Al446 AASLD ABSTRACTS

6557

DOES THE HFE GENE PROTECT AGAINST ANAEMIA IN PREG ·NANCY?Neil Haslam . Graham Worsley, Jo D. Unsworth , Robert B. Locke , Jona­thon L. Brown , Gloucestershire Royal Hosp, Glouce ster, United Kingdom;Cranfield Univ, United Kingdom; Southmead Hosp, Bristol, United King­dom.

Introduct ion Genetic haemoch romatosis is the commonest autosom al re­cissive disorder in Caucasian populations with a carrier frequency ofapproximatlely I in 10 (I). The gene (HFE) was first identified in 1996 (2)and over 90% of cases are due to one of two single amino acid subst itu­tions. which result in a cysteine to tyrosine at position 282 (C282Y) orhistidine to aspartic acid at position 63 (H63D). The homozygous state canleads to iron overload and can result in cirrhosis , diabetes and a card io­myopathy (I). There must be a survival advantage that has resulted in thismutation becoming the commonest genetic disorder in caucasians and Datzet al have suggested that the mutation may protect young women againstiron deficiency (3). We aimed to investigate the hypothesis that the HFEmutation protects women against iron deficiency and anaemia in pregnancyto give them a reproductive advantage. Patients and Methods Forty sevenconsecutive pregnant women had blood samples collected at a 16-weekante-natal booking clinic. Blood was taken for a full blood count and apolymerase chain reaction (PCR) and immuno-electrophoresis performedto detect the presence of either the C282Y or H63D mutation of the HFEgene. The PCR was performed by an operator blinded to the results of thefull blood count. The mean haemoglobin levels of the women with the HFEmutaion were then compared to those of the normal controls and analysedstatistically using the Student ' s t-test. Results Of the 47 women, two wereheterozygous for C282Y . ten heterozygous for H63D and one homozygousfor H63D. The mean haemoglobin of the women either homozygous orheterozygous for the HFE mutation was 11.8g/dl (SD 0.8g1dl) compared tothe normal controls mean haemoglobin of 11.9g1dl (SD l.1g1dl). Theseresults are clearly not significantly different. Conclu sion The HFE mutationdoes not appear to influence the haemoglobin levels of pregnant women .This makes the hypothes is of a reproductive advantage for carriers of theHFE mutation via this mechan ism unlikely. I)Crawford DGH et al. Bail­lieres Clin ical Gastroen terology 1998;12(2) :209-225. 2)Feder JN et al.Nature Genetics 1996;13:399-408. 3)Datz C et al. Clinical Chemi stry1998;44(12):2429-32.

6558

THE ROLE OF HAART ON HCV DISEASE SEVERITY IN HIV!HCV COINFECTION.Tarek I. Hassanein, Nina Aronson, Cynthia Behling, Francesca Torriani,Eileen R. Chatfield. Peter Chen, Christopher Mathews, UCSD Med Ctr,San Diego, CA.

Treatment of HIVIHCV coinfected patients with highly active antiretro vi­ral therapy (HAART) is believed to playa role in the progression of theliver disease. We matched 45 consecutive HIVIHCV patients from theHIVlHepatology Clinic by age and sex to a control group of HCV infectedpatients. 30/45 (68%) were on a HAART regimen . of which 83% containeda protease inhibitor. Biopsies were examined by a single pathologist, whowas not aware of the viral status of the patients . All biopsies were gradedand staged according to a modified Knodell score. The patients were 39 M,6F in each group. The majority of patients were middle-aged white male.HCV genotype I was detected in 84% of the coinfected group and 74% ofthe control group . The major risk factor for HCV infection was IVDU in40% and 47% respectivel y. Among the HIVIHCV coinfected patients 67%had CD4 counts > 200. Results: No difference in HCV viral titers wasdetected between the two groups, even in patients who were on HAART .No difference in HAl score or fibrosis was detected, however the co­infected group on HAART had less fibrosis and lower HIV viral titers thanthe no HAART group. Conclu sion: I) there was no difference in theseverity of HCV disease between HIVIHCV coinfected patients comparedto a control group of HCV patient s; 2) HAART may have a role in slowingHCV disease progression. This data provides a rational for treating HIV1HCV coinfected patients.

HIV/HCV HIVIHCV No P HIVIHCV HCV PHMRT HAART all only

N 30 t5 45 45HAl 5.63 ± .68 621:t .88 NS 5.82± .54 6.33 ± .35 NSFO t21304O% 2115 14% 0.09 14/4531% 1214527% NSF1, F2 11/3037% 8/15 53% NS 19/4542% 22/4549% NSF3, F4 7/30 23% 5/15 33% NS 1214527% 11 /45 24% NSHIV< 400 17/3057% 1/7 14% 004 18/3749% NACD4 >200 20/30 67% 8/12 67% NS 28/4267% NAHCVRNA<2X10' 58% 67% NS 60% 59% 093

F=FibrosisStage

GASTROENTEROLOGY Vol. 118, No.4

6559

AST TO ALT RATIO AS A MARKER OF LIVER CIRRHOSISAMONG PATIENTS WITH HEPATITIS C.Lyndon Joseph V. Hernandez, Aboud Affi, Nalini Guda, Cristino Canga ,Jennifer Cohn, Jerrold Jacobson, Thom as R. Puetz, Vincents 1. Dindzans,Univ of Wisconsin Med School- Milwaukee Campus, Milwaukee , WI;Univ of Wisconsin- Milwaukee Campu s. Milwaukee , WI.

Introduct ion: The presence of cirrhosi s plays a major role in the manage­ment and response to treatment among patients with chronic hepatitis C.The development of cirrhosis is silent in the majority of these patients, andmany well-compensated cirrhotic patients lack signs of cirrhosis by routinebedside and laboratory testing . The predictive value of laboratory param­eters, such as aspartate aminotransferase (AST) to alanine aminotransferase(ALT) ratio, remains uncertain . Our aim was to determine the usefulness ofAST to ALT ratio in detecting cirrhosis among patients with chronichepatiti s C. Methods: We reviewed the medical records of 231 patientswith chronic hepatitis C in a commun ity gastrointestinal specialty clinic .Ninety-eight patients who underwent liver biopsies (1988 to October 1999)were included in the analysis. Serum transaminase levels were obtainedwithin 60 days of performing the liver biopsy. Cirrhosi s was defined asstage 3 or 4 fibrosis with the presence of regenerating nodules. Results:Demographics were as follows: mean age 35 y, 78% males, 79% caucasian,and 41% with intravenou s drug use as risk factor. A comparison of themean AST to ALT ratio of of the patients with cirrhosis (n= 15) and thosewithout cirrhosis (n = 83) revealed that patient s with cirrhosis had a signif­icantly higher mean (± SD) AST to ALT ratio (1.05 ± 0.41. 95% CI 0.82to 1.28) than patients without cirrhosis (0.69 ± 0.26,95% CI 0.63 to 0.74).There was no significant correlation between alcohol use and an elevatedAST to ALT ratio. Conclusion: AST to ALT ratio may be a useful markerof cirrhosis among patients with chronic hepatitis C.

6560

SYNERGISTIC INHIBITION OF HEPATOMA CELL PROLIFER·ATION WITH A COMBINATION OF 9-CIS·RETINOID ACID, TA·MOXIFENE AND THE ANGIOGENESIS INHIBITOR TNP.Christoph Herold , Marion Ganslmayer, Thom as Strefeld , Eckhart G. Hahn.Detlef Schuppan, Med Dept I, Erlangen, Germany .

Aim:Drug therapy does not have a prominent role in the treatment of HCC.Muto et al (N Engl J Med, 1996, 334, 1561) reported a prolonged post­operative survival after resection for HCC with retinoid acid derivatives .Tamoxifen (TAM), retionoid acids (RA), the rnatrixmetalloproteinases­inhibitor Squalamine (SQA) and the angiogenesis-inhibitor TNP 470(TNP) alone have shown limited or no effect on HCC cell growth in vitroand in vivo. Combin ation therapy has not been investigated . Methods :Hepatoma cell lines HeplB, HepG2 and Hepa 1-6 were cultured in 10%fetal calf serum (FCS) and incubated with TAM, 9-cis-RA (CRA), all­trans-RA (ATRA), SQA and TNP alone (104 to 1O'9M) or in combination.Cell proliferation was measured using bromo-deoxyuridin -incorporation(BrdU-Elisaj and cell counting. Results: TAM inhibited proliferation ofHeptB (10' M: 55% compared to untreated), but not of HepG2 and Hepa1-6 cells. CRA (104 M: 70,62,55%. resp.) and TNP (l0·4M: 45. 70, 62%.resp.) alone inhibited cell growth, whereas ATRA and SQA alone were noteffective . The combinations (104 M each) of TAM/CRA (36. 40. 48%resp.), TAMrrNP (24. 36, 25%, resp.) and CRAffNP (25, 24, 24% resp.)as well as the triple combin ation (l0·4M each) of TAM/CRAlTNP (16, 19,20%. resp.) showed a synergistic antiproliferative effect. Combinations ofSQA with the other mentioned drugs were not better than single therapy.The BrdU-ELISA correlated with cell counting. Conclusion: ) TAM alonewas only effective in HeplB cells . 2) CRA and TNP showed a moderateantiproliferative effect in all hepatoma cells. 3) ATRA and SQA alone werenot effective. 4) The combination of TAM/CRA, TAMrrNP and CRA!TNP as well as triple therapy of TAM/CRAlTNP showed a synergisticantiproliverative effects. 5) Combinat ion therapy may be far superoir tomonotherapy for HCC.

6561PREVALENCE OF ADVERSE EVENTS DURING COMBINATIONTHERAPY, INTERFERON A·2B AND RIBAVIRINE, FORCHRONIC VIRAL HEPATITIS C.Sophie Herve, Remi Varin , Guillaume Savoye, Ghassan Riachi, OdileGoria, Nathalie Donnadieu, Raymond Colin , Grad , Rouen , France; Phar­macy Dept. Univ Hosp, Rouen, France.

The combination of interferon a -2b (INF-a) and ribavirine has been shownto be more effective in the treatment of chronic hepatitis C than IFN alone.Aims: To assess efficacy and safety of combination therapy (lNF-a +riba­virine) in chronic hepatiti s C patients non-responding or relapsing to INFalone in our university hospital. Patients and methods: From January 1997and January 1999, a total of 81 consecutive patients with chronic hepatitisC were enrolled in this study. They were 55 male and 26 female , mean age:48.2 years. range: 31-68. Forty heights (59.3%) of them were non-re­sponder and 33 (40.7%) were relapser to a previous treatment by INF-a.Genotype Ib was present in 29 patients (35.8%). Each patient receivedinterferon a-2b 3MU three times a week with concomitant ribavirine1000-1200 mg per day. adapted to the body weight. For each patient wenoticed all the adverse events during treatmen t. The response to treatmentat six month was defined by the absence of detectable HCV RNA and couldbe assessed among 62 of them. Results: Thirty nine patients (only II with