Ethnic differences in patients with primary biliary cirrhosis in USA

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AASLD ABSTRACTS

HEPATOLOGYO c t o b e r 2 0 0 1

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HEPATOCELLULAR CARCINOMA AND SURVIVAL IN PATIENTS W I T H PRIMARY BILIARY CIRRHOSIS. Akitaka Shibuya, Kitasato University School of Medicine, Sagamihara Japan; Katsuaki Tanaka, Yokohama City University, Yokohama Japan; Minoru Shibata, Showa University, Tkyo Japan; Hiroshi Miyakawa, Teikyo University, Kawasaki Japan; Toshio Morizane, Kanagawa dental college, Yokosuka J a p a n

EXPRESSION OF UNCOUPLING PROTEIN-2 IN BILIARY EPITHELIAL CELLS IN PRIMARY BILIARY CIRRHOSIS. Eitaro Taniguchi, Masaru Harada, T a k u m i Kawaguchi, Hironori Koga, Hiroto K u m e m u r a , Shinichiro Hanada, Shouiehiro Shishido, Shinji Baba, Ryukichi Kumashiro, Takato Ueno, K u r u m e university of medicine, K u r u m e Japan; Shotaro Sakisaka, F u k u o k a university of medicine, F u k u o k a Japan; Miehio Sata, K u r u m e university of medicine, K u r u m e J a p a n

Background a n d Aims: The rate of hepatoeellular carcinoma (HCC) developm e n t in patients with primary biliary cirrhosis (PBC) are not well known. The aims of this study are to determine H C C development rate a n d survival, a n d to assess risk factors associated with these outcomes in patients with PBC. Method: W e collected information o n 396 patients with PBC w i t h o u t hepatitis B or hepatitis C virus infection at enrollment a n d followed-up from 6 to 271 months. HCC was detected by scanning with u h r a s o n o g r a p h y and/or comp u t e d t o m o g r a p h y every 4-6 months. Life expectancy was a p p r o x i m a t e d using the declining exponential a p p r o x i m a t i o n of life expectancy. Results: 14 patients developed HCC. The cumulative appearance rate of H C C in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (4.4% a n d 0% b y the fifth year, 12.3% a n d 7.7% by the tenth year, respectively. P = 0 . 0 2 1 ) . Proportional hazards analysis showed three factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, a n d history of b l o o d transfusion. Age, male gender, history of b l o o d transfusion, a n d advanced-stage PBC were associated with survival, b u t H C C development was not. The disease-specific annual mortality rate was estimated to be 0.008 for females a n d 0.028 for males with advanced-stage PBC. Conclusions: The development of H C C is not rare in patients with advanced-stage PBC, b u t H C C does n o t affect the patients' survival.

Background: U n c o u p l i n g proteins (UCPs) are recently believed to play key roles to protect from oxidative stress. Because UCP-2 is expressed in liver and, oxidative stress is involved in pathogenesis of liver diseases, UCP-2 is pres u m e d to be expressed a n d to protect liver from oxidative stress in liver diseases. However, the correlation between UCP-2 a n d liver diseases remains unclear. Aims: The aim of the present study is to clarify UCP-2 expression in liver diseases including primary biliary cirrhosis (PBC). Materials a n d methods: Specimens from histologically normal livers (n = 10) a n d livers with chronic viral hepatitis (CVH) positive for s e r u m hepatitis B surface antigen or RNA of hepatitis C virus (n = 21), a u t o i m m u n e hepatitis (AIH)(n = 11) or primary biliary cirrhosis (PBC) (n = 38) were used. Immunohistochemistry was performed to investigate UCP-2 expression in the liver specimens. Results: UCP-2 expression was observed in some hepatocytes a r o u n d central veins, nearby fatty drops, a n d adjacent to fibrous tissues. However, the degree of UCP-2 expression in hepatocytes was not significantly different between the liver diseases a n d histologically n o r m a l liver. O n the other hand, UCP-2 was exclusively expressed in biliary epithelial cells (BECs) in PBC b u t not those in the other liver diseases a n d histologically n o r m a l liver, The percentage of UCP-2-positive bile ducts in PBC was significantly higher than that in the other liver diseases a n d histologically normal liver. The percentage of UCP-2-positive bile ducts in liver specimens from PBC patients treated with ursodeoxycholic acid was significantly lower than that from PBC patients untreated. Conclusions: UCP-2 in BECs m a y he involved in the process of progressive destruction of interlobular a n d septal bile ducts in PBC.

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IMPACT OF PRIMARY BILIARY CIRRHOSIS O N OUTCOMES OF PREGNANCY AND S O C I O E C O N O M I C P O S I T I O N . Jayant Talwalkar, Andrea Gossard, Roberta Jorgensen, Paul Angulo, Keith D Lindor, Mayo Clinic a n d Foundation, Rochester, MN

ETHNIC DIFFERENCES IN PATIENTS W I T H PRIMARY BILIARY CIRRItOSIS IN USA. Marion G Peters, University of California at San Francisco, San Francisco, CA; Adrian Di Bisceglie, Saint Louis University, Saint Louis, MO; N a n c y Flye, Robert L Carithers, University of W a s h i n g t o n , Seattle, WA; Burton Combes, University of Texas, Soutwestern, a n d The PUMPS Study Group, Dallas, TX

BACKGROUND: Previous investigations have examined the outcomes of pregnancy in women who have or develop primary biliary cirrhosis (PBC). However, little information exists regarding the impact of parity and socioeconomic position on pregnancy-related outcomes in PBC. AIMS: 1) To determine the parity frequency and risk of adverse fetal outcomes (miscarriage, abortion, stillbirth) among women with PBC as compared to agematched controls. 2) To determine the impact of PBC on socioeconomic position among women as compared to age-matched controls. METHODS: Female subjects with PBC, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) evaluated between July 1, 1998 and December 31, 2000 at Mayo Clinic Rochester comprised the study population. Cases (PBC subjects) were selected at random and matched by age with individuals from each control group (IBS and GERD subjects, respectively). Data abstraction from medical records after obtaining IRB approval included years of education completed, employment status (current or retired, homemaker, unemployed), marital status (married, single, divorced, widowed), and current or past history of abuse (physical, emotional, and sexual). Primary outcomes included the following: overall frequency of pregnancy,proportion of live births, frequency of live births (0,1,2, 3 or greater), frequency of miscarriages/abortions,and frequency of stillbirths. Tests of significance (p level<.05) were performed to determine the strength of association between predictor variables and primary outcomes. RESULTS: 510 patients (97 with PBC, 210 with IBS, 203 with GERD) comprised the study cohort. Among subjects with PBC, a mean age of 57.9 years (range, 31-69) was observed. Subjects were found to have histologic stage I (22%), stage 2 (41%), stage 3 (20%), and stage 4 (15%) disease. Average Mayo Risk Score was 4.4 ~ 1.6. Mean education level was 13 years (range, 8-17 years). Employment status included gainfully employed or retired (72%), homemaker (23%), and unemployed (5%). Marital status included current (78%), never married (7%), divorced (4%), and widowed (10%). A history of abuse was reported among 16% of PBC subjects. Compared to IBS and GERD controls, there were no significant differences in the overall frequency of pregnancy, proportion of live births, and frequency of miscarriages/abortions or stillbirths among PBC subjects (p>.05 for all). Education level, employment status, marital status, and current or past history of abuse were also similar between PBC subjects and controls (p>.05 for all). No differences in all pregnancy-related outcomes and socioeconomic variables were observed between IBS and GERD controls as well (p>.05 for all). No differences in the frequency of PBC subjects reporting a history of 0, 1, 2, and 3 or more pregnancies compared to IBS and GERD controls was observed (p>.05 for all). Comparisons between a history of pregnancywith education level, employment status, marital status, and current or past history of abuse failed to reveal any significantassociations among PBC subjects and controls (p>.05 for all). CONCLUSIONS: 1) PBC does not have a significant impact on favorable or adverse outcomes of pregnancy when compared to age-matched controls. 2) No significant differences in socioeconomic position (education level, employment status, marital status) or reported history of abuse between women with PBC and age-matched controls were observed. 3) Future investigations of outcomes in PBC should include an assessment of health state preferences and social status among women.

BACKGROUND. Few large population studies of Primary Bfliary Cirrhosis (PBC) have been reported because of the uncommon nature of this chronic cholestatic liver disease. In addition, there is little information about ethnic differences in PBC. AIM. To study the demographicsof PBC in a large geographicallydiverse group of patients in the USA from 11 different university referral centers. PATIENTS AND METHODS. 535 patients with PBC were screened for entry into a large multicenter trial of ursodeoxycholic acid and methotrexate. 265 were finally randomized into the study. We evaluated the demographics, symptoms, patient reported functional activity (normal to bed rest), physical findings and laboratory tests of all screened patients and then compared different ethnic groups, gender and AMA status. Those who were randomized were compared to those who did not enter the study. RESULTS:Of screened patients, 93% were female; 91% were AMA positive; 20% were of child-bearingage. Functional activity was recorded as normal or near normal with regular activity in 80% overall, but was worse in Black and Hispanic patients. Other differences between ethnic groups are noted in the table. Significantly more Black and Hispanic patients failed to meet inclnsion criteria or were excluded because of more severe liver disease. 80 patients declined to participate, because they did not want to take methotrexate; the study took too much time or had too many procedures: there was no difference between ethnic groups. CONCLUSION. This group represents a large US based cohort of patients with diverse ethnicity. A significant number of minority patients were screened for this study. Although of similar age, Hispanic and Black patients had more advanced disease and were excluded because of disease severity. It is not clear whether these patients have more rapid disease or developed it at an earlier age. Although PBC remains a disease of Caucasian women, when it occurs in other ethnic groups it may be more severe. All Caucasian Black ........ Flispan!c ....... N (%) ..... 535 462 (86,4) 21 (3.9) 42 (7,9) Hx ascites,UGIB,PSE# 33 (6%) 21 (4%) 3 (14%) 7 (16%)** Poor functional activity 12% 10% 24% 28%** Severepruritus 10% 10% 28%** 12% AMA positive 91% 88% 83% 90% Albumin -<3gldl 2.6% 1,7% 9.5%* 9,5%** 8ilirubin >-3 mg/dl 5.6% 4,3% 9.5% 14.3%* Met inclusion criteria 72% 75% 48% 48% Had exclusioncriteria 10% 8% ~9% 26% ~ ! i n e d to participate 15% 15% 19% 12% #Hx ascites, UGIB, PSE=Historyof ascites, vaficeal bleedor hepaticencephalopathy p value ~0.05", -<0,005'*by Chitest,