SEARCH · PubMed Health

Results for “NASH”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed2006

Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis.

Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.

Acetamides↗

PubMed2002

The utility of radiological imaging in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: This prospective study evaluates the role of radiological modalities in establishing the diagnosis of nonalcoholic steatohepatitis (NASH). METHODS: Consecutive patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were enrolled (2000-2001). Patients with other liver diseases and significant alcohol consumption (>20 g/day) were excluded. Clinicodemographic data were gathered at the time of liver biopsy. Each biopsy specimen was assessed by a hepatopathologist. Each patient underwent a limited abdominal ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI). Films were interpreted by a radiologist who used a predetermined radiological protocol. Each radiological study was reread by the same radiologist and a second radiologist. RESULTS: Patients with NASH had greater aspartate aminotransferase levels (P = 0.03), greater ferritin levels (P = 0.05), more hepatocyte ballooning (P < 0.0001), and more fibrosis (P = 0.002). None of the radiological features distinguished between NASH and other types of NAFLD. No radiological modality detected the presence of hepatocyte ballooning, Mallory's hyaline, or fibrosis, which are important features in the diagnosis of NASH. The presence of >33% fat on liver biopsy was optimal for detecting steatosis on radiological imaging. CONCLUSIONS: Differences between NASH and nonprogressive NAFLD were not apparent with any radiological modality. Of the pathologic features important for establishing the diagnosis of NASH, only the severity of steatosis was reflected in these radiological modalities. Good intraobserver agreement was evident for each modality (US, CT, and MRI) that was superior to interobserver agreement.

Adult↗

PubMed2003

Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis.

The relations of dietary habits to insulin sensitivity and postprandial triglyceride metabolism were evaluated in 25 patients with nonalcoholic steatohepatitis (NASH) and 25 age-, body mass index (BMI)-, and gender-matched healthy controls. After a 7-day alimentary record, they underwent a standard oral glucose tolerance test (OGTT), and the insulin sensitivity index (ISI) was calculated from the OGTT; an oral fat load test was also performed in 15 patients and 15 controls. The dietary intake of NASH patients was richer in saturated fat (13.7% +/- 3.1% vs. 10.0% +/- 2.1% total kcal, respectively, P =.0001) and in cholesterol (506 +/- 108 vs. 405 +/- 111 mg/d, respectively, P =.002) and was poorer in polyunsaturated fat (10.0% +/- 3.5% vs. 14.5% +/- 4.0% total fat, respectively, P =.0001), fiber (12.9 +/- 4.1 vs. 23.2 +/- 7.8 g/d, respectively, P =.000), and antioxidant vitamins C (84.3 +/- 43.1 vs. 144.2 +/- 63.1 mg/d, respectively, P =.0001) and E (5.4 +/- 1.9 vs. 8.7 +/- 2.9 mg/d, respectively, P =.0001). The ISI was significantly lower in NASH patients than in controls. Postprandial total and very low density lipoproteins triglyceride at +4 hours and +6 hours, triglyceride area under the curve, and incremental triglyceride area under the curve were higher in NASH compared with controls. Saturated fat intake correlated with ISI, with the different features of the metabolic syndrome, and with the postprandial rise of triglyceride. Postprandial apolipoprotein (Apo) B48 and ApoB100 responses in NASH were flat and strikingly dissociated from the triglyceride response, suggesting a defect in ApoB secretion. In conclusion, dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism. Our findings provide further rationale for more specific alimentary interventions, particularly in nonobese, nondiabetic normolipidemic NASH patients.

Adult↗

PubMed2001

Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.

Many subjects with cryptogenic cirrhosis have underlying nonalcoholic steatohepatitis (NASH). The natural history of NASH-related cryptogenic cirrhosis after orthotopic liver transplantation (OLT) is not well defined. A primarily retrospective study of patients with the clinical histological phenotype of NASH-related cirrhosis undergoing OLT was performed. Data were compared with 2 sets of age- and weight-matched controls with (1) primary biliary cirrhosis or primary sclerosing cholangitis or (2) alcoholic liver disease. After OLT, all patients were managed by a standard immunosuppressive protocol. Liver biopsies were performed at 6 and 12 months after OLT and at 1- to 2-year intervals thereafter, as well as when liver enzyme levels were elevated enough to warrant diagnostic biopsy. Twenty-seven subjects with cryptogenic cirrhosis and a clinical histological phenotype of NASH and 3 patients with a long-standing diagnosis of NASH before OLT were included. The 30-day perioperative mortality was 1 in 30 patients. During a median follow-up of 3.5 +/- 2.7 years, 2 additional patients died of sepsis. There was a time-dependent increase in the risk for allograft steatosis that approached 100% by 5 years compared with only an approximately 25% incidence of steatosis in the control groups (P <.009, log-rank test). On multivariate analysis, only the cumulative steroid dose correlated with time to development of allograft steatosis. Three patients developed histological progression from hepatic steatosis to steatohepatitis. Of these, 1 patient developed progressive fibrosis. Four patients experienced at least 1 episode of acute cellular rejection; however, no patient developed chronic rejection or graft failure. In conclusion, nonalcoholic fatty liver disease occurs frequently after OLT in patients with the phenotype of NASH-related cirrhosis. Despite the frequent histological recurrence of disease, clinical outcomes are similar to those of other groups of patients undergoing OLT.

Adult↗

PubMed2002

Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH), the association of steatosis with an inflammatory response, is a novel liver disease of unknown pathogenesis and prognosis. Triacylglycerols and their precursors, the fatty acids, are the likely candidates to accumulate in the hepatocyte. Disturbed fatty acid metabolism can be involved in the pathogenesis of NASH but there is no information concerning its plasma fatty acid profile. The aim of this study was to evaluate plasma total (esterified plus free) and free fatty acids concentrations to assess the association of NASH with plasma fatty acid accumulation. MATERIALS AND METHODS: Overnight fasting blood samples from 22 biopsy-proven NASH patients and of 6 matched age healthy controls were studied. RESULTS: NASH patients had significantly higher concentration of total and free fatty acids than controls (P<0.05), higher total saturated and monounsaturated levels in both studied lipid fractions (P<0.05), mainly due to the increase of hexadecanoic, hexadecenoic and octadecenoic acids. Absolute polyunsaturated fatty acids (PUFA) concentrations were similar in both groups. The C20:4/C18:2 and the C18:1/C18:0 ratios as well as the peroxidability index were not significantly different. CONCLUSION: In overweight/obese patients NASH is associated with deranged fatty acid metabolism which may be involved in its pathogenesis and/or progression.

Adult↗

PubMed2003

Serum lipids, lipoproteins and apolipoproteins levels in patients with nonalcoholic steatohepatitis.

GOALS/BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. STUDY: The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. RESULTS: Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. CONCLUSIONS: Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH.

Adult↗

PubMed1992

A comparative study of computed tomographic and plain radiographic methods to measure vertebral rotation in adolescent idiopathic scoliosis.

A comparative analysis of two methods of measuring vertebral rotation in adolescent idiopathic scoliosis is reported in this article. Nash and Moe's pedicle shift method (using plain anteroposterior radiographs) is compared with a new method using computed tomographic scans. The computed tomographic scans of the whole length of the major curve and the scout films obtained from seventeen girls aged 12.5-14 years were measured for rotation of each vertebra of the curve (total number of vertebrae measured by two methods = 173). This study has three interesting new findings: 1) Those vertebrae with Nash & Moe grade 0 had up to 11 degrees of vertebral rotation when measured using the computed tomographic method. Therefore, Nash & Moe's grade '0' is not a neutrally rotated vertebra; 2) For Nash & Moe grade 1 and 2, the computed tomographic method revealed statistically significantly greater rotation for lumbar vertebrae than thoracic vertebrae. There was a similar pattern for Nash & Moe grade 0 but these differences were not statistically significant; and 3) Simple formulae are reported to convert Nash & Moe's grades into angle of vertebral rotation as obtained by CT method separately for thoracic and lumbar vertebrae.

Adolescent↗

PubMed2004

Should a liver biopsy be done in patients with subclinical chronically elevated transaminases?

In 10% of the patients with chronic abnormal alanine aminotransferase (ALT) levels no cause is found. The prognosis of this liver disease, the increased risk of liver fibrosis regardless of the types of histological lesions and the need for a liver biopsy are unknown. Nearly 50% of these cases are explained by non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate, in patients with accidentally detected chronically elevated ALT levels, the prevalence of fibrosis and NASH, and the clinical and biological factors associated with each entity. Retrospectively, 67 patients (mean age, 46.6 +/- 12.1 years; 45 males) were included. All patients had a liver biopsy and were hepatitis B virus, hepatitis C virus, human immunodeficiency virus seronegative without alcohol, drug, autoimmune or genetically induced liver disease, with ALT > N (the upper limit of normal). NASH was evaluated according to necroinflammatory lesions and fibrosis. Fibrosis was evaluated according to the METAVIR score. Statistical analyses were performed using Student's t test, the Mann-Whitney rank-sum test and the chi-square test. Fibrosis scores were: F0, 37.3%; F1, 32.8%; F2, 26.9%; F3, 1.5%; and F4, 1.5%. NASH was absent in 59.7% and present in 40.3%. Significant differences were observed between F < 2 and F > or = 2 fibrosis patients for aspartate aminotransferase (AST) and ALT and between patients with NASH or without for body mass index. Overall, the risk of F > or = 2 fibrosis was increased in patients with AST > N, ALT > 2N or AST > N and ALT > 2N. The prevalence of F > or = 2 fibrosis and NASH in patients with unexplained chronic abnormal ALT are 30% and 40%, respectively. Since the risk of F > or = 2 fibrosis is significantly increased in patients with AST > N and/or ALT > 2N, liver biopsy should be performed only in patients with AST > N or ALT > 2N.

Adolescent↗

PubMed2005

Total body metabolism of 13C-octanoic acid is preserved in patients with non-alcoholic steatohepatitis, but differs between women and men.

OBJECTIVES: Among numerous factors which account for the pathogenesis of non-alcoholic steatohepatitis (NASH), hepatic mitochondrial beta-oxidation is considered to play a pivotal role. We performed a (13)C-based breath test with a medium-chain fatty acid to non-invasively assess total body beta-oxidation in patients with NASH and in healthy controls. METHODS: We performed a simplified (13)CO(2)-based breath test in 16 patients with histologically proven NASH and 24 healthy controls. One hundred milligrams of sodium (13)C-octanoate dissolved in 200 ml of water were orally administered and breath samples were collected before and during 3 h following administration. The samples were analysed for the cumulative (13)CO(2) recovery (%-cum-dose) by non-dispersive infrared spectrometry. Additionally, data of 69 patients who had undergone a C-octanoate breath test for the assessment of gastric emptying were retrospectively evaluated for the %-cum-dose. RESULTS: The cumulative (13)CO(2) recovery 3 h after the administration of the substrate did not differ among patients with NASH and controls (34.6 +/- 7.0% vs. 34.6 +/- 6.5%, P = 0.90). Compared with men, women yielded a significantly higher cumulative (13)CO(2) excretion in both controls (30.1 +/- 5.7% vs. 38.5 +/- 4.4%, P = 0.0008) and NASH patients (30.2 +/- 5.4% vs. 39.0 +/- 6.5%, P = 0.031). Forty-two of 69 patients (61%) of the gastric emptying group showed a normal gastric emptying rate. Among these patients, women also demonstrated a tendency for a higher (13)CO(2) recovery compared with men (P = 0.055). This was not the case in 27 patients with delayed gastric emptying (P = 0.47). CONCLUSIONS: Though hepatic mitochondrial function might be impaired in patients with NASH, total beta-oxidation of octanoic acid remains normal. Gender-specific metabolic modifications seem to account for significant differences of the cumulative (13)CO(2) recovery in women and men. This may have further consequences for the appraisal of (13)C breath tests which involve octanoic acid. Further trials focusing on the assessment of body composition and energy expenditure could contribute essential further information.

Adult↗

PubMed2005

Clinical significance of soluble TNF receptor in Japanese patients with non-alcoholic steatohepatitis.

BACKGROUND: Soluble tumor necrosis factor receptor (sTNFR) is reported to be a good indicator of TNF production and severity in inflammatory diseases. To investigate the clinical significance of sTNFR in non-alcoholic steatohepatitis (NASH), we measured the serum levels of soluble TNF receptor-1 and -2. PATIENTS AND METHODS: We analyzed 82 NASH patients and 15 healthy subjects (control). The grades of fibrosis, inflammation and fatty deposit were evaluated on liver biopsy. The serum levels of sTNFR-1 and -2 were measured by ELISA. RESULTS: There was significant correlation between platelet count and sTNFRs. The titers of sTNFR-2 in NASH patients with diabetes mellitus (DM) were higher than in those without DM. The serum levels of sTNFRs in NASH patients with advanced fibrosis were increased compared with those of control and NASH patients with low-grade fibrosis. Soluble TNFRs in patients with moderate inflammation were increased compared to those of control and patients with mild inflammation. There was no significant association between fatty deposit grade and sTNFRs. CONCLUSION: Soluble TNFRs have a significant correlation with fibrosis in NASH.

Adolescent↗

PubMed2004

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.

BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Fatty Liver↗

PubMed2024

Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis through extracellular vesicles.

BACKGROUND AND AIMS: Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell-derived EVs in the pathogenesis of NASH are unclear. APPROACH AND RESULTS: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an in vitro cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated acetyl-CoA carboxylase 2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes through pEVs to increase the number of lipid droplet-bound mitochondria. An increase in dysfunctional lipid droplet-bound mitochondria in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial reactive oxygen species production, and apoptosis. CONCLUSIONS: We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEV components and inhibiting their uptake. Additional experiments are required to confirm this potentiality.

Non-alcoholic Fatty Liver Disease↗

PubMed1997

Review: nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non-progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non-progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.

Diabetes Complications↗

PubMed1999

The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease.

OBJECTIVE: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is often greater than 2:1 in alcoholic hepatitis. The purpose of this study was to determine whether this ratio may be used to distinguish nonalcoholic steatohepatitis (NASH) from alcoholic liver disease. METHODS: Patients with NASH were matched with controls with alcoholic liver disease based on age, gender, and date of diagnosis. The diagnosis of alcoholic liver disease was based on exclusion of other causes and a significant history of alcohol consumption. The diagnosis of nonalcoholic steatohepatitis was based on exclusion of other causes of liver disease and a liver biopsy showing > 10% steatosis and inflammation. The two sided Student t test was used for statistical analysis. RESULTS: From 1990 to 1996, 70 patients with NASH were matched with 70 subjects with alcoholic liver disease. Patients with NASH had a mean AST to ALT ratio of 0.9 (range 0.3-2.8, median 0.7) and subjects with alcoholic liver disease a mean ratio of 2.6 (range 1.1-11.2, median 2.0). The mean AST levels were 66 U/L and 152 U/L, and the mean ALT levels 91 U/L and 70 U/L, in the nonalcoholic steatohepatitis and alcoholic liver disease groups, respectively. Although the absolute aminotransferase levels were significantly different in the two groups (p < 0.05), the greatest difference was observed in the AST to ALT ratio (p < 0.000001). Subset analysis of patients with NASH revealed mean AST to ALT ratios of 0.7, 0.9, and 1.4 for subjects with no fibrosis, mild fibrosis, or cirrhosis, respectively. The differences among these ratios were statistically significant (p < 0.05). CONCLUSIONS: The AST to ALT ratio appears to be a useful index for distinguishing nonalcoholic steatohepatitis from alcoholic liver disease. Although values < 1 suggest NASH, a ratio of > or = 2 is strongly suggestive of alcoholic liver disease.

Alanine Transaminase↗

PubMed2001

A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis.

OBJECTIVES: Troglitazone is a thiazolidinedione and peroxisome proliferator-activated receptor gamma (PPARgamma) ligand used to treat diabetes mellitus type II. Because hyperinsulinemia may be a factor in nonalcoholic steatohepatitis (NASH), we postulated that troglitazone could have beneficial effects in this disorder. Our study was initiated before reports of idiosyncratic hepatitis induced by this agent and was completed before its recent withdrawal from the market. METHODS: We studied 10 female patients (age 44 +/- 16) with histological NASH. All but two were obese (mean body mass index, BMI = 38 +/- 6). One had type 2 diabetes, and three had well-compensated cirrhosis with NASH. Troglitazone was given at a dose of 400 mg/day for < or = 6 months. Responders (defined as normal ALT at the end of treatment) were rebiopsied. Paired specimens were compared in blinded fashion. Mitochondria were quantitated using ultrathin electron microscopy. RESULTS: Seven of ten patients responded with normal ALT at the end of treatment. One of three nonresponders initially normalized ALT but returned to pretreatment level at 3 months. In this patient, therapy was stopped, and the ALT has remained at the baseline level with no other clinical or laboratory findings. In the responders, ALT fell from 87 +/- 38 before to 39 +/- 9 at the end of treatment (p = 0.01), and AST decreased from 77 +/- 23 to 30 +/- 8 (p = 0.002). Biopsy comparisons before and after therapy showed persistent steatohepatitis in all cases, although four of seven showed a one-point improvement in the necroinflammatory grade. Electron microscopy revealed elongation of the mitochondria after therapy. CONCLUSIONS: Normal ALT was seen in 70% of NASH patients at the end of treatment, but this biochemical response was associated with only mild histological improvement, and all follow-up biopsies had evidence of NASH. Normalization of the liver enzymes in patients with NASH who are treated with thiazolidinediones should be viewed with reservation. Follow-up biopsy is essential to evaluate the efficacy of these agents, which, at the histological level, appears to be relatively modest.

Adult↗

PubMed2001

Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis.

OBJECTIVE: The aim of this study was to define in patients with hyperferritinemia and normal transferrin saturation the relationships among hyperferritinemia, iron overload, HFE gene mutations, the presence of metabolic alterations, and nonalcoholic steatohepatitis (NASH). METHODS: Forty patients with increased serum ferritin, resistant to dietary restriction and normal transferrin saturation, 90 with ultrasonographic evidence of hepatic steatosis, and 60 obligate heterozygotes for hemochromatosis, all negative for alcohol abuse, hepatitis virus infections, and inflammation were studied. Transferrin saturation, serum ferritin, uric acid, lipids, glucose tolerance, insulin resistance, HFE gene mutations, liver histology, and hepatic iron concentration were analyzed. RESULTS: Of the 40 patients with hyperferritinemia, 29 (72%) had biochemical metabolic abnormalities, 18 of the 26 examined (69%) had insulin resistance, 26 (65%) had the presence of one of the two HFE gene mutations (normal controls, 33 of 128 [26%], p < 0.0001), and all had increased liver iron concentration. Thirty-one patients (77%) had histology compatible with NASH. At univariate analysis, NASH was significantly associated with the presence of metabolic alterations, the C282Y mutation, and severity of fibrosis. At multivariate analysis, NASH was associated with the coexistence of multiple metabolic alterations (odds ratio = 5.2, 95% CI = 0.95-28.7). The risk of having NASH augmented in the presence of higher values of ferritin and liver iron concentration. Among the 90 patients with ultrasonographic evidence of hepatic steatosis, 24 (27%) had increased serum ferritin with normal transferrin saturation, but only six remained hyperferritinemic after dietary restriction. CONCLUSION: Increased ferritin with normal transferrin saturation is frequently found in patients with hepatic steatosis, but it reflects iron overload only in those patients in whom it persists despite an appropriate diet. The simultaneous disorder of iron and glucose and/or lipid metabolism, in most of the cases associated with insulin resistance, is responsible for persistent hyperferritinemia and identifies patients at risk for NASH.

Analysis of Variance↗

PubMed2001

Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a common but poorly understood liver disease. Our aim was to study a large group of patients referred for Hepatology consultation to further characterize this disorder, in particular its demographics and range of severity. We also sought to better understand its etiology and its relationship to the insulin resistance syndrome, known as the metabolic syndrome or syndrome X. METHODS: Retrospective review of 90 patients seen over a 4-yr period. RESULTS: Ninety patients aged 14-70 with NASH seen at the Liver Clinics at either the University of Tennessee or the Medical University of South Carolina. Eleven had complications of portal hypertension and seven of these had undergone or were awaiting transplantation. NASH was seen in nine families either in siblings or in subsequent generations. Diabetes or insulin resistance were present in almost all in this cohort of patients with NASH. Diabetes, hyperlipidemia, hypertension, and atherosclerotic disease, the components of syndrome X, were common in this population. CONCLUSION: NASH affects males and females equally, and presents over a wide age range. Despite its usually benign course, 28% of patients had cirrhosis and almost half of those had complications of portal hypertension, necessitating liver transplantation. Obesity was common in affected patients and cirrhosis was more common in the morbidly obese. Familial clustering was common, with 18% of patients having a similarly affected first degree relative. The clinical features that define syndrome X (diabetes, hypertension, hyperlipidemia, and atherosclerotic disease) are common in affected patients. Studies of glucose tolerance demonstrated unsuspected diabetes in six, and insulin resistance (the hallmark of syndrome X) in 85% of those tested. We hypothesize that NASH is a disorder of genetic etiology and is the hepatic manifestation of syndrome X, the insulin resistance syndrome.

Adolescent↗

PubMed2003

The natural history of nonalcoholic fatty liver disease: a clinical histopathological study.

OBJECTIVES: We aimed to define nonalcoholic steatohepatitis (NASH) histopathological change over time and to correlate changes with clinical characteristics. METHODS: We retrieved nonalcoholic fatty liver cases from our histopathology database covering 1985 to 2001. We also identified patients in clinic with NASH on biopsy >1 yr prior. All patients were evaluated and clinical data obtained in clinic. Those patients qualifying for NASH therapeutic trials underwent liver biopsy pretreatment. One pathologist (S.T.) read all slides using a NASH grading and staging system. RESULTS: A total of 22 patients had repeat biopsies a mean of 5.7 yr (range 1.4-15.7 yr) after the first biopsy. Nine were women, nine had diabetes, 11 had hypertension, and 14 had hyperlipidemia. Mean body mass index was 33.8 kg/m(2) (range 26.5-48.6 yr). Mean age was 50.6 yr (range 33-64 yr). Ten patients (45%) had fibrosis stage 1 or 2, and two patients (9%) had bridging fibrosis or cirrhosis (stage 3 or 4) on first biopsy. Seven (32%) had increases in fibrosis score. Four patients (18%) had decreases in fibrosis score. The percentage of patients with stage 3 or 4 increased from 9% to 18%. In two patients the disease progressed rapidly (fibrosis scores from 1 to 3 in 1.4 yr and from 2 to 4 in 2.6 yr). Only serum AST at last biopsy correlated with histological change, being higher in those with disease progression. Three patients progressed from steatosis to steatohepatitis with fibrosis. CONCLUSIONS: NASH has a variable histological course. However, one third of patients have fibrosis progression, and one third of these have rapid progression to advanced fibrosis. Histological progression correlated with higher serum AST but no other clinical factors. Steatosis alone may progress to NASH with fibrosis.

Adult↗