Connexin32 deficiency is associated with liver injury,inflammation and oxidative stress in experimental non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non‐alcoholic steatohepatitis remains unclear. Connexin32^?/? mice and their wild‐type littermates were fed a choline‐deficient high‐fat diet. The manifestation of non‐alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read‐outs, including histopathological examination, diverse indicators of inflammation and liver damage, in‐depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid‐related biomarkers. Overall, more pronounced liver damage, inflammation and oxidative stress were observed in connexin32^?/? mice compared to wild‐type animals. No differences were found in insulin and glucose tolerance measurements and liver regeneration. However, two lipid‐related genes, srebf1 and fabp3, were upregulated in Cx32^?/? mice in comparison with wild‐type animals. These findings suggest that connexin32‐based signalling is not directly involved in steatosis as such, but rather in the sequelae of this process, which underlie progression of non‐alcoholic steatohepatitis.     

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults

Aliment Pharmacol Ther 2011; 34: 274–285

Summary

Background Non‐alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. Aim To review epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. Methods An in‐depth search of PubMed (1980–2010) was based on five search terms: ‘non‐alcoholic fatty liver disease’ OR ‘non‐alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content. Results Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre‐existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma. Conclusions Non‐alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades.     

Fatty liver and drugs

Drug-induced liver diseases (DILD) are clinico-pathologic patterns of liver injury caused by drugs or other foreign compounds. Steatohepatitis is a rare form of DILD, and drugs account for fewer than 2% of non-alcoholic steatohepatitis (NASH). Drugs known to be capable of inducing steatosis and steatohepatitis can be divided into three broad groups: those that cause steatosis and steatohepatitis independently (e.g., amiodarone, perhexiline maleate); drugs which can precipitate latent NASH (e.g., tamoxifen); drugs whic duce sporadic events of steatosis/steatohepatitis (e.g., carbamazepine). Clinical DILD syndromes include acute viral hepatitis-like injury, acute liver failure, cholestatic hepatitis,liver disease with signs of hypersensitivity, autoimmune hepatitis-like injury, acute venous-Outflow obstruction, chronic cholestasis, ciirrhosis, steatosis and steatohepatitis. The clinical picture is by no means dependent on the mechanism of injury (direct hepatotoxicity, idiosyncratic reactions, hypersensitivity reactions). Reliable diagnosis of drug-induced liver disease requires demonstration of close correlation between the patient history and clinical, laboratory, and histological data.     

Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels

Background  Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear.
Aim  To evaluate the metabolic and histological features of NAFLD patients with different ALT levels.
Methods  A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared.
Results  Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis.
Discussion  Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 × ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level.     

Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non‐alcoholic steatohepatitis

Objectives Non‐alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non‐alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non‐alcoholic steatohepatitis. Methods The seed extract was given in the drinking water to fats being fed a methionine‐choline‐deficient diet for 15 weeks. Key findings Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet‐only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal was lower in the rats given the seed extract than in the diet‐only group. In the former, liver tissue levels of transforming growth factor‐β and collagen were also decreased. Conclusions Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non‐alcoholic steatohepatitis.     

Review article: nonalcoholic fatty liver disease and hepatitis C virus--partners in crime

Background Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) are frequent causes of chronic liver disease. In recent years, there have been significant revelations as regards the relationship between NAFLD and CHC. Aim To conduct a systematic, evidence‐based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. Methods The terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatitis and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included. Results Hepatic steatosis affects up to 80% of patients with CHC and is dependent on both viral and host factors. While insulin resistance (IR) is associated with hepatic steatosis and hepatitis C virus, genotype‐specific pathogenic mechanisms have been identified and are currently the focus of intense investigation in the literature. Clinical implications of concurrent NAFLD, CHC and IR include increased disease progression, elevated risk of hepatocellular carcinoma, and decreased response to antiviral therapy. Conclusions NAFLD and IR are common in patients with CHC virus infection. IR is a driving force in the development of hepatic steatosis. Because of the clinical implications of hepatic steatosis and IR in the setting of CHC, further studies evaluating treatments, which may increase response to antiviral therapy, are needed.     

Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis

Background Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis. Aim To investigate the role of insulin sensitizers in the treatment of individuals with non‐alcoholic steatohepatitis (NASH). Methods A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 ± 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. Results With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment‐insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 ± 24.2 to 33.3 ± 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 ± 46.3 to 47.3 ± 34.5 IU/L, P < 0.001] and histological features (median non‐alcoholic fatty liver disease activity score: 5.0–3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 ± 11.1 to 30.0 ± 8.6 IU/L, P < 0.01; ALT: 66.9 ± 28.9 to 42.0 ± 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high‐sensitivity C‐reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. Conclusion Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.     

Models for non-alcoholic fatty liver disease: a link with vascular risk

Non alcoholic fatty liver disease (NAFLD) is often part of the metabolic syndrome which includes central obesity, dyslipidaemia, insulin resistance/type 2 diabetes mellitus and hypertension. In turn, NAFLD may be associated with an increased vascular risk. Several experimental models which express histological steatosis or steatohepatitis with fibrosis have been described. This review identifies those models of NAFLD with features of vascular risk.     

Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2012; 35: 66–75

Summary

Background Thiazolidinediones (TZDs) have been used in the treatment of non‐alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically. Aim To conduct a meta‐analysis of randomised, placebo‐controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH. Methods Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters. Results Four good quality RPCTs derived from three continents were included. The meta‐analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.33–3.36), 2.58 (95% CI, 1.68–3.97) and 3.39 (95% CI, 2.19–5.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.03–14.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.02–2.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment. Conclusions Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo‐controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis.     

Impact of liver steatosis on virological response in [corrected] Italian patients with chronic hepatitis C treated with peg-interferon alpha-2b plus ribavarin

BACKGROUND: Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion. AIM: To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naive patients treated with pegylated interferon alpha-2b plus ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus-related in most cases) has no impact on virological response.     

Toll‐like receptor‐4 signalling in the progression of non‐alcoholic fatty liver disease induced by high‐fat and high‐fructose diet in mice

The aim of the present study was to investigate Toll‐like receptor‐4 (TLR4) signalling at different stages of non‐alcoholic fatty liver disease (NAFLD) induced by a high‐fat, high‐fructose (HFHFr) diet in mice. Both TLR4 wild‐type (WT) and mutant (TLR4^mut) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4^mut mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non‐alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.     

Pioglitazone in the treatment of NASH: the role of adiponectin

Background Plasma adiponectin is decreased in NASH patients and the mechanism(s) for histological improvement during thiazolidinedione treatment remain(s) poorly understood. Aim To evaluate the relationship between changes in plasma adiponectin following pioglitazone treatment and metabolic/histological improvement. Methods We measured in 47 NASH patients and 20 controls: (i) fasting glucose, insulin, FFA and adiponectin concentrations; (ii) hepatic fat content by magnetic resonance spectroscopy; and (iii) peripheral/hepatic insulin sensitivity (by double‐tracer oral glucose tolerance test). Patients were then treated with pioglitazone (45 mg/day) or placebo and all measurements were repeated after 6 months. Results Patients with NASH had decreased plasma adiponectin levels independent of the presence of obesity. Pioglitazone increased 2.3‐fold plasma adiponectin and improved insulin resistance, glucose tolerance and glucose clearance, steatosis and necroinflammation (all P < 0.01–0.001 vs. placebo). In the pioglitazone group, plasma adiponectin was significantly associated (r = 0.52, P = 0.0001) with hepatic insulin sensitivity and with the change in both variables (r = 0.44, P = 0.03). Increase in adiponectin concentration was related also to histological improvement, in particular, to hepatic steatosis (r = ?0.46, P = 0006) and necroinflammation (r = ?0.56, P < 0.0001) but importantly also to fibrosis (r = ?0.29, P = 0.03). Conclusions Adiponectin exerts an important metabolic role at the level of the liver, and its increase during pioglitazone treatment is critical to reverse insulin resistance and improve liver histology in NASH patients.     

Renal function‐dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle‐aged and elderly Chinese population

相似文献   

Clinical predictors of fibrosis in patients with chronic liver disease

Aliment Pharmacol Ther 31 , 1085–1094

Summary

Background Patients with chronic liver disease and components of metabolic syndrome may be at higher risk for fibrosis. Aim To assess the impact of clinicodemographic factors on hepatic fibrosis in CLD. Methods Of 1028 chronic liver disease patients, 964 were included in the analysis. Extensive clinico‐demographic and histological data were available. Significant baseline fibrosis (METAVIR stage ≥2) and fibrosis progression (increase of ≥1 stage in subsequent biopsy) were compared between groups using univariate and multivariate analyses. Results Compared with HCV and HBV, NAFLD patients were more obese (higher BMI and waist circumference), diabetic, hypertensive and hyperlipidaemic. Significant fibrosis occurred in 55%, 43% and 20% of HCV, HBV and NAFLD, respectively. Factors independently associated with fibrosis in NAFLD included DM, elevated AST and ALT. For viral hepatitis, independent predictors of fibrosis were low platelet count (HBV and HCV), age (HBV) and elevated AST and ALT (HCV). A second biopsy was available for 96 patients with follow‐up of about 4 years. Factors independently associated with progression of fibrosis were HCV infection, higher ALT and lower platelet count. Conclusions Diabetes mellitus is an independent risk factor for fibrosis only in NAFLD. Elevated aminotransferases and/or low platelet counts are independently associated with significant baseline fibrosis or progression of fibrosis, in patients with chronic liver disease.     

Caffeine is protective in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 76–82

Summary

Background Non‐alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the most common cause of primary liver disease. Although recent studies have found that coffee drinking is protective against end stage chronic liver disease, there are scarce caffeine intake data in NAFLD specifically. Aim To investigate the effects of dietary behaviour in NAFLD patients, using four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES 2001–2008). Methods Using data from four continuous cycles of NHANES, dietary intake questionnaires that list 62 nutrition components. Logistic regression was used to identify independent predictors of NAFLD among nutrition components after adjustment for potential clinical confounders. All analyses were run using sas 9.1 and sudaan 10.0 (SAS Institute Inc., Cary, NC, USA). Results Of the 62 nutrient components used for the univariate analysis, 38% were significant (P‐value <0.05) in NAFLD with caffeine consumption being higher in the control group (P‐value <0.001). The multivariate analysis using demographics, clinical parameters and nutritional components found five factors independently associated with NAFLD [African American Race P‐value <0.001); Male gender P‐value <0.001); Obesity (BMI ≥ 30) P‐value <0.001); Caffeine intake (mg) P‐value <0.001) and total plain water consumption (g) P‐value ≤0.02)]. Conclusions Our analysis shows that caffeine intake is independently associated with a lower risk for NAFLD suggesting a potential protective effect. These data necessitate further research to elucidate the mechanism by which caffeine can protect against NAFLD.     

Are statins ‘IDEAL’ for non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and cause of elevated serum liver enzyme activities in the developed world1. Obesity, diabetes mellitus (DM), and dyslipidaemia, common components of the metabolic syndrome (MetS), are frequently associated with NAFLD; 75–100% of patients with MetS or DM have NAFLD2. NAFLD is characterized by hepatic triglyceride (TG) infiltration in the absence of alcohol abuse or chronic liver disease1. NAFLD includes a spectrum of conditions varying from steatosis to steatosis with inflammation [steatohepatitis (NASH)], necrosis, fibrosis or cirrhosis that rarely progresses to hepatocellular carcinoma3. NAFLD and NASH are the hepatic manifestations of MetS and are associated with increased cardiovascular disease (CVD) risk4. Most NAFLD/NASH patients die from CVD rather than from liver disease4,5. There is no universally accepted treatment for NAFLD1-5.     

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C

Aliment Pharmacol Ther 2011; 33: 138–148

Summary

Background Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. Aim To validate and compare the diagnostic performance of non‐invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. Methods The performances of Forns’ score, AST to platelet ratio index (APRI), FIB‐4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. Results Forns’ score, APRI, FIB‐4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB‐4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non‐1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. Conclusions Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.     

非酒精性脂肪性肝病的治疗进展

目前全球非酒精性脂肪性肝病的发病率增加,并与代谢综合征,尤其是肥胖及糖尿病密切相关.越来越多的证据表明,胰岛素抵抗是代谢综合征患者发生脂肪性肝炎的关键病因,其可增加脂肪变性及肝脏游离脂肪酸聚集,刺激氧化应激反应,促进脂质过氧化及炎症细胞因子产生.非酒精性脂肪性肝病的治疗以改善代谢综合征为主,尚缺乏已验证的疗效理想的治疗药物.近年来随着对其发病机制的深入理解,一些尚处于动物试验及前期临床研究的新药值得关注.     

Histological progression of non-alcoholic fatty liver disease in Chinese patients

BACKGROUND: Non-alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non-alcoholic fatty liver disease is not well understood especially in Asian populations. AIM: To investigate the histological progression in Chinese patients with biopsy-proven non-alcoholic fatty liver disease. METHODS: Chinese patients who had liver biopsy at least 3 years ago and confirmed to have non-alcoholic fatty liver disease were invited for a second liver biopsy. Clinical and laboratory parameters related to their liver function and metabolic syndrome were recorded and analysed. Liver biopsies were scored for the degree of steatosis, necroinflammation and fibrosis. Correlation coefficients were calculated to assess the association between changes in histological scores and metabolic parameters. RESULTS: Seventeen patients who had been followed up for a median period of 6.1 (range: 3.8-8.0) years underwent a second liver biopsy. Nine (53%) patients had progressive disease with worsening of fibrosis score. No statistically significant correlation was found between the changes in histological scores and metabolic parameters. Seven patients developed hypertension or diabetes mellitus during the period of follow-up. CONCLUSIONS: Non-alcoholic fatty liver disease is a progressive disease in Chinese patients as in their Caucasian counterparts. Diagnosis of non-alcoholic fatty liver disease may predate development of new components of metabolic syndrome.