4 5 2 A A A S L D A B S T R A C T S HEPATOLOGY October 1995

1381 MECHANISM OF EARLY'BILIARY STENT BLOCKAGE IN A PORCINE MODEL N Maillot*. C Moesch. P Aucher.D Sautereau. G Grollier. S Robert; D Bon. M Carretier: C Silvain. M Beauchant. Dept. of Surgery, Hepatology Unit, Dept of Anesthesie, INRA Surg~res*, University of Poitiers and Limoges, France

The mechanism of polyethylene biliary stem (PBS) clogging is poorlly understood. Adhesion of sludge mediated by protein of bacterial origin seems to play a major role. The aim of this study was to identify the contents of clogged PBS in a porcine model. Fifteen large-white pigs (aged 8 to 10 weks, weight: 20 to 30 kg) were stented through choledocotomy and bile duct ligation with 5F (n=8) or 7F (n=7) PBS (Wilson Cook). All stents were positioned with distal end openned in the duodenum. The PBS were surgically removed and the stent content w~ts analyzed by polarizing miCrOscopy and Fourier tranform infrared x spectroscopy. Bacterial analysis (10/15) included aero- anaerobic cultures and measurement of phospholipase (lecithinase, lipase) and 13 glucuronidase activity of strains. Results: pigs died from sepsis and]or jaundice (n=10), or were sacrificed (weight loss: n=4, no symptoms: n=l) (median follow-up until death: 9 days, range: 4 to 56 days). PBS were clogged in I0 out of 15 cases (5F: n=6; reed 7 days; 7F: n=4; reed 10 days). 3 were totally occluded: mucoprnteins (n=2) or wheat starch (n=l); 7 were partially occluded by mucopmteins (66%), wheat starch (17%), calcium bilirubinate (6%), calcium ursodeoxycholate(2%), apatite (6%), and calcite (3%). Presence of multiple bacteria was constant in the 10 stents studied: Clostridium perfringens (n=10), other strict anaerobic strains (n=8), E Coli (n=8), Streptococcus sp (n=10), and Staphylococcus sp (n=7). Anaerobic and Streptococcus strains were present in large quantities. Phospholipase and high glucuronidase activity was only observed in strict anaerobic strains (Clostridium and less often anaerobic Streptococcus strains). Conclusion: Early PBS occlusion is characterized by high mucoprotein deposition and presence of multiple bacteria species. Anaerobic strains mainly Clostridium perfringens appeared to play a major role and had high phospholipase and glucuronidase activity. Pigment deposition is rare in the early phase of PBS occlusion in this porcine model.

1 Moesch et al. Hepatology 1991; 14: 1142-46.

1382 lnterleukin 6 and chronic hepatitis C Malaguamera M., Di Fazio 1., Laurino A., Rizzo M., Tomasello F.B. Trovato B.A. Department of Internal Medicine end Geriatrics - University of Catania P.O. "Cannizzaro" via Messina 829 - 95126 Catania (Italy)

lnterlenkin 6 (IL-6) is a pleiotropic cytokine produced by a wide variety of

lymphoid end non lymphoid tissues. In the liver IL-6 is produced by

fihroblasts, Kupffer cells end endothelial cells. Interleuldns, especially IL-

6, play an important role in regulating hepatocyte functions. 1L-6 reach

liver via the portal system: the liver is the main detoxification site of

eytokine production inductors. Detoxifieation is determined by co-

operation between hepatoeytes and Kupffer cells. We studied the

relationship between IL-6 and the liver in an attempt to elucidate this

eytokine's role in hepatitis C induced liver inflammation. We investigated

the behaviour of ser0m IL-6 in 20 patients with chronic hepatitis C (divided

into three groups depending on severity) end in 15 healthy controls. Oar

results showed a significant increase in serum IL-6 levels in chronic

hepatitis C patient s e0mpared with healthy controls 21.40 + 2.76 pghnl

versus 9.7 + 5.9 pg/ml (p<0.0001). Although the increase in IL-6 plasma

concentration as the liver progresses is not significant, this rise may be the

expression of the hepatitis C induced inflammatory state. This is further

demonstrated by the finding that tbe increase of IL-6 is positively related to

chronic hepatitis C, but not to aspecifie hepatitis.

1383 MINOCYCLINE-INDUCED LIVER INJURY. A Malcolm, TR Heap, RP Eckstein*, and MR Lunzer ; Depa r tmen t s o f G a s t r o e n t e r o l o g y and "Pathology, Royal Nor th Shore Hospital, Sydney, Australia.

Minocycline, a semi-synthet ic tetracycline, is c o m m o n l y used in the t reatment of facial acne. Minocycline is not generally recognised to be hepatotoxic. We report six cases of minocycline-induced liver injury seen in a 12 mon th per iod in our inst i tut ion. Five pat ients had an acute hepati t ic illness whils t one patient had a more prolonged course wi th histological evidence of chronic active hepatitis.

The patients were young (mean age 22 years); males and females were affected equally. The dosage range was 100-200 mg daily and the m e a n durat ion of t reatment was 31 weeks. Present ing s y m p t o m s inc luded mala ise ( fou r pat ients) , epigastr ic pa in (two pat ients) , jaundice ( two pat ients) , nausea (two patients), arthralgia (one patient) and fever and rash (one patient). All symp t oms subs ided after cessation of minocyc l ine . A s s o c i a t e d f ea t u r e s i nc l uded e l eva ted an t inuc lear an t ibody (three pat ients) , posi t ive d o u b l e s t r anded DNA (one patient) , blood eos inophi l ia (three patients) and t i ssue eosinophil ia (one patient). The liver injury was predominant ly hepatocellular wi th peak se rum a lan ine t r a n s a m i n a s e r a n g i n g f rom 257 to 3824 U /L . Normalisat iOn of liver tests occurred after a mean of 31 weeks.

Minocycline may cause both acute hepati t is and chronic active hepat i t is . Minocycline hepatotoxicity m a y be much more common than appreciated and patients receiving long term minocycline should be monitored by regular checks of their liver biochemistry.

1384 UNUSUALLY HIGH PREVALENCE OF HCV GENOTYPES 2A AND 2B IN U.S. MILITARY VETERANS. MA Manbeck, JD McCracken. Loma Linda University Medical Center, Division of Gastroenterology, Loma Linda, CA.

Hepatitis C virus (HCV) infection is classified into genotypes based on NT sequence variations in the 5' UTR region. HCV genotype distribution among the infected population is variable: the North American cohort is predominantly genotype la and lb, whereas Asian and Middle Eastern cohorts have higher proportions of 2a, 2b and 3. U.S. military veterans are potentially exposed to HCV while deployed to foreign countries; therefore, the HCV genotype distribution in the cohort of HCV-infected veterans may differ from the general U.S. population. In order to test this hypothesis we performed HCV genotyping on U.S. veterans referred for the treatment of HCV. METHODS: 17 male veterans with symptomatic hepatitis C (confirmed by RIBA 2) and abnormal LFTs were studied. RT PCR was performed using primers flanking the 5' UTR region, the product was hybridized to genotype- specific probes (Line Probe Assay, Innogenetics, Belgium). Patients were classified as genotype la, lb, 2a, 2b, 3, 4, or indeterminate. RESULTS: 16/17 veterans tested wereclassifiable. 8/16 (50%) were genotype la or lb. 7/16 (43%) were genotype 2a, 2b, or mixed 2b and 3 . 1/17 (7%) was unclassifiable. No association was found between mode of transmission (IVDU or transfusion) and genotype, or military travel history and genotype (T test). CONCLUSIONS: This pilot study indicates that a higher proportion of U.S. military veterans have genotypes 2 and 3 as compared with the general U.S. population. HCV military Veterans may have disease characteristics and a therapeutic outcome that differs from the native POPulation.

*Sponsored by an educational grant from Schering-Plough Corporation.