Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease:an update

Non-alcoholic fatty liver disease(NAFLD) is considered to be an independent cardiovascular disease(CVD)risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis(NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease(CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness(AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis(mainly by simple non-invasive tests), CKD,and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.     

Association of non-alcoholic fatty liver disease with gallstone disease in the United States hospitalized patient population

BACKGROUND Gallstones and cholecystectomy have been proposed as risk factors for nonalcoholic fatty liver disease(NAFLD). The reason for this may be that both gallstones, as well as NAFLD share several risk factors with regards to their development. Currently, there is a lack of sufficient evidence showing an association between these clinical conditions.AIM To determine whether there is a meaningful association between gallstones and cholecystectomy with NAFLD.METHODS We queried the National Inpatient Sample database from the years 2016 and 2017 using International Classification of Diseases, 10 th revision, Clinical Modification diagnosis codes to identify hospitalizations with a diagnosis of gallstone disease(GSD)(includes calculus of gallbladder without cholecystitis without obstruction and acquired absence of gallbladder) as well as NAFLD(includes simple fatty liver and non-alcoholic steatohepatitis). Odds ratios(ORs) measuring the association between GSD(includes gallstones and cholecystectomy) and NAFLD were calculated using logistic regression after adjusting for confounding variables.RESULTS Out of 14294784 hospitalizations in 2016-2017, 159259 were found to have NAFLD. The prevalence of NAFLD was 3.3% in patients with GSD and 1% in those without. NAFLD was prevalent in 64.3% of women with GSD as compared to 35.7% of men with GSD. After controlling for various confounders associated with NAFLD and GSD, multivariate-adjusted analysis showed that there was an association between NAFLD with gallstones [OR = 6.32; 95% confidence interval(CI): 6.15-6.48] as well as cholecystectomy(OR = 1.97; 95%CI: 1.93-2.01). The association between NAFLD and gallstones was stronger in men(OR = 6.67; 95%CI: 6.42-6.93) than women(OR = 6.05; 95%CI: 5.83-6.27). The association between NAFLD and cholecystectomy was stronger in women(OR = 2.01; 95%CI: 1.96-2.06) than men(OR = 1.85; 95%CI: 1.79-1.92). P value was less than 0.001 for all comparisons.CONCLUSION NAFLD is more prevalent in women with GSD than men. The association between NAFLD and cholecystectomy/gallstones indicates that they may be risk factors for NAFLD.     

Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The relationship of NAFLD with thyroid function parameters and hypothyroidism remains controversial.AimTo clarify the effect of thyroid function parameters and hypothyroidism on the development of NAFLD and progression to nonalcoholic steatohepatitis (NASH).MethodsPubMed, EMBASE, and Cochrane library databases were searched. Study quality was assessed. Weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated.ResultsTwenty six studies involving 61,548 participants were eligible, most of which were of high quality. NAFLD/NASH patients had significantly higher TSH levels than controls in adults (NAFLD versus health: WMD = 0.105, 95%CI = 0.012–0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI = 0.005–0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136–0.944) and children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104–1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267–.703). Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180–2.183; NASH versus NAFLD: OR = 2.317, 95%CI = 1.425–3.768) and children/adolescents (NAFLD versus overweight/obese controls: OR = 2.015, 95%CI = 1.246–3.258). However, the statistical results were inconsistent among the subgroup meta-analyses of subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4 levels was heterogeneous among population.ConclusionTSH level may be an important risk factor for the development and progression of NAFLD, independent of thyroid hormones.     

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis(NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6 SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression.AIM To investigate PNPLA3 and TM6 SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients.METHODS This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients(n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis(n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis(n = 94). The control group(n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwentPNPLA3 and TM6 SF2 genotype analysis.RESULTS PNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls(P 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD(OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH(OR = 3.50, 95%CI: 1.84-6.64, P 0.001). The chance of NASH was even higher with GG homozygosis(OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity(OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis(OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6 SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls(P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features.CONCLUSION PNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6 SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.     

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.     

常见慢性疾病与新型冠状病毒肺炎患者重症化风险的系统评价及荟萃分析

目的:探讨合并各种常见慢性疾病与新型冠状病毒肺炎(COVID-19)患者重症化风险的相关性。方法:检索PubMed、Embase、Cochrane等外文数据库,中国知网数据库、万方数据库、中国生物医学文献数据库等中文数据库,以及3个预印文本网站(medRxiv、SSRN和ChinaXiv)中2020年1月24日至3月5日发表的有关重症、非重症COVID-19患者合并慢性疾病的临床和流行病学研究。分析COVID-19患者合并慢性阻塞性肺疾病、糖尿病、高血压、恶性肿瘤、心血管疾病、脑血管疾病、慢性肾脏病和慢性肝脏疾病的患病率,并计算重症患者、非重症患者常见慢性疾病患病率的比值比(odds ratio,OR)和95%可信区间(confidence interval,CI)。采用R 3.6.3软件进行荟萃分析。结果:从2455篇相关文献中筛选纳入19篇文献,共计4792例患者进行分析。COVID-19患者中男性占55.0%(95%CI 40.0%~80.0%),合并慢性疾病的总体患病率为30.4%(95%CI 24.0%~37.0%)。其中最常见的是高血压[16.9%(95%CI 14.0%~20.0%)],其次是糖尿病[8.3%(95%CI 8.0%~9.0%)]。重症COVID-19患者中男性的比例高于非重症患者(64.4%比52.8%,OR=1.49,95%CI 1.08~2.05,Z=4.63,P<0.01)。重症患者合并慢性阻塞性肺疾病、脑血管疾病、糖尿病、慢性肾脏病、高血压、心血管疾病、恶性肿瘤的患病率分别是非重症患者的5.77倍(95%CI 3.80~8.74)、4.47倍(95%CI 2.71~7.38)、3.55倍(95%CI 2.86~4.40)、3.05倍(95%CI 1.76~5.28)、2.82倍(95%CI 1.96~3.97)、2.39倍(95%CI 1.77~3.23)、2.15倍(95%CI 1.27~3.66),两组间差异均有统计学意义(Z=8.37、6.01、11.60、4.20、5.46、5.71、3.12,均P<0.01)。重症患者慢性肝脏疾病的患病率与非重症患者相比差异无统计学意义(OR=1.35,95%CI 0.84~2.17,P=0.11)。结论:伴有慢性疾病的COVID-19患者重症化风险较高,由高到低依次为慢性阻塞性肺疾病、脑血管疾病、糖尿病、慢性肾脏病、高血压、心血管疾病、恶性肿瘤。     

The epidemiology of non-alcoholic steatohepatitis (NASH) in the United States between 2010-2020: a population-based study

Introduction and objectivesNon-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that can progress to liver cirrhosis, liver failure and hepatocellular carcinoma. It is the second leading cause of liver transplant in the US. We aim to investigate the prevalence, demographics and risk factors NASH patients in the US.Patients and methodsWe used a large database (Explorys IBM) that aggregates electronic health records from 26 nationwide healthcare systems. We identified adults with NASH between 2010-2020. Demographics including age, gender and race were collected. NASH risk factors including Diabetes Millets (DM), Hyperlipidemia (HLD), Hypertension (HTN) and Obesity were also collected. Cochran-Armitage test was used to assess the statistical significance of year-by-year trend. Univariable and multivariable logistic regression were used to estimate the odds ratio (OR) of risk factors.ResultsNASH annual prevalence rate increased from 1.51% in 2010 to 2.79% in 2020 (p < 0.0001). The proportion of patients with NASH by gender was 54.1% female vs 45.9% male (OR 1.04 [0.91-1.11]). Caucasian had higher odds of NASH than non-Caucasian (OR 1.42 [1.31-1.54]). NASH is strongly associated with DM and obesity (OR 18.61 [17.35-19.94]) and (OR 20.97 [17.87-23.21]), respectively. Other components of metabolic syndrome were associated with NASH to a lesser degree; HTN (OR 3.24 [3.20-3.28]) and HLD (OR 4.93 [4.85-4.01]).ConclusionThe prevalence of NASH has significantly increased in the US in the last decade. This is likely related to the increased prevalence of risk factors as well as increased awareness of the disease.     

Non-alcoholic fatty liver disease is not associated with a lower health perception

AIM: To examine the association between nonalcoholic fatty liver disease(NAFLD) and general health perception.METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a subsample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index.RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213(32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association(OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception(OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception(compared to "else") increased among men(OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity(OR = 1.01, 95%CI: 1.00-1.01, P 0.001, per every minute/week) and decreased with increasing level of BMI(OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m~2) and older age(OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception(OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed(naive) and previously diagnosed(at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician's visits(general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups.CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on selfhealth perception.     

主动脉根部内径与心血管疾病的关系

目的 分析北京社区中老年人群主动脉根部内径与心血管疾病危险因素及心血管疾病的关系.方法 2004至2005年在北京首钢地区对1061名居民进行流行病学调查,选取超声心动资料齐全者共1041名进行分析.采用超声心动图测量主动脉根部内径、左心室质量、室间隔和左心室后壁厚度以及左心室大小,同时调查相关心血管危险因素及心血管疾病.采用spearman相关计算主动脉根部内径与其他心血管危险因素的关系.采用多因素logistic回归计算主动脉根部内径与心血管疾病的关系.结果 近端升主动脉内径(AAD)和平均根部内径(MRD)与年龄、体重、体质指数(BMI)、收缩压和舒张压相关(P<0.01),还与左心房大小、左心室质量、室间隔及左心室后壁厚度,左心室大小相关(P<0.01).以AAD和MRD下四分之一位数为参考,女性AAD上四分之一位数卒中、心力衰竭、总体心血管疾病OR值分别为2.20(95%CI:1.03~4.72,P=0.04),2.62(95%CI:1.49~4.61,P=0.001),2.52(95%CI:1.51,4.21,P<0.001);MRD上四分之一位数心力衰竭、总体心血管疾病的OR值分别为2.19(95%CI:1.26~3.80,P=0.01),2.20(95%CI:1.32~3.68,P=0.002).调整年龄、BMI、吸烟史、总胆固醇、高血压和糖尿病后,上述结果不再具有统计学意义(P>0.05).结论 主动脉根部内径相关指标与某些心血管疾病危险因素相关,但不与心血管疾病独立相关,可能是心血管疾病的一个中间指标.联合主动脉根部内径及传统的心血管疾病危险因素或许可以更好地评估心血管疾病.

Abstract：

Objective To analyze the relation among aortic root dimension(ARD) measured by echocardiography, cardiovascular disease risk factors and cardiovascular disease in adult Beijing community population.Methods Echocardiography was performed in 1041 individuals in a suburban community of Beijing from 2004 to 2005. ARD and other echocardiographic parameters including left atria dimension, left ventricular mass, septal and posterior wall thickness and dimension were analyzed. Histories of cardiovascular disease as well as risk factors were obtained. Spearman correlation was used to determine the relation between ARD and other cardiovascular risk factors. Multifactorial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ARD and cardiovascular disease.ResultsAscending aortic dimension (AAD) and mean root dimension(MRD) were positively associated with age, weight, BMI, systolic and diastolic blood pressure, left atria dimension, left ventricular mass, left ventricular septal and posterior wall thickness, and left ventricular dimension. With the lowest quintile of AAD and MRD as the reference, ORs for the highest quintile of AAD for specific cardiovascular diseases in female were as follows: stroke (OR=2.20,95%CI:1.03-4.72,P=0.04),chronic heart failure (OR=2.62, 95%CI:1.49-4.61,P=0.001),total cardiovascular disease (OR=2.52, 95%CI:1.51-4.21,P<0.001).ORs of MRD were as follows: chronic heart failure (OR=2.19, 95%CI:1.26-3.80,P=0.01), total cardiovascular disease (OR=2.20, 95%CI:1.32-3.68,P=0.002). After adjustment for age, BMI, smoking status, TC,hypertension, diabetes mellitus, the ORs were not statistically significant (P>0.05).Conclusion ARD was positively associated with several CHD risk factors, but was not independent risk factor for cardiovascular disease. ARD may act as an intermediate risk factor for cardiovascular disease. Combined ARD and traditional cardiovascular disease risk factors might enhance the predict power for cardiovascular disease.     

Gallstone Disease Does Not Predict Liver Histology in Nonalcoholic Fatty Liver Disease

Background/Aims

We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score.

Methods

We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy.

Results

Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84).

Conclusions

The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.     

Impact of current treatments on liver disease,glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

Aims/hypothesis  

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD.     

非酒精性脂肪性肝炎患者外周血跨膜蛋白6超家族成员2基因表达与心血管疾病的关系

目的 探究非酒精性脂肪性肝炎(NASH)患者跨膜蛋白6超家族成员2(TM6SF2)基因表达与心血管疾病(CVD)的关系.方法 2018年9月～2020年9月我院收治的93例NASH患者,根据其是否合并CVD分为NASH组及CVD组,应用TaqMan探针法检测两组患者的TM6SF2基因rs58542936位点多态性,采用...     

非酒精性脂肪性肝病的自然史和危险因素

非酒精性脂肪性肝病(NAFLD)是一种肝组织病理学改变,与酒精性肝病相类似,但无过量饮酒史的临床病理综合征.现有的研究提示大多数NAFLD是一个良性病变,但一些患者仍可导致肝硬化、肝癌和肝功能衰竭.肥胖、胰岛素抵抗、C-反应蛋白及糖尿病、高血脂、高血压、HCV等在NAFLD的发病过程中都是重要的危险因素,因此预防和治疗相关的危险因素对于NAFLD的发生和发展至关重要.     

The association between non-alcoholic hepatic steatosis and mean platelet volume in an obese Korean population

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease. Since the prevalence of NAFLD in overweight/obese people is rather high, there is a general concern about the possibility that NAFLD may have an association with cardiovascular risk factors and atherosclerosis. Mean platelet volume (MPV) is becoming of increasing interest as a new independent cardiovascular risk factor. Accordingly, the aim of our study was to evaluate the relationship between NAFLD and MPV in obese patients. The study was performed at the health promotion center in Gangnam Severance Hospital between July 2007 and June 2008. A total of 6499 healthy subjects (age range, 20–65 years) were recruited in Seoul. We performed a cross-sectional study to evaluate the association with non-alcoholic hepatic steatosis (NAHS) and MPV in 628 obese subjects. The population was divided into three groups according to MPV values. (T1?:?MPV?≤?7.7 fL, T2?:?7.7?<?≤?8.4, T3?:?>?8.4) The odds ratios (ORs) for NAHS were calculated across all three groups. The prevalence of NAHS was significantly higher according to increased MPV values after adjustment for confounding variables. The adjusted OR for NAHS according to the three groups were 1.00, 2.01(1.14?～?3.56), and 2.12(1.11?～?4.06) in obese subjects. In summary, there was a significant association between NAHS and MPV in obese study population.     

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.     

Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evalu...     

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P 0.01),predominantly female(71.4 vs 56.3,P 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P 0.01) and Fib-4 index(1.65 vs 1.06,P 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P 0.01) and ballooning(27.3 vs 13.3,P 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.     

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.     

中老年人血清铁与非酒精性脂肪肝的相关性研究

目的:研究血清铁与非酒精性脂肪肝(NAFLD)患病风险的相关性。方法:在上海40岁以上社区居民中进行问卷调查,并进行体格检查、高分辨率超声检查以及血清铁、血脂、胰岛素、空腹及口服葡萄糖耐量试验(OGTT)2 h血糖(2hPG)、肝功能、肾功能等生化检测,对其中数据完整的2120名居民进行分析。分别采用线性回归分析血清铁离子浓度与NAFLD危险因素的相关性,多元Logistic回归模型分析血清铁与NAFLD患病风险之间的关系。结果:NAFLD的患病率为27.4%。从血清铁离子浓度第1四分位组到第4四分位组,NAFLD患病率呈增高趋势,分别为20.8%、29.2%、28.4%、31.2%(组间趋势P=0.0005)。多元Logistic回归分析显示,与血清铁离子浓度第1四分位组(≤14.3 μmol/L)相比,第2四分位组(14.4~17.8 μmol/L)、第3四分位组(17.9~21.9 μmol/L)及第4四分位组(>21.9 μmol/L)NAFLD的患病风险比值比(OR)分别是1.57[95%可信区间(CI):1.19~2.08]、1.51(95%CI:1.14~2.00)、1.72(95%CI:1.30~2.28)(趋势P=0.0005),在校正年龄、性别、吸烟、饮酒、体质量指数(BMI)、收缩压(SBP)、脂代谢指标、空腹血糖对数值(lg FPG)等相关混杂因素后,3组NAFLD患病风险OR分别是1.31(95%CI 0.91~1.89)、1.44(95%CI 0.99~2.09)、1.48(95%CI 1.01~2.19)(趋势P=0.0274)。结论:上海社区40岁以上人群中,高浓度血清铁离子与NAFLD的患病风险显著相关。     

Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and its association with cardiovascular disease

Introduction

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disease that ranges from hepatic steatosis to non-alcoholic steatohepatitis. Obesity and diabetes mellitus are the prime risk factors for NAFLD. The aim of this study was to find out the prevalence of NAFLD among patients with type 2 diabetes mellitus and to detect the association of NAFLD with cardiovascular disease in them.