Liver Unit

London, United Kingdom

Liver Unit

London, United Kingdom
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Abu-Mouch S.,Liver Unit | Fireman Z.,Hillel Yaffe Medical Center | Jarchovsky J.,Hillel Yaffe Medical Center | Zeina A.-R.,Liver Unit | Assy N.,Technion - Israel Institute of Technology
World Journal of Gastroenterology | Year: 2011

AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naïve patients with chronic HCV genotype 1 infection significantly improves the viral response. © 2011 Baishideng.

Raimondi S.,Italian National Cancer Institute | Maisonneuve P.,Italian National Cancer Institute | Bruno S.,Liver Unit | Mondelli M.U.,Research Laboratories
Journal of Hepatology | Year: 2010

Recently released clinical practice guidelines and consensus conference statements point to the importance of hepatitis B virus (HBV) genotyping in therapeutic algorithms for the treatment of chronic hepatitis B. This information usually comes from post hoc analyses of clinical trials which were not designed to study associations with the HBV genotype. We have performed a literature search through to April 2009 and have selected randomized clinical trials of currently approved anti-HBV drugs providing information on HBV genotypes and (i) baseline characteristics of study subjects, (ii) any response to antiviral therapy, (iii) interaction between HBV genotypes and the type of therapy. There were several intrinsic features and weaknesses in the majority of clinical trials conducted so far which make it difficult to reach firm conclusions about the role of HBV genotypes in response to antiviral therapy. Indeed, most trials were necessarily multicenter in order to reach a sufficient statistical power, but pooling together patients of different ethnicities may have revealed false-positive associations between response to antiviral therapy and HBV genotype. Moreover, endpoint definitions, especially for the composite ones, varied substantially among studies, leading to lack of homogeneity. Finally, possible interactions between the type of therapy and the HBV genotype were only seldom analysed. The present review highlights several caveats regarding current indications proposed by the major clinical practice guidelines and consensus conference statements published thus far and emphasise the need for further long term studies in the field. © 2010 European Association for the Study of the Liver.

Raoul J.-L.,French Institute of Health and Medical Research | Sangro B.,Liver Unit | Sangro B.,CIBER ISCIII | Forner A.,University of Barcelona | And 4 more authors.
Cancer Treatment Reviews | Year: 2011

Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options. Results of an extensive literature review into the treatment of unresectable HCC with TACE were combined with our own clinical experience to identify factors that may predict survival after TACE. We also report contraindications to TACE and propose a treatment algorithm for the repetition of TACE. In addition, we have constructed a number of expert opinions that may be used as a guide to help physicians make treatment decisions for their patients with intermediate-stage HCC. The data included in the literature review related almost exclusively to conventional TACE, rather than to TACE with drug-eluting beads. Therefore, the findings and conclusions of the literature review are only applicable to the treatment of HCC with conventional TACE. Treating physicians may want to consider other treatment options for patients with intermediate-stage HCC who are not suitable for or do not respond to TACE. By distinguishing those patients who represent good candidates for TACE from those where little or no benefit might be expected, it may be possible to make better use of current treatment options and improve outcomes for patients. © 2010.

The current standard of care for the treatment of hepatitis C virus (HCV) is a combination of pegylated interferon alpha (PeglFN] -2a/2b and ribavirin for 24-48 weeks, according to the viral genotype. This treatment is associated with significant side effects and achieves sustained virologic response (SVR) in only 40%-50% of genotype 1 HCV-infected patients. The recent development of direct-acting antiviral agents (DAAs] targeting critical steps of the virus life-cycle led to a major breakthrough in the management of HCV infection. The DAAs include protease inhibitors and polymerase inhibitors. The recently approved protease inhibitors boceprevir and telaprevir, when given with PeglFN and ribavirin in HCV genotype 1 patients, result in a much higher SVR rate [70%] among treatment-naïve and treatment-experienced patients, compared with Peg-IFN and ribavirin. In specific groups of patients this enables a shorter duration of treatment. The DAA-containing regimens are approved for HCV genotype 1 infection in HCV treatment-naïve and HCV treatment-experienced including cirrhotic patients. The Israeli Ministry of Health has recently approved the use of boceprevir (Victretis) and telaprevir (Incivo) in combination with PeglFN and ribavirin for the current standard of care treatment of HCV genotype 1 patients. The consensus opinion of a panel of national HCV-experts appointed by the Israeli Association for the Study of the Liver is presented in this report. These Israeli consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.

Assy N.,Liver Unit | Assy N.,Technion - Israel Institute of Technology
World Journal of Gastroenterology | Year: 2011

Fatty liver is the most common liver disease world-wide. Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases. Hyperglycemia and hyperinsulinemia induce lipogenesis, thereby increasing the hepatic pool of fatty acids. This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue. Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease (NAFLD). Among the dietary constituents, combination of vitamin D, vitamin E, and omega-3 fatty acids shows promise for the treatment of NAFLD. © 2011 Baishideng All rights reserved.

Mangia A.,Liver Unit | Ripoli M.,Liver Unit
Hepatology International | Year: 2013

Epidemiological studies have shown an increased occurrence of metabolic disorders such as insulin resistance (IR) and steatosis in patients with hepatitis C virus (HCV) infection. IR is believed to represent one of the central clinical features of the "metabolic syndrome" and the major pathogenetic factor for type 2 diabetes mellitus. In patients with chronic HCV hepatitis, IR may have several dangerous consequences such as accelerated progression of liver fibrosis, resistance to antiviral therapy and development of hepatocellular carcinoma. According to recent evidence, the global epidemic of metabolic disorders related to incorrect diets will lead physicians to deal with 1.2 billion patients with diabetes in the world in 2025. Given the high prevalence of HCV infection in several countries, metabolic manifestations will contribute to increasing morbidity and mortality in patients with HCV chronic infection in the near future. HCV treatment, shown able to decrease both the occurrence of HCV-related IR and diabetes, may reduce the risk of the associated morbidities. © 2013 The Author(s).

Portopulmonary hypertension (PPHTN) is a rare complication in patients with portal hypertension. A role of endothelin 1 (ET-1) and other cytokines was demonstrated in primary pulmonary hypertension but not in PPHTN. We evaluated the possible role of ET-1, interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α) in the pathogenesis of PPHTN. Plasmatic concentrations of ET-1, IL-6, IL-1β, and TNF-α were measured in patients with pulmonary systolic arterial pressure (PAPs) >30 mm Hg and in patients with cirrhosis. In all, Six out of 11 patients with PAPs >30 mm Hg had PPHTN on right heart catheterization. The remaining 10 patients had an hyperdynamic circulation (HC). In PPHTN patients, ET-1 and IL-6 were significantly higher compared with HC and patients with cirrhosis. Endothelin 1 and IL-6 could be implicated in the pathogenesis of PPHTN. On the basis of these results, ET-1 receptor antagonists or anti-IL-6 could have a rationale in the treatment of PPHTN.

Assy N.,Liver Unit | Djibre A.,Liver Unit | Farah R.,Ziv Medical Center | Grosovski M.,ORT Braude College | And 2 more authors.
Radiology | Year: 2010

Purpose: To evaluate the relationship between nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) and to define determinants of CAD in patients with or without metabolic syndrome. Materials and Methods: This study was approved by the local ethics committee; informed consent was obtained. Twenty-nine subjects (mean age, 53 years ± 7 [standard deviation ]) with low to intermediate risk for CAD and with fatty liver were included. Thirty-two sex- and age-matched individuals without NAFLD served as controls. CAD was defined as a stenosis of more than 50% in at least one major coronary artery. Fatty liver was assessed by means of an attenuation of -10 HU or higher (calculated as liver attenuation minus spleen attenuation) by using computed tomography (CT), coronary plaques and stenosis by using CT coronary angiography, and biomarkers of insulin resistance, lipotoxicity, systemic inflammation, and oxidant and antioxidant status. A logistic regression analysis was performed to study multivariable associations. Results: When compared with controls, NAFLD patients showed a higher prevalence of calcified and noncalcified coronary plaques(67% vs 34% and 52% vs 29%, respectively; both P < .001), higher prevalence of nonobstructive coronary stenosis(34% vs 14%; P < .008), higher homeostasis model assessment of insulin resistance(3.8 μU/mL 3.6 vs 2.6 μ U/mL ± 3.2; P < .005) and higher triglyceride levels (208 mg/dL ± 87 vs 148 mg/dL ± 70; P < .005). Fatty liver proved to be a strong predictor of coronary atherosclerosis (odds ratio [OR], 2; P > .04), independent of indicators for metabolic syndrome (OR, 1.2; P > .2) and C-reactive protein levels(OR, 0.7; P > .4). Conclusion:Patients with NAFLD, even without metabolic syndrome, are at high risk for atherosclerosis. Assessment of NAFLD may be helpful for cardiovascular risk stratification. © RSNA, 2010.

Bosch J.,Liver Unit | Abraldes J.G.,Liver Unit | Fernandez M.,Liver Unit | Garcia-Pagan J.C.,Liver Unit
Journal of Hepatology | Year: 2010

Portal hypertension is the main cause of complications in patients with chronic liver disease. Over the past 25 years, progress in the understanding of the pathophysiology of portal hypertension was followed by the introduction of an effective pharmacological therapy, consisting mainly of treatments aimed at correcting the increased splanchnic blood flow. It is only recently that this paradigm has been changed. Progress in our knowledge of the mechanisms of increased resistance to portal blood flow, of the formation of portal-systemic collaterals, and of mechanisms other than vasodilatation maintaining the increased splanchnic blood flow have opened entirely new perspectives for developing more effective treatment strategies. This is the aim of the current review, which focuses on: (a) the modulation of hepatic vascular resistance by correcting the increased hepatic vascular tone due to hepatic endothelial dysfunction, and (b) correcting the abnormal angiogenesis associated with portal hypertension, which contributes to liver inflammation and fibrogenesis, to the hyperkinetic splanchnic circulation, and to the formation of portal-systemic collaterals and varices. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Nseir W.,Holy Family Hospital | Nassar F.,Western Galilee Hospital | Assy N.,Liver Unit | Assy N.,Technion - Israel Institute of Technology
World Journal of Gastroenterology | Year: 2010

Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and infam-mation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD. © 2010 Baishideng. All rights reserved.

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