518 Family history of gallstone disease determine the susceptibility to developing gallstone disease in mexicans patients

AASLDAl469

April 2000

6655

6657

518 FAMILY HISTORY OF GALLSTONE DISEASE DETERMINE THE SUSCEPTIBILITY TO DEVELOPING GALLSTONE DISEASE IN MEXICANS PATIENTS. Nahum Mendez-Sanchez, Raul Pichardo, Luis Guevara-Gonzalez, Misael Uribe, Medical Sur Clin & Fdn, Mexico, Mexico.

SERUM LEPTIN LEVELS IN CIRRHOSIS. Manuela Merli, Valentina Valeriano, Andrea Masini, Cesare Efrati, Pierluigi Fiore, Giorgia Nicolini, Frida Leonetti, Maria Cristina Ribaudo, Oliviero Riggio, Clin Medicine, Rome, Italy; Endocrinology, Rome, Italy. BACKGROUND AND AIM. Leptin is a peptide secreted by adipocytes. This hormone is involved in the regulation of metabolism and is known to decrease food intake and increase energy expenditure. Serum leptin levels are higher in females than in males. It has been proposed that insulin increases leptin secretion. Cirrhotic patients frequently present a reduced body fat mass and increased leptin levels. The aim of this study was to evaluate leptin levels and to investigate the relationship between this hormone and the body mass index (BMI), body fat mass (FM) and fasting insulin levels in cirrhotic patients. MATERIAL AND METHODS. We studied 38 consecutive cirrhotic patients (l2F-26M; mean age 55.4± 14.5 yr.) Origin of liver disease was post-viral in 24, post-alcoholic in 8, cryptogenic in 3 and primary biliary cirrhosis in3 patients. FM was evaluated both by anthropometry (FM-A) and, only in 13 patients, by DEXA (FM-D). RESULTS. The results are shown in the table below. Fasting insulin levels in cirrhotics were higher than normal values. Leptin levels were higher than normal values particularly in females. Leptin correlates with FM-A (r=0.67-p<0.001) and with FM-D (r=0.84-p<0.001). Leptin also correlates with insulin levels (r=0.74-p<0.001), this correlation was higher in women (r=0.94-p<0.001). CONCLUSIONS. Our data show that leptin levels are higher in cirrhosis particularly in women. The reason of this alteration is still to be completely cleared. Leptin correlates with FM-A, FM-D and insulin levels. These correlations suggest an important role of this hormone in the alteration of metabolism in cirrhotic patients.

Backgroud: Gallstone disease (GD) is a major source of morbidity in Western countries including United States, as well as in Latin American countries such as Chile and Mexico. The etiology of GD is considered multifactorial. We recently have reported that risk factors for GD in Mexicans are similar to those found in Mexican-Americans (Dig Dis Sci 1998;43:935-9). In addition, it has been proposed that some lith genes are involved in the susceptibility of GD in inbred mice (J Lipid Res 1997;38: 1395-1411). However, we have not explored the genetic family history (GFH) as a risk factor for GD in our population. Aim: To investigate the frequency of GFH of GD in a group of Mexican patients with and without GD. Methods: This study was conducted in a group of patients who were refereed to gastroenterology department for evaluation of their gastrointestinal symptoms from September 1998 through September 1999. The screening protocol included a questionnaire with socioeconomic data, medical history, physical and gallbladder ultrasonographic and blood tests. The diagnosis of gallstones was made using commonly accepted criteria. Nutritional data were obtained during the medical examination by means of a semiquantitative food-frequency questionnaire with a 24-hour dietary recall. Anthropometric measurements, including weight and hei§ht, were registered for BMI. Obesity was defined as a BMI of >27 kg/m . Values expressed as means ± SD. Results: A total of 430 patients were assessed, (mean age 44.5± 15.7 yr) and divided in two groups according to the diagnosis of GD. 801 518Conclusions: The results of the present study suggest that GFH of GD are very frequent in Mexican patients. Furthermore, since both age and BMI were higher in the group of patients with GD. The results are consistent with the hypothesis that in development of GD the interaction of genetic and environmental factors are very important.

8MI

FM·A('!o)

To1(38) Men (26) Women (12)

26±4 26±3 25+5

27±8 25±6 33±10

FM·OEXA ('!o) Leptin(ng/ml) Insulln(flUlml) 29±10 26±7 34±14

12±11 10±9 19+13

19±18 17±13 22±11

Normal values: Leptin,;10ng/ml. Insulin 10±3 flU/ml

Results Groups GO Control

Cirrhotics

109 321

Age (Yr)

Ratio (M/F

8MI

GFH(%)

52.1±14.0' 419+15.5

42/67 151/170

264±5.0" 254±41

25/109 (23)' 194/321(60)

'p<0001, bp<0.03; 'p<0.001

6656 HORMONE REPLACEMENT THERAPY IS SAFE AND EFFECTIVE IN DECREASING BONE LOSS IN POSTMENOPAUSAL PATIENTS WITH PRIMARY BILIARY CIRRHOSIS. Kozhikode V. Menon, Paul Angulo, Jill Keach, E. Rolland Dickson, Keith D. Lindor, Mayo Clin, Rochester, MN. Osteoporosis and atraumatic fractures have been recognized as potential complications in patients with chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC). No effective medical therapy is currently available for these patients. Hormone replacement therapy (HRT) is effective in preventing bone loss in otherwise healthy postmenopausal women; however, the potential benefit of HRT on patients with PBC is still unknown. Our AIM was to evaluate the safety profile and to determine the efficacy of HRT in decreasing the rate of bone loss in postmenopausal patients with PBe. METHODS: Forty-six unselected postmenopausal women, median age of 55.8 years (range, 38-68), with well-defined PBC are the subjects of the current analysis. All these patients were on HRT. Bone mineral density of the lumbar spine L2-L4 (BMD-LS) was measured by dual energy x-ray absorptiometry (DEXA) at annual intervals during a median follow-up of 4 years (range, 1-9 years). Each patient was randomly matched by age, gender and ethnic group with another patient with PBC but not on HRT. All BMD-LS measurements were also compared with the expected BMD-LS for the normal population adjusted for age, gender and ethnic group. Routine clinical, biochemical and histological variables were also measured at regular intervals during follow-up. All patients with PBC were on ursodeoxycholic acid (13-15 mg/kg/day) therapy during followup. RESULTS: Both groups of patients with PBC were comparable at baseline in terms of body mass index (p = 0.5), histologic stage (p = 0.7) and first BMD-LS value (p = 0.8). PBC patients on HRT had a significantly lower rate of bone loss than the matched PBC controls who were not on HRT (-0.002 ± 0.004 vs -0.009 ± 0.003 g/cm squared/year, respectively, p = 0.05). However, the rate of bone loss in PBC patients on HRT was similar to that expected in the normal age-. gender- and ethnic group-matched population (-0.002 ± 0.004 vs -0.006 ± 0.000 g/cm squared/year, respectively, p = 0.4). No patient had significant worsening of cholestasis due to HRT during follow-up. CONCLUSIONS: Hormone replacement therapy is well tolerated and is associated with a significant decrease in the rate of bone loss in postmenopausal PBC patients who are on ursodeoxycholic acid therapy. Based on our results, hormone replacement therapy should be considered in all postmenopausal PBC patients with osteopenic bone disease.

6658 QUANTITATIVE RT-PCRANALYSIS OF MMP AND TIMP MRNA EXPRESSION IN CORRELATION TO LIVER HISTOLOGY IN PATIENTS WITH CHRONIC HEPATITIS C. Dirk Michels, Christian I. Haberkorn, Burkhard Arndt, Michael P. Manns, Med Hochschule Hannover, Hannover, Germany. Background/Aims:To study whether the hepatic expression of matrix metalloproteinases (MMPs) and their inhibitors (TiMPs) correlates with extent and activity of liver fibrogenesis in chronic hepatitis C, we measured mRNA levels of MMP-2, MMP-7, and MMP-9 in relation to TIMP-I, TIMP-2, and TIMP-3 in liver biopsies, and compared it to hepatic histology in patients with chronic hepatitis C (CAH). Methods: Quantitative RT-PCRlELISA assays were performed for MMP and TIMP mRNA in liver samples from 14 normal livers (N), 31 liver biopsies from patients with chronic ~epatit.is C. (CAH) and 14 biopsies from patients with HCV-mduced ClIThOSIS (CI). Results were correlated to inflammatory activity and fibrosis in the histology according to the "Ishak-score", Results: Mean values for all measured MMP's and TIMp's .were elevated in Ci as compared to N, but correlation of MMP and TIMP mRNA expression in CAH with the histologic activity of inflammation and extent of fibrosis revealed significant differences as shown in the table below. Conclusion: TIMP expression in liver tissue sho.weda close correlation to inflammatory activity, but correlated poorly With the extent of fibrosis. In contrast MMP-2, MMP-7, and MMP-9 expression in the liver correlate to the extent of fibrosis.

TIMP·1 TIMp·2 TIMP·3

Inflammation

Fibrosis

r=O.77 p<0.0001 r=0.54 p=0.002 r=044 p=0.02

r=0.33 p=0.08 r=0.34 p=0.07 r=036 p=0.05

MMP·2 MMp·7 MMP·9

Inflammation

Fibrosis

r=0.44 p=0.02 r=-0.1 p=0.6 r=0.03 p=09

r=0.55 p=0.002 r=058 p<0.001 r=046 p·0.01

Correlation coefficients and significance levels forthe corelation between hepatic mRNA expression and the inflammation orfibrosis score incoresponding liver biopsies according toIshak