West Jerusalem, Israel
West Jerusalem, Israel

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Maor Y.,Sheba Medical Center | Morali G.,The Liver Unit | Bashari D.,The Israeli National Haemophilia Center | Penaranda G.,Laboratoire ALPHABIO | And 3 more authors.
Haemophilia | Year: 2013

Single-nucleotide polymorphisms (SNPs) near the IL28B gene were identified as major predictors of treatment response (sustained virologic response - SVR) and spontaneous clearance of HCV. Haemophilia patients have the highest prevalence of HCV, and are a unique target for genetic studies. The Israeli population is ethnically heterogeneous; therefore, genetic variability is anticipated. To determine the IL28B haplotypes in HCV-infected haemophilia patients and association with SVR and spontaneous viral clearance. IL28B polymorphism at SNPs rs12979860 and rs8099917 was determined in sera obtained from 130 HCV-infected haemophilia patients. The frequency of the various haplotypes was analysed according to treatment response, spontaneous HCV clearance, viral load and degree of fibrosis. The CC haplotype at SNP rs12979860 was found in 31% of patients, whereas the TT genotype at SNP rs8099917 was detected in 57% of cases. SVR was achieved in 70% of patients carrying the CC haplotype (P = 0.0196 vs. CT/TT), and 50% of the TT genotype at SNP rs8099917 (P = 0.0227 vs. TG/GG). Thirty-five percent of patients carrying the CC haplotype and 26% with the TT genotype at SNP rs8099917 showed spontaneous clearance of HCV infection (P = 0.00262 vs. CT/TT; and P = 0.00371 vs. TG/GG respectively). The C-allele frequency was exceptionally high (71%) in immigrants from the Asian republics of Russia. In HCV-infected haemophilia patients, SVR was more commonly achieved among patients who had the CC (rs12979860) or TT (rs8099917) genotype. Likewise, patients who possess harbour the CC or TT genotypes were more likely to clear HCV infection spontaneously. A unique distribution of the CC genotype was observed in some ethnic groups. © 2012 Blackwell Publishing Ltd.


Tai F.W.D.,The Liver Unit | Syn W.-K.,The Liver Unit | Syn W.-K.,Institute of Hepatology | Alazawi W.,The Liver Unit | Alazawi W.,Queen Mary, University of London
Diabetic Medicine | Year: 2015

The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients. © 2015 Diabetes UK.


Zelber-Sagi S.,The Liver Unit | Zelber-Sagi S.,Haifa University | Ratziu V.,University Pierre and Marie Curie | Oren R.,The Liver Unit | Oren R.,Tel Aviv University
World Journal of Gastroenterology | Year: 2011

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. The high prevalence of NAFLDis probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. The efficacy and safety profile of pharmacotherapy in the treatment of NAFLDremains uncertain and obesity is strongly associated with hepatic steatosis; therefore, the first line of treatment is lifestyle modification. The usual management of NAFLD includes gradual weight reduction and increased physical activity (PA) leading to an improvement in serum liver enzymes, reduced hepatic fatty infiltration, and, in some cases, a reduced degree of hepatic inflammation and fibrosis. Nutrition has been demonstrated to be associated with NAFLDand Non-alcoholic steatohepatitis (NASH) in both animals and humans, and thus serves as a major route of prevention and treatment. However, most human studies are observational and retrospective, allowing limited inference about causal associations. Large prospective studies and clinical trials are now needed to establish a causal relationship. Based on available data, patients should optimally achieve a 5%-10% weight reduction. Setting realistic goals is essential for long-term successful lifestyle modification and more effort must be devoted to informing NAFLD patients of the health benefits of even a modest weight reduction. Furthermore, all NAFLDpatients, whether obese or of normal weight, should be informed that a healthy diet has benefits beyond weight reduction. They should be advised to reduce saturated/trans fat and increase polyunsaturated fat, with special emphasize on omega-3 fatty acids. They should reduce added sugar to its minimum, try to avoid soft drinks containing sugar, including fruit juices that contain a lot of fructose, and increase their fiber intake. For the heavy meat eaters, especially those of red and processed meats, less meat and increased fish intake should be recommended. Minimizing fast food intake will also help maintain a healthy diet. PA should be integrated into behavioral therapy in NAFLD, as even small gains in PA and fitness may have significant health benefits. Potentially therapeutic dietary supplements are vitamin E and vitamin D, but both warrant further research. Unbalanced nutrition is not only strongly associated with NAFLD, but is also a risk factor that a large portion of the population is exposed to. Therefore, it is important to identify dietary patterns that will serve as modifiable risk factors for the prevention of NAFLDand its complications. © 2011 Baishideng. All rights reserved.


Zelber-Sagi S.,Haifa University | Zelber-Sagi S.,The Liver Unit | Ben-Assuli O.,Ono Academic College | Rabinowich L.,The Liver Unit | And 7 more authors.
Liver International | Year: 2015

Background and Aims: Elevated serum uric acid levels reflect and also cause both oxidative stress and insulin resistance and are frequently observed in patients with the metabolic syndrome. A strong association exists between the metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to test the association between uric acid and elevated alanine aminotransferase (ALT), as a surrogate for NAFLD, using real-world data. Methods: Data used for the cross-sectional study were obtained from Maccabi Healthcare System, a 2-million member health maintenance organization in Israel. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and uric acid between 1997 and 2012. Individuals with secondary liver disease, celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was performed in subjects who were given the diagnosis of fatty liver in their medical records (n = 2628). Results: The study population included 82 608 people (32.5% men, mean age 43.91 ± 10.15 years). There was a significant positive dose-response association between serum uric acid levels and the rate of elevated serum ALT (P for trend <0.001). In multivariable model, controlling for potential confounders, the association between uric acid and elevated ALT persisted (OR = 2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association was maintained in all categories of gender and BMI. Similar results were observed among patients diagnosed with fatty liver (OR = 1.77, 1.22-2.57). Conclusions: Serum uric acid is independently associated with elevated ALT, as a surrogate for NAFLD, and thus may serve as a serum marker for liver damage and should be further investigated as a risk factor for NAFLD. © 2015 John Wiley & Sons A/S.


PubMed | The Liver Unit, Ono Academic College, Maccabi Healthcare Services and Haifa University
Type: Journal Article | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2015

Elevated serum uric acid levels reflect and also cause both oxidative stress and insulin resistance and are frequently observed in patients with the metabolic syndrome. A strong association exists between the metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to test the association between uric acid and elevated alanine aminotransferase (ALT), as a surrogate for NAFLD, using real-world data.Data used for the cross-sectional study were obtained from Maccabi Healthcare System, a 2-million member health maintenance organization in Israel. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and uric acid between 1997 and 2012. Individuals with secondary liver disease, celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was performed in subjects who were given the diagnosis of fatty liver in their medical records (n = 2628).The study population included 82,608 people (32.5% men, mean age 43.91 10.15 years). There was a significant positive dose-response association between serum uric acid levels and the rate of elevated serum ALT (P for trend <0.001). In multivariable model, controlling for potential confounders, the association between uric acid and elevated ALT persisted (OR = 2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association was maintained in all categories of gender and BMI. Similar results were observed among patients diagnosed with fatty liver (OR = 1.77, 1.22-2.57).Serum uric acid is independently associated with elevated ALT, as a surrogate for NAFLD, and thus may serve as a serum marker for liver damage and should be further investigated as a risk factor for NAFLD.


Salomone F.,Ospedale di Acireale | Godos J.,University of Catania | Zelber-Sagi S.,The Liver Unit | Zelber-Sagi S.,Haifa University
Liver International | Year: 2016

Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


PubMed | University of Catania, Ospedale di Acireale and The Liver Unit
Type: Journal Article | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2016

Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications.


PubMed | The Liver Unit
Type: Journal Article | Journal: World journal of gastroenterology | Year: 2011

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. The efficacy and safety profile of pharmacotherapy in the treatment of NAFLD remains uncertain and obesity is strongly associated with hepatic steatosis; therefore, the first line of treatment is lifestyle modification. The usual management of NAFLD includes gradual weight reduction and increased physical activity (PA) leading to an improvement in serum liver enzymes, reduced hepatic fatty infiltration, and, in some cases, a reduced degree of hepatic inflammation and fibrosis. Nutrition has been demonstrated to be associated with NAFLD and Non-alcoholic steatohepatitis (NASH) in both animals and humans, and thus serves as a major route of prevention and treatment. However, most human studies are observational and retrospective, allowing limited inference about causal associations. Large prospective studies and clinical trials are now needed to establish a causal relationship. Based on available data, patients should optimally achieve a 5%-10% weight reduction. Setting realistic goals is essential for long-term successful lifestyle modification and more effort must be devoted to informing NAFLD patients of the health benefits of even a modest weight reduction. Furthermore, all NAFLD patients, whether obese or of normal weight, should be informed that a healthy diet has benefits beyond weight reduction. They should be advised to reduce saturated/trans fat and increase polyunsaturated fat, with special emphasize on omega-3 fatty acids. They should reduce added sugar to its minimum, try to avoid soft drinks containing sugar, including fruit juices that contain a lot of fructose, and increase their fiber intake. For the heavy meat eaters, especially those of red and processed meats, less meat and increased fish intake should be recommended. Minimizing fast food intake will also help maintain a healthy diet. PA should be integrated into behavioral therapy in NAFLD, as even small gains in PA and fitness may have significant health benefits. Potentially therapeutic dietary supplements are vitamin E and vitamin D, but both warrant further research. Unbalanced nutrition is not only strongly associated with NAFLD, but is also a risk factor that a large portion of the population is exposed to. Therefore, it is important to identify dietary patterns that will serve as modifiable risk factors for the prevention of NAFLD and its complications.


PubMed | The Liver Unit
Type: Journal Article | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2015

The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients.


PubMed | The Liver Unit
Type: Journal Article | Journal: Scandinavian journal of gastroenterology | Year: 2014

INTRODUCTION. The impact of preformed donor-specific antibodies (DSA) is incompletely understood in liver transplantation. The incidence and impact of preformed DSA on early post liver transplant were assessed and these were correlated with compliment fragment C4d on allograft biopsy. METHODS. Pretransplant serum from 41 consecutive liver transplant recipients (brain dead donors; DBD = 27 and cardiac death donors; DCD = 14) were tested for class-specific anti-human leukocyte antigen (HLA) and compared against donor HLA types. Liver biopsies were taken during cold storage (t-1) and post-reperfusion (t0) stained with C4d and graded for preservation-reperfusion injury (PRI). RESULTS. Of the 41 recipients, 8 (20%) had anti-HLA class I/II antibodies pretransplant, 3 (7%) were confirmed preformed DSA; classes I and II (n=1) and class I only (n=2). No biopsies showed definite evidence of antibody-mediated rejection. Graft biopsies in overall showed only mild PRI with ischemic hepatocyte C4d pattern similar in both positive and negative DSA patients. One DSA-positive (33%) compared with four DSA-negative patients (10%) had significant early graft dysfunction; severe PRI causing graft loss from primary nonfunction was seen only in DSA-negative group. Allograft biopsy of preformed DSA-positive patient demonstrated only minimal PRI; however, no identifiable cause could be attributed to graft dysfunction other than preformed DSA. CONCLUSION. Preformed DSA are present in 5-10% liver transplant recipients. There is no association between anti-HLA DSA and PRI and C4d, but preformed DSA may cause early morbidity. Larger studies on the impact of DSA with optimization of C4d techniques are required.

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