Liver International
1478-3223
1478-3231
Anh Quốc
Cơ quản chủ quản: WILEY , Wiley-Blackwell Publishing Ltd
Lĩnh vực:
Hepatology
Phân tích ảnh hưởng
Thông tin về tạp chí
Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.
Các bài báo tiêu biểu
micro<scp>RNA</scp>‐122 regulates hypoxia‐inducible factor‐1 and vimentin in hepatocytes and correlates with fibrosis in diet‐induced steatohepatitis Abstract Background & Aims miR‐122 is the most abundant miRNA in the liver particularly in hepatocytes where it targets cholesterol metabolism. Steatosis, a key component of non‐alcoholic fatty liver disease, is regulated by hypoxia‐inducible factor‐1α (HIF ‐1α). Here, we hypothesized that reduced miR‐122 has a pathogenic role in steatohepatitis. Methods miR‐122 and its target genes were evaluated in mouse livers and/or isolated hepatocytes after methionine–choline‐deficient (MCD ) or methionine–choline‐supplemented (MCS ) diet. Results Liver and hepatocyte miR‐122 expression was significantly decreased in steatohepatitis. A maximum reduction in miR‐122 occurred at the fibrosis stage (8 weeks of MCD diet). MAP 3K3, a miR‐122 target gene, was induced at all stages of non‐alcoholic steatohepatitis (NASH ; 3–8 weeks) only at the mRNA level. Increased NF ‐κB activation was found in MCD diet‐fed mice and MAP 3K3 regulated the NF ‐κB DNA binding in naive hepatocytes. HIF ‐1α mRNA and DNA binding and expression of the HIF ‐1α target gene, profibrotic lysyl oxidase, was increased in advanced steatohepatitis (8 weeks). In addition, increase in vimentin and Sirius red staining (liver fibrosis) was found at 8 weeks of MCD diet. Using miR‐122 overexpression and inhibition approaches, we confirmed that HIF ‐1α, vimentin and MAP 3K3 are novel miR‐122 targets in hepatocytes. We report transcriptional repression of miR‐122 in NASH . Decreased liver miR‐122 was associated with elevated circulating miR‐122 in both exosome‐rich and protein‐rich serum fractions. Conclusions Our novel data suggest that decreased liver miR‐122 contributes to upregulation of modulators of tissue remodelling (HIF ‐1α, vimentin and MAP 3K3) and might play a role in NASH ‐induced liver fibrosis.
Tập 35 Số 2 - Trang 532-541 - 2015
Gender‐incompatible liver transplantation is not a risk factor for patient survival Abstract Background/Aims: Clinical data may be suggestive for differences in patient survival in gender‐incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively linked to circulating hormones. We therefore investigated patient survival as well as metabolism of steroids to identify possible causes of improved graft survival in gender‐mismatched OLT.Methods: We examined our single‐centre database of 1355 recipients of first liver transplants for overall patient survival by non‐parametric and parametric analysis of multivariance taking the age of recipient and donor, ischaemia time, underlying liver disease and the time period of transplantation into account. Furthermore, the metabolism of androgens in gender‐incompatible OLT was studied in cultures of primary human hepatocytes obtained from male and female patients.Results: Unlike previous studies we were unable to determine overall significant differences in patient survival in gender‐incompatible OLT, even though a statistically significant improved patient survival was observed when male donor livers were transplanted into female recipients in univariant analysis (P =0.047). However, when the overall patient management was taken into account no difference in survival was determined in multivariant analysis. Importantly, the metabolism of testosterone did not differ between male and female hepatocyte cultures, except for the production of 6‐α‐hydroxy‐testosterone (P <0.001).Conclusions: Taken collectively, clinical observations may tend to suggest a slightly improved patient survival in gender‐incompatible OLT but this cannot be explained on the bases of androgen metabolism. Overall, we view gender‐incompatible liver transplantation not to be a confounder in patient survival after OLT.
Tập 29 Số 2 - Trang 196-202 - 2009
The burden of alcoholism in fifteen years of cirrhosis hospital admissions in <scp>P</scp>ortugal Abstract Background & Aims Deploying a longitudinal perspective, we observe how cirrhosis caused mortality rates in P ortugal are converging with the levels reported in the E uropean U nion (15 countries). However, we still lack analysis of the burden of alcoholic cirrhosis in terms of hospital admissions and associated mortality. As P ortugal may be considered a paradigmatic case in E urope, our aim was to characterize the evolution of hospital admissions for alcoholic cirrhosis between 1993 and 2008 and draw conclusions for other countries. Methods Retrospective analysis of the hepatic cirrhosis admissions in 97 P ortuguese state hospitals was carried out based on the National Registry. Results We report a convergence in terms of mortality rates resulting from cirrhosis between P ortugal and E uropean U nion (a differential of 6.7 deaths per 100 000 habitants in 1994 to 0.4 in 2008). We accounted for 81 543 hospital admissions for cirrhosis: 84% for alcoholic cirrhosis and 16% for non‐alcoholic cirrhosis. Hospital admissions have increased 29% in men and with no increase in women. In the male, alcoholic cirrhosis patient group aged between 40 and 54, the rise in hospital admissions was more pronounced with an increase of around 45%. These patients underwent longer lengths of stay and reported higher mortality rates and passing away 20 years earlier than the average national expectancy of life. Conclusions These data draw attention to the burden of alcohol consumption not only in Portugal but also in other countries and its impacts on hospital systems and on policy making.
Tập 35 Số 3 - Trang 746-755 - 2015
Non‐alcoholic fatty liver disease – a common and benign finding in octogenarian patients Kagansky N, Levy S, Keter D, Rimon E, Taiba Z, Fridman Z, Berger D, Knobler H, Malnick S. Non‐alcoholic fatty liver disease – a common and benign finding in octogenarian patients.
Liver International 2004: 24: 588–594. © Blackwell Munksgaard 2004 Abstract: Background: Non‐alcoholic fatty liver disease (NAFLD), a common entity in the general population, has been shown to be linked with insulin resistance and metabolic syndrome. Several of the components of the metabolic syndrome are more common in the aged population. The aims of the current study were to determine in the aged, the prevalence and the clinical presentation of NAFLD, as well as the relation to the underlying metabolic abnormalities.Method: In this prospective study, we evaluated 91 octogenarians with a mean age of 85.56±3.76 years, who were admitted to the rehabilitation departments of a geriatric hospital. Clinical evaluation included: abdominal ultrasound (US), fasting glucose and lipid levels, serum liver enzymes, ferritin, iron and transferrin saturation. Elderly patients with NAFLD were compared with 46 young patients with NAFLD.Results: NAFLD diagnosed by US was a common finding in this aged population, is present in 42/91 patients (46.2%). No significant differences were observed between the patients with or without NAFLD in the following: age, gender, chronic illnesses, anthropometric parameters, lipid profile, fasting glucose levels, metabolic syndrome prevalence, serum levels of transaminases, ferritin and iron. Young patients with NAFLD had significantly higher serum levels of triglycerides and a significantly higher prevalence of glucose intolerance, obesity and the metabolic syndrome compared with the elderly patients with NAFLD.Conclusions: NAFLD was a common finding in our group of elderly patients and the prevalence was higher than reported in the general population. In contrast to the well‐described association between the metabolic syndrome and NAFLD in the general population, we did not find this association in the aged group. In addition, none of the patients had stigmata of advanced liver disease. These data suggest that NAFLD is a common and benign finding in the elderly population, but is not associated with the metabolic syndrome.
Tập 24 Số 6 - Trang 588-594 - 2004
Prevalence of primary non‐alcoholic fatty liver disease in a population‐based study and its association with biochemical and anthropometric measures Abstract: Background/Aims: Only a few studies have assessed the epidemiology of non‐alcoholic fatty liver disease (NAFLD). The aim was to evaluate the prevalence of primary NAFLD in a population‐based study in Israel and to determine independent risk factors.Methods: A cross‐sectional study of a subsample of the Israeli national health survey (n =352). Individuals with a known etiology for secondary NAFLD were excluded. Each participant underwent an abdominal ultrasound, biochemical tests and an anthropometric evaluation.Results: Three hundred and twenty‐six subjects (53.4% male, mean age 50.5±10.3 standard deviaton [SD]) met the inclusion criteria. The prevalence of primary NAFLD was 30% (25–35% 95% confidence intervals [CI]). NAFLD was more prevalent in men than women (38% vs. 21%; P =0.001). Compared with ultrasonography, the sensitivity of serum alanine transaminase ( ALT) for the diagnosis of primary NAFLD was 8.2%. Risk factors independently associated with NAFLD included male gender (odds ratios (OR)=2.8, 95% CI 1.5–5.3), abdominal obesity (OR=2.9, 95% CI 1.3–6.4), homeostasis model assessment (OR=5.8, 95% CI 2.0–17.2), hyperinsulinemia (OR=2.3, 95% CI 1.2–4.3, P =0.01) and hypertriglyceridemia (OR=2.4, 95% CI 1.3–4.5).Conclusions: NAFLD is prevalent in the general Israeli population and closely related to the metabolic syndrome. The use of ALT as a marker for NAFLD seriously underestimates its prevalence.
Tập 26 Số 7 - Trang 856-863 - 2006
Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm Abstract Background & Aims Nonalcoholic fatty liver disease (NAFLD) is known to increase the risk of adenomatous colonic polyps. However, the role of screening colonoscopy in patients with biopsy‐proven NAFLD in detecting advanced colorectal neoplasm is not clearly evidence‐based. Therefore, we investigated whether the histological severity of NAFLD is associated with advanced colorectal neoplasm. Methods This study included patients ≥18 years old who underwent screening colonoscopy between 2013 and 2018 within a biopsy‐evaluated prospective NAFLD cohort. Advanced colorectal neoplasm was defined as an adenomatous polyp greater than 10 mm in diameter and/or with villous histology and/or with high‐grade dysplasia or adenocarcinoma. Results Among the 476 patients with clinically suspected NAFLD, 379 patients were diagnosed with biopsy‐proven NAFLD and 97 patients had no evidence of NAFLD histologically, who were analyzed as healthy controls. The prevalence of advanced colorectal neoplasm was 11.1% (n = 53). Patients with advanced colorectal neoplasm had higher grade of steatosis (P = 0.004) and higher stage of hepatic fibrosis (P = 0.044) than those with normal colonoscopic findings or low‐grade adenomatous polyp. Multivariable logistic regression analysis revealed that the presence of nonalcoholic steatohepatitis (NASH) was an independent risk factor for both colorectal polyp (odds ratio [OR], 2.08; 95% confidential interval [CI], 1.12‐3.86; P = 0.020) and advanced colorectal neoplasm (OR, 2.81; 95% CI, 1.01‐7.87; P = 0.049). Conclusions The presence of biopsy‐proven NASH was significantly associated with an increased risk of advanced colorectal neoplasm among patients with NAFLD. This finding may alert physicians to conduct screening colonoscopy in patients with NASH to detect advanced colorectal neoplasm early.
Tập 39 Số 9 - Trang 1722-1731 - 2019
Prevalence and associated factors of non‐alcoholic fatty liver disease in patients with type‐2 diabetes mellitus Abstract Background/Aims: Diabetic patients have an increased prevalence and severity of non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence and the factors associated with the presence of ultrasonographic NAFLD in type‐2 diabetic individuals.Methods: In a cross‐sectional design study, 180 type‐2 diabetic patients were submitted to a complete clinical and laboratory evaluation and abdominal ultrasonography for NAFLD detection and grading. Statistical analysis included bivariate tests, analysis of variance (anova , for increasing severity of steatosis) and multivariate logistic regression.Results: The prevalence of ultrasonographic NAFLD was 69.4% [95% confidence interval (CI): 58.3–82.7%]. Patients with NAFLD were more obese, had a higher waist circumference and serum triglyceride and alanine aminotransferase (ALT) levels than those without steatosis. Neither diabetic degenerative complication, nor glycaemic control was associated with liver steatosis. On multivariate analysis, a high serum triglycerides level [>2.82 mmol/L, odds ratio (OR): 3.7–4.1, 95% CI: 1.2–13.3] and a high‐normal ALT level (≥40 U/L, OR: 2.5–2.7, 95% CI: 1.2–5.9) were independently associated with hepatic steatosis, together with either the presence of obesity (OR: 7.1, 95% CI: 3.0–17.0) or of increased waist circumference (OR: 4.8, 95% CI: 1.9–12.2).Conclusions: Type‐2 diabetic patients have a high prevalence of ultrasonographic NAFLD and its presence is associated with obesity, mainly abdominal, hypertriglyceridaemia and high‐normal ALT levels. Non‐alcoholic fatty liver disease in diabetic patients may develop and progress independent of the diabetes progression itself.
Tập 29 Số 1 - Trang 113-119 - 2009
Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells Abstract Background & Aims Neuropilin‐1 (NRP‐1) activates signalling pathways as multifunctional co‐receptors in cancer cells. However, its role and how it is regulated by miRNAs in cholangiocarcinoma (CCA) have not yet been investigated. Methods The expression of NRP‐1, miR‐320 and key molecules involved in cell proliferation, migration and related signalling pathways were detected by immunohistochemistry, immunoblotting and qRT‐PCR. Stable transfectants depleted of NRP‐1 were generated. The regulatory effect of miR‐320 on NRP‐1 was evaluated by luciferase reporter assays. Cell proliferation, cell cycle distribution and migration were examined. Xenograft tumour models were established to assess tumourigenesis, tumour growth and lung metastasis. Results Cholangiocarcinoma tissues expressed higher levels of NRP‐1 than adjacent normal biliary tissues, and its expression negatively correlated with miR‐320. NRP‐1 depletion inhibited cell proliferation and induced cell cycle arrest in the G1/S phase by upregulating p27, and downregulating cyclin E and cyclin‐dependent kinase 2; and reduced cell migration by inhibiting the phosphorylation of focal adhesion kinase. NRP‐1 depletion suppressed tumourigenesis, tumour growth and lung metastasis by inhibiting cell proliferation and tumour angiogenesis in experimental animals. Depletion of NRP‐1 inhibited the activation of VEGF/VEGFR2, EGF/EGFR and HGF/c‐Met pathways stimulated by respective ligands. MiR‐320 negatively regulated the expression of NRP‐1 by binding to the 3′‐UTR of NRP‐1 promoter, and miR‐320 mimics inhibited cell proliferation and migration, and the growth of established tumours in animals by downregulating NRP‐1. Conclusions The present results indicate that NRP‐1 is negatively regulated by miR‐320, and both of them may be potentially therapeutic targets for CCA.
Tập 38 Số 1 - Trang 125-135 - 2018
Evaluating the association of serum ferritin and hepatic iron with disease severity in non‐alcoholic fatty liver disease Abstract Background & Aims Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non‐alcoholic fatty liver disease (NAFLD ). However, it is unclear whether it reflects hepatic inflammation or true iron‐overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD . Methods We selected 468 patients with biopsy‐proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial cells were assessed and graded. Diagnosis of non‐alcoholic steatohepatitis (NASH ) and fibrosis staging were performed. Results A total of 122 (26%) patients had hyperferritinemia, whereas stainable hepatic iron was found in 116 (25%) patients (38% predominantly in hepatocytes, 20% in reticuloendothelial cells and 42% in both). Subjects with stainable hepatic iron, particularly those with a mixed pattern, had higher serum ferritin and transaminases but only a mixed pattern of iron deposition was among the variables significantly associated with presence of NASH . Serum ferritin was not associated with presence of NASH , however it increased with worsening fibrosis stage (F3 compared to F0‐F1), and significantly decreased in stage F4. Conclusions A mixed pattern of hepatic iron deposition is associated with the presence of steatohepatitis, while serum ferritin increases with worsening fibrosis up to pre‐cirrhotic stage. In individual NAFLD patients, serum ferritin could be evaluated as part of non‐invasive diagnostic panels but not on its own.
Tập 39 Số 7 - Trang 1325-1334 - 2019
Genetic, immunological and clinical risk factors for biliary strictures following liver transplantation Abstract Background Biliary strictures after liver transplantation (LT ) are a major cause of morbidity and reduced graft survival. Aims The purpose of this study was to investigate genetic, immunological and clinical risk factors for the occurrence of post‐LT ischaemic type biliary lesions (ITBL s) and biliary anastomotic strictures (AS ). Methods Clinical and laboratory data, chemokine receptor (CCR ) genotypes, chemotactic cytokines and anti‐major‐histocompatibility complex antibodies in serum were investigated in 162 LT patients. Results In the univariate analysis, older donor and recipient age, partial LT , high peak aspartate aminotransaminase (AST ) levels and CC chemokine receptor 5 delta32 loss‐of‐function mutation (CCR 5Δ32) were associated with ITBL , whereas LT for acute liver failure (ALF ), ABO ‐compatible non‐identical LT , presence of donor‐specific anti‐human leucocyte antigen (HLA ) class II antibodies and fractalkine receptor (CX 3CR 1)‐249II allele were associated with AS . In the multivariate analysis, CCR 5Δ32 was an independent risk factor for ITBL , whereas LT for ALF , ABO ‐compatible non‐identical LT , and CX 3CR 1‐249II allele remained predictive for AS . Serum levels of interferon‐gamma and interleukin (IL )‐6 as well as IL ‐10 were significantly increased in patients with biliary strictures. Conclusion Specific chemokine receptor polymorphisms of the recipient are associated with development of post‐LT biliary strictures. Altered cytokine profile may contribute to enhanced fibrotic tissue remodelling and biliary stricture formation. Screening of anti‐HLA antibodies might be useful for early identification of at‐risk patients who could benefit from closer surveillance and tailored immunosuppressive regimen. Our findings may have relevance for prediction and management of post‐LT biliary strictures.
Tập 32 Số 8 - Trang 1253-1261 - 2012