Abstract:
BACKGROUND & AIMS:Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in elucidating the aetiology of NC-SVT. METHODS:DNA samples from 80 patients (75 with idiopathic or exclusively local factor [Idiop/loc-NC-SVT] and 5 with MPN and NC-SVT [SVT-MPN] negative for Janus kinase 2 gene [JAK2] [V617F and exon 12], calreticulin gene [CALR], and thrombopoietin gene [MPL] mutations by classic techniques) were analysed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR, and MPL genes were categorised as high-molecular-risk (HMR) variants or variants of unknown significance. RESULTS:In 2/5 triple-negative SVT-MPN cases (40%), a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with Idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining Idiop/loc-NC-SVT had at least 1 HMR variant. Sixty-two patients with Idiop/loc-NC-SVT were not receiving long-term anticoagulation and 5 of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR variants than in those without. CONCLUSIONS:NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR variants in approximately one-third of patients with Idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT. LAY SUMMARY:Next-generation sequencing (NGS) performs massive sequencing of DNA allowing the simultaneous evaluation of multiple genes even at very low mutational levels. Application of this technique in a cohort of patients with non-cirrhotic non-tumoral portal vein thrombosis (NC-SVT) and a negative study for thrombophilic disorders was able to identify patients with a mutation in exon 12 not previously detected by conventional techniques. Moreover, NGS detected High Molecular Risk (HMR)-variants (Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes) in approximately one third of patients. These patients appear to be at increased risk of rethrombosis. All these findings supports NGS as a potential useful tool in the management of NC-SVT.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Magaz M,Alvarez-Larrán A,Colomer D,López-Guerra M,García-Criado MÁ,Mezzano G,Belmonte E,Olivas P,Soy G,Cervantes F,Darnell A,Ferrusquía-Acosta J,Baiges A,Turon F,Hernández-Gea V,García-Pagán JCdoi
10.1016/j.jhep.2020.06.045subject
Has Abstractpub_date
2021-01-01 00:00:00pages
89-95issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(20)30456-6journal_volume
74pub_type
杂志文章abstract:BACKGROUND & AIMS:Reactive cholangiocytes acquire a neuroendocrine-like phenotype, with synthesis and local release of neuropeptides and hormones. The mechanism that drives such phenotypical changes is still undefined. Pancreatic Duodenal Homeobox-1 (PDX-1) is a transcription factor required for pancreatic development,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.04.022
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND/AIMS:This study aims at describing the natural history and outcome of small duct primary sclerosing cholangitis (PSC). METHODS:Thirty-two patients with small duct PSC were studied. The average time taken for diagnosis was 69 (1-168) months. The median follow-up time was 63 (1-194) months. RESULTS:All patie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00036-3
更新日期:2002-05-01 00:00:00
abstract::A case of HIV superinfection observed in an HBsAg/HBeAg-positive male homosexual with chronic persistent hepatitis is described. Soon after the appearance of clinical and serological features of acute HIV infection, a rapid fall to a normal value of ALT was noted with simultaneous recrudescence of HBV replication last...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80478-1
更新日期:1988-10-01 00:00:00
abstract:BACKGROUND/AIMS:Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. METHODS:The JNK activati...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.07.037
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND & AIMS:Liver failure is associated with progressive cytotoxic brain oedema (astrocyte swelling), which underlies hepatic encephalopathy (HE). Ammonia and superimposed inflammation are key synergistic factors in HE, but the mechanism(s) involved remain unknown. We aimed to determine whether aquaporin-4 (AQP4)...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2010.02.020
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND/AIMS:Repetitive indomethacin administration induces down-regulation of hepatic cytochrome P450 (CYP) enzymes. We tested the hypothesis that an increase in intestinal permeability by indomethacin-induced intestinal injury leads to entry of bacterial endotoxin and reaching into liver via the portal vein, resul...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00244-7
更新日期:2003-09-01 00:00:00
abstract::A quantitative immunohistochemical study of Kupffer cells in liver biopsies from alcoholics was carried out. Two markers were compared, lysozyme and an antimacrophage monoclonal antibody EMB/11. The results showed that there is no significant reduction in Kupffer cell numbers in acute and chronic alcoholic liver disea...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90005-6
更新日期:1989-03-01 00:00:00
abstract::Worldwide, the increasingly dominant model of laboratory testing is the centralised laboratory, in which automation of analytical processes increases, enabling the analysis of large numbers of samples at a relatively low cost. However, this trend does not fulfil the requirements for care of patients with chronic hepat...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2018.05.017
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND & AIMS:Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free regimen with oral direct-acting antiviral drugs are tolerable in aged patients, with fewer adverse effects than IFN-based therapies. We investigated the efficacy and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, a...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.jhep.2016.11.012
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND & AIMS:The MELD score predicts short-term mortality in patients with cirrhosis; however, some patients with low scores develop complications and die unexpectedly. Consequently, we evaluated the diagnostic accuracy of the methacetin breath test (MBT), an assay of liver metabolic function, and the MELD score, ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.07.021
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND/AIMS:Herpes simplex virus (HSV) is known to induce fulminant hepatic failure. The aim of this study is to clarify the molecular basis of liver injury in HSV-induced hepatitis. METHODS:Immunocompetent mice were inoculated with HSV or ultraviolet-inactivated HSV (UV-HSV) intravenously. Extent of liver injury ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00385-4
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND/AIMS:The pathogenesis of post-transplantation bone loss is poorly understood, although glucocorticoid therapy is believed to play an important role. In the present study we have measured plasma parathyroid hormone concentrations in the first few months after orthotopic liver transplantation, in order to exam...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80243-1
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND/AIMS:Interleukin-12 (IL-12), a cytokine with antitumor activity, was examined for the suppressive effect on hepatocellular carcinoma (HCC) in mouse model, and its mechanism of antitumor activity was analyzed. METHODS:Mice implanted with MIH-2 HCC cells were treated with recombinant mouse IL-12 (500 ng/mouse...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.05.018
更新日期:2006-11-01 00:00:00
abstract::The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in un...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80182-5
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND & AIMS:Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstone...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.08.025
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2020.11.024
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND & AIMS:Hepatic stellate cell activation is a wound-healing response to liver injury. However, continued activation of stellate cells during chronic liver damage causes excessive matrix deposition and the formation of pathological scar tissue leading to fibrosis and ultimately cirrhosis. The importance of sus...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2015.04.011
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND/AIMS:A distinct subgroup of angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been reported to suppress the development of hepatic steatosis. These effects were generally explained by selective peroxisome proliferator-activated receptor (PPAR) gamma modulating properties of ARBs, independent of thei...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.01.018
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND/AIMS:The pathogenesis of the inflammatory lesion in primary sclerosing cholangitis is unknown. The clinical picture is characterized by i.a. episodes of fever, the cause of which also remains speculative. Previous studies of bacterial isolates in the liver or bile ducts in primary sclerosing cholangitis have...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80316-4
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND & AIMS:The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. METHOD...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.05.031
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND & AIMS:The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and develop...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.12.014
更新日期:2020-05-01 00:00:00
abstract::The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with a...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2013.07.014
更新日期:2013-12-01 00:00:00
abstract::One hundred and eight patients with cirrhosis (23 grade A, 46 grade B and 39 grade C, according to Pugh's classification) underwent hemodynamic studies and plasma catecholamine concentration measurements. Blood samples were withdrawn from the pulmonary artery (n = 108), the hepatic vein (n = 108), the azygos vein (n =...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90810-x
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND/AIMS:Thrombin and MC tryptase, which are agonists for proteinase-activated receptors-1 and -2, respectively, are both increased in injured liver. We have examined if rat stellate cells express these receptors and if receptor agonists influence stellate cell activation. METHODS:Expression of mRNA for protein...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00285-9
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND/AIMS:In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. METHODS:C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched cont...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.03.026
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND/AIMS:To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment. METHODS:Eleven non-responders to previous therapy with 3-6 MU interfe...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80343-7
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND & AIMS:Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.030
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND/AIMS:In acute liver injury, fibronectin (FN) is deposited at the site of hepatocellular necrosis. We have previously shown that liver inflammatory mononuclear phagocytes (MNP), in contrast to quiescent hepatic macrophages, synthesize abundant amounts of FN. We now analyzed effects of agents known to influenc...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2003.12.013
更新日期:2004-04-01 00:00:00
abstract::The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units unti...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0168-8278(90)90166-o
更新日期:1990-01-01 00:00:00
abstract::We describe two cases of terbinafine-associated hepatic injury, in which a mixed cholestatic-hepatocellular type of hepatitis was present. In both cases extrahepatic cholestasis and viral hepatitis were excluded and involvement of other drugs was unlikely. In the first patient all abnormalities have disappeared, but i...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80146-0
更新日期:1994-07-01 00:00:00