Methylenetetrahydrofolate Reductase C677T Mutation and Nonalcoholic Fatty Liver Disease

A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is known as one of the causes of hyperhomocyteinemia. The oxidation products of homocysteine can initiate lipid peroxidation, which has a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to assess the possible role of the MTHFR C677T mutation in the progression of simple steatosis to an advanced form of NAFLD. Thirty-four patients with NAFLD diagnosed by histologic analysis and 282 healthy controls were included in the study. The discrimination of nonalcoholic steatohepatitis (NASH) from another NAFLD was made by NAFLD activity score (NAS), and a NAS≥5 was considered NASH. Patients with either NASH or nonalcoholic fatty liver (NAFL) and controls were evaluated for frequency of the MTHFR C677T mutation. The frequency of the MTHFR C677T mutation was 53.5% (CT, 44.7%; TT, 8.9%) in controls and 41.5% (CT, 37.7%; TT, 3.8%) in patients (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34–1.12). There was no statistical difference in the frequency of this genotype between patients with NAFL and those with NASH (36% [CT, 28%; TT, 8%] vs 46.4% [CT, 46.4; TT, 0%]; OR, 0.65; 95% CI, 0.22–1.96). According to this study, the MTHFR C677T mutation does not seem to be a risk factor for the progression of NAFL to NASH.     

儿童非酒精性脂肪性肝病研究进展

非酒精性脂肪性肝病（NAFLD）是导致儿童及青少年肝病的最常见原因。近年来,由于肥胖症的发病率逐年升高,NAFLD的患病率也明显增加。对于非酒精性脂肪性肝炎（NASH）的确诊及分级依赖于组织活检。一些非创伤性的检测指标及影像技术的发展有助于在NAFLD高风险人群中进行大范围筛查。在儿童患者中存在两种组织类型不同的NASH,其临床特征及人群特征也有差异。至今并未有儿童NAFLD的最佳治疗方案,但研究人员认为生活方式干预如饮食控制或锻炼具有一定作用。维生素E和二甲双胍对儿童NAFLD的治疗作用正处于临床研究之中。     

Nonalcoholic fatty liver disease in developing countries

TO THE EDITOR Nonalcoholic fatty liver disease (NAFLD) is an increasingly known medical entity with high prevalence, about 1 0 to 24 percent in general population and up to 74% in obese population[1]. The prevalence of the disease is expected to increase worldwide, as we are encountering the global obesity epidemic and the trend in developing countries toward the Western lifestyles. However, it looks that there are some differences between the demographic and epidemiologic features of NAFLD in developing and developed countries.     

Nonalcoholic fatty liver disease in severely obese individuals: The influence of bariatric surgery: Original Article

Background: Obesity is the most frequent risk factor associated with NAFLD, and bariatric surgery (BAS) is traditionally indicated for the treatment of severely obese individuals. Here, we discuss the behavior and prognosis of this liver disease following post-surgical weight loss. Aim: To evaluate the influence of the BAS on the clinical and biochemical parameters of NAFLD in severely obese patients. Methodology: An intervention study included obese individuals (BMI≥ 35kg/m²), who had been submitted to liver biopsy during BAS and had NAFLD. HAIR (hypertension, ALT and insulin resistance and BAAT (BMI, ALT, age and triglycerides) scores and FLI (Fatty Liver Index) were used to compare the patients at the time of surgery, and 12-30 months following weight loss. Results: From October 2004 to September 2007, 122 patients were diagnosed with NAFLD, 40 of whom agreed to participate in the study. The mean age was 37.7 ± 12.5 years, 60% were women and 80% had steatohepatitis (NASH) with fibrosis upon analysis of the liver biopsy performed during BAS. Mean weight loss was 46.0 ± 2.0 kg. After 21 ± 5.8 months of follow-up, a significant improvement was found in all the variables analyzed (79.3% according to the HAIR scores, 95.2% as measured by the BAAT score and 72.5% by the FLI. Conclusion: The results suggest that treatment of obesity by bariatric surgery may influence the prognosis of NAFLD. In addition to weight loss, we observed improvement in the clinical and biochemical parameters related to NAFLD, such as anthropometrics index, hypertension, aminotransferases, triglycerides and insulin resistance.     

Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.     

Nonalcoholic fatty liver disease: pharmacologic and surgical options

The last decade has seen many studies examining the prevalence and natural history of NAFLD in the United States and it is clear that this disease is likely to be an important cause of liver-related morbidity in the future. Several pharmacologic therapies have shown some promise; currently, vitamin E and insulin-sensitizing agents such as pioglitazone can be considered in appropriate cases. Conservative measures to promote weight loss still have a role to play, but the obesity epidemic in the Western World has reached such proportions that bariatric surgery is proving to be an attractive option for patients with a BMI greater than 35 to 40 kg/m2. Well-designed prospective studies are required to ensure that all of these therapies are safe and effective in the long term. Newer agents will likely be investigated as the pathogenesis of NAFLD and fibrosis progression in NASH are further elucidated.     

Predictors of Cirrhosis in Hispanic Patients with Nonalcoholic Steatohepatitis

It is estimated that 43% of patients with nonalcoholic steatohepatitis (NASH) will progress to liver fibrosis or cirrhosis. Although NASH is more common in Hispanics, most studies have been conducted on Caucasians, and there is scarce information regarding ethnic differences in this disease. The aim of this study was to identify the independent predictors of cirrhosis in Hispanic patients with NASH. A retrospective case-control study was conducted on 80 patients with biopsy-proven NASH. Forty-two were Hispanic (study group) and 38 were Caucasians controlled for age and BMI (control group). Clinical, biochemical, and histologic features were analyzed for correlation with cirrhosis. There were no significant differences in demographic features between the two groups. In multivariate analysis, independent predictors of cirrhosis among Hispanic patients were age (OR, 1.07; 95% CI, 1.01–1.14) and AST/ALT ratio (OR, 10.56; 95% CI; 2.46–45.29), while independent predictors among non-Hispanic patients were age (OR, 1.085; 95% CI, 1.0–1.186), and diabetes mellitus (OR, 6.46; 95% CI, 1.19–35.07). In patients with NASH, predictors of cirrhosis varied according to ethnic background. Age was an independent predictor in both groups, however, AST/ALT ratio was found to be an independent predictor of cirrhosis only in Hispanic patients, and diabetes mellitus only in non-Hispanic patients.     

肥胖症与非酒精性脂肪性肝病的关系及其治疗进展

非酒精性脂肪性肝病（NAFLD）是一种除外酒精和其他明确肝损因素的慢性肝脏疾病，其发病与肥胖、胰岛素抵抗等密切相关。肿瘤坏死因子（TNF）-α、脂联素等脂肪因子在NAFLD的发生、发展中起重要作用。在肝细胞脂肪变性的基础上发生氧化应激，引起炎症损伤的“二次打击”学说，是目前广泛认可的对NAFLD发病机制的解释。对肥胖患者行饮食、运动、行为、药物、手术治疗等可改善肥胖相关慢性炎症环境，是防治NAFLD重要而有效的手段。     

Nonalcoholic steatohepatitis-associated hepatocellular carcinoma:Our case series and literature review

Recently,nonalcoholic steatohepatitis(NASH) has been considered to be another cause of liver cirrhosis and hepatocellular carcinoma(HCC).The natural history and prognosis of NASH are controversial.Accordingly,we assessed the clinicopathological features of NASH-associated HCC in our experience and reviewed the literature of NASH-associated HCC.We experienced 11 patients with NASH-associated HCC(6 male,5 female;mean age 73.8 ± 4.9 years) who received curative treatments.Most(91%) patients had been diagnosed ...