conventional treatment and establish the role and correction of HyperAmmonemia with O.A. Therapy such patients.Methods and Materials: 144 patients referred to our center with pro-longed viral hepatitis of more than 1.5 months were included in this study(Jan. 1999 to Jan. 2000). Patients who consume alcohol or benzo diazipeneswere not included in this study. None of these patients had features of H.E.All these patients apart from routine LFT and hematological workupincluding B.U.N. and ultrasound of abdomen were screened for PA afterwritten consent.Results:The age of the patients varied from 3 years to 85 yrs. Males weremore affected than females (109 males and 35 females). The serum bili-rubin ranged from 44.2 mg% (highest) to 2.8 mg% (lowest). The SGPTranged from 2760 I.U/lt (highest) to 97 I.U/lt (lowest). The viral markersshowed Hep A in 40, Hep B in 42 and Hep E in 40. There was coinfectionlike Hep B 1 E 1 CMV and/or leftospirosis in 22 patients. PA waselevated 11⁄2 to 4 times in all these patients rating from 212 m.moles/lt(highest) to 97 m.moles/lt (lowest) (normal being 15–50 m.moles/lt) (kitused RAICHEM—U.S.A.). PA was elevated in parallel with SGPTlevels despite the serum bilirubin. All these patients were admitted andalong with conventional treatment for viral hepatitis were given O.A.infusion upto the dose of 25 gms in adults and 5 gms in children below12 yrs. The LFT along with PA were repeated every 10th day. There wasdefinite lowering of PA upto 50% along with a similar fall of SGPT inall these patients. After discharge all these patients were given O.A.granules oral therapy with 15 gms for adults and 3 gms in children. Overa period of 30 days the PA, the entire LFT and serum bilirubin came tonormal.Conclusion: Hence we postulate that Plasma Ammonia is a very goodprognostic marker and correction of hyper ammonemia in all these patientswith conventional therapy accelerates recovery in patients with prolongedviral hepatitis despite the pattern of viral pathogens.

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An unusual overlap syndrome in a male with chronic activehepatitisAlex E. Baum, MD, Tanveer Iman, MD, Carmen Sarita, MD, AnirudhMasand-Rai, MD, Fredric Regenstein, MD. Tulane University School ofMedicine, New Orleans, LA, USA.

A 27 y/o African-American male with an insidious history of jaundice andgeneral malaise for one year was referred to us for further work-up andtreatment. The patient complained of easy fatigability, and generalizedarthralgias for the past 6 months, and had been taking Ibuprofen on a PRNbasis. Physical examination showed a palpable spleen, but was otherwiseunremarkable. Labs were notable for AST 64 IU/L, ALT 105 IU/L, Alk.Phos 360, Total Protein 8.4 g/dl, Gamma Globulin 27.1%, PT 15.9/INR1.29, WBC 4.0 K/cc, Hgb 14/Hct 42, PLT 43 k/cc1ANA 1:320 homo-geneous,1Anti Smooth Muscle AB 1:160, negative AntiLKM AB, neg-ative Antimitochondrial AB, Iron 128, TIBC 412, negative Hepatitis A/B/Cserology, normal copper and ceruloplasmin levels. A CT scan revealed ahomogeneous liver without duct dilation. He underwent a liver biopsywhich showed chronic active hepatitis with early features of cirrhosis andwas scheduled for an ERCP. At this time he was started on Prednisone 20mg/d Folic acid 1 mg/d, OsCal 500 mg TID. The ERCP demonstratedmultiple short irregular strictures with beading irregularities of the intra-hepatic ducts. At this time Ursodeoxycolic acid 250 mg TID was added.

The patient has done well receiving such treatment, and the AST, ALTand Globulin have normalized and the Alk. Phos has decreased after 5months, the PLT count remains low, and he continues the same treatmentregimen.

Several overlap syndromes have been noted to occur in patients withfeatures of Autoimmune hepatitis, PBC, PSC and Wilson’s disease. Themajority of these patients are women. Clear-cut criteria for these overlapsyndromes are currently being developed. The best described is calledautoimmune cholangitis and appears as antimitochondrial-antibody-nega-tive PBC sometimes with high ANA or ASMA titers. Patients with these

syndromes may respond to corticosteroids or ursodeoxycholic acid; theautoimmune component usually responds, as it does in typical AIH. Wepresent an unusual overlap syndrome in a male with good response totreatment.

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Low dose interferon-ribavirin therapy is as efficacious as regularstrength RebetronR for the treatment of naive hepatitis C patientsDavid Bernstein, M.D. FACG, Maly Tiev, R.N., Stephen E. Steinberg,M.D. FACG. North Shore University Hospital, Manhasset, NY 11030.

Introduction: Combination interferon-ribavirin therapy is currently ap-proved for the treatment of previously untreated hepatitis C patients. Theribavirin dose used is either 1000 or 1200 mg a day. These dosages havebeen associated with significant side effects often requiring dose reduc-tions.Aim: To evaluate the role of low dose ribavirin in the treatment naivehepatitis C patients.Methods: Randomized, controlled, open label trial comparing standardinterferon alpha-2b 3 million units three times a week plus 1000 mg ofribavirin daily to interferon alpha-2b 3 million units three times a week plusribavirin 600 mg a day. The duration of therapy was one year. A liverbiopsy was performed prior to initiating therapy. The primary endpoint oftherapy was a virologic response as measured by a negative HCV-RNA byPCR performed by the NGI Superquant assay six months after completingtherapy. Patients were considered a treatment failure if the six, twelve or 18month HCV-RNA was positive.Patients: 33 patients were randomized into the trial. 17 received ribavirin600-mg and 16 got ribavirin 1000-mg. There were no significant differ-ences between the two groups in regards to age, weight, gender, race, viralload, genotype or histology. The only cirrhotic patient in the study was inthe low dose ribavirin group.Results: In the 600 mg ribavirin group, 11 of 17 (65%) had an end oftreatment response and 9 of 17 (53%) had a sustained viral response. Thelone cirrhotic patient was a sustained responder. In the standard 1000 mga day of ribavirin group, 9 of 16 (56%) had an end of treatment responseand 7 of 16 (43%) were sustained responders. No patients in the low doseribavirin group required dose reduction while 4 patients in the 1000 mggroup required dose reduction. There were no significant differences in sideeffects between the two groups although there was a trend towards loweranti-depressive therapy requirements in the low dose ribavirin group.Conclusions:Low dose ribavirin plus interferon appears to be effective forthe treatment of naı¨ve hepatitis C patients. The anemia encountered withlow dose ribavirin is less severe requiring fewer dose modifications. Sideeffects, especially depression, appear to be fewer with 600 mg of ribavirin.This dose should be further evaluated in larger studies.

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Low dose ribavirin plus high dose interferon for 1 year is effectivein the treatment of hepatitis C patients who were initially eitherrelapsers or non-responders to interferon monotherapyDavid Bernstein1, MD, FACG, Maly Tiev1, RN, Lennox Jeffers2, MD,FACG, Gerond Lake-Bakaar3, MD. Division of Gastroenterology,North Shore University Hospital, Manhasset, NY1; Univ of MiamiSchool of Medicine/Miami VA Medical Center, Miami, FL2; NorthportVA Medical Center, Northport, NY3.

Introduction: Combination interferon-ribavirin therapy is currently ap-proved for the treatment of hepatitis C patients who relapse after initialinterferon monotherapy. The approved ribavirin dose is either 1000 or 1200mg a day. Non-responders to interferon monotherapy have historicallyresponded poorly to combination therapy.Aim: To evaluate the safety and efficacy to low dose ribavirin withinterferon in the treatment of both relapsers and non-responders to inter-feron monotherapy.

2506 Abstracts AJG – Vol. 95, No. 9, 2000

Methods: Relapse and non-responder patients were treated with interferonalpha-2b at 5 million units (MU) TIW plus either 600 mg or 1000 mg ofribavirin daily for 6 mos followed by interferon monotherapy at a dose of5 MU TIW for 6 mos. Patients were considered treatment failures if theHCV-RNA was positive at either 6, 12, or 18 mos.Results: 59 nonresponders and 17 relapsers were enrolled. No significantdifferences were noted between any groups in viral load, genotype orhistology. 6 of 29 (21%) nonresponders treated with the 600 mg dose ofribavirin had a sustained virologic response. 9 of 30 (30%) of nonre-sponders treated with 1000 mg of ribavirin were sustained virologic re-sponders. 7 of 11 (64%) of relapse patients treated with 600 mg of ribavirinwere sustained virologic responders. 5 of 6 (83%) of relapse patients treatedwith 1000 mg of ribavirin were sustained virologic responders. Side effectsand dose reductions were greater in the 1000-mg ribavirin group.Conclusions:The addition to ribavirin to high dose interferon increases thesustained response rates to therapy in relapsers or nonresponders to initialinterferon monotherapy. Low dose ribavirin plus high dose interferon is notas effective as standard dose ribavirin plus high dose interferon for thetreatment of previous relapsers or non-responders to interferon mono-therapy.

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A randomized, controlled trial of high dose daily induction (HDDI)interferon (IFN) plus ribavirin (RVN) versus Rebetron fortreatment of chronic HCVAS Bhatia, CM Hofmann, RK Sterling, VA Luketic, AJ Sanyal, MJContos, V Araya, J Strohaker, K Kohagen, ML Shiffman. The MCVCooperative Hepatitis Treatment Group, MCV-VCU, Richmond, VA.

Although superior to IFN monotherapy, the combination of IFN plus RVNremains suboptimal for treating chronic HCV. Recent studies have dem-onstrated that virologic response (VR) is greater in pts treated with HDDI-IFN, however this response is not sustained. Since RVN is effective inreducing relapse we have hypothesized that a combination of HDDI-IFNplus RVN might improve VR in pts with chronic HCV.Methods: 181 pts with chronic HCV, a hx of elev ALT, HCV-RNA(1)and no coexistent liver disorders, were randomly assigned to tx with eitherRebetron (IFN-a-2b 3 mU TIW plus RVN 1000–1200 mg/day3 12 mos)or a HDDI regimen (86 pts) as follows: 5 mU IFN-a-2b QD 3 1 mos, 5mU IFN QD 1 RVN 3 1 mos, 5 mU IFN TIW1 RVN 3 1 mos, 3 mUIFN TIW 1 RVN 3 9 mos. Tx was discontinued in all pts who remainedHCV-RNA(1) at 6 mos. All pts underwent LBX at baseline. HCV-RNAwas assessed by NGI assay.Results: The groups were well matched. Mean age 44.4 yrs, 66% male,78% Caucasian, mean ALT 1166 14 IU/l, Log HCV-RNA titer 6.2160.05, 71% genotype 1, Knodell score 6.66 0.1 and 13% cirrhosis. For ptstreated with Rebetron, 19, 41, 57 and 51% were HCV-RNA undetectible at1, 3, 6 and 12 mos versus 20, 48, 63 and 60% when treated with HDD,respectively (p5 NS). 25% and 24% of pts in each group (p5 NS)discontinued tx secondary to side effects. Predictors of VR included race(Caucasian. Blacks) HCV genotype non-1 and an HCV-RNA titer,2million copies/ml.Conclusions: HDDI-IFN 1 RVN during mos 1–3 did not improve VRover that observed with Rebetron. Pts continue to be followed for assess-ment of SVR, but given the similar degree of response at 12 mos this isunlikely to be superior in the HDDI group. The rate of discontinuation wasnot greater with HDDI-IFN.

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Combined hepatitis C virus and hepatitis B virus infection andhepatocellular carcinoma in African AmericansParvinder K Birdi, M.D., Sonja Wustrack, MPH, Luis A Balart, M.D.FACG*. Louisiana State University Health Sciences Center, NewOrleans, Louisiana, United States.

Purpose:To determine the impact of hepatitis C and hepatitis B infectionon the incidence rates of primary HCC among African Americans andCaucasian population.Methods: We retrospectively reviewed charts from two local institutionsserving a heterogeneous population. Between 1994 and 1999, there were113 patients histologically diagnosed with HCC and 75 patients (40 Cau-casians, 30 African Americans and 5 others) had complete records. Hep-atitis B surface antigen and/or hepatitis B core antibody, and HCV antibodyinformation was documented in 39 patients.Results:

Race HBV only HCV only HCV and HBV Neither Total

Caucasians 2 7 1 4 14African Americans 0 7 8 7 22Others 0 1 1 1 3

The presence of combined HCV and HBV infection among African Amer-icans was 36% while it was 7% among Caucasians. Thus African Amer-icans represented 80% of combined HCV and HBV infection.

Conclusions: Though the overall incidence of HCC was 53% in Cauca-sians and 40% in African Americans in this study population, the combi-nation of HCV and previous or current infection with HBV may explain thehigher prevalence and increased mortality rates of HCC in African Amer-icans nationwide. Further studies with a larger population are needed tovalidate this association.

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The effect of orthotopic liver transplantation on the QTc interval inpatients with end-stage liver diseaseE. J. Carey, David C. Mulligan, Vijayan Balan, M. Edwyn Harrison,Jorge Rakela, D. D. Douglas. Mayo Clinic Hospital, Phoenix, AZ, USA.

Purpose: Autonomic dysfunction is a recognized complication of end-stage liver disease, occurring equally in patients with alcoholic and non-alcoholic cirrhosis. The corrected QT interval (QTc) on ECG has been usedas a marker of autonomic dysfunction. Prolongation of the QTc has beenassociated with severity of liver disease and has been suggested as a poorprognostic sign. A few small studies have suggested that QTc may nor-malize after orthotopic liver transplant (OLT), but the mechanism of thiscorrection is not well understood. A recent study (Gastroenterology 2000;118:A984, Abstract #1109) found 12% of patients with abnormal QTcactually worsened after OLT, suggesting the cause of this prolongation maybe multifactorial. We sought to determine how liver transplantation affectsthe QTc interval in patients with end-stage liver disease.Methods: A retrospective analysis of QTc intervals of OLT patients wasperformed. Data were collected from 23 patients who received OLT atMayo Clinic Scottsdale and 28 patients who were transplanted elsewherebut have received follow-up care at MCS. The QTc interval from thepre-transplant evaluation was compared with the 4-month post-transplantfollow-up using the Wilcoxin Matched-Pairs Signed-Rank test.Results:29/51 (57%) of patients showed evidence of prolonged QTc (440ms or greater) at the pre-transplant evaluation. The mean QTc among allpatients prior to transplant was prolonged and improved to within normalrange after transplant (p, .000006). Those who started out with a pro-longed QTc (mean 470 ms) showed a significant improvement in QTc aftertransplant (428 ms, p, .000049) whereas those whose QTc was normalinitially showed no change. These relationships held when patients onmedications that could prolong the QTc interval were excluded. 2/24 (8%)of patients with abnormal QTc worsened after OLT. There was no rela-tionship between QTc prolongation and Child’s score, age, or etiology ofliver disease.Conclusion: These results confirm that the majority of patients withend-stage liver disease and prolonged QTc will have significant improve-ment in this parameter after OLT, however 8% of patients in our study hadworsening of their QTc after OLT suggesting another etiology for their

2507AJG – September, 2000 Abstracts