Title | Maintained viral suppression and excellent safety profile of entecavir monotherapy in 418 NUC-naïve patients with chronic hepatitis B : a 4-year field practice, multicenter study |
Speaker: | Pietro Lampertico |
Author: | P. Lampertico1*, R. Soffredini1, F. Invernizzi1, M. Viganò2, F. Facchetti1, E. Minola3, O. Fracassetti4, F. Suter4, S. Zaltron5, A. Vavassori5, G. Carosi5, E. Angeli6, G. Gubertini6, C. Magni6, A. Testa7, G. Antonucci7, M. Vinci8, G. Pinzello8, E. Fatta9, S. Fargion9, P. Del Poggio10, B. Coco11, M. Brunetto11, M. Andreoletti12, A. Colli12, M. Fasano13, T. Santantonio14, G. Colloredo15, L. Pasulo16, S. Fagiuoli16, A.E. Colombo17, G. Bellati17, F. Fumagalli Maldini18, M. Milanese18, M. Pozzi19, N. Terreni20, G. Spinzi20, M. Quagliuolo21, M. Borzio21, G. Lunghi22, M. Colombo1 |
Affiliation: | 11st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 2U.O. Epatologia, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, 3Servizio Malattie Epatiche e Infettive, Humanitas Gavazzeni, 4Infectious Diseases, Ospedali Riuniti di Bergamo, Bergamo, 5II Divisione Malattie Infettive, Azienda Ospedaliera Spedali Civili, Brescia, 6I and II Division Infectious Diseases, Ospedale Luigi Sacco, Milan, 7INMI, IRCCS L. Spallanzani, Roma, 8SC Epatologia e Gastroenterologia, Ospedale Niguarda Cà Granda, 9Internal Medicine 1b, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, 10U.O. Epatologia, Ospedale di Treviglio, Treviglio, 11U.O. Epatologia, Azienda Ospedaliero Universitaria Pisana, Pisa, 12S.C. Medicina Generale, Ospedale A. Manzoni, Lecco, 13Clinic of Infectious Diseases, Università di Bari, Bari, 14Clinic of Infectious Diseases, Università di Foggia, Foggia, 15Division of Medicine, Policlinico San Pietro, Ponte San Pietro, 16Gastroenterology Unit, Liver and Lung Transplantation Center, Ospedali Riuniti di Bergamo, Bergamo, 17Unità Operativa di Medicina, Servizio di Epatologia, Ospedale Sant'Anna, Como, 18Liver Center, Clinica Medica, Azienda Ospedaliera San Gerardo, Università Milano Bicocca, Monza, 19U.O. Medicina, Ospedale Fatebenefratelli, Erba, 20U.O. Gastroenterologia, Ospedale Valduce, Como, 21U.O. Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano, 22Istituto di Medicina Preventiva, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. *[email protected] |
Aim: Aim of the studywas to assess the long term effectiveness and safety of Entecavir (ETV)monotherapy in NUC-naïve patients.
Methods: 418 consecutive NUC-naïve patients with CHBwere recruited in 21 Liver Units in Italy and treated with ETV 0.5 mg for 42months (2-53). At baseline, age was 58 years, 76% males, 83% HBeAg-negative, HBVDNA 6.0 log IU/ml, 85% with elevated ALT, 49% cirrhotics, 56% with concomitantdiseases/medications. Liver function tests and HBV DNA, were assessed by asensitive assays every 3 months. Virological breakthrough was defined as > 1log U increase of viremia, a “blip” was the occurrence of detectable viremia(< 100 IU/ml) in a virological responder.
Results: The rates of undetectable HBV DNA, progressively increasedover time, from 85% at year 1, 95% at year 2, 96% at year 3 and 99% at year 4.A primary non response occurred in 1%, a partial response at week 48 in 12%, ablip of viremia in 11%, a virological breakthrough in 4% and drug resistance in< 1% of the patients. HBeAg seroconversion and HBsAg loss rates progressivelyincreased up to 56% and 21% at year 4, respectively. ALT levels became normalin 90% of patients. Among 164 cirrhotics, the 4-year cumulative probability ofHCC development was 10%. No safety issues were reported. Serum creatinineremained unchanged during treatment [from 0.90 (0.50-9.0) at baseline vs 0.91(0.47-8.0) mg/dl at year 4] as well as the proportion of patients with serumcreatinine > 1.5 mg/dl (2% at baseline vs 2% at year 4). Less than 1% of thepatients showed > 0.5 mg increase of creatinine and/or < 2 mg/dl ofphosphorus or significant proteinuria. Overall, 6% of the patients died, 3%were transplanted, 6% required treatment adaptation (PEG or ETV+TDF), 2%stopped ETV following HBsAg clearance and 8% were lost to follow-up.
Conclusion: HBV replication wasefficiently suppressed during 4 years of ETV monotherapy in most patients inthe context of an excellent safety profile. Hepatocellular carcinoma, not clinicaldecompensation, continued to occur in cirrhotic patients. |
Title | Lamivudine and Entecavir treatment in patients with chronic hepatitis B liver failure: a large, multicenter, placebo controlled, prospective study in China |
Speaker: | Lanjuan Li |
Author: | Y. Yang1, J. Huang1, H. Jia1, Q. Xie2, Z. Gao3, Y. Wang4, Z. Duan5, H. Wang6, S. Lin7, T. Hao8, J. Gan9, C. Pan10, L. Li1*, Chinese Study Group for HBV Related Liver Failure |
Affiliation: | 1Dept. of Infectious Diseases, 1st Affiliated Hospital of Zhejiang University, Hangzhou, 2Dept. of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 3Dept. of Infectious Diseases, 1st Affiliated Hospital of Sun Yat-sen University, Guangzhou, 4Dept. of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, 5Beijing Youan Hospital, Capital Medical University, 6302 Military Hospital, Beijing, 7The First Affiliated Hospital of Medical College of Xi’an Jiao Tong University, Xi'an, 8Tianjin Third Central Hospital, Tianjin, 9The First Affiliated Hospital of Suzhou University, Suzhou, 10Affiliated Infectious Hospital of Fujian Medical University, Fuzhou, China. *[email protected] |
Background and aim: Currently there is a lack of large cohort study to demonstrate the effectiveness of antiviral treatment for chronic hepatitis B liver failure. There is no head-to-head study to compare the efficacy of lamivudine, entecavir and placebo in patients with chronic hepatitis B liver failure.
Method: We consecutively enrolled 931 patients with chronic hepatitis B liver failure, among them a total of 315 patients refused to sign an informed consent form to receive nucleoside analogue treatment were served as control. 326 patients received lamivudine treatment and 290 patients received entecavir treatment. The relationship between baseline HBV DNA levels and 12-week mortality rate of patient chronic hepatitis B liver failure was firstly investigated. The cumulative survival rate during 12-week follow-up of three groups was evaluated.
Results: Firstly our results clearly indicated that the cumulative mortality rate of chronic hepatitis B liver failure was highly associated with serum HBV DNA levels. Besides the HBV DNA levels, the high baseline bilirubin levels, high INR values, low platelet numbers, and cirrhosis were found to be significantly related to mortality of these group of patients. Lamivudine and entecavir treatment significantly reduce HBV DNA level from 8 weeks than that of in placebo group, but there were no significant difference between lamivudine and entecavir group. The number of patients in lamivudine and entecavir group with undetectable HBV DNA was 30.5% and 36.6% at week 12 respectively, there was significant difference between two groups (P< 0.05). . Among patients with HBeAg positive diseases, 45.3% patients in lamivudine group and 44.7% in entecavir group lost HBeAg at follow up week 12 respectively, whereas none in placebo group. 36.0% patients in lamivudine group and 34.2% in entecavir group had HBeAg seroconversion at week 12, while none of patient in placebo had HBeAg seroconversion at follow up period.
Conclusion: Antiviral treatment therapy can significantly reduce the mortality of patients with chronic hepatitis B liver failure. Both lamivudine and entecavir can be prescribed as an initial treatment in patients with chronic hepatitis B liver failure to reduce the mortality. |