494A

1549

A A S L D A B S T R A C T S HEPATOLOGY O c t o b e r 1995

PHENPROCOUMON-INDUCED CIRRHOSIS OF THE LIVER. BM Stadler. KP Maier. Department of Intema! Medicine, Municipal Hospital, Esslingen, Germany.

Although widely used for prophylaxis of~romboembolic disorders, there are very few reports of hepatotoxicity of the coumarin anticoagulant phe~- preeoumon (Marcumar). We present the case of an otherwise healthy 54- year-old man who developed jatmdice 7 months after aortic valve replacement and oral anticoagnlation with phenprocoumon. The patient had no history of liver disease and no exposure to blood products. Liver function tests prior to cardiovascular surgery were normal. His alcohol consumption was munmal and except for sotalol (a drug, which has not been reported to cause severe liver damage) he did not take any drugs. Seven months after initiating the phenproeoumon-therapy semm-bilirubin was 8 mg/dt (normal < 1.2 mg/dl); alkaline phoephatase (AP) 234 U/l (normal < 200U/I); 7-ghttamyl transferase (7-GT) 292 U/l (normal < 28 U/l); aspartute aminotransferase (AST) 490 U/1 (nonnal< 18 U/l)i alanine aminotransferase (ALT) 680 U/l (normal < 28 U/l) and cholinesterase (CHE) 2905 U/l (normal > 3000 U/l). Tests for viral hepatitis (hepatitis A, B, C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus ffISV) and human immanodeficiency wins (HIV)) and for antinuclear and antlmitochondrial antibodies were all negative. There were no Signs of dysfunction of the prosthetic valve. Two months later the patient was referred to our hospital because of increasmg jaundice, ascites and edemas of the lnnbs. Phmprocoumcn was diseeminued and the patient was put on continuous intravenous heparin. His elevated liver enzymes and liver function unproved. Medicatton was changed to subcutaneous low molecular weight heparin (Embolex* 03 ml/d) and aspirin 100 mg/d. Three months later liver biopsy revealed cirrhosis of the liver, the histological picture being consistent with dmg-inducad liver damage. Hepatic function and liver enzymes almost have returned to normal (Bilirubin 0.8 mg/dl; AP 140 U/l; T-GT 174 U/I; AST 37 U/l; albumme 38 g/l and CHE 3992 U/l) and the patient has remained well since then. Conclusion: Because of the widespread use of phenprecoumon physicians should be aware of this possible hepatotoxic side-effect.

1550 CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) IS ELEVATED IN PREMENOPAUSAL AND IN PREGNANT WOMEN. RE Stauber, B Jauk, P F~ckert. MCH H~usler*. Depts. of Medicine / ~0bstetrics & Gynecology, university of Graz, Austria.

The determination of carbohydrate- deficient transferrin (CDT) in serum has been found useful as a marker of chronic ethanol consumption of )60 g per day. It is currently unknown why CDT values are higher in women (normal range 0-26 U/I) than in men (normal range 0-20 u/l). We

investigated 200 consecutive patients (105 women, 95 men) admitted to the clinic of preventive medicine, who represent an unselected, population of 'normal consumers' of ethanol. CDT was measured by CDTect TM radioimmunoassay (Pharmacia). While CDT values (means ± SD) were similar in women (19 ± 8 U/l) and men (18 ± 11 U/l), CDT was different in premenopausal (20 ± 8 U/l) versus postmenopausal ~ (15 ± 4 u/l) women (p<0.001). No age-related difference of CDT values was found among men. In 60 pregnant women admitted to the obstetric clinic, CDT increased with the duration of pregnancy (first trimester: 16 ± 4 U/l, second trimester: 17 ± 4 U/l, third trimester: 19 ± 3 U/l, p<0.05 by ANOVA). The level of CDT was weakly correla£ed with the week of gestation (r=0.29, p<0.05).

CONCLUSIONS: (I) CDT is elevated both in premenopause and in late pregnancy and should be interpreted with caution in these conditions. (2) These findings suggest an influence of female sex steroids on CDT.

1 5 5 1 INCREASING SIZE OF TRUE CUT NEEDLE IS ASSOCIATED WITH INCREASED BLEEDING IN PORCINE LIVER BIOPSIES. RK Sterling,. DM Pleeha. AB Post. TE Herbener. JR Haaga. ' Departments ot Medicine and Radiology, Case Western Reserve University, Cleveland, Ohio.

Liver biopsy is an invaluable tool for the assessment of liver disease. Although the use of larger caliber needles for liver biopsy are felt to carry an increased risk of bleeding, this hypothesis has not been rigorouslY studied. The aim of this study was to compare the amount of blood loss during liver biopsies from 14 G, 18 G, and 20 G True Cut liver biopsy needles. METHODS Live Yorkshire pigs had laparotomy under general anesthesia. Fifty-three biopsies oftbe liver were performed under direct visualization by each of three calibers of True Cut needles (14 G, 18 G, and 20 G) on 11 pigs for a total of 159 biopsies. A preweighed gauze pad was placed over the biopsy site to absorb blood until hemostasis was achieved. The amount of blood loss, measured in grams, was determined by the difference in weight of the gauze pad before and after hemostasis. Students t was used for statistical analysis. RESULTS:

BIOPSY GAUGE 14 G 18 G 20 G

N 53 53 53

MEAN (grams) 1.94 0.84 0.42

STD ERROR 0.33 0.1"3 0.06

RANGE 0.20 - 9.65 0.01 - 4.30 ' ' 0.01 - 1.80 Mean blood loss increased significantly as the size oftbe needle increased: 14 G vs lg G (p < 0.001), 14 G vs 20 G (p< 0.0001), and 18 G vs 20 G (p< 0.001). The variability of blood lost also increased as the caliber of the needle increased which was not inter- or intra-animal dependent. CONCLUSIONS Increased True Cut needle caliber is associated with increased blood loss in our porcine model. These results suggest that a smaller needle size may be safer in patients at increased risk for bleeding from liver biopsy. Confirmatory studies in humans are needed.

1552 HCV OENOTYPES: RELEVANCE IN LONG TERM FOLLOW UP AFTER ALPHA IFN THERAPY FOR CHRONIC HEPATITIS C (HCV). Robert J. Stoffa. Andrew Conrad. Peter Schmid. Charles Rice. Alexander Kolvkhalov and Marion Peters. Depts of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO and National Genetics Institute, Los Angeles, CA.

Few studies are available comparing the long term (4-6 yr) response to !FN:a therapy with genotype of HCV. Aim: We compared HCV genotype with long term serum ALT and HCV RNA in 31 HCV patients treated with IFN-a2a (Roche Labs). Stored serum samples from patients were analyzed for genotype using a line probe assay (J Gen Virol 74:1093;1993). Results: All patients were PCR + pre-treatment. ALT response and genotype at end o f lFN and long term (LT) are shown.

ALT response at end IFN LT response

genotype # responder relapser non responder R NR

la 10 2 3 5 1 9

lb 9 2 2 5 0 9

2a 5 4 1 4 1

2b 1 0 1

3a 1

1 or3 1

indeterminate 3 1 1 1

1 1

1

2 OLT

Of those who lost viremia after IFN, 6 patients (40%) continue HCV RNA negative LT and have normal ALT: their HCV genotypes are 2a(3), 2b(1) and 3a(1). 3 patients have rd ALT but are viremic (Type la ; I or 3). Genotype la and lb patients did not have LT viremic responses although one patient has a normal ALT. 4/5 genotype 2a patients have normal ALT and 3/5 are not viremie. Loss of virernia correlated with normal ALT and genotype 2. Conclusion: L~r responses are seen in patients wi th genotypes 2 and 3 but not genotype 1. Spontaneous viral clearance was not seen.