Benjamin Yip

Low hepatitis B envelope antigen seroconversion rate in chronic hepatitis B patients on long-term entecavir 0.5 mg daily in routine clinical practice.

Aim Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44–90 patients from centers in Asia, Europe, and South America. Materials and methods In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion. Results Sixty-one percent of HBeAg-positive patients were men, mean age 39±12 years, median hepatitis B virus DNA 7.48 (3.7–9.8) log10 IU/ml, median alanine aminotransferase 67 (14–1077) U/l, and median treatment duration 18 (6–60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV. Conclusion In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.

High rate of complete viral suppression with combination therapy in patients with chronic hepatitis B and prior treatment failure.

Background Combination therapy for chronic hepatitis B virus (HBV) infection is recommended for patients with antiviral resistance (AVR) or partial response (PR) to earlier antiviral therapy; however, data on outcomes are limited. Goals To determine the rate of complete viral suppression (CVS) with combination therapy and to compare CVS among different indications and treatment regimens. Methods A cohort of 109 consecutive patients with chronic hepatitis B from 3 liver clinics in Northern California was retrospectively studied. All patients started combination therapy between April 2004 and August 2009 for the following indications: AVR (n=29), PR (n=60), or others (n=20). Combination treatments included lamivudine (LAM), adefovir (ADV), telbivudine (LdT), entecavir (ETV), tenofovir (TDF), and emtricitabine (FTC). CVS was defined as undetectable serum HBV DNA <100 IU/mL. Results Among the patients, who were nearly all Asian (99%), 73% had ≥2 prior treatments and 82% had treatment failure (AVR or PR). Median treatment duration of combination therapy was 21 months (range, 6 to 50 mo). The majority (77%) achieved CVS after 6 months of various combination regimens: 80% for ETV+TDF, 76% for TDF+LAM or FTC or LdT, 75% for ETV+ADV, and 69% for ADV+LAM or LdT (P=0.86). After 6 months of therapy, CVS was observed in a similar proportion of patients treated for PR and AVR (72% and 74%, respectively). Conclusions Although the majority of 109 treatment-experienced patients had prior treatment failure, high rates of CVS were rapidly achieved and did not significantly differ between indications of AVR and PR or between ETV-based and TDF-based regimens.

Treatment of Acute Hepatitis C Infection with Pegylated Interferon and Ribavirin in Patients Coinfected with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

Background/Aims: Of the 35 million human immunodeficiency virus (HIV)-positive patients worldwide, 10-40% are coinfected with chronic hepatitis C virus (HCV). Compared to HCV-monoinfected patients, those coinfected experience decreased spontaneous HCV clearance, accelerated liver fibrosis, and a decreased response to anti-HCV therapy. We conducted a meta-analysis to estimate the efficacy of treating acute HCV in HIV-positive patients with peginterferon and ribavirin combination therapy. Methods: Two authors independently searched MEDLINE and EMBASE (2014) for English articles, and reviewed bibliographies and abstracts from major liver and HIV conferences (2011-2013). Original studies featuring at least 10 treatment-naive, HIV-positive adults infected with acute HCV and treated with peginterferon and ribavirin were included. Analyses were calculated using a random-effects model. Heterogeneity was assessed using the Cochrane Q test (p < 0.05) and the I2 statistic (>50%). Results: From 12 studies (450 patients), the pooled sustained virological response (SVR) was 71.4% (95% CI 64.7-77.4; Q statistic = 22.20, p = 0.023, I2 = 50.44). The rapid virological response (RVR; 7 studies, 196 patients) was 47.4% (95% CI 40.6-54.7), and the early virological response (EVR; 9 studies, 283 patients) was 82.8% (95% CI 67.0-92.0). The probability of an SVR was 93.1% (95% CI 84.9-97.0) in those who obtained an RVR (6 studies, 82 patients) and 85.9% (95% CI 78.7-91.0) if an EVR (7 studies, 168 patients) was reached. Conclusion: Peginterferon with ribavirin is an effective option for treating acute HCV in HIV-positive patients, especially if they achieve an RVR or an EVR.

Re-treatment of patients with chronic hepatitis C virus genotype 4 infection with pegylated interferon and ribavirin: a meta-analysis

Background An estimated 170 million people worldwide are infected with hepatitis C virus (HCV). HCV genotype 4 (HCV-4)—the most prevalent hepatitis C strain in the Middle East and Africa—is difficult to treat, with an estimated sustained virological response (SVR) of 53% when using pegylated interferon and ribavirin (P/R) in treatment-naïve patients with HCV-4 infection. In regions where access to direct-acting antivirals is limited, re-treatment of patients who failed therapy with another course of P/R may be an option if the success rate is acceptable. Objectives We aimed to determine the SVR from retreatment with P/R in treatment-experienced patients with HCV-4 infection. Methods We performed a meta-analysis using MEDLINE and EMBASE searches, and by reviewing article bibliographies and abstracts from recent Liver Society Meetings. Original studies featuring at least 10 adult, treatment-experienced patients with HCV-4 infection failing prior interferon-based therapy and receiving subsequent re-treatment with P/R were included. Results 3 studies were included. Overall pooled SVR was 32.7%, or 41/126 patients. No significant heterogeneity existed among the studies. One study reported higher SVR of 50% in previous relapsers, compared with 23% in previous non-responders. Conclusions As expected, treatment-experienced patients achieved lower rate of SVR compared with previously reported SVR for treatment-naïve patients with HCV-4 infection. The abysmal rate of success from re-treatment with P/R supports the use of direct-acting antivirals whenever re-treatment is considered, even in resource-limited regions.

716 Differential Survival in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma (HBV/HCC) Compared to Hepatitis C Virus-Related Hepatocellular Carcinoma (HCV/HCC)

Background/Aims: Detection of circulating tumor cells (CTC) is associated with poor progression free and overall survival in patients with breast, prostate, and colon cancer. There is limited information about the prognostic value of CTC in patients with cholangiocarcinoma (CCA). The aim of this study are (1) to quantify circulating tumor cells in the peripheral blood of patients with CCA; and (2) to test the hypothesis that the presence of circulating tumor cells is associated with larger tumor burden of CCA and poor overall survival. Methods: A total of 45 patients with CCA seen at Mayo Clinic Rochester were prospectively enrolled between June 2010 and September 2012. 10 ml peripheral blood was drawn into CellSave Preservative Tubes. Blood samples were processed within 96 hours after the blood draw. The CellSearch system by Veridex was used for the capture, enrichment, identification and enumeration of CTC of epithelial origin in 7.5 ml of peripheral blood from the patients. The CellSearch system has an estimated sensitivity of approximately 20-30% for detecting CTC at a prognostic level . The association between baseline characteristics and detection of CTC was analyzed. Overall survival was estimated by the Kaplan Meier method and compared using the Log Rank test. Results: The mean age of patients was 61 and 29 (64%) patients were male. CTC were detected in 13 (28%) patients. Patients with CTC tended to have larger tumor size, more tumor nodules, a higher CA19-9 level, increased CEA, lymph node involvement, and metastatic disease compared to patients without CTC. (Table) There was no significant association between CTC and demography (age, gender, and race) or underlying liver dysfunction . There was a trend towards poorer survival in patients with CTC compared to patients without CTC (p=0.09). Conclusion: CTC are detectable in patients with cholangiocarcinoma. The presence of CTC was associated with tumor burden and metastatic cancer. The prognostic implications of CTC in patients with CCA need further validation in a larger patient group.

Mo2026 Epidemiology and Clinical Outcomes of Asians With Hepatocellular Carcinoma (HCC) Compared to Non-Asian Patients

Background : Endoscopic ultrasonography (EUS) is considered to be the best modality to predict the neoplastic polyps of the gallbladder. However, EUS has several limitations following as 1) the considerable experience of investigators, 2) presence of the interobserver variations and 3) unavailability of EUS in some centers. Multidetector computed tomography (MDCT) provides fine section image of gallbladder and allows to reduce the interobserver variations. We evaluated the accuracy of MDCT combined with high resolution ultrasonography (HRUS) for gallbladder polyps smaller than 2cm compared with EUS. Methods : From Dec 2005 to June 2010, 109 patients who underwent cholecystectomy due to gallbladder polyps were enrolled. Subjects were divided in two groups (reference group : 63 patients who were performed MDCT and HRUS vs. validation group : 46 patients who underwent MDCT, HRUS, and EUS). New scoring system was developed from reference group, and applied to validation group, while previously reported EUS scoring system was applied to the same validation group. Results : In reference group, size (p,0.001), number (p=0.015), shape (p=0.001), and CT/US size ratio of polyps (p=0.008) were significant variables in univariate analysis. Area under the ROC curve draw by new scoring system was 0.859 and cut-off value was set to 3. In validation group, new scoring system showed comparable accuracy (65.2%) with previously reported EUS scoring system(73.9%, p=0.434). Conclusion : MDCT combined with HRUS provide comparatively high accuracy in small gallbladder polyps in distinguishing between neoplastic and non-neoplastic polyps as preoperative diagnostic modality.

613 Hepatitis C Virus (HCV) Diagnosis and Clinical Outcomes of Patients With HCV-Related Hepatocellular Carcinoma (HCC): A Comparative Study of Asians Versus Non-Asians

BACKGROUND AND AIMS: In addition to hepatitis B virus, HCV is also an important cause of HCC in Asians; however, it is often overlooked. This study aims to examine baseline characteristics, timing of HCV diagnosis and long-term survival of HCV-related HCC in Asians compared to non-Asian patients. METHODS: We conducted a retrospective cohort study of 798 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC who were identified via computer query using ICD-9 diagnosis at a U.S. university medical center between 7/1996 and 6/2012. Individual records were reviewed. RESULTS: Asians were much older (66 [38-88] vs. 56 [31-87] years, P ,0.0001) and more likely to be female (33% vs. 19%, P,0.0001). A significantly larger proportion of Asians were also diagnosed with HCC within only 2 years of HCV diagnosis compared to non-Asians (35% vs. 20%, p=0.001). Non-Asians were more likely to have decompensated liver disease and had higher median Child-Turcotte-Pugh score (6 [5-11] vs. 7 [5-13], P ,0.0001). Asian patients were more likely to undergo liver-directed palliative therapy (46% vs. 28%) and much less likely to be listed for liver transplantation(20% vs. 48%) (P ,0.001), despite similar rates of meeting Milan criteria for liver transplantation (52 vs.58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians compared to non-Asians (30 vs. 21 months, P=0.091). Among those who were listed for liver transplantation, there was no statistically significant difference in survival between Asians and non-Asians in the first 2 years (72% vs. 68%) but there was divergence with Asians having higher survival afterwards (61% vs. 51%) (Figure 1). However, among those undergoing liver-directed palliative therapy, Asians had significantly higher long-term survival compared to non-Asians (5-year survival: 28% vs. 10%, P,0.0001) (Figure 2). On multivariate Cox proportional hazards model also inclusive of age, sex, BCLC staging, Child-Pugh score, meeting Milan criteria, liver transplantation listing, non-Asian ethnicity was an independent predictor for lower overall survival (HR=0.70 [0.52-0.86]). CONCLUSIONS: Despite being older and having a lower rate of liver transplantation listing, Asian HCV/HCC patients had higher median survival compared to non-Asian patients, particularly among those undergoing palliative therapy. Non-Asians were more likely to have decompensated liver disease and non-Asian ethnicity was an independent predictor for poorer long-term survival. Compared to non-Asians, Asians with HCV-related HCCwere also muchmore likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development in this ethnic population with a disproportionate HCC disease burden.