脂肪肝方（方名调脂复肝汤）

方药：茵陈、丹参、生山楂各30克，决明子、泽泻、何首乌各20克，广郁金12克，法夏、陈皮、柴胡各10克。

抗脂肪肝1号方治疗脂肪肝30例疗效观察

目的:观察抗脂肪肝1号方治疗脂肪肝的临床疗效。方法:对30例脂肪肝患者运用抗脂肪肝1号方(组成:茵陈、小蓟、枸杞子、决明子、山楂、瓜蒌、苍术、薏苡仁、橘皮、佩兰、熟大黄、生甘草等)治疗,主要观察临床疗效及治疗前后临床症状、体征和肝功能、血脂指标的变化。结果:治愈8例,显效16例,有效3例,无效3例,总有效率90％。治疗后主要症状、体征均有明显改善,而肝功能(ALT、AST、γ-GT)及血脂(TG、TC)指标均较治疗前有显著下降(P<0.01)。治疗后B超复查肝脏脂肪性变均有不同程度的改善。结论:抗脂肪肝1号方是治疗脂肪肝的有效方剂。

Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children

AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease (NAFLD) in Chinese obese children. METHODS: Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups. Group1, consisting of 38 obese children, was an untreated control group without any intervention. Group 2, consisting of 19 obese children in summer camp, was strictly controlled only by life style intervention. Group 3, consisting of 19 obese children, received oral vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TCHO) and homeostasis model assent- insulin resistance (HOMA-IR) were measured at baseline and after one month. All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups. RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were successfully improved except in group 1. BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44 ± 0.82 vs 1.45 ± 0.80, P = 0.001; 88.58 ± 39.99 vs 63.69 ± 27.05, P = 0.040, respectively).CONCLUSION: Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children. Compared with vitamin E, lifestyle intervention is more effective. Therefore, lifestyle intervention should represent the first step in the management of children with NAFLD.

Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

AIM： To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease （NAFLD）. METHODS： A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group （n = 8） were on chow diet （Group 1）, rats （n = 6） on methionine choline-deficient diet （MCDD） （Group 2）, rats （n = 6） on MCDD enriched with olive oil （Group 3）, rats （n = 6） on MCDD with fish oil （Group 4） and rats （n = 6） on MCDD with butter fat （Group 5）. After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters. RESULTS： The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD ＋ fish oil and in MCDD ＋ butter fat groups, but not in MCDD and MCDD ＋ olive oil groups. The increase in hepatic triglycerides （TG） levels was blunted by 30% in MCDD ＋ olive oil group （0.59 ±0.09） compared with MCDD group （0.85 ±0.04, P 〈 0.004）, by 37% compared with MCDD ＋ fish oil group （0.95 ±0.07, P 〈 0.001）, and by 33% compared with MCDD ＋ butter group （0.09 ±0.1, P 〈 0.01）. The increase in serum TG was lowered by 10% in MCDD ＋ olive oil group （0.9 ±0.07） compared with MCDD group （1.05 ±0.06）. Hepatic cholesterol increased by 15-fold in MCDD group [（0.08 ±0.02, this increment was blunted by 21% in MCDD ＋ fish oil group （0.09 ±0.02）]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD ＋ olive oil, MCDD ＋ fish oil and MCDD ＋ butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group （1.58 ±0.08）, hepatic MDA contents in MCDD ＋ olive oil （3.3 ±0.6）, MCDD ＋ fish oil （3.0 ±0.4）, and MCDD ＋ butter group （2.9 ±0.36） were increased by 108%, 91% and 87%, respectively （P 〈 0.004）. Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD ＋ olive oil group （-68%）.CONCLUSION： Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity.

Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a signifi- cant correlation between hepatic steatosis, cardiovascu- lar disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to devel- op hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. There- fore, training programmes in internal medicine, gastroen- terology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and con- comittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging tech- niques and the readily available therapeutic options.

Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease （NAFLD） is highly prevalent and can result in nonalcoholic steatohepatitis （NASH） and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors （PPARs） in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.

Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia

AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.

The blind men 'see' the elephant-the many faces of fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a group of diseases with excess fat in liver in the absence of a poorly defined limit of alcohol consumption. Most common variety, a universal public health problem, is associated with insulin resistance caused by a host of genetic and epigenetic defects modulated by life style and environmental factors. In fact the term NAFLD is loose to incorporate so many etiologies except alcoholism and few other etiologies, presenting as fat in liver. However as a sign fatty liver is very important in predicting the risk of diabetes, cardiovascular disease, stroke, cirrhosis and cancer. Abnormal fat accumulation can result from several defects in nuclear receptors associated with lipid sensing, synthesis and oxidation like LXR, FXR, SREBP, ChREBP and PPAR; defects in the lipid influx-efflux channels, insulin signaling, proteins involved in fatty acid catabolism, defects in adipose tissue development and function, inappropriate nutrition and finally defects in neural regulatory mechanisms. The progress of the disease is determined by the basic defects which results in fat accumulation, an individual’s immunological response to the accumulated fat and its derivatives and the oxidant stress response. Congregation of unrelated genetic defects under same diagnosis ‘NAFLD’ can result in inefficient patient management. Further studies are required to understand the molecular basis of fatty liver to enable a personalized management of diseases presenting as fatty liver in the absence of alcohol abuse.

Role of alcohol in the regulation of iron metabolism

Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.

Nutrition and physical activity in NAFLD:An overview of the epidemiological evidence

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.

Betaine and nonalcoholic steatohepatitis: Back to the future?

Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recurrent NASH after liver transplantation. There is currently no approved therapy for NASH, and treatment is directed at risk factor modification and lifestyle changes. Betaine has been used for NASH, with mixed results, and may show promise in conjunction with other agents in clinical trials.

Blood F_2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis

AIM: To investigate oxidative stress and lipid peroxi-dation in hepatic steatosis and the underlying implica-tions in pathological mechanisms of non-alcoholic fatty liver disease (NAFLD). METHODS: F_2-isoprostanes (iPF2α-) in blood and liver samples from steatotic (n = 9) and control (n = 7) rats were measured as in vivo marker of lipid peroxida-tion by a mass spectrometric approach. The lipid pro-fi le and endogenous antioxidant status (SOD and CAT) in the rats were also analyzed. RESULTS: Signifi cantly higher levels of iPF2α-(mean 3.47 vs 2.40 pmol/mg tissue, P = 0.004) and lower activities of SOD (mean 1.26 U vs 1.40 U, P < 0.001) and CAT (mean 1026.36 U/mg vs 1149.68 U/mg pro-tein, without signifi cance) were observed in the livers of steatotic rats. Plasma total iPF2α-was signifi cantly correlated with the abnormalities of blood lipids as well as alanine aminotransferase (ALT) levels in the rats with simple steatosis, whereas no similar tendencies were observed in the control rats. CONCLUSION: Enhancement of hepatic oxidative imbalance occurring at the steatotic stage of NAFLD suggests a possibility that manifestation of the local ⅢⅢⅢoxidative damage precedes that of systemic oxidative imbalance. Predominant metabolic features of the in-creased lipid peroxidation further suggest a close asso-ciation of the oxidative imbalance and the dyslipidemia with functional deterioration of the steatotic liver. The fi ndings need to be further evaluated, especially in hu-man studies.

Effects of lifestyle modification on liver enzyme and Fibroscan in Indian patients with non-alcoholic fatty liver disease

Background and aims:Non-alcoholic fatty liver disease(NAFLD)is remarkably increasing in developing countries like India,in parallel with the increasing incidence of obesity.Lifestyle modification is a recommended treatment for NAFLD.In most of the previous studies,improvement after lifestyle modification was assessed by liver fibrosis through liver biopsy,but we cannot do a serial liver biopsy in every NAFLD patient.Liver fibrosis can also be assessed by fibroscan non-invasively in NAFLD.This study was designed to evaluate the effect of lifestyle modification on liver enzymes and Fibroscan values in a population with NAFLD.Methods:Initially,50 NAFLD patients were included in this prospective follow-up study;however,after 6 months of lifestyle modification,only 39 participants were studied.During both the first and second consultations,Fibroscan was carried out.All participants underwent a careful interview,anthropometry measurements and radiological and biochemical tests during every consultation.Results:After 6 months of lifestyle modification,Fibroscan values improved significantly(8.3160.11kPa vs 7.8760.12kPa,p¼0.009).Alanine aminotransferase(ALT)values also showed improvement during the second consultation(97.2562.62 U/L vs 66.6963.95 U/L,p<0.001).Conclusion:Measured by Fibroscan and liver enzymes,it has been found that lifestyle modification is an effective therapy to downgrade hepatic injury in NAFLD patients.Serial Fibroscan can be used to assess the treatment response in NAFLD patients due to its non-invasive nature.