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566

Liver Biochemical Course, Serum HBV DNA and Liver Stiffness Measurementfor Therapeutic Decisions in HBeAg-Negative Chronic Hepatitis B InfectionPhunchai Charatcharoenwitthaya, Pochamana Phisalprapa, Pimpattana Rungkaew,Sorrayut Kajornvuthidej, Wimolrak Bandidniyamanon, Siwaporn P. Chainuvati, NonthaleePausawasdi, Supot Nimanong, Watcharasak Chotiyaputta, Somchai Leelakusolvong, KanitAtisook, Tawesak Tanwandee

Background & Aims: Assessment of liver histology in patients with HBeAg-negative chronichepatitis B virus (HBV) infection allows clinicians to determine the extent of hepatic inflamma-tion and fibrosis and consequently to assess suitability for treatment. It is, however, poorlyaccepted by patients due to procedure-related complications. Thus, we evaluated the abilityof various noninvasive methods in determining the presence of histological indication fortreatment (at least grade A2 or stage F2 by METAVIR scoring) in this population. Methods:Consecutive HBeAg-negative patients with serum HBV DNA levels >2,000 IU/ml and serialmeasurement of alanine aminotransferase (ALT) were enrolled to perform liver stiffnessmeasurement using Fibroscan followed by liver biopsy on the same day. Individual liverspecimens were evaluated independently by 2 pathologists without knowledge of the clinicaldata. Differences in interpretation were settled by consensus of the pathologists. Results: Atotal of 399 patients had a mean age of 47.5±9.6 years and 42% were female. Mean bodymass index at baseline was 23.9±3.8 kg/m2. Using the normal range of serum ALT <40 IU/L, 142 patients (36%) had persistently normal ALT levels (PNALT) whereas 257 patientshad persistently or intermittent elevated ALT (PIEALT) in previous 1 year prior to liverbiopsy. The proportion of PIEALT patients with moderate to severe necroinflammation (48%vs. 13%, p<.0001) and significant fibrosis (43% vs. 13%, p<.0001) was higher than thoseof PNALT patients. Histological indication for treatment was present in 57% of PIEALTpatients and 22% of PNALT patients (p<.0001). In PNALT patients defined by criteria ofnormal ALT; 30 IU/L for men and 19 IU/L for women on the day of liver biopsy, HBVcarriers with ALT levels less than updated cut-off values had no difference in the frequencyof histological indication for treatment compared to those with ALT levels higher thanupdated cut-off values (18% vs. 28%, p=.2). Among patients with HBV DNA of 2,000-19,999, 20,000-199,999, and ≥200,000 IU/mL, histological indication for treatment waspresent in 40%, 45%, and 71% of PIEALT patients and 15%, 31%, and 36% of PNALTpatients, respectively. In PNALT patients with HBV DNA <20,000 IU/L, the use of liverstiffness value <7 pKa in determining nonsignificant histology can avoid liver biopsy in 89%of patients and miss only 13% of patients who indeed had histological indication fortreatment. In PIEALT patients with HBV DNA >200,000 IU/L, the measurement of liverstiffness ≥7 pKa can predict histological indication for treatment reducing the need for liverbiopsy in 56% of patients with a false-positive of 17%. Conclusions: The combination ofserial measurement of liver enzymes, serum HBV DNA, and liver stiffness is a noninvasiveapproach that may be useful for therapeutic decision in HBeAg-negative patients.

S-896AASLD Abstracts

567

Proportion of Patients Who Were Previously Ineligible for Anti-HBV TherapyWho Became Eligible After 12 Months of Follow-up: Application of U.S. Paneland AASLD GuidelinesJessica T. Ristau, Shu Zhang, Huy N. Trinh, Ruel T. Garcia, Huy A. Nguyen, Khanh K.Nguyen, Mindie H. Nguyen

PURPOSE: Given the dynamic nature of chronic hepatitis B (CHB) and the fluctuation ofcertain clinical parameters used to determine patient treatment eligibility by treatmentguidelines (U.S. Panel 2008 and AASLD 2009), many patients who were initially ineligiblemay become treatment eligible during follow up. Our goal was to study such patientpopulations and examine the reasons and timeline for future treatment eligibility. METHODS:We performed a retrospective cohort study with 190 consecutive treatment-naïve CHBpatients who were treatment ineligible when they first presented between 3/07-1/09 andhad≥ 12months of follow upwith laboratory testing every 6-12 months at 2 U.S. communityGI clinics. US Panel 2008 eligibility requirements are as follows; ALT >30 IU/mL for males,>19 IU/mL for females and HBV DNA >2,000 IU/mL for HBeAg negative patients and>20,000 IU/mL for HBeAg positive patients. AASLD 2009 eligibility included ALT >60 IU/mL for males, >38 IU/mL for females and HBV DNA >20,000 IU/mL regardless of HBeAgstatus. RESULTS: The majority of patients were over 35 years old (74%) and Asian (97%).The proportion of patients who became eligible was described in the table. Of those whobecame eligible according to US Panel 2008 guidelines, 33% became eligible by 12 months,47% by 24 months and the remaining 20% by 36 months. Accounting for variance in totalfollow-up time, the proportions of patients becoming eligible were as follows; 9% with 12months of follow up, 5% of patients with 18 months of follow up and 12% of patients with24 months of follow up. Corresponding data for AASLD 2009 guidelines were: 2%, 2% and3% at 12, 18 and 24 months of follow-up, respectively. On multivariate analysis also inclusiveof age, gender, and HBeAg status, significant predictors of later eligibility by AASLD guidelinesat follow-up were higher ALT at baseline (0.5-1.0 xULN) (OR=5.01, p=0.031) and serumHBV DNA at baseline (>20,000 IU) (OR=4.6, p=0.05). No significant predictors were foundfor later eligibility by US Panel guidelines. CONCLUSION: While the majority of patientswho were initially ineligible for anti-HBV therapy continued to require no therapy, approxim-ately one-fifth may meet treatment criteria on even short to medium term follow-up (median23 months). This data suggests that all CHB patients should continue to have regular follow-up with periodic review of their disease status and potential need for antiviral therapy.

568

Tenofovir Disoproxil Fumarate (TDF) Shows Similar Virologic Suppressionand Safety Between Asians and Non-Asians With Chronic Hepatitis B (CHB)Calvin Pan, Sing Chan, Huy N. Trinh, Alan Yao, Ho Bae, Patrick Marcellin, E. JennyHeathcote, Betty Chiang, Lillian Lou

Background: TDF has demonstrated potent antiviral activity upon initiation of treatment inCHB patients. Two TDF registration trials in CHB (127 Asian and 299 non-Asian patients)and an open-label trial (90 Asians) were analyzed in a cross sectional study to compareefficacy and safety of TDF in Asians versus non-Asians during the first 48 weeks (W) oftreatment. Methods: Eligibility criteria were similar between registration vs. open-label trialsexcept for HBV DNA >=10^5 vs. >=10^4 copies(c)/mL and ALT >2x vs. >1x ULN [HBeAg(+)patients], respectively. All three trials were analyzed independently and compared side-by-side. Subsequently, 217 Asians were combined, and compared with 299 non-Asians stratifiedfor HBeAg status. Results: 288 HBeAg(-) and 228 HBeAg(+) CHB patients were availablefor the analysis. Baseline characteristics were similar between Asians vs. non-Asians exceptfor mean weight, height and BMI (65.6 vs. 79.3 kg, 165 vs. 173 cm^2, and 24.1 vs. 26.4kg/m^2, respectively). HBeAg(-) Asians (n=102) and non-Asians (n=186) patients hadmedian(quartiles Q1, Q3) baseline HBV DNA of 6.4 (5.5, 7.7) and 7.0 (5.9, 7.8) log10 c/mL, whichdecreased by 3.1 log10 (both) at 4W; 96% and 98% patients achieved <400 c/mL HBVDNA at 48W, respectively. HBeAg(-) patients grouped by baseline HBV DNA ranges (from<10^6 to >10^9 c/mL at intervals of 10) showed median HBV DNA declined from baselineto 4W by similar levels upon TDF treatment (2.8 to 3.2 log10 c/mL). In HBeAg(+) patients,Asian (n=115) and non-Asians (n=113), showed median (Q1, Q3) baseline HBV DNA of8.7 (8.0, 9.2) and 9.1 (8.6, 9.5) log10 c/mL, which decreased by 3.1 log10 (both) at 4W;83% and 79% patients reached <400 c/mL HBV DNA at 48W, respectively. HBeAg(+)patients by the same grouping of baseline HBV DNA (ranges of 10) showed decline frombaseline to 4W of 2.9 to 3.4 log10 c/mL in patients with baseline HBV DNA ranges from10^7 to >10^9 c/mL, and 2.0 or 2.4 in those with <10^6 or 10^6-10^7 c/mL. Percentageof normal ALT at baseline was 17/9% vs. 6/4% (HBeAg-/+) for Asians vs. non-Asians, andincreased to 78/71% vs. 81/74%, respectively, at 48W. Loss/seroconversion for HBeAg andHBsAg at 48W were lower for Asians vs. non-Asians; 15/14% vs. 26/24%, and 0/0% vs.4.5/1.8%, respectively. No patient developed resistance to TDF. Mean creatinine clearanceswere stable and maintained within the normal range. No patient had a confirmed >=0.5mg/dL increase in serum creatinine or decrease to <50 mL/min in creatinine clearancefrom baseline. Conclusion: TDF demonstrated similar ALT normalization, rapid virologicsuppression, and good safety profile in Asian and non-Asian CHB patients. No resistanceto TDF developed in 48W.