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Hepatitis C virus genotype: is it an independent predictor ofprogression of liver disease?Sanjay Agrawal1*, Savant Mehta1, Qin Liu2, Chung C Hseih2, Herbert LBonkovsky1 and Raymond S Koff1. 1Gastroenterology, Liver-Biliary-Pancreas Center, University of Massachusetts Medical School,Worcester, MA, United States USA; and 2UMASS Cancer Center.

Purpose: We performed a retrospective analysis to assess the relationshipbetween HCV genotypes and progression of liver disease.Methods: Patients referred to the hepatology and liver transplant clinicbetween 7/99 and 4/01 had HCV ELISA confirmed by RIBA. Sero-positivepatients had a HCV PCR for viral load and genotype. A multivariateanalysis of age, sex and genotype comparing the two sets of patients wasperformed to determine their relationship to progression of liver disease.Results: Of 242 patients referred for transplant evaluation 89 were positivefor anti-HCV of which 74 patients had HCV genotype determination (5were HCV PCR -ve, 1 not typable, 9 genotype not available). Genotypewas available in 343 patients in the non-transplant group (controls). Of the74 transplant patients, 60 (81%) had genotype 1/4 (1 or 4) with a mean ageof 50.25 � 6.75 yrs, and a M:F ratio of 4:1; 14 patients (19%) hadgenotypes 2/3 with a mean age of 50.14 � 5.57 yrs and a M:F ratio of 2.5:1.The overall mean age in this group was 50.24 � 6.55 yrs with a M:F ratioof 4:1. Among the 339 controls 238 patients (67.3%) were genotype 1/4with a mean age of 43.56 � 9.36 years and a M:F ratio of 1.8 :1 and 101patients (32.8%) were genotype 2/3 with a mean age of 44.39 � 8.04 anda M:F ratio of 1.6:1. The overall mean age in this group was 43.81 � 8.98years with a M:F ratio of 1.8:1.

Patients evaluated for transplant were older than the control group (50.24vs 43.81 yrs; p � 0.05 students t-test) and the M:F ratio was higher (�2testp � 0.05). Genotypes 1/4 were more common in the transplant group (�2

test p � 0.05). On multivariate regression analysis age and sex wereindependently correlated with increased likelihood of being referred forliver transplant evaluation, a surrogate marker for advanced liver disease(p � 0.0001 for age, p � 0.03 for sex respectively). Genotypes 1/4 showeda strong trend towards being more common in the transplant group but didnot reach statistical significance in the multivariate analysis (p � 0.07).Overall the mean ages and M:F ratio of genotypes 1/4 were comparable togenotypes 2/3 (44.88 vs 45.09 yrs; �2 � 0.41 NS).Conclusions: HCV genotype does not seem to be a strong independentcorrelate of being referred for liver transplant evaluation, a surrogatemarker for decompensated liver disease. Genotypes 1/4 are however morecommon in patients referred for liver transplant. Older age and male sexcorrelated with more advanced liver disease. Overall, the age of patientswith genotype 1/4 is comparable to that of genotype 2/3. Effective treat-ments for genotype 2/3 would thus tend to significantly lower the burdenof patients requiring OLT.

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Value of AST and AST/ALT ratio in predicting histologic grade inchronic hepatitis C (HCV)Frank M Moix, MD1 and Jean-Pierre Raufman, MD, FACG1*.1Division of Gastroenterology, University of Arkansas for MedicalSciences, Little Rock, AR, United States.

Purpose: To assess the value of AST and AST/ALT ratio in predicting thedegree of fibrosis in patients with HCV.Methods: Between 1996–99, 35 serial patients with HCV and nl ALT(�1.4 � 50 IU/L) within 6 mos of liver biopsy were identified. During thesame interval, 35 patients with elev. ALT (�1.4 � 50 IU/L) within 6 mosof biopsy were also identified. After analysis, no significant correlationbetween ALT and histological grade was demonstrated (Am J Med 2000;109:62). The present study represents a reanalysis of these 70 patientsfocusing on AST and AST/ALT ratio. Patients were reassigned to 2 groupsbased on AST values. 39 patients had nl AST (�1.4 � 40 IU/L). Theremaining 31 patients had elev. AST (�1.4 � 40 IU/L). Demographic data

were compared using a two-tailed t-test. Liver biopsies were graded by ablinded pathologist. The extent of periportal necrosis, intralobular degen-eration/focal necrosis, portal inflammation, and bridging fibrosis or cirrho-sis was scored. The total score represents the Histological Activity Index(HAI). Correlations between AST and HAI as well as AST/ALT ratio andHAI were made by simple linear regression.Results: After regrouping, it was noted that patients with elev. AST wereolder than those with nl AST (48.0 � 8.3 vs. 43.7 � 8.7 yrs, mean � SD,P � .035). There were no differences in sex, race, EtOH use, or risk factorsfor hepatitis. As expected, AST levels in the 2 groups were different(33.5 � 10 vs 100.1 � 40 IU/L, P � 0.001). AST/ALT ratios were notdifferent (.95 � .43 vs .92 � .44, P � .753). Mean HAI scores were 4.4 �2 in patients with nl AST vs. 6.8 � 3 in patients with elev. AST (P �0.001). Among patients with nl AST, 5 (12.8%) had bridging fibrosis and4 (10.3%) had cirrhosis. Among patients with elev. AST, 12 (38.7%) hadbridging fibrosis and 7 (22.6%) had cirrhosis. Mean AST and AST/ALTratio were 86 � 47 and .93 � .43 in patients with advanced disease(bridging fibrosis/cirrhosis) as compared with 45 � 30 (P �.001) and .95 �.43 (P � .84) in those with less advanced disease. Subgroup analysis ofEtOH use in patients with advanced disease did not reveal a difference fromthose with less advanced disease (P � .94). Overall, a modest positivecorrelation (r � .50, P � 0.001) was noted between AST and HAI.However, AST/ALT ratio did not correlate with HAI (r � .008, P � .94)Conclusions: AST is more predictive of fibrosis in patients with HCV thaneither ALT or AST/ALT ratio. Nevertheless, a normal AST does notexclude advanced liver disease.

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Rebetron for HCV in US veterans: Success or failure?Joseph Morelli1, Anthony Balistreri1, Chris Kim1 and Ira Willner1*.1Division of Gastroenterology and Hepatology, Medical University ofSouth Carolina, Charleston, SC, United States.

Purpose: Hepatitis C in the veteran population has a reported prevalenceof about 8%. We report our experience at the VA with combination therapy(Interferon plus Ribavirin) in a non-study environment.Methods: Medically and psychologically fit patients who had a liverbiopsy and offered therapy were studied. They were 88 patients (85 malesand 3 females) of which 51 (58%) were Caucasian (CA), 35 (40%) wereAfrican American (AA), and 2 (2%) were Hispanic Americans (HA). 13had cirrhosis (11CA, and 2AA); 10 had stage 3 disease (5 CA, and 5 AA);45 had stage 2 disease (24 CA, 19 AA, 2 HA); 16 had stage 1 disease (9CA, 7 AA); 2 had stage 0 disease (1 CA, 1 AA). The population waspredominately genotype 1a/b 76 (86%) (43 CA, 33 AA); genotype 2a/b 4(4.5%) (2 CA, 1AA, 1HA); genotype 3a 4 (4.5%) (2 CA, 1 AA, 1HA). In4 the genotype was not available.Results: 84/88 initiated treatment. 4 declined treatment. At the time of thisreview, 16/84 were active in therapy. 72/88 patients were no longer intreatment. 46 patients completed therapy. 12 patients discontinued therapysecondary to anemia, renal insufficiency, or persistent flu like symptoms.14 patients who started therapy missed more than 3 consecutive appoint-ments and were discontinued. 8/46 (2 genotype 1a/b, 1 genotype 2a/b, 2genotype 3a, 3 genotype unknown) had an end of treatment response. Ninewith genotype 1 had a negative PCR after 6 months of therapy, but only 2/9had a negative PCR at completion. One patient relapsed at 6 months. 3/13with cirrhosis had viral clearance after 6 months of therapy, but at the endof treatment were positive.Conclusions: 8/46 (17%) of patients completing treatment including allgenotypes had an end of treatment response (ETR). However, ETR in theAfrican American population was 0%. We did not achieve a sustainedresponse in 13 cirrhotic patients regardless of genotype. 2/8 who had ETRrelapsed 6 months post treatment. 26/84 (31%) of our unselected popula-tion were either unable to tolerate treatment or lost to follow up. Using anintention to treat analysis only 11% had end of treatment response. Giventhese findings, a more effective treatment in this population needs to be

S130 Abstracts AJG – Vol. 96, No. 9, Suppl., 2001