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This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

To study the combination of 5FUDR, recombinant leukocyte interferon (IFN), and doxorubicin in patients with unresectable hepatocellular carcinoma. IFN was administered at a dose of 6 miu/m2 subcutaneously followed in 2 h by doxorubicin 20 mg/m2 intravenously. After doxorubicin, 5FUDR was given as a 24-h infusion at a starting dose of 80 mg/kg. The dose of IFN was escalated to three times a week if tolerated. Both doxorubicin and 5FUDR were administered once weekly. There were 30 patients entered into the study. Among the 30 patients, there were two partial responses (7%) and one patient had stable disease. Toxicity was generally tolerable with fever, and chills, fatigue, and myelosuppression as the most common side effects. This chemotherapy combination was generally well tolerated, but has limited activity in unresectable, advanced hepatocellular carcinoma.

1359 FIRST SVR DATA WITH THE NUCLEOSIDE ANALOGUE POLYMERASE INHIBITOR MERICITABINE (RG7128) COMBINED WITH PEGINTERFERON/RIBAVIRIN IN TREATMENT-NAIVE HCV G1/4 PATIENTS: INTERIM ANALYSIS FROM THE JUMP-C TRIAL P. Pockros, D. Jensen, N. Tsai, R.M. Taylor, A. Ramji, C. Cooper, R. Dickson, A. Tice, S. Stancic, D. Ipe, J.A. Thommes, J.M. Vierling. Scripps Clinic Research Center, La Jolla, CA, Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, Hawaii Medical Center, Honolulu, HI, The University of Kansas Hospital Medical Center, Kansas City, KS, USA; Division of Gastroenterology, University of British Columbia, Vancouver, BC, The Ottawa Hospital, Ottowa, ON, Canada; Dartmouth-Hitchcock Medical Center, Lebanon, NH, Infections Limited Hawaii, Honolulu, HI, Roche, Nutley, NJ, Genentech, South San Francisco, CA, Baylor College of Medicine, Houston, TX, USA E-mail: pockros.paul@scrippshealth.org Introduction: Mericitabine (RG7128, MCB) is a potent, selective nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase with activity across all HCV genotypes. MCB has demonstrated a high barrier to resistance without treatmentemergent resistance observed to date. Methods: JUMP-C is an ongoing randomised, double-blind, placebocontrolled phase 2b study in treatment naive patients infected with HCV G1/4. The trial objective was to compare a response guided therapy regimen of MCB plus peginterferon alfa-2a/ribavirin (P/R) with P/R alone. Patients randomised to arm A achieving an extended RVR (eRVR; HCVRNA

BACKGROUND & AIMS: Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis. METHODS: A preliminary, single-center, dose- escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period. RESULTS: The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation. CONCLUSIONS: This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial. (Gastroenterology 1997 Dec;113(6):1930-7)

A high prevalence of antibodies to the hepatitis C virus (anti-HCV) has been demonstrated among patients with alcoholic liver disease, whereas the prevalence of HCV viremia in these patients remains uncertain. The aims of this study were to determine the prevalence of anti-HCV in alcoholic patients both with and without clinically apparent liver disease and to determine the presence of HCV RNA in those patients who tested positive for anti-HCV by RIBA II (Chiron Corporation, Emeryville, CA). One hundred male patients consecutively admitted to an alcoholic rehabilitation program were included. Group 1 was comprised of 40 patients with clinically apparent liver disease. Group 2 was comprised of 60 patients without clinically apparent liver disease. Anti-HCV was performed by a second-generation ELISA assay and confirmed by RIBA II. HCV RNA was performed by Quantiplex assay (Chiron Corporation) and a nested reverse transcriptase-polymerase chain reaction. No significant differences were found between the two groups with regards to age, quantity and duration of alcohol intake, or accepted risk factors for HCV. The overall prevalence of anti-HCV in our patients was 23%, with 43% of these in group 1 and 10% in group 2. HCV RNA tested positive in 94% of the anti-HCV-positive patients in group 1 and in 67% of the anti-HCV-positive patients in group 2. These data suggest that HCV infection is an important cofactor in the pathogenesis of liver disease among alcoholic patients.

Background/Aims: A strong association exists between ulcerative colitis and primary sclerosing cholangitis (PSC). Previously, the presence of a unique epitope shared by colon and biliary epithelial cells was shown by using the novel monoclonal antibody (MAb) 7E12H12 developed against a colonic epithelial protein. In the present study, the presence of circulating autoantibody in PSC against this peptide was examined. Methods: Sera from 16 patients with PSC, 13 with primary biliary cirrhosis, 6 with secondary biliary stricture, and 6 with chronic liver diseases and 10 normal subjects were used. An inhibition immunoperoxidase assay using the 7E12H12 MAb was developed against sections of bile duct and gallbladder. Sera were also examined in an enzyme-linked immunosorbent assay (ELISA) against the gallbladder extract enriched in 7E12H12-reactive protein. Results: About two thirds of the sera from patients with PSC blocked the binding of 7E12H12 MAb on the bile duct and gallbladder, whereas non-PSC sera did not. In the ELISA, 93% of PSC sera had circulating immunoglobulin G antibodies against the enriched gallbladder extract. The reactivity of sera from the PSC group was significantly (P Conclusions: Sera from patients with PSC contains autoantibodies against a cross-reactive peptide shared by colon and biliary epithelial cells.

At the University of Miami liver transplantation for chronic liver disease in HCV-positive patients has shown good results, with a 92% patients survival rate (follow up 8 to 57 months, median 21). None the less, we found that a large number of patients are expected to develop serious histological graft damage and may need retransplantation, which may place a further strain on the already scarce donor resources. We have conducted a preliminary investigation on the importance of parameters which may correlate with the prognosis of HCV grafts. We found no impact of HLA match or typing. An interesting hypothesis, which deserves further investigation, is that some HCV strains could be more virulent than others and play a role as an independent risk factor. We have identified six strains among our patients and the BK serotype shows a trend to be associated with a worse outcome. We have found that patients developing and maintaining higher liver enzyme levels (ALT and GGT) after transplant and those with higher levels of viremia may be at risk to develop serious damage to their grafts.

Background and Aim: Hepatitis C continues to be a major cause for chronic hepatitis. Presently, alpha interferons are available to treat it with limited success. Interferon/Ribavirin treatment has been shown to be efficacious in sustaining virological, biochemical, and histological remission. In some cases, there have been a discordance between virologic and biochemical responses, e.g. persistence of ALT elevation despite undetectable HCV-RNA. The aim of this study is to determine if hypertriglyceridemia or other factors explain the discordance between ALT and HCV-RNA responses. Patient and Methods: 37 patients who were part of an Interferon/Ribavirin protocol for non-responders and relapsers were evaluated. Ages ranged from 32 to 53 years (mean age 44 years); there were 23 males and 14 females. All patients were treated with alpha interferon, 5 million units t.i.w, and Ribavirin 600 -1000 mg/day based on randomization. HCV-RNA, ALT and AST were evaluated at baseline and at 12 weeks. Results: 27/37 patients had >50% reduction in HCV-RNA with normalization of ALT (Group 1). 10/37 patient had >50% reduction in HCV-RNA, but had ~ersistent elevation of ALT (Group 2).