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PubMed2004

Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis.

BACKGROUND AND AIM: Products of systemic lipid peroxidation are important in the pathogenesis of cardiovascular disease. Subjects with NASH have increased hepatic lipid peroxidation, but it is unknown if they have increased oxidative stress and lipid peroxidation systemically. Therefore, we conducted a study to measure the circulating levels of lipid peroxidation products and their metabolic and nutritional correlates in patients with NASH and controls. METHODS: Systemic lipid peroxidation was assessed by measuring the levels of oxidized LDL (ox-LDL) and thiobarbituric acid-reacting substances (TBARS) in 21 subjects with NASH and 19 controls. Correlations were made between serum lipid peroxidation and nutritional determinants of oxidative stress and defense, serum lipids, insulin resistance, transaminases, and liver histology. The short-term nutrient intake was analyzed by maintaining a 3-wk dietary diary. RESULTS: The serum levels of ox-LDL were significantly higher in NASH patients compared to controls (56 +/- 16 U/L vs 40 +/- 12 U/L, respectively, p < 0.001). Similarly, serum TBARS were significantly higher in NASH patients compared to controls (3.4 +/- 1.3 vs 1.8 +/- 0.9 nmols/ml, respectively, p= 0.0001). Insulin resistance was independently associated with ox-LDL (p= 0.01) and TBARS levels (p= 0.01). We found no differences in the intake of various macro- and micronutrients between the two groups and there was no association between nutrient intake and ox-LDL or TBARS. CONCLUSION: Subjects with NASH have significantly higher systemic levels of lipid peroxidation products and this could indicate an increased risk of cardiovascular disease. More studies are needed to evaluate this possibility.

Adult↗

PubMed2006

Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent problem. Treatment options are still under investigation. The primary aim of the study was to determine whether weight loss, achieved through Roux-en-Y gastric bypass (RYGBP), improved histopathology in obese patients with biopsy proven NASH. METHODS: One hundred and forty-nine patients were identified from a surgical database as having RYGBP for obesity and concomitant intra-operative liver biopsies from October 2001 to September 2003. Thirty-five patients were found to have evidence of NASH at the time of surgery. Nineteen patients were contacted and underwent repeat percutaneous liver biopsies. Biopsies were evaluated and compared in blinded fashion by an experienced hepatopathologist. Fasting lipid panel, insulin and glucose, hemoglobin A1c (HgbA1c), and liver enzymes were obtained. RESULTS: Significant differences were noted in the following variables pre- and post-bypass surgery: body mass index 46.8-28.8 kg/m2 (p < 0.001); body weight in kilograms 132.1-79.7 (p < 0.001); glucose 102.9-94.1 mg/dL (p = 0.015); Hgb A1c 5.79-5.15% (p = 0.026); high density lipoprotein 45.7-64.4 mg/dL (p < 0.001); low density lipoprotein 112-88.6 mg/dL (p = 0.003); triglycerides 132.1-97 mg/dL (p = 0.013). Significant improvements in steatosis, lobular inflammation, portal, and lobular fibrosis were noted. Histopathologic criteria for NASH were no longer found in 17/19 patients (89%). CONCLUSIONS: Weight loss after gastric bypass surgery in obese patients with NASH results in significant improvement in glucose, HgbA1c. and lipid profiles. Furthermore, RYGBP results in significant improvement in the histological features of NASH with resolution of disease in a majority of these patients.

Adult↗

PubMed2004

Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin.

Obesity and type 2 diabetes are associated with nonalcoholic steatohepatitis (NASH), but an obese/diabetic animal model that mimics human NASH remains undefined. We examined the induction of steatohepatitis and liver fibrosis in obese and type 2 diabetic db/db mice in a nutritional model of NASH and determined the relationship of the expressions of osteopontin (OPN) and leptin receptors to the pathogenesis of NASH. db/db mice and the corresponding lean and nondiabetic db/m mice were fed a diet deficient in methionine and choline (MCD diet) or control diet for 4 wk. Leptin-deficient obese and diabetic ob/ob mice fed similar diets were used for comparison. MCD diet-fed db/db mice exhibited significantly greater histological inflammation and higher serum alanine aminotransferase levels than db/m and ob/ob mice. Trichrome staining showed marked pericellular fibrosis in MCD diet-fed db/db mice but no significant fibrosis in db/m or ob/ob mice. Collagen I mRNA expression was increased 10-fold in db/db mice, 4-fold in db/m mice, and was unchanged in ob/ob mice. mRNA expressions of OPN, TNF-alpha, TGF-beta, and short-form leptin receptors (Ob-Ra) were significantly increased in db/db mice compared with db/m or ob/ob mice. Parallel increases in OPN and Ob-Ra protein levels were observed in db/db mice. Cultured hepatocytes expressed only Ob-Ra, and leptin stimulated OPN mRNA and protein expression in these cells. In conclusion, our results demonstrate the development of an obese/diabetic experimental model for NASH in db/db mice and suggest an important role for Ob-Ra and OPN in the pathogenesis of NASH.

Animals↗

PubMed2002

Nonalcoholic steatohepatitis in nondiabetic obese patients.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a major disorder in patients with persistent changes in aminotransferase activity who test negative for viral markers and autoantibodies. Although NASH has been correlated with obesity, no study has been carried out exclusively with nondiabetic obese patients. OBJECTIVES: To evaluate the occurrence of NASH in obese patients without diabetes mellitus and to assess the severity of histological involvement of the liver. PATIENTS AND METHODS: Serum aminotransferase levels were evaluated in 912 obese patients seen at an outpatient clinic in Porto Alegre, Brazil, from 1997 to 1999. Sixty-eight patients were found to have altered aminotransferase levels in more than one test. Thirty-five patients were excluded due to the presence of diabetes mellitus (n=12), the presence of viral markers (n=11), alcohol consumption (n=8) and the use of hepatotoxic drugs (n=4). NASH was diagnosed when histological findings revealed macrovesicular steatosis associated with lobular inflammatory infiltrate and hepatocellular injury. RESULTS: Of the 912 obese patients studied, 33 patients with altered aminotransferase levels underwent liver biopsy. Four patients were excluded because they had steatosis only; the remaining 29 patients (3.18%) fulfilled the diagnostic criteria established for NASH. The mean age of the 29 patients was 42.2 +/- 11.9 years; 65.52% of the patients were women. Grading of histological findings revealed mild disease in 58.6% of cases; important proliferation of fibrous tissue was absent in most cases. CONCLUSIONS: NASH is a common disease among nondiabetic obese patients with altered aminotransferase levels, and it usually manifests as a mild clinical condition, although more severe lesions may be observed.

Adult↗

PubMed2003

Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH. METHODS: This prospective study included 44 adult patients (24 men, 20 women) with a mean age of 48.90+/-7.69 years and mean body mass index (BMI) of 29.40+/-3.82. Ten patients had a history of diabetes. Serological markers for viral hepatitis were negative in all patients and there was no history of alcohol or drug abuse. Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy was performed before therapy to confirm the diagnosis. Among NASH patients, 17 normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six months. The BMI, serum lipids, liver function tests and liver density, assessed by computerized tomography, were evaluated before and after the treatment period. The BMI, serum aminotransferase levels, histological parameters (steatosis, inflammation, fibrosis scores) and liver densities were not statistically different between the groups at the beginning of therapy. RESULTS: The BMI, serum glucose, and triglyceride levels did not change in either group after the treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels reduced significantly. Liver densities increased only in group 2, probably as a result of diminishing fat content of liver. The normalization of transaminases was also more prevalent in group 2. Liver steatosis was closely correlated with liver density, but inflammation and fibrosis were not. CONCLUSIONS: The use of atorvastatin in NASH patients with hyperlipidemia was found to be both effective and safe. The benefit of statin and UDCA therapy in normolipidemic patients with NASH requires confirmation with further placebo-controlled trials.

Adult↗

PubMed2000

CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) and alcoholic liver disease have similar pathological features. Because CYP2E1 plays a key role in alcoholic liver disease with its ability to stimulate lipid peroxidation, we tested the proposal that CYP2E1 could also be a factor in the development of NASH. In a dietary model - mice fed a methionine- and choline-deficient (MCD) diet - liver injury was associated with both induction of CYP2E1 and a 100-fold increase in hepatic content of lipid peroxides. Microsomal NADPH-dependent lipid oxidases contributed to the formation of these lipid peroxides, and in vitro inhibition studies demonstrated that CYP2E1 was the major catalyst. To further define the role of CYP2E1 as an initiator of oxidative stress in NASH, Cyp2e1(-/-)mice were administered the MCD diet. CYP2E1 deficiency neither prevented the development of NASH nor abrogated the increased microsomal NADPH-dependent lipid peroxidation, indicating the operation of a non-CYP2E1 peroxidase pathway. In Cyp2e1(-/-) mice with NASH (but not in wild-type mice), CYP4A10 and CYP4A14 were upregulated. Furthermore, hepatic microsomal lipid peroxidation was substantially inhibited by anti-mouse CYP4A10 antibody in vitro. These results show that experimental NASH is strongly associated with hepatic microsomal lipid peroxidation. CYP2E1, the main enzyme associated with that process in wild-type mice, is not unique among P450 proteins in catalyzing peroxidation of endogenous lipids. We have now identified CYP4A enzymes as alternative initiators of oxidative stress in the liver.

Animals↗

PubMed2006

Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome.

CONTEXT: Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH). OBJECTIVE: The objective of the study was to determine the prevalence and characteristics of NASH and abnormal aminotransferase activity in women with PCOS. DESIGN: The study is a retrospective chart review. SETTING: The setting is an academic endocrinology clinic. PATIENTS: Patients were 200 women with PCOS, defined as irregular menses and hyperandrogenism. MAIN OUTCOME MEASURES: Biopsy-documented NASH and aminotransferase levels were the main outcome measures. RESULTS: Fifteen percent (29 of 200) had aspartate aminotransferase and/or alanine aminotransferase more than 60 U/liter. Women with aminotransferase elevations had lower high-density lipoprotein (HDL) (41 vs. 50 mg/dl, P = 0.006), higher triglycerides (174 vs. 129 mg/dl, P = 0.024), and higher fasting insulin (21 vs. 12 microIU/ml, P = 0.036) compared with women with normal aminotransferases. Six women (mean age 29 yr) with persistent aminotransferase elevations underwent liver biopsy. All six had NASH with fibrosis. Compared with the 194 of 200 PCOS women who did not undergo biopsy, women with biopsy-documented NASH had lower HDL (median 34 vs. 50 mg/dl, P < 0.001), and higher triglycerides (245 vs. 132 mg/dl, P = 0.025), fasting insulin (26 vs. 13 microIU/ml, P = 0.038), aspartate aminotransferase (144 vs. 22 U/liter, P < 0.001), and alanine aminotransferase (143 vs. 28 U/liter, P < 0.001). CONCLUSION: Abnormal aminotransferase activity is common in women with PCOS. Low HDL, high triglycerides, and high fasting insulin were associated with abnormal aminotransferase activity. Some women already had evidence of NASH with fibrosis. Further studies are needed to evaluate whether to screen PCOS women for liver disease at an earlier age than is currently recommended for the general population.

Adolescent↗

PubMed2003

Prevalence of non-alcoholic steatohepatitis in morbidly obese subjects undergoing gastric bypass.

BACKGROUND: Obesity is the most common cause of non-alcoholic steatohepatitis (NASH). This is a prospective study to determine the incidence and severity of NASH in patients undergoing Roux-en-Y gastric bypass (RYGBP) for morbid obesity. We also examined the relationship between NASH and potential risk factors. METHODS: In 48 consecutive patients at RYGBP, a core liver biopsy was obtained from the left lateral segment. A single liver pathologist reviewed the histology for steatosis, ballooning/disarray, necroinflammation, and fibrosis. RESULTS: 84% of patients were female, and average BMI was 51. 18% had WHR >1. The following risk factors were present: DM 16%; hyperlipidemia 61%; HTN 47%; and abnormal LFTs 18%. 90% had abnormal liver histology, and 56% qualified for the diagnosis of NASH. Only DM and abnormal LFTs were found to be significantly related to NASH. CONCLUSIONS: NASH is a common co-morbidity of obesity and requires systemized grading and staging to develop accurate knowledge of the incidence, severity, natural history and impact of weight loss.

Age Distribution↗

PubMed2005

Peroxisome proliferator-activated receptor alpha L162V polymorphism in nonalcoholic steatohepatitis and genotype 1 hepatitis C virus-related liver steatosis.

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) plays important roles in lipid metabolism. A recently discovered L162V polymorphism of the PPARalpha gene is associated with enhanced transcriptional activity. In this study, the frequency of L162V was investigated in nonalcoholic steatohepatitis (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis. METHODS: Seventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without steatosis) and 119 healthy controls were included. L162V polymorphism of the PPARalpha gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: PCR and RFLP analysis of the related gene segment was successful in 93%, 96%, and 100% of NASH and HCV-infected patients and controls, respectively. The frequency of the L162V polymorphism was similar in the NASH and HCV-infected patients and controls (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this polymorphism was observed in HCV-infected patients with or without significant liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. CONCLUSIONS: Neither NASH nor genotype 1 HCV-related liver steatosis seems to be associated with the PPARalpha L162V polymorphism. This polymorphism may have no association with the presence of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH and HCV-infected patients.

Adult↗

PubMed1997

Nonalcoholic steatohepatitis.

OBJECTIVE: To determine the clinical relevance of nonalcoholic steatohepatitis (NASH) and to review the available literature on the epidemiology, clinical features, histology, pathogenesis, clinical course, and management of this condition. DATA SOURCES: Pertinent articles in English identified through a MEDLINE search (1966 to the present) and the bibliographies of relevant articles. STUDY SELECTION: All studies, including case reports, evaluating the salient features and clinical profile of NASH. DATA EXTRACTION: Data were selected from all articles that fit the study selection criteria. DATA SYNTHESIS: Nonalcoholic steatohepatitis is a distinct clinical entity characterized by elevated plasma liver enzyme levels and liver biopsy findings that are identical to those seen in alcoholic hepatitis; patients with NASH, however, do not consume alcohol in quantities known to cause liver injury. Patients with NASH are typically obese, middle-aged women with asymptomatic hepatomegaly who are diabetic or hyperlipidemic and present with an unrelated medical problem. Analysis of liver biopsy specimens is the cornerstone of diagnosis; hepatic morphologic findings range from mild fatty degeneration and inflammation to cell degeneration, fibrosis, and cirrhosis with or without the presence of Mallory hyaline bodies. Elevated levels of free fatty acids in the liver are thought to be responsible for the development of steatohepatitis. Although NASH is most often a benign disease with an indolent course, patients with this condition occasionally develop cirrhosis, portal hypertension, and hepatic failure. In some cases, NASH may be reversed with weight reduction. CONCLUSION: Nonalcoholic steatohepatitis is an important differential diagnosis for asymptomatic patients with chronically elevated plasma liver enzyme levels, especially if obesity, diabetes, or hyperlipidemia are present. Analysis of liver biopsy specimens is necessary for diagnosis and must be done in all patients with unexplained abnormal liver function and negative results on a noninvasive workup. Prognosis is good in most patients. The precise role of weight reduction and ursodeoxycholic acid therapy in the favorable alteration of the natural history of this disorder needs to be addressed in large, well-controlled studies.

Female↗

PubMedDate not supplied

Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C.

BACKGROUND/AIMS: Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. METHODOLOGY: We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. RESULTS: We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). CONCLUSIONS: The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.

Adult↗

PubMed2002

Diabetes mellitus, obesity, and hepatic steatosis.

Nonalcoholic fatty liver disease is emerging as the most common liver disease in North America. The histological spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to steatohepatitis and to the most serious form--nonalcoholic steatohepatitis (NASH). An increasing body of evidence suggests that NASH is associated with the development of progressive fibrosis and eventually cirrhosis in approximately 20% of cases. These data emphasize the need to develop effective therapy for the treatment of NASH. Cases occur most commonly in obese middle age women with diabetes. However, NASH may also occur in children and normal weight men with normal glucose and lipid metabolism. The pathophysiology involves 2 steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Nascent clinical trials suggest that a number of therapies may be beneficial. These include anti-oxidants such as vitamin E and betaine, bile acid therapy with ursodeoxycholic acid, and improved insulin sensitivity with metformin. Another potential therapeutic strategy is the reduction of inflammatory cytokines.

Algorithms↗

PubMed2003

[The effects of weight reduction in reversing fatty liver changes in overweight and obese patients].

OBJECTIVE: To study the effects of weight loss on nonalcoholic steatohepatitis (NASH) in obese patients. METHODS: It is a prospective study. Blood biochemical parameters were examined in 220 overweight or obese patients without alcoholic consumption and without detectable HBsAg. Ultrasonographic examination was performed by a fixed doctor. 45 obese patients followed a program of weight loss, including diet restriction, exercise or drug for a trial period of one year. Weight, blood biochemical tests and ultrasonic examination of liver were compared before and after the trial in all the patients. RESULTS: 75.9% of the patients were diagnosed as NASH. Logistic regression analysis revealed that the risk factors of NASH were body mass index (BMI, beta = 0.926, P = 0.021), age (beta = 0.973, P = 0.021), 2-hour postprandial glucose (beta = 0.987, P = 0.012), 1-hour postprandial net insulin in serum (beta = 1.027, P = 0.032), waist circumference (beta = 1.091, P = 0.038)and low density lipoprotein cholesterol (beta = 0.980, P = 0.041). After the treatment, 65.7% of the patients with NASH improved. The level of ALT in these patients decreased significantly (P = 0.040). The improvement of NASH correlated positively with the reduction of BMI (beta = 3.032, P = 0.010), triglycerides (TG, beta = 1.041, P = 0.025) and waist circumference (beta = 1.115, P = 0.029). The decrease of ALT level correlated with the decrease of BMI (beta = 1.165, P = 0.002), TG (beta = 0.986, P = 0.005), waist circumference (beta = 0.736, P = 0.041), and the increase of high density lipoprotein cholesterol (beta = -0.772, P = 0.016). CONCLUSION: NASH is one of the most important complications of obesity. Weight loss is the mainstay of treatment for obese patients.

Adolescent↗

PubMed2004

Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis.

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.

Adult↗

PubMedDate not supplied

Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report.

INTRODUCTION: Insulin resistance plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Insulin-sensitizing drugs like metformin may have a role in the treatment of this disease. OBJECTIVE: To determine insulin resistance and the role of metformin in the treatment of NASH. METHODS: We prospectively studied 25 patients with NASH over a period of one and a half years. In addition to clinicopathological profile, we studied the insulin resistance by insulin tolerance test in 10 of them; seven of them, who did not respond to 3 months of low-calorie, low-fat diet, exercise, weight reduction and ursodeoxycholic acid (UDCA), were treated with metformin for six months. Results were compared with control groups. RESULTS: All 10 patients with NASH tested had low insulin sensitivity; there was significant difference in the rate constant for insulin sensitivity (Kitt) between patients with NASH and normal volunteers. Thirteen (52%) patients responded to dietary restriction, exercise, weight reduction and UDCA. Four of 7 patients treated with metformin had normalization of ALT. CONCLUSION: Patients with NASH have insulin resistance. Metformin may have a role in the treatment of these patients.

Adult↗

PubMed2004

[The prevalence of metabolic syndrome in patients with nonalcoholic fatty liver disease].

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD. We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. METHODS: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons who visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. RESULTS: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance was the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. CONCLUSIONS: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis.

Adult↗

PubMed2005

[Nonalcoholic steatohepatitis].

Nonalcoholic steatohepatitis (NASH) is a condition characterized by excessive deposition of fat in the liver (steatosis), inflammation and hepatocellular necrosis. While steatosis alone is generally a benign and stable condition, NASH can have a dire prognosis in a minority of patients, mainly because of fibrosis occurrence and progression to cirrhosis. Life-threatening complications such as liver failure and hepatocellular carcinoma have been described in NASH-induced cirrhosis. Insulin resistance is almost universally found in patients with NASH and the main risk factors for this condition are overweight and diabetes. Improvement in insulin sensitivity, whether achieved by diet, exercise and/or pharmacological interventions, results in a dramatic reduction of liver fat and inflammation and fibrosis as well. Therefore NASH should be viewed as the hepatic phenotypic manifestation of insulin resistance and a bona fide component of the metabolic syndrome. Liver injury should be assessed in diabetic and/or obese patients and the mechanisms by which insulin resistance promotes liver damage needs to be elucidated. The encouraging results of the use of PPARgamma agonists and, in particular, rosiglitazone, in human or experimental models of NASH, justifies future large-scale, randomized controlled trials.

Chronic Disease↗

PubMedDate not supplied

The value of ultrasonography and computerized tomography in estimating the histopathological severity of nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Liver biopsy is the gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but is an invasive method. There is a need for non-invasive methods that can reflect the histopathological severity of NASH. The aim of this study was to compare the ultrasonography and computerized tomography findings with the histopathological severity in patients with NASH. MATERIAL AND METHODS: Twenty-two consecutive patients with biopsy proven NASH and 20 age- and sex-matched healthy individuals were enrolled. Clinical and demographic data were collected at the time of liver biopsy. Histopathological grading and staging were made by an expert pathologist. Each patient underwent ultrasonography and computerized tomography. RESULTS: Liver ultrasonographic findings were not correlated with histopathological grade and stage (r: 0.134, P > 0.05; r: 0.130, P > 0.05). Mean liver densities obtained by computed tomography of NASH patients were lower than that of controls (P < 0.05) and liver/spleen density ratios were lower than that of controls (P < 0.05). These results were significantly correlated with histopathological grade (r: -0.716, P < 0.001; r: -0.663, P: 0.001), but not with the histopathologic stage (r: -0.416, P: 0.05; r: -0.356, P: 0.1). CONCLUSIONS: Ultrasonography findings do not reflect histopathological severity in patients with NASH. Computed tomography attenuation of the liver is significantly correlated with histopathologic grade but not with histopathological stage.

Adult↗