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S1272

Effect of High-Dose Ribavirin (RBV), Alinia (Nitazoxanide) and PegylatedInterferon (pegIFN) Alfa-2a in Attaining Sustained Virologic Response (SVR)in Treatment of Chronic Hepatitis C (ERAIS-C Trial) in Naïve Genotype 1PatientsP. Patrick Basu, Krishna Rayapudi, Tommy Pacana, Niraj James Shah, NithyaKrishnaswamy, Robert S. Brown

Purpose: PegIFN and Ribavirin (RBV) remain the backbone of therapy of chronic hepatitisC and achieve a sustained virologic response(SVR) rate of ~50% globally in all geno-types(~30% in African Americans). Alinia(nitazoxanide[NTZ]), an interferon inducer mayincrease SVR in combination with PegIFN and RBV. Very rapid virologic response(VRVR)defined as undetectable HCV RNA 14 days after initiation of combination therapy maypredict even higher SVR rates. We assessed NTZ in combination with high-dose RBV andPegIFN alfa-2a in Hepatitis C treatment. Methods: Prospective, open-label, pilot study ofnaïve patients with chronic hepatitis C GT1.23 Patient were enrolled.Exclusions: uncontrolleddiabetes mellitus ,decompensated cirrhosis etc. Patients received NTZ 500 mg bid for first2 weeks; RBV 800 mg in AM and 600 mg at night added to NTZ for next 2 weeks;subcutaneous PegIFN alfa-2a 180 mcg weekly added to RBV and NTZ at the same dose(triple regimen) for next 12 weeks. Patients who achieved EVR continued PegIFN alfa-2aand RBV for the next 36 weeks at the same dose. VRVR, Rapid Viral Response(RVR), EarlyViral response(EVR), End Treament Viral Response(ETR), and Sustained Viral Response(SVR)were assessed.(COBAS TaqMan HCV Test v2.0, Roche Diagnostics).Results: See table-1.Demographics:Caucasian (n=9, 39%), Hispanic (n=4, 17%), African-American (n=5, 21%)and Asian (n=5, 21%). Patients had a mean BMI of 27.9 and a mean HCV RNA of 600,000IU/ml. The majority had a fibrosis score of F2 (57%). Epoetin (52%), filgrastim (30%),and Elthrombopag (8.6%) were used to minimize dose reductions. African-American SVR-40%(2).Adverse effects:macular skin rash-9(39%); neutropenia(mean-400/microliter)-11(47.8%)given filgrastim; thrombocytopenia(mean-30,000/microliter)-10(43.4%)givenElthrombopag;anemia(mean-9 g/dl)-12(52%)given epoetin; and 2(8.7%) discontinued dueto side events. None had dose reductions. Conclusions: Combination of NTZ, high-doseRBV and PegIFN alfa-2a enhances RVR over historical controls and offers an improved SVRrate of 56.5%(compared to standard global 46% with GT1) and an enhanced SVR inAfrican americans(40%)Table-1:

S1273

The Natural History of Liver Fibrosis Progression Rate in Hepatitis CInfectionDavid Yamini, Benjamin Basseri, Anush Arakelyan, Pedram Enayati, Tram T. Tran, GraceM. Chee, Fred Poordad

Background: Factors that determine the rate of progression of liver fibrosis in hepatitis Cvirus infection (HCV) are difficult to identify given the indolent and chronic nature of HCV.We previously reported the association between multiple comorbidities-and other variables-and liver fibrosis score from a single biopsy. This study was designed to assess liver fibrosisrate and identify variables associated with accelerated fibrosis in patients with multiplebiopsies. Methods: A cross-sectional retrospective review of demographic and clinical datafrom a cohort of 800 patients with HCV evaluated between 1998 and 2007. Demographicand social behavior patient data was collected in a prospective fashion using a standardizedquestionnaire at the first encounter. Variables evaluated included demographics, comorbidi-ties, tobacco and alcohol use, high risk social behaviors, treatment with interferon (IFN),and lab data. Statistical analysis was performed using univariate linear regression with andwithout correction for duration of HCV. Results: 72 patients with >1 liver biopsy wereidentified. The mean interval between biopsies was 4.2±3.1 (range 0.1-19.0) years and theoverall liver fibrosis progression rate was 0.17±0.52 Metavir fibrosis points (MFP)/year.Twelve patients (16.7%) had lower fibrosis stage on subsequent biopsy, 34 patients (47.2%)had no change and 26 patients (36.1%) had increased fibrosis stage on subsequent biopsy.Twenty six patients (36.1%) failed IFN therapy prior to the first liver biopsy, with a liverfibrosis progression rate of 0.14 ±0.63 MFP/year. Amongst the 46 patients (63.9%) whodid not receive IFN therapy, the overall liver fibrosis progression rate was higher at 0.19 ±0.45 MFP/year. The difference in liver fibrosis progression rates between the IFN-treated

S-218AGA Abstracts

group and non-IFN-treated group was not significant (p=0.60). There were no significantassociations appreciated between fibrosis progression rate and variables evaluated includingage at time of HCV acquisition and first biopsy, gender, alcohol use, smoking, risk factorsfor HCV transmission, diabetes, previous treatment with IFN, HIV status and lab values.Conclusions: Change in fibrosis score between liver biopsies was variable. One-third of ourpopulation progressed over 4 years, but there were no variables that clearly correlated withfibrosis progression. Given the progression rates, it is reasonable to stage fibrosis every 3-5 years even in those without the known factors that accelerate fibrosis progression. Thebest modality for staging remains liver biopsy, but serial non-invasive tests should be studiedto determine if they can supplant biopsy.

S1274

19-Year Follow-up of Patients in a Double-Blind Trial of Colchicine PlusUrsodiol Versus Methotrexate Plus Ursodiol in the Treatment of PrimaryBiliary CirrhosisJohn Leung, Alan Bonder, Morris Sasson, Peter Bonis, Marshall Kaplan

INTRODUCTION: The efficacy of colchicine and methotrexate (MTX) in combination withursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis remains controversial.Few studies have reported long-term clinical outcomes on combination therapy. METHODS:We reviewed the clinical course of a group of 29 patients who had been treated with UDCAwith colchicine or MTX who were followed for up to 19 years. The group represented asubset of 85 patients who were originally enrolled in a randomized controlled trial comparingcolchicine and MTX. UDCA was added in both groups after two years. A total of 29 patientscompleted 10 years of follow-up on their study drugs (11 on MTX plus UDCA and 18 oncolchcine plus UDCA) and were previously reported [Hepatology, 2004 Apr;39(4):915-23].Both groups demonstrated significant improvement in serum alkaline phosphatase levelsand liver histology compared with baseline. After completion of the trial, the randomizationcode was broken and patients were treated according to their clinical response, personalpreference and tolerance to therapy. Here we report additional clinical follow-up in thesepatients. RESULTS: 21 patients continued to be followed at our institution while 8 werefollowed by their referring physicians for a mean of 8.7 additional years (range 7.5-10.4)after the trial. At follow up, 6 patients were maintained on UDCA, 1 on colchicine, 3 onMTX plus UDCA, 16 on colchicine plus UDCA, and 3 on triple therapy of MTX, colchicineand UDCA. Of the 11 patients randomized to methotrexate plus UDCA, 2 died of causesunrelated to liver disease at the age of 79 and 70. Of the 18 patients randomized to colchicineplus UDCA, 2 underwent orthotopic liver transplant (OLT) and 3 died of unrelated causesat the age of 73, 76 and 76 respectively. The mean age of the 22 patients who survivedfree of OLT was 66 years (range 55-82). They all remain well and continue to have normalbiochemical tests of liver function after 19 years of follow-up. No patient developed evidencefor portal hypertension or other features of decompensated liver disease despite having amean histological stage scores of 2.5 out of 4.0 at the beginning of the study. CONCLUSION:Treatment with UDCA combined with MTX and/or colchicine was associated with sustainedclinical remission in a subset of patients with PBC. Further studies are needed to clarify theextent to which the benefits are attributable to treatment rather than the natural history ofPBC and to clarify predictors of response to combination therapy.

S1275

Decreased Sustained Virologic Response in Patients With Elevated AlanineAminotransferase (ALT) During the Treatment of Chronic Hepatitis CRabin Rahmani, Vadim Nobel, Nidhi Mishra, Gokulan Ratnarajah, Ian Wall, ElenaIvanina, Kadirawel Iswara, JianJun Li, Scott M. Tenner, Michael D. Bernstein

During the treatment of Chronic Hepatitis C with pegylated interferon and ribavirin, patientsare occasionally found to have an elevation in alanine and aspartate aminotransferase. Oftenthese elevations in aminotransferase have been shown to persist despite clearance of HepatitisC viral RNA. Although a previous study suggested that a rapid decrease of ALT and itsnormalization during treatment can be considered an indicator of favorable response totreatment, it remains unclear if this biochemical feature has a role in predicting a sustainedvirologic response (SVR). In order to determine whether an elevated ALT during the courseof treatment affects SVR, we performed the following prospective study. The study was asingle center, prospective evaluation of a consecutive series of patients treated for ChronicHepatitis C who cleared the virus within 12 weeks of initiating treatment. All patients weretreated with pegylated interferon and ribavirin. Duration and dosage with interferon andribavirin was based on current guidelines for genotype and weight. Patients were followed asclinically indicated and with the standard-of-care monthly laboratory testing which includedserum ALT. HCV RNA quantitative analysis was performed at 4 weeks, 12 weeks, and 6months after treatment and as deemed appropriate by the treating physician. The study wasapproved by the institutional review board (IRB). Forty-nine patients were enrolled in thestudy. During the course of treatment, 22/49 patients were found to have an elevated ALTafter 3 months of initiating therapy. Compliance with the recommended dosage of medica-tions during the course of treatment was confirmed through close supervision of nursingstaff. 27/49 patients had normal ALT throughout the course of treatment. There were nosignificant differences in age (46 + 17 vs 44 + 19 years), gender (44 % male vs 48 % female),genotype (67 % genotype 1 vs 71 % genotype 1), and initial viral load between the patientswho had normal ALT compared to those with elevated ALT (p > 0.05). Six months followingsuccessful completion of treatment, 5/22 (22 percent) of patients with an elevated ALTrelapsed as defined by a positive HCV RNA quantitative and qualitative exam. However,none of the 27 patients (0%) with normal ALT levels relapsed (p = 0.03). In conclusion,an elevated ALT is significantly associatedwith a risk for relapse following successful treatmentof chronic hepatitis C. Clinicians may consider continuing therapy for an additional 3-6months in these patients to increase the likelihood of a sustained virologic response.