A1468 AASLD ABSTRACTS GASTROENTEROLOGY Vol. 118, No.4

6654

RESISTANCE OF HCV GENOTYPE 4 TO INTERFERON (IFN)ALONE OR TO INTERFERON-RIBAVIRINE.Marianne Melki, Francois Gallet, Marc Bourliere, Isabelle Bartolomei­Portal, Francois Blanc, Pierre Blanc, Pascal Perney, Jacques Reynes,Jacques Ducos, Andre-Jean Remy, Dominique Larrey, Hosp Saint Eloi,Montpellier Cedex 5, France; Fondation, Hosp Saint Joseph, Marseille,France; Hosp Lapeyronie, Montpellier, France; Hosp Gen, Perpignan,France.

The efficacy of antiviral treatment is dependent on viral genotype. Type 1is relatively resistant whereas type 2 and 3 are sensitive. The aim of thisstudy was to evaluate the efficacy of treatment for patients with HCV type4 chronic hepatitis (CH). 76 treatments were done in 61 patients: 61naivetreatments, 16 retreatments in 6 relapsers (R) and 14 non responders (NR).Patients characteristics were: 40 males (66%) and 21 females (34%) ; allpatients had histologically proved CH and none had cirrhosis; mean age:40 yrs (15-70), mean age at comtamination : 24 yrs (3-53) ; route ofinfection: IV drug addiction: 32 pts (53%), blood transfusion: 13 (21%),another cause : 16 (27%) ; Treatment characteristics were: monotheraoy(IFN or PEG-IFN) 3 or 6MU 6 or 12 months (mo) or bitherapy (IFN 12 moor PEG-IFN 6 mol plus ribavirine (0,6-1,2 g/j). Results: see the table.Sus­tained response (SR) was defined by normal ALT and absence of serumHCV RNA, 6 months after treatment. Conclusion: HCV type 4 is particu­lary resistant not only to IFN alone but also to IFN-ribavirine.

disease; all had liver biopsies and monitoring of ALTs, HCV by PCR,depression index. Demographics: 27 patients entered to date. Ethnic break­down: 24 African Americans (AA) (92%), 3 Caucasian (17%). 13 male, 14female. Genotypes: 23 type 1, 2 type 2b, I type 4b/c, I indeterminate.Average age 47.9. Cirrhosis seen in 4 (14.8%). Presence of virus in allpatients was confirmed with a second generation Roche assay kit. I3 AApatients randomized to 15ug and 10 to 9ug at week 6; 3 Caucasian patientsrandomized tol5ug. Results: 15 of 15 AA pts and one Caucasian patienthad significantly decreased virau at week 6, with 6/16 (38%) AA with virus<1,000 copies/ml at week 6.3 (19%) AA had an increase in viral levels atweek 6, and by week 24, all 6 of 6 AA so far tested had a rebound in viruson TIW therapy. The Caucasian patient <1,000 at week 6 was undetectedat week 24. Side effects were tolerable though troublesome in mostpatients, and included malaise, difficulty concentrating, myalgia, hair loss,weight loss. Two patients, both diabetic and hypertensive, developednephrotic syndrome and a kidney biopsy in one showed membranousglomerulonephritis. II removed from protocol (dropped out or removedbecause of persistent virus at week 24). Conclusion: Induction therapy with6 weeks of 15ug/day interferon alfacon-I lowers viral levels in mostpatients to < 1,000 copies/ml with tolerable side effects. In AA patientshowever, decreasing to TIW at 6 weeks results in rebound of virus andelevated ALT levels. African Americans will need daily doses of interferonalfacon-l, perhaps because of a difference in viral/interferon kinetics.Additional information as the stndy is ongoing will provide a more com­plete picture of response patterns.

6653

SCREENING FOR HEREDITARY HEMOCHROMATOSIS IN ARHEUMATOLOGY CLINIC.Fiona McLaughlin, Eleanor Ryan, Valerie Byrnes, Stephen Stewart, MillieStone, Conor McCarthy, John Crowe, mater Hosp, Dublin, Ireland.

Hereditary Hemochromatosis (HH), characterised by increased total bodyiron content, is the most common autosomal recessive disease in individ­uals of Northern European descent and is associated with the C282Ymutation in the HFE gene. The aim of this project was to verify theassociation of C282Y homozygosity with osteoarthritis (OA). Informedconsent was obtained from patients with various documented arthropathies.Finger prick blood samples were taken onto Gutherie cards from whichDNA was extracted using the Chelex method. Following PCR amplifica­tion using a primer encompassing the C282Y mutation site, the amplifiedDNA was digested with RsaI enzyme. Digests were separated on Agarosegel and viewed under UV light. Results were obtained from 244 individuals(rheumatoid arthritis, 113; OA, 81; and inflammatory arthritis, 50). 51 wereheterozygous, indicating a C282Y carrier frequency of 21.5%, correspond­ing to that of the Irish population. 4 (1.7%) were homozygous for C282Y.All 4 of the C282Y homozygotes were of the OA subgroup (n= 81),representing 5% of that group. Using Fisher s exact test, a significantassociation between C282Y homozygosity and a diagnosis of OA wasfound (p~O.OI). Given that 75% of individuals with the C282Y genotypeexpress HH, it would be appropriate to initiate a screening programme forHH in patients with OA.

6650

PREV ALENCE AND HISTOLOGICAL FINDINGS OF NON·AL·COHOLIC STEATOHEPATITIS (NASH) IN OBESE PATIENTS.Angelo A. Mattos, Idilio Zamin, Claudio G. Zetler, Julio C. Pereira-Lima,Dept of Gastroenterology of Santa Casa Hosp, Porto Alegre, Brazil; Deptof Pathology of Santa Casa Hosp, Porto Alegre, Brazil.

Aims: The aims of this study are to averiguate in a prospective fashion theprevalence of NASH in a group of non-selected obese patients, as well asto verify, if there is an association among severity of histological findings,body mass index, aminotransferases levels and the prevalence of dyslipi­daemia. Methods: 912 non-diabetic obese patients from the endocrinologyoutpatient care unit were prospectively evaluated. Of them, 68 (7.4%)presented with elevated aminotransferases, however, 35 of these patientswere excluded because of alcohol abuse or positive viral markers or use ofpotentially hepatotoxic drugs. The remaining 33 patients (3.6%)(meanage=42.2 yr.; 22F, II M) underwent liver biopsy. Results: NASH waspresent in 29 of the 33 cases and in 3.18% (95% CI: 2.2-4.6) of the wholepopulation. In these patients, liver histology was considered mild in 17(58.6%), moderate in 6 (20.7%) and severe in other 6 cases (20.7%). Therewere no cases of cirrhosis. Body mass index in the obese patients withnormal and abnormal aminotransferases was 37.1 ::+: 6.0 kg/m2 and 38.4 ::+:7.4 kg/m2, respectively (p>0.05). No association was also encounteredamong body mass index, dyslipidaemia level, aminotransferases levels andhistological severity. Conclusion: The prevalence of NASH with abnormalaminotransferases in the studied population was 3.18%. There was noassociation between body mass index in obese patients and NASH, as wellas between histological severity of NASH and body mass index, dyslipi­daemia and serum aminotransferases levels.

6651

EFFECT OF DAILY INTERFERON ALFACON-I ON RESPONSERATES OF PREVIOUSLY TREATED NON-RESPONDERCHRONIC HEPATITIS C PATIENTS, WITH EMPHASIS ONRATES IN AFRICAN AMERICAN AND GENOTYPE 1 POPULA·TIONS-A PRELIMINARY REPORT.Jonathan McCone, Julie Baldwin, Bonnie McCone, Alexandria, VA.

Background: Hepatitis C is epidemic with millions in the US and world­wide poised to become ill with major liver disease. With conventionaltherapy, most patients have either not responded or relapsed. Retreatmentwith high dose Infergen monotherapy or combination therapy is lesseffective in nonresponders than relapsers and African Americans (AA),genotype I patients and patients with high viral loads respond even lesswell to conventional therapy. Methods: Previously treated chronic hepa­titis C patients were randomized to 48 weeks of either 9 or 15ug dailyInterferon alfacon-l therapy. Screening eliminated other liver disease,pregnancy, malignancy, decompensated cirrhosis, or HIV disease; all hadliver biopsy and monitoring of ALTs, HCV by PCR, depression index.Demographics: 17 patients entered to date. Ethnic breakdown: 10 AA (59per cent) 5 Caucasian (29 per cent) 1 Asian, I Pakistani. 11 male, 6 female.Genotypes: 14 type 1, one 2a, one 2b, one 3a. Average age 42. Cirrhosisseen in 4 (24 per cent). Presence of virus in all patients confirmed with asecond generation Roche assay kit. Randomization: 6 of 9 AA to 9ug, 4tol5 ug. 4 Caucasians to 9ug, I to 15ug. I Asian 9ug, 1 Pakistani 15ug.Results: 6/9 AA, 5/5 Caucasians the Pakistani and Asian patient decreasedvirus at week 4 with 6 of 9 AA being < 1,000; 3 of 9 AA had undetectablevirus at week 4. These same 3 AA patients were still undetectable at week12. 4 of 5 Caucasians had virus undetectable at week 4. ALTs decreased ina parallel fashion. Side effects (tolerable but troublesome in most patients)included malaise, difficulty concentrating, myalgia, hair loss, weight loss.5 patients removed because of symptoms, one far advanced cirrhoticpatient for hepatic decompensation. Conclusion: Daily interferon alfa­con-l therapy is effective in lowering virus to to undetectable levels inmost non-responder patients studied with tolerable though significant sideeffects. All but two patients to date including 10 AA patients have re­sponded with markedly lowered or undetectable levels of virus withcorresponding decreases in ALT levels. Either a 9 or 15ug dose seems tobe effective in lowering viral levels to an undetectable extent even inAfrican American patients and in those with genotype I, historically poorlyresponding groups. Continued follow-up will determine if responses aresustained.

6652

ABSTRACT: THE EFFECT OF INTERFERON ALFACON·ITHERAPY ON RESPONSE RATES OF NAIVE CHRONIC HEPA­TITIS C PATIENTS WITH EMPHASIS ON RATES IN THE AFRI·CAN AMERICAN AND GENOTYPE 1 POPULATIONS-PRELIMI­NARY REPORT.Jonathan McCone, Bonnie McCone, Alexandria, VA.

Background: Hepatitis C is epidemic with millions in the US and world­wide poised to become ill with liver failure, cirrhosis, transplantation andliver cancer. With conventional therapy, most patients have either notresponded or relapsed. Despite dose variation, interferon type and combi­nation therapy, sustained response rates are relatively low, relapse rateshigh, and side effects significant. Methods: Naive patients were treatedwith 6 weeks of interferon alfacon-l (l5ug), then randomized to a TIWschedule of either 15 or 9ug for 42 weeks more. Screening eliminated otherliver disease, pregnancy, malignancy, decompensated cirrhosis, or HIV

Table:

SR(6Mo after ttt)Total:

MonotherapyNa'ive Retreated6/57 0/76/64: 9%

BitherapyNaive0/40/13: 0%

Retreated0/9