- Email: [email protected]
Fibrotic Burden, Not Antiviral Agent, Determines Clinical Outcome in Chronic Hepatitis B Patients: A Propensity-Score Matched Analysis
POSTER PRESENTATIONS and mandatory for antiviral therapies, but a long-term, comparative outcome among the antiviral therapies is limited. We evaluated over 5-years of efficacy and safety of telbivudine (LdT) and entecavir (ETV) treatment in HVL CHB patients. Methods: 116 HVL CHB patients (HBV-DNA ≥ 1 × 107 copies/mL) were consecutively evaluated for viral response, drug-resistance, safety and off-therapy relapse. HBV-DNA, HBV serology, HBV gene mutation, biochemistries, and the incidence of liver-related events were determined during the treatment and the follow-up period. Results: The baseline features between LdT and ETV treated patients were comparable. The rates of HBV-DNA negativity were 96.1% and 100% for LdT (n = 66) and ETV (n = 50) at year 5. The rates of an early viral response (EVR), defined as HBV-DNA undetectable (<1000 copies/mL) under LdT and ETV treatment at month 6 were 88.2% and 64.0%, respectively ( p < 0.05). HBeAg and HBsAg seroconversion rates were 63.4%, 3.0% (2/66) in LdT, compared with 25%, 0% in ETV ( p < 0.01). Three cases of detectable viral mutations and eight cases of elevated serum creatine kinase were found in LdT, but none in ETV. Conclusions: Both LdT and ETV inhibited HBV replication in HVL CHB patients within 5-years. Higher rates of EVR and HBeAg, HBsAg seroconversion were found in LdT, whereas a low drug-resistance and less adverse effect favored in ETV. This result may specify candidates in optimally treating HVL CHB patients.
one year of follow-up were excluded in a sensitivity analysis (HR 0.57; 95% CI 0.39-0.84, p = 0.0045). The beneficial effect of antiviral therapy was seen in both HBeAg-seropositive and -seronegative patients, and was most prominent in men and in patients with older age (>43 years), abnormal ALT (>ULN), high HBV DNA levels (≥200,000 IU/mL), or high REACH-B score (≥10 points).
FRI-120 ANTIVIRAL THERAPY FOR THE PREVENTION OF LONG-TERM CIRRHOSIS RISK IN PATIENTS WITH CHRONIC HEPATITIS B H.-I. Yang1, J. Hoang2, D. Lin3, J. Liu1, H.-H. Hu1, M.-H. Lee4, N.H. Nguyen2, Y. Kim2, C.-L. Jen1, V. Vu2, A. Le2, K. Chaung2, V. Nguyen2, H. Trinh5, J. Li6, J. Zhang7, A. Hsing8, C.-J. Chen9, M.H. Nguyen2. 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan; 2Division of Gastroenterology and Hepatology; 3Department of Internal Medicine, Stanford University Medical Center, Palo Alto, CA, United States; 4 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 5San Jose Gastroenterology, San Jose; 6Palo Alto Medical Foundation, Mountain View Division, Mountain View, CA; 7Chinese Hospital, San Francisco, CA; 8Cancer Prevention Institute of California, Fremont, CA, United States; 9Academia Sinica, Taipei, Taiwan E-mail: [email protected]
Conclusions: In this large cohort comprised of clinical and community participants with long-term follow-up, antiviral therapy was significantly associated with risk reduction in cirrhosis progression.
Background and Aims: The goal of antiviral therapy for patients with chronic hepatitis B (CHB) is to prevent long-term complications including cirrhosis and hepatocellular carcinoma. While most current evidence demonstrated that antiviral treatment was associated with improvement in liver histology and even reversal of cirrhosis, its effect on the long-term prevention of cirrhosis development remains to be elucidated. We aimed to investigate this question using a reallife clinical cohort and a historical cohort of untreated CHB patients. Methods: A total of 1,446 CHB patients (723 treated and 723 untreated) who were free of cirrhosis at study entry were selected from a United States cohort and the community-based Taiwanese REVEAL-HBV cohort using the propensity score matching (PSM) method with a 1:1 ratio. The baseline variables used for PSM included sex, age, hepatitis B e antigen (HBeAg) serostatus, and serum alanine (ALT) and HBV DNA levels. Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of developing cirrhosis with adjustment of aforementioned PSM factors. Results: During a total of 9662.7 person-years of follow-up, 147 cirrhosis cases were newly diagnosed. The cumulative incidence of developing cirrhosis at the 10th year of follow-up was 9.5% and 16.7% for treated and untreated patient group, respectively ( p = 0.0056). The incidence rates were 1115.1 and 1823.9 per 100,000 person-years, respectively. After adjustment of sex, age, HBeAg serostatus, serum levels of ALT and HBV DNA, the HR (95% CI) of developing cirrhosis was 0.53 (0.38-0.73) for treated patients compared to untreated CHB patients ( p = 0.0001). The effect of antiviral treatment on cirrhosis incidence remained significant when patients who developed within
FRI-121 FIBROTIC BURDEN, NOT ANTIVIRAL AGENT, DETERMINES CLINICAL OUTCOME IN CHRONIC HEPATITIS B PATIENTS: A PROPENSITYSCORE MATCHED ANALYSIS H.S. Kim1, B.K. Kim1, S.U. Kim1, J.Y. Park1, D.Y. Kim1, S.H. Ahn1, K.J. Song1, J. Won Park1, Y.J. Kim1, O. Baatarkhuu2, K.H. Han1. 1Yonsei University College of Medicine, Seoul, South Korea; 2Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia E-mail: [email protected] Background and Aims: We investigated whether entecavir (ETV) can reduce the risk of hepatocellular carcinoma (HCC) development compared to lamivudine (LAM) among patients with chronic hepatitis B (CHB) after adjusting for fibrotic burden. Methods: To adjust for the imbalance between LAM-treated and ETV-treated patients, propensity-score matching (PSM) was performed at 1:1 ratio using seven [PSM-1: age, gender, hepatitis B e antigen (HBeAg), alanine aminotransferase, serum albumin, platelet count, and liver stiffness (LS) by transient elastography] and eight [PSM-2: seven variables of PSM-1 plus ultrasonographic cirrhosis] variables. Rescue therapy was performed for resistant strains. Results: Four hundred thirty-five and 644 patients received LAM and ETV, respectively, as first-line therapy. During follow-up, 91 (8.4%) patients developed HCC. In multivariate analyses, fibrotic burden (as assessed using LS value; adjusted hazard ratio 1.02, p < 0.05), not antiviral agents (LAM vs. ETV), independently predicted HCC risks. Propensity-score matching resulted in 342 pairs using PSM-1 variables and 338 pairs using PSM-2 variables. The cumulative rates of HCC development in LAM-treated and ETV-treated patients were similar in both models (PSM-1: 9.7% vs. 9.9% at 5-years and 10.5% vs. 9.9% at 7-years; PSM-2: 10.2% vs. 10.3% at 5-years and 11.9% vs. 12.0% at 7-years; all p > 0.05). When propensity-score matching was applied in the same manner in sub-cohorts with LS ≤ 13 kPa and LS > 13 kPa, cumulative risks between LAM-treated and ETV-treated patients remained similar overall (all p > 0.05). Conclusions: Underlying fibrotic burden, not antiviral agent, independently influenced HCC risk. Therefore, fibrotic burden should be assessed during antiviral therapy for effective surveillance.
Journal of Hepatology 2016 vol. 64 | S425–S630
S591
one year of follow-up were excluded in a sensitivity analysis (HR 0.57; 95% CI 0.39-0.84, p = 0.0045). The beneficial effect of antiviral therapy was seen in both HBeAg-seropositive and -seronegative patients, and was most prominent in men and in patients with older age (>43 years), abnormal ALT (>ULN), high HBV DNA levels (≥200,000 IU/mL), or high REACH-B score (≥10 points).
FRI-120 ANTIVIRAL THERAPY FOR THE PREVENTION OF LONG-TERM CIRRHOSIS RISK IN PATIENTS WITH CHRONIC HEPATITIS B H.-I. Yang1, J. Hoang2, D. Lin3, J. Liu1, H.-H. Hu1, M.-H. Lee4, N.H. Nguyen2, Y. Kim2, C.-L. Jen1, V. Vu2, A. Le2, K. Chaung2, V. Nguyen2, H. Trinh5, J. Li6, J. Zhang7, A. Hsing8, C.-J. Chen9, M.H. Nguyen2. 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan; 2Division of Gastroenterology and Hepatology; 3Department of Internal Medicine, Stanford University Medical Center, Palo Alto, CA, United States; 4 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 5San Jose Gastroenterology, San Jose; 6Palo Alto Medical Foundation, Mountain View Division, Mountain View, CA; 7Chinese Hospital, San Francisco, CA; 8Cancer Prevention Institute of California, Fremont, CA, United States; 9Academia Sinica, Taipei, Taiwan E-mail: [email protected]
Conclusions: In this large cohort comprised of clinical and community participants with long-term follow-up, antiviral therapy was significantly associated with risk reduction in cirrhosis progression.
Background and Aims: The goal of antiviral therapy for patients with chronic hepatitis B (CHB) is to prevent long-term complications including cirrhosis and hepatocellular carcinoma. While most current evidence demonstrated that antiviral treatment was associated with improvement in liver histology and even reversal of cirrhosis, its effect on the long-term prevention of cirrhosis development remains to be elucidated. We aimed to investigate this question using a reallife clinical cohort and a historical cohort of untreated CHB patients. Methods: A total of 1,446 CHB patients (723 treated and 723 untreated) who were free of cirrhosis at study entry were selected from a United States cohort and the community-based Taiwanese REVEAL-HBV cohort using the propensity score matching (PSM) method with a 1:1 ratio. The baseline variables used for PSM included sex, age, hepatitis B e antigen (HBeAg) serostatus, and serum alanine (ALT) and HBV DNA levels. Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of developing cirrhosis with adjustment of aforementioned PSM factors. Results: During a total of 9662.7 person-years of follow-up, 147 cirrhosis cases were newly diagnosed. The cumulative incidence of developing cirrhosis at the 10th year of follow-up was 9.5% and 16.7% for treated and untreated patient group, respectively ( p = 0.0056). The incidence rates were 1115.1 and 1823.9 per 100,000 person-years, respectively. After adjustment of sex, age, HBeAg serostatus, serum levels of ALT and HBV DNA, the HR (95% CI) of developing cirrhosis was 0.53 (0.38-0.73) for treated patients compared to untreated CHB patients ( p = 0.0001). The effect of antiviral treatment on cirrhosis incidence remained significant when patients who developed within
FRI-121 FIBROTIC BURDEN, NOT ANTIVIRAL AGENT, DETERMINES CLINICAL OUTCOME IN CHRONIC HEPATITIS B PATIENTS: A PROPENSITYSCORE MATCHED ANALYSIS H.S. Kim1, B.K. Kim1, S.U. Kim1, J.Y. Park1, D.Y. Kim1, S.H. Ahn1, K.J. Song1, J. Won Park1, Y.J. Kim1, O. Baatarkhuu2, K.H. Han1. 1Yonsei University College of Medicine, Seoul, South Korea; 2Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia E-mail: [email protected] Background and Aims: We investigated whether entecavir (ETV) can reduce the risk of hepatocellular carcinoma (HCC) development compared to lamivudine (LAM) among patients with chronic hepatitis B (CHB) after adjusting for fibrotic burden. Methods: To adjust for the imbalance between LAM-treated and ETV-treated patients, propensity-score matching (PSM) was performed at 1:1 ratio using seven [PSM-1: age, gender, hepatitis B e antigen (HBeAg), alanine aminotransferase, serum albumin, platelet count, and liver stiffness (LS) by transient elastography] and eight [PSM-2: seven variables of PSM-1 plus ultrasonographic cirrhosis] variables. Rescue therapy was performed for resistant strains. Results: Four hundred thirty-five and 644 patients received LAM and ETV, respectively, as first-line therapy. During follow-up, 91 (8.4%) patients developed HCC. In multivariate analyses, fibrotic burden (as assessed using LS value; adjusted hazard ratio 1.02, p < 0.05), not antiviral agents (LAM vs. ETV), independently predicted HCC risks. Propensity-score matching resulted in 342 pairs using PSM-1 variables and 338 pairs using PSM-2 variables. The cumulative rates of HCC development in LAM-treated and ETV-treated patients were similar in both models (PSM-1: 9.7% vs. 9.9% at 5-years and 10.5% vs. 9.9% at 7-years; PSM-2: 10.2% vs. 10.3% at 5-years and 11.9% vs. 12.0% at 7-years; all p > 0.05). When propensity-score matching was applied in the same manner in sub-cohorts with LS ≤ 13 kPa and LS > 13 kPa, cumulative risks between LAM-treated and ETV-treated patients remained similar overall (all p > 0.05). Conclusions: Underlying fibrotic burden, not antiviral agent, independently influenced HCC risk. Therefore, fibrotic burden should be assessed during antiviral therapy for effective surveillance.
Journal of Hepatology 2016 vol. 64 | S425–S630
S591