury. Since OPN is protective for the intestinal mucosa, we postulated that enhancing OPN expression in the liver and consequently in the blood and/or in the gut could protect from early alcohol-induced liver injury. Results: Wild-type (WT), OPN knockout (Opn(-/-) ) and transgenic mice overexpressing OPN in hepatocytes (Opn(HEP) Tg) were chronically fed either the control or the ethanol Lieber-DeCarli diet. Ethanol increased hepatic, plasma, biliary and fecal OPN more in Opn(HEP) Tg than in WT mice. Steatosis was lesser in ethanol-treated Opn(HEP) Tg mice as shown by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower ALT activity, hepatocyte ballooning degeneration, LPS levels, the inflammation score and the number of macrophages and TNF?(+) cells. To establish if OPN could limit LPS availability and its noxious effects in the liver, binding studies were performed. OPN showed affinity for LPS and the binding prevented macrophage activation, reactive oxygen and nitrogen species generation and TNF? production. Treatment with milk OPN (m-OPN) blocked LPS translocation in vivo and protected from early alcohol-induced liver injury. Conclusion: Natural induction plus forced overexpression of OPN in the liver and treatment with m-OPN protect from early alcohol-induced liver injury by blocking the gut-derived LPS and TNF? effects in the liver. (Hepatology 2013;).
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.