The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver en...The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.展开更多
AIM:To investigate whether nonalcoholic fatty liver disease(NAFLD)affects coronary artery disease(CAD)and identify candidate mediators.METHODS:Patients who underwent coronary angiography were consecutively recruited.T...AIM:To investigate whether nonalcoholic fatty liver disease(NAFLD)affects coronary artery disease(CAD)and identify candidate mediators.METHODS:Patients who underwent coronary angiography were consecutively recruited.The patients were classified into four groups by coronary artery stenosis:A,insignificant;B,one-vessel disease;C,two-vessel disease;and D,three-vessel disease.Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade:0,no evidence;1,mild;2,moderate;and 3,severe.We measured not only known CAD risk factors,but also serum insulin,HOMA-index,adiponectin,interleukin-6,tumor necrosis factor-αand high-sensitivity C-reactive protein levels.RESULTS:Of the 134 patients who met the inclusion criteria,82(61.2%)had ultrasonographically diagnosed NAFLD.Among the 46 patients with CAD,37(80.4%)had evidence of a fatty liver.The two groups(A vs B-D)were significantly different in terms of age,total cholesterol,triglycerides,low-density lipoprotein levels and fatty liver.Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner(P=0.025).In binary logistic regression,NAFLD was a significant independent predictor of CAD(P=0.03,OR=1.685;95%CI:1.051-2.702).Among the candidate mediators,the serum adiponectin level showed a trend toward lowering based on CAD progression(P=0.071).CONCLUSION:NAFLD is an independent risk factor for CAD in a grade-dependent manner.Moreover,adiponectin might be related to the pathogenesis of NAFLD.展开更多
Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore ...Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.展开更多
Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFL...Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.展开更多
The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, li...The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3Kpropagated signaling by dephosphorylating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. In addition to the well-established role of PTEN as a tumor suppressor, increasing evidence now suggests that a dysregulated PTEN expression and/or activity is also linked to the development of several hepatic pathologies. Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. Thus, it appears that alterations of PTEN expression and activity in hepatocytes are common and recurrent molecular events associated with liver disorders of various etiologies. These recent f indings suggest that PTEN might represent a potential common therapeutic target for a number of liver pathologies.展开更多
AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectivel...AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to <sup>13</sup>C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD.RESULTS: Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD.CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.展开更多
Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, N...Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.展开更多
AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory...AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.展开更多
AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral ther...AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.Moreover,a direct association has been observed between serum titers of HCV and transmission rates of the virus.The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS:Fifty patients with HCV infection were included in the study.These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique.Linear regression analysis was performed between serum viral titers and liver tests.In addition,for the purpose of comparison,the subjects were divided into two groups:those with low viral liters (≤50 genome mEq/mL) and high titers (>50 mEq/mL). RESULTS:All subjects were men,with a mean±SD age of 47±7.8 years.The mean HCV RNA level in the blood was 76.3×10~5±109.1 genome equivalents/mL.There was no correlation between HCV RNA levels and age of the patients (r=0.181),and the history or amount (g/d) of alcohol consumption (r=0.07).Furthermore,no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r=0.175),bilirubin (r=0.217),ALT (r=0.06) and AST (r=0.004) levels.Similarly,no significant difference was observed between patients with low viral titers and high liters with respect to any of the parameters. CONCLUSION:Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus.These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.展开更多
BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs...BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.METHODS A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter score.Subjects were recruited from two tertiary hospitals.Genetic alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping Assay.RESULTS Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly associated.Hypertriglyceridemia,high BMI,and PNPLA3 GG are independent predictors of MAFLD.展开更多
AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease...AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease(NAFLD) patients.METHODS: Fifty-three consecutive,biopsy-proven NAFLD patients(31 males and 22 females,mean age 42.5 ± 9.6 years) and 26 age- and gender-matched,healthy controls(14 males and 12 females,mean age 39 ± 10.7 years) were included.The patientswith NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy.The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses.The histological evaluation was conducted according t o t he N AF LD ac t ivi ty scoring syst em recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.The serum LOX-1 levels were measured using an ELISA kit(Life Science Inc.USCN.Wuhan,Catalog No.E1859Hu) in both patients and healthy controls.A receiver operating characteristic(ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis(NASH) and healthy controls.A P-value < 0.05 was considered statistically significant.RESULTS: NAFLD and healthy control groups were similar in terms of age and sex.NAFLD patients consisted of 8 patients with simple steatosis(15%),27 with borderline NASH(51%) and 18 with definitive NASH(34%).Metabolic syndrome was found in 62.2% of the patients with NAFLD.The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/m L compared to 4.08 ± 4.32 ng/m L in healthy controls(P = 0.001).The LOX-1 levels were significantly different between controls,simple steatosis and NASH(borderline+definite) cases(4.08 ± 4.32 ng/m L,6.1 ± 6.16 ng/m L,8.92 ± 6.45 ng/m L,respectively,P = 0.004).When the cut-off value for the serum LOX-1 level was set at 5.35 ng/m L,and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%,respectively.CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls.Additionally,the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.展开更多
文摘The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.
基金Supported by A 2009 Research Grant from Kangwon National University
文摘AIM:To investigate whether nonalcoholic fatty liver disease(NAFLD)affects coronary artery disease(CAD)and identify candidate mediators.METHODS:Patients who underwent coronary angiography were consecutively recruited.The patients were classified into four groups by coronary artery stenosis:A,insignificant;B,one-vessel disease;C,two-vessel disease;and D,three-vessel disease.Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade:0,no evidence;1,mild;2,moderate;and 3,severe.We measured not only known CAD risk factors,but also serum insulin,HOMA-index,adiponectin,interleukin-6,tumor necrosis factor-αand high-sensitivity C-reactive protein levels.RESULTS:Of the 134 patients who met the inclusion criteria,82(61.2%)had ultrasonographically diagnosed NAFLD.Among the 46 patients with CAD,37(80.4%)had evidence of a fatty liver.The two groups(A vs B-D)were significantly different in terms of age,total cholesterol,triglycerides,low-density lipoprotein levels and fatty liver.Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner(P=0.025).In binary logistic regression,NAFLD was a significant independent predictor of CAD(P=0.03,OR=1.685;95%CI:1.051-2.702).Among the candidate mediators,the serum adiponectin level showed a trend toward lowering based on CAD progression(P=0.071).CONCLUSION:NAFLD is an independent risk factor for CAD in a grade-dependent manner.Moreover,adiponectin might be related to the pathogenesis of NAFLD.
基金Grants from the Ministry of Science and Technology of China[2018YFC1311705,2016YFC1305600,and 2016YFC1304904]the National Natural Science Foundation of China[81770842,81941017,and 81870604]+1 种基金the Shanghai Science and Technology Commission[YDZX20173100004881]the Shanghai Shen-Kang Hospital Development Center[SHDC12016202]。
文摘Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.
基金from Jeju National Univer-sity Hospital(2021-04).
文摘Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.
基金Supported by The Swiss National Science Foundation (Grant 310000-120280/1)the Foundation for Cancer Research in Swit-zerland (Grant KFS - 02502-08-2009)the Eagle Foundation and the Gertrude von Meissner Foundation (to Foti M)
文摘The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3Kpropagated signaling by dephosphorylating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. In addition to the well-established role of PTEN as a tumor suppressor, increasing evidence now suggests that a dysregulated PTEN expression and/or activity is also linked to the development of several hepatic pathologies. Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. Thus, it appears that alterations of PTEN expression and activity in hepatocytes are common and recurrent molecular events associated with liver disorders of various etiologies. These recent f indings suggest that PTEN might represent a potential common therapeutic target for a number of liver pathologies.
基金We would like to thank Kyung-Do Han from the Catholic University of Korea College of MedicineDepartment of Biostatisticsfor providing statistical support
文摘AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to <sup>13</sup>C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD.RESULTS: Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD.CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.
文摘Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.
文摘AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.
文摘AIM:The significance of hepatitis C virus (HCV) serum titers has been examined in several clinical situations. There is much evidence that patients with a lower viral load have better response rates to anti-viral therapy compared to those with higher levels.Moreover,a direct association has been observed between serum titers of HCV and transmission rates of the virus.The aim of the present study was to determine if there was any correlation between HCV viral load and the severity of liver disease. METHODS:Fifty patients with HCV infection were included in the study.These comprised of 34 subjects with a history of alcohol use and 16 non-alcoholics.Quantitative serum HCV RNA assay was carried out using the branched DNA (bDNA) technique.Linear regression analysis was performed between serum viral titers and liver tests.In addition,for the purpose of comparison,the subjects were divided into two groups:those with low viral liters (≤50 genome mEq/mL) and high titers (>50 mEq/mL). RESULTS:All subjects were men,with a mean±SD age of 47±7.8 years.The mean HCV RNA level in the blood was 76.3×10~5±109.1 genome equivalents/mL.There was no correlation between HCV RNA levels and age of the patients (r=0.181),and the history or amount (g/d) of alcohol consumption (r=0.07).Furthermore,no correlation was observed between serum HCV RNA levels and the severity of liver disease as judged by the values of serum albumin (r=0.175),bilirubin (r=0.217),ALT (r=0.06) and AST (r=0.004) levels.Similarly,no significant difference was observed between patients with low viral titers and high liters with respect to any of the parameters. CONCLUSION:Our results indicate that the severity of liver disease is independent of serum levels of hepatitis C virus.These findings are important since they have a direct impact on the current debate regarding the role of direct cytopathic effect of hepatitis C virus versus immune-mediated injury in the pathogenesis of HCV-related liver damage.
文摘BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.METHODS A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter score.Subjects were recruited from two tertiary hospitals.Genetic alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping Assay.RESULTS Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly associated.Hypertriglyceridemia,high BMI,and PNPLA3 GG are independent predictors of MAFLD.
文摘AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease(NAFLD) patients.METHODS: Fifty-three consecutive,biopsy-proven NAFLD patients(31 males and 22 females,mean age 42.5 ± 9.6 years) and 26 age- and gender-matched,healthy controls(14 males and 12 females,mean age 39 ± 10.7 years) were included.The patientswith NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy.The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses.The histological evaluation was conducted according t o t he N AF LD ac t ivi ty scoring syst em recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.The serum LOX-1 levels were measured using an ELISA kit(Life Science Inc.USCN.Wuhan,Catalog No.E1859Hu) in both patients and healthy controls.A receiver operating characteristic(ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis(NASH) and healthy controls.A P-value < 0.05 was considered statistically significant.RESULTS: NAFLD and healthy control groups were similar in terms of age and sex.NAFLD patients consisted of 8 patients with simple steatosis(15%),27 with borderline NASH(51%) and 18 with definitive NASH(34%).Metabolic syndrome was found in 62.2% of the patients with NAFLD.The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/m L compared to 4.08 ± 4.32 ng/m L in healthy controls(P = 0.001).The LOX-1 levels were significantly different between controls,simple steatosis and NASH(borderline+definite) cases(4.08 ± 4.32 ng/m L,6.1 ± 6.16 ng/m L,8.92 ± 6.45 ng/m L,respectively,P = 0.004).When the cut-off value for the serum LOX-1 level was set at 5.35 ng/m L,and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%,respectively.CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls.Additionally,the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.