627

N-Acetyl cysteine Attenuates AlcohoHnduced Oxidative Stress in the Rat Reeat Ozaras, Veysel Tahan, Hafize Uzun, Seval Aydin, Saflye Dondurmaci, Hakan Santurk, Cerrahpasa Medical Faculty, Istanbul Turkey

There is increasing evidence that alcohol-induced liver damage may be associated with increased oxidative stress. We aimed to investigate free-radical scavenger effect of n-acetyl cysteine in rats intragaetrically fed with ethanol. Thirty four rats divided into three groups were fed with ethanol(6 g/kg/day, Group 1), ethanol and n-acetyl cysteine/lg/kg, group 2), or isocaloric dextrose (control group, Group 3) for 4 weeks. Then animals were sacrificed with ether anesthesia, intracardiac blood and liver tissues were obtained. Malondialdehyde (MDA)level was studied by TBARS method. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were studied by commercial kits. KruskaI-Wallis test was used fur statistical analysis. ALT and AST in Group 1 (154 U/L) and 302 U/L respectively) were higher than those in Group 2 (94 U/L and 155 U/L) and Group 3 (99 U/L and 168 U/L)(p=O.OOl for both). Serum and liver tissue levels of MDA in Group 1 (1.84 nmol/ml and 96 nmol/lOO mg protein) were higher than Group 2(0.91 nmol/ml and 64 nmol/lO0 mg protein) and Group 3(0.94 nmol/ml and 49 nmol/lO0 mg protein)(p<O.O01 for both). On the other hand, serum GSH-Px level in Group 1 (8.21U/o-Hb) was lower than that in Group 2(16 U/g-Hb) and Group 3 (16 U/g-Hb)(p<O.O01). Serum and tissue levels of SOD in Group 1(11 U/ml and 26 U/IO0 mgprotein)were lower than those in Group 2 (18 U/ml and 60 U/IO0 mgprotein) and Group 3 (20 U/ml and 60 U/IO0 mg protein)(p<O.O01 for both). This study demonstrated that othanol-induced liver damage is associated with oxidative stress and co-administration of n- acetyl cysteine attenuates this damage effectively in rat model.

628

Alcohol Consumption Patterns in Heavy Drinkers With and Without Alcoholic Liver Disease (ALD) Keith L E Dear, Martin P. Bradley, Keith McCormack, Dept of Gastroenterology, Royal Hallamshire Hosp, Sheffield United Kingdom; Robert J. Peck, Dept of Radiology, Royal Hallamshire Hosp, Sheffield United Kingdom; Dermot C. Gleeson, Dept of Gastroenterology, Sheffield United Kingdom

BACKGROUND: The risk of ALD increases with increasing alcohol consumption; it is unclear whether the risk is also related to drinking pattern or to type of alcoholic beverage consumed. AIM: To compare patterns of lifetime alcohol intake in two cohorts of heavy drinksra(Hepatology 2000; 32:A420) (~60U~k(M) or 40U~k(F) for >5yr): one with decompensated ALD (patients: n = 149,107M, age 48 + SDlOyr) and one with no clinical, laboratory or ultrasonic evidence of serious liver disease (controls; n = 98, 79M, age 48 + 9yr). METHODS: Lifetime total alcohol intake (LTA) and intake of beer/lager, spirits, wine/sherr and cider to first decompensation (patient~) or to interview (controls) was assessed using the time-line follow back method. Correlation of LTA between repeated testing and between spouse estimates were 0.86 (n = 9) and 0.81 (n=9) respectively. RESULTS: LTA was higher in controls (median 138840U, IQR lOO0776-190424)than in patients (median 114712, IQR 80262-165984); p<O.2 by Mann- Whitney (M-W). Spirits, wine and cider consumption increased with time in both cohorts: in contrast beer/lager consumption either did not change (patients) or fell (controls). Controls drank more beer/lager (median 10064, IQR 41912 to 156312) than did patients (median 61152, IQR 21658-109733);M-W p<O.01. In contrast, spirit consumption tended to be higher in patients (median oU, IQR 0-54080) than in controls (median OU, IQR 0-25688); whilst this difference was not significant by M-W, the distribution of patients tended towards higher levels of spirit consumption than did that of the controls (2x5 Chi squared = 16.9. p<O.05). Cider and wine consumption did not differ between the cohorts. The proportions of time spent in constant (->-5days/wk), weekend-only drinking, binge drinking and abstinence were similar in the two cohorts. SUMMARY: This data suggests factors other than total alcohol consumption are important in the development of ALD

629

The Polistena Project on Non-AIcaholic Fatty Liver Disease (NAFLD): A Study of Risk Factors Amedeo Lonardo, Modena City Hosp, Modena Italy; Paola Loria, Francesca Leonardi, Univ Hosp, Modena Italy; Patrizia Neri, Maurizio Pulvirenti, Modena City Hosp, Modena Italy; Andrea Borsatti, Anna M. Verrone, Marco Bortolotti, Univ Hosp, Modena Italy; Enrico A. De Micheli, Modena City Hosp, Modena Italy; Nicola Carulli, Univ Hosp, Modena Italy

BACKGROUND/METHODS - The relative role of insulin resistance (IR) and iron overload in the pathogenesis of NAFLD is uncertain (1). In 1998 a prospective survey on NAFLD (Polistena project) was planned in Modena, northern Italy. In short, general practitioners were invited to refer to participating centers all newly diagnosed patients with bright liver (an ultrasonographic feature of fatty liver) irrespective of the reasons why ultrasonography had been performed. To the ends of this study, NAFLD was defined by the concurrence of 3 criteria: a) bright liver, b) absent-to-low alcohol consumption ( -<30g alcohol/day for men and -<20g for women) and c) exclusion of viral (HBV and HCV), genetic (~_antitrypsin, hypobetalipoproteinemia, Wilson's disease) and autoimmune etiologies. The data of 53 patients enrolled in the Polistena study in the fall 1999-june 2000 period of study were compared to those of an historical population of 98 subjects without NAFLD [formerly enrolled in a survey on the epidemiology of gallstone disease in the same geographic area: the MICOL study(2)] that were used as controls. RESULTS - Subjects with HAFLD were younger (p<.01), more often obese (p<.01) and diabetic (p<.01) than controls. Age-corracted mean values of ALE, GGT, uric acid, fasting insulin, serum iron and ferritin were significantly higher (p<.01) in NAFLG as compared to controls, while transferrin was lower (p<.01). Eight/35 cases (22.85%) were heterozygotes for the HIS63ASP mutation of HFE gone, but no tissue iron overload was shown in liver biopsy of 2 of them who underwent the test. Overall, 10 patients underwent liver biopsy that disclosed fatty liver in 1 patient and NASH in 9. At univariate analysis the relative risk (RR) for NAFLD was significantly increased for those who were in the 3rd tertile of uric acid (RR 23.04), fasting insulin (RR 16.41), ALT (RR 16.95), 8MI (RR 13.74), %transferrin saturation (RR 6.01), TG (RR 4.87), GGT (RR 4.5) and ferritin (RR 2.97). In contrast, being in the 3rd

tertile for transferrin decreased the risk of having NAFLD (RR 0.17). Logistic regression analysis disclosed age, gender, uric acid, fasting insulin, TG and transferrin to be indipendent predictors of NAFLD (p<.O5). CONCLUSIONS Parameters belonging to IR domain such as fasting insulin, TG and uric acid, but not iron and ferriUn are independent risk factors for NAFLD.The correction of IR is the key therapeutic target in NAFLD. REFERENCES l.Ferrannini E.Lancet 2000;355:2181-2.2.Attili AF,Oarulli N, Roda E, et al. Am J Epidemiol 1995; 141:158-65.

630

Prevalence Of Nonalcoholic Steatohepatitis Among Ethnic Groups Luisa Santos, Enrique G. Molina, Univ of Miami, Miami, FL; Lennox Jeffers, Rajender Reddy, Eugene Schiff, Ctr for Liver Diseases, Miami, FL

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is frequently associated with obesity, non-insulin-dependent diabetes mellitus, female gender, and/or hyperlipidemia. Differences in prevalence among ethnic groups have not been identified. Recently it was reported that Atrican Americans (hA) are underreprasented among patients with NASH or cryptogenic cirrhosis (Hepatology 2000;32(4):418A). AIM: To determine the prevalence of NASH among ethnic groups in a large population of patients evaluated in a Hepatology clinic. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 861 consecutive patients who attended our Hepatology clinic at Jackson Memorial Hospital from 12/1997 until 05/ 1999. Categorical variables were compared using Chi-square. RESULTS: Overall, 431 (50%) patients were Hispanics (H), 223 (26%) were hA, and 207 (24%) were Caucasians (C). Most common etiologies of liver disease included: hepatitis C (40%), hepatitis B (10%), alcohol (8%), hepatitis C and alcohol (8%), NASH (6%), autoimmune (4%), cryptogenic cirrhosis (3%), and other etiologies 21%. There were no statistically significant differences among ethnic groups with regard to hepatitis C, alcoholic liver disease, autoimmune hepatitis, and cryptogenic cirrhosis. When compared to H and C, hA had and increased prevalence of hepatitis B: 18% vs 7% and 8% (p=O.OOO02). NASH was very rare among AA (1.4%) as opposed to H (8%) and C (7%)(p =0.0029). Of the total population with NASH (n = 51), hA represented 6%, compared to 27% C (p = 0.0082), and 67% H (p = 0.0011). CONCLUSIONS: The prevalence of NASH is significantly lower in African-Americans compared to other causes of liver diseases among ethnic groups.

631

High Prevalence of NASH Among Mexican American Females with Type II Diabetes Mellitos Nyingi M. Kemmer, Kevin H. McKinney, Shu - Yuan ×lag, Harbans Singh, Richard Murray, Basil Abdo, Mohsen Eledrisi, Ravi S. Bikinna, Hongbao Ma, Daryl T-Y Lau, Univ of Texas Medical Branch, Galveston, "IX

Background/Objective: NASH is a common cause of liver disease with a broad clinical spectrum from steatohepatitis to cirrhosis. HASH is especially prominent among pts with diabetes, obesity and hyperlipidemia. The aims of this study were to determine the racial prevalence and severity of NASH in pts with Type II diabetes and to identity clinical features predictive of NASH. Methods: Study pts were enrolled prospectively from the Endocrinology clinics at UTMB. The MAAST questionnaire was applied to exclude pts with alcoholism from the study. In addition to the clinical, biochemical and demographic data, liver panel and abdominal CT scan were obtained on each subject. Ultrasound (US) guided liver biopsies were performed on pts who had either abnormal liver enzymes (ALT/AST, GGT, AIk.P), CT scan evidence of fatty liver, or both. US examination for fatty liver was also done at time of biopsy. The liver specimens were graded based on the degree of steatosis, inflammation (grade 0-3), and fibrosis (stage 0-4). The diagnosis of NASH was only made if there was inflammation in addition to fat. Other causes of abnormal liver tests, including hemochromatosis, were ruled out. Results: To date, 60 pts with a mean age of 56 yrs completed the study. Among them, there were 30 Caucasians (M = 14, F = 16), 21 African Americans (M = 7, F = 14), 8 Mexican Americans (M = 2, F= 6) and t male Asian. 22 patients (37%) met the criteria for liver biopsy. NASH was identified in 14 (64%) and steatosis alone was present in 5 (23%). Furthermore, NASH was present in 12 of the 16 (75%) pts with CT scan evidence of fatty liver hut only 2 of 6 (33%) pts with abnormal liver enzymes alone. The correlation between CT scan and US for fatty liver is 100%. However, neither CT scan, US or liver enzymes could distinguish NASH from steatusis. Pts with NASH had a mean age of 58 yrs, and they were predominantly females (F= 12; 85%). Among the females, NASH was identified in 5 (83%) Mexican Ameri- cans, 3 (21%) African Americans and 4 (25%) Caucasians. Five (36%) pts with NASH had significant fibrosis (Stage 3 and 4), of which 3 were Mexican American females, 1 African American female and 1 Asian male. A BMI greater than 35 was found in 80% of pts with steatosis alone, but in only 43% with NASH. Neither the 8MI, lipid profile nor HBAlc levels could predict the prevalence of NASH in this population. Conclusion: Advanced NASH is particularly common among Mexican American females with Type II diabetes. CT scan and US are valuable screening tools for NASH but liver biopsy remains the gold standard in assessing disease severity.

632

Concurrence of SteatohepaUtis with Chronic Hepatitis C and Other Chronic Liver Diseases Sunil Ramrakhiani, Barry Cordes, Elizabeth M. Brunt, Adrian M. Di Bisceglie, Saint Louis Univ Sch of Med, St. Louis, MO

Background: Non-alcoholic steatohepatitis(NASH)is a chronic liver condition being recognized with increasing frequency. Hepatic stenosis may also be found with chronic hepatitis C. Aim: We evaluated the coexistence of histologic features of steatohepatitis (SH) and other forms of chronic liver diseases (CLD), including chronic hepatitis C. Methods: We searched the pathology files of Saint Louis U. Hosp. for non-allograft liver biopsies between 9/97 and 4/ OO showing features of SH with perisinusoidal fibrosis and another CLD. Biopsies were then re-evaluated for the degr~ of staatosis, sinusoidat fibrosis and Mallory's hyaline. Medical

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