1014 THE SHORT-TERM EFFICACY OF ANTIVIRAL TREATMENT IN PATIENTS WITH ACUTE-ON-CHRONIC HEPATITIS B LIVER FAILURE

POSTERS 1014 THE SHORT-TERM EFFICACY OF ANTIVIRAL TREATMENT IN PATIENTS WITH ACUTE-ON-CHRONIC HEPATITIS B LIVER FAILURE X. Qihuan, C. Lubiao, S. Xin, X. Zhen, C. Ni, X. Qifeng, L. Gang. Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China E-mail: [email protected] Introduction: Liver failure often leads to significantly high mortality. Acute-on-chronic liver failure (ACLF) is defined as a syndrome that acute liver decompensation occurs on the patients with chronic liver disease. Particularly in China, chronic hepatitis B (CHB) is the most common cause of ACLF. At present, there is still no definite conclusion on the antiviral therapy for ACLF associated with hepatitis B. Objective: To investigate the short-term efficacy of antiviral therapy on ACLF associated with hepatitis B. Methods: A total of 348 patients with ACLF associated with hepatitis B were divided into two groups (antiviral and control). Antiviral group received the treatment of Lamivudine, Entecavir or Telbivudine combined with the supportive therapy, and control group received the supportive therapy only. The clinical features, survival rate and the short-term antiviral efficacy were compared between these two groups. The SPSS13.0 was used to do the statistical analysis. Comparison of rates from different groups was analyzed using X2 -test. Enumeration data was done by using analysis of variance. And the survival analysis was done using Kaplan–Meier method, while comparison of survival rates between groups using the log-rank test. Results: Before treatment, there were no significant differences (P > 0.05) between these two groups in demology, baseline HBV DNA level, ratio of HBeAg/anti-HBe, clinical stage of liver failure and liver function tests including TBIL, ALT, AST, ALB, PT and INR. After 4 weeks treatment, differences were statistically significant in both the serum level of TBIL and the decreasing amplitude of HBV DNA between these two groups (t = 2.036, P = 0.042; t=-4.73, P = 0.000). After 24 week treatment, the survival rates of antiviral group with both low (HBV DNA <105 copies/ml) and high (HBV DNA≥105 copies/ml) viral load were higher than those in control group (c2 = 26.362, P = 0.000; c2 = 9.47, P = 0.002). Cox regression analysis indicated that antiviral therapy is the favorable factor to influence clinical prognosis.

Conclusions: Antiviral therapy can improve the survival rate of the acute-on-chronic liver failure associated with hepatitis B, even if the patient with a low serum viral load. 1015 SAFETY AND EFFICACY OF A VACCINE CONTAINING BOTH HBSAG AND HBCAG IN PATIENTS WITH CHRONIC HEPATITIS B AT BANGLADESH M.A. Mamun1 , S.M.F. Akbar2 , S. Rahman1 , J.C.R. Aguilar3 , S. Mishiro2 . 1 Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 2 Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan; 3 Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba E-mail: [email protected] Background and Aims: Hepatitis B surface antigen (HBsAg)-based vaccines have been used to induce therapeutic immunity in patients with chronic hepatitis B (CHB), but, the clinical outcome is inconclusive. As immune responses to both HBsAg and hepatitis B core antigen (HBcAg) are essential for containment of hepatitis B virus (HBV), this study was conducted in CHB patients to assess safety and immunogenecity of HBsAg/HBcAg combination vaccine. Methods: After receiving permission from Institutional Review Board and written consents, 17 treatment-naïve patients with CHB (HBeAg-positive: 7, HBeAg-negative: 13) were immunized 5 times with a vaccine containing both HBsAg (50 mg) and HBcAg (50 mg) (Center for Genetic and Biotechnology, Havana, Cuba) through nasal route using a special device. All patients were followed up regularly, once in every two weeks, for 6 consecutive months. Peripheral blood mononuclear cells (PBMC) were isolated from these patients one month after end of the 5 vaccinations to assess immunogenecity of combined HBsAg and HBcAg vaccine in CHB patients. Results: Nasal vaccinations were safe for all patients, and only 2 patients felt nasal irritation after vaccination that persisted only for less than one hour. Vital signs, parameters of general inflammation and kidney functions remain within normal limit in all patients. Flare of alanine aminotransferase (ALT) was not seen in any patient due to vaccinations. Although all patients were expressing HBV DNA in the sera before vaccination, HBV DNA became undetectable (levels of detection of HBV DNA: 200 copies/ml) in the sera in 6 patients, reduced in 5 patients, and remained almost unchanged in 6 patients after vaccination. The serum levels of interleukin (IL)-8, TNF-alpha, IL-1 beta, and IL-6 were significantly increased after 5 nasal vaccinations compared to their pre-vaccinated levels (p < 0.05). The peripheral blood mononuclear cells of vaccinated patients produced significantly higher levels of IFN-gamma and TNF-alpha due to stimulation with HBsAg and HBcAg, compared to cultures stimulated with non-relevant antigens (p < 0.05). Conclusions: Safety, partial efficacy and overcome of tolerance by a new and novel vaccine containing both HBsAg and HBcAg inspired optimism of a new immune therapeutic approach in CHB patients.

Figure 1. Comparison of cumulative survival of patients between antiviral group and control group. S392

Journal of Hepatology 2010 vol. 52 | S319–S457