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or Tenofovir in Hepatitis B Cirrhotic Patients
M1901 Low Rates of Nucleos(T)Ide-Associated Adverse Events in the Long-Term Experience With Entecavir Albert D. Min, Naoky Tsai, Michael P. Manns, Ulus S. Akarca, Ting-Tsung Chang, William Sievert, Seung Kew Yoon, Andreas Pangerl, Suzanne Beebe, Miao Yu, Suchat Wongcharatrawee Background and aims: In Phase III studies evaluating treatment of chronic hepatitis B (CHB), entecavir demonstrated superior efficacy compared to lamivudine and a comparable safety and tolerability profile. Long-term safety data from the rollover study ETV-901 are reviewed, focusing on adverse events (AEs) with a potential nucleos(t)ide association. Methods: Long-term cumulative safety and tolerability results are based on investigatorreported AEs, regardless of causal relationship. Results: Median exposure to entecavir in ETV-901 was 168 weeks. Of the 1,045 treated patients, 402 (38%) had received entecavir for ≥5 years at the time of analysis. Also, 488 (47%) patients had additional prior entecavir exposure from Phase II or III participation. Baseline characteristics were: mean age 41 years; 804 (77%) male, 539 (52%) Asian, and 480 (46%) Caucasian. The most common AEs (≥10%) were upper respiratory tract infection, headache and nasopharyngitis. On-treatment alanine aminotransferase (ALT) flares were reported in 3% of patients. The cumulative rate of serious AEs was 15%. Discontinuations due to AEs were 1% (n=13), and generally (n= 11) occurred during the first 2 years of ETV-901. Selected AEs with a potential nucleos(t)ide association are described in the table below. Conclusions: Entecavir is a safe and welltolerated treatment for patients with CHB and compensated liver disease. Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. Spontaneous reports of AEs potentially associated with nucleos(t)ide use occurred at low rates.
M1899
AASLD Abstracts
The Efficacy of Interferon Treatment in HBeAg Positive Chronic Hepatitis B is Very Low in an Area With Exclusively D Genotype Hakan Senturk, Birol Baysal, Resat Ozaras, Hasan Zerdali, Fehmi Tabak, Ali Mert, Billur Canbakan, Ibrahim Hatemi, Omur Tabak, Gulsen Ozbay Background and aims: Previous studies reported encouraging results with interferon-based treatments in HBeAg positive chronic hepatitis B (CHB). The impact of genotype on response and relapse rate emerged very recently. Genotype D appeared as the least responsive. In this country the genotype is exclusively D. We report here very long-term results of interferonalfa treatment in HBe Ag positive CHB. Methods: We reviewed the data of HBeAg positive CHB patients treated with interferon-alfa 2b (IFN), 10 MU, subcutaneously 3 times per week for 6 months and were followed up for at least 120 months untreated as the response is going on were included. All patients had elevated ALT levels over 2X upper limit of normal for at least 6 months and had histological evidence of chronic hepatitis B (necroinflammatory activity >3, according to Knodell scoring) before therapy. At the admission serum HBV-DNA was detectable with molecular hybridization technique without amplification. The response to treatment was defined as HBeAg seroconversion with HBV-DNA undetectability and ALT normalization. The responders were followed- up 3-6 monthly intervals over ten years. Results: In a period of seven years, 71 patients with HBeAg positive chronic hepatitis B treated with IFN were eligible for inclusion. There were 10 females and 61 males, the mean age was 29±12 (range:16-62) years. After treatment twenty-eight patients (39.4%) achieved HBeAg seroconversion. While 25 developed seroconversion in the treatment period, 3 developed within 12 months after the end of the treatment. The responders were followed up with a median period of 152 months (range:123-181). In the follow-up period 21 of 28 responders relapsed (75%) 3 of them had e antigen reversion (14.3%). The sustained response (persistently normal ALT levels and serum HBV DNA level ≤ 2000 IU/ml) was present in 7 patient (9.8%). HBsAg disappeared in 2 patients, anti-HBs developed only in one patient . Serious side effects precluding completion of treatment occurred in three patients (4.2%). Conclusion: Although HBeAg seroconversion rate with IFN was relatively high in this study, relapse, especially with the so-called mutant type of infection, occurred in the majority and the sustained response rate was unacceptably low.
*
Multiple adverse events per individual patient are possible. laboratory parameter (reactive only).
No prospective testing for
M1902
M1900
Efficacy and Safety of Entecavir and/or Tenofovir in Hepatitis B Cirrhotic Patients Mireia Miquel, Oscar Nuñez Martinez, Maria Trapero-Marugan, Antonio Diaz-Sanchez, Miguel Jimenez, Juan I. Arenas, Antonio Palau
Screening and Prevention of Viral Hepatitis B Reactivation for Patients With Inflammatory Bowel Diseases (IBD): A Study on Practices at General Hospitals in France Stephane Nahon, Cécile Poupardin, Jean-Francois Cadranel, Claire Charpignon, Jacques Denis, Herve Hagege, Bruno Lesgourgues, Christophe Renou
AIMS: To investigate the efficacy and safety of Entecavir (ETV) and/or Tenofovir (TDF) in chronic hepatitis B (CHB) patients with compensated or decompensated cirrhosis. METHODS: Spanish, multi-centre, longitudinal and retrospective study of CHB cirrhotic patients who initiated ETV and/or TDF in clinical practice. 42 patients were included, 3 were excluded due to coinfection by HDV (2) and HCV (1). Analytical, virological and clinical variables (adverse events, liver decompensation, developing hepatocellular carcinoma (HCC), liver transplantation or death) were analysed in CHB decompensated (Child-Pugh ≥7) or compensated cirrhotic patients during treatment. The efficacy endpoint was determined by undetectability of HBV-DNA. RESULTS: 39 patients (34 males; mean age 56±13 years), caucasians (87%) were treated. HBeAg was negative in 31 (79.5%). Nine (28%) presented decompensated cirrhosis at the beginning of treatment. Before treatment, 8 patients had experienced ascites, 1 encephalopathy, 15 had esophageal varices, 1 had spontaneous bacterial peritonitis and two suffered variceal bleeding. ETV and/or TDF were the first line therapy in 59% of patients; the other 41% were experienced (4 LAM, 7 ADV and 5 LAM+ADV). In those patients, the main reason to switch therapy was suboptimal response in 7 (43.7%), resistance in 7 (43.7%) and renal insufficiency in 2 (12.5%). Patients received: ETV monotherapy in 29, TDF in 7 (2 added to LAM) and 3 ETV plus TDF. HBV-DNA was undetectable in 17 patients at 3 month and in 22 at 6 month. Mean basal HBV-DNA, at 3, 6 and 9 months were respectively: 9.7±7.5; 5.±4.6; 3.9±4.5; 2.8±3.4 logs UI/mL.. No statistically significant differences between compensated and decompensated cirrhotics were found regarding efficacy at 3 months (p<0.6) or 6 months (p<0.9), or if patients were naïve vs. experienced. No clinical relevant adverse events were found. Median of follow-up: 10.8 (0.67-31.2) months. At the end of follow-up, 5 patients presented decompensated cirrhosis, and 3 (decompensated at the beginning of therapy) developed clinical decompensation. Eight patients developed HCC (20.5%), 4 (10.3%) underwent liver transplantation (3 due to HCC), and 2 died (5%). CONCLUSIONS: In patients with CHB and decompensated cirrhosis, treatment with ETV and/or TDF seems to be effective and safe.
Introduction: EASL and ECCO recently stressed the importance of establishing patients' HBV status before initiating immunosuppressor treatment or prescribing pre-emptive treatment (PET) in the presence of AgHBs. The aim of this survey was to assess how hepatogastroenterologists working at general hospitals in France manage HBV in patients with IBD. Patients and Methods: A questionnaire was e-mailed to all the active members of the French National Association of General Hospital Practitioners. Volunteers responded to this computer-based questionnaire containing both simple and multiple-choice questions. Results: eighty-seven hospital practitioners answered all the questions in the survey. Their field of activity was gastorenterology in 34% of cases, hepatology in 15%, and mixed in 51%. Screening for HBV markers was carried out by 91% of the respondents, rarely at the diagnosis of IBD (28%) and more frequently before starting immunosuppressive treatment (72%). The screening was mostly based on serological tests (78%). Forty-nine percent of the practitioners systematically recommended HBV vaccination for seronegative patients, whereas 35% vaccinated only patients with a risk of viral infection. Detection of anti-HBs antibodies was carried out by 25% of the respondents after vaccination. PET was prescribed by 70% of the practitioners on inactive AgHBs carriers (HBV DNA levels <2000 UI/L). HBV DNA levels were determined by 75% of the respondents in patients with isolated anti-HBc. In this particular situation, PET was prescribed by 50% of them when the viral DNA was positive, and in 9% when it was negative. The PET prescribed consisted of lamivudine (22%), tenofovir (24.5%) and entecavir (31%). The PET was stopped 6 months after the end of immunosuppressor treatment in the case of inactive AgHBs carriers by 65.5% of the practitioners. Conclusion: The practices of hepato-gastroenterologists working at general hospitals in France are mostly in keeping with the current recommendations on the management of HBV in IBD patients. However, early HBV screening, which makes it possible to vaccinate non-immunised patients before starting treatment with immuno-suppressors, is carried out by only one quarter of the respondents. In addition, PET, which should be systematically proposed to inactive HBV carriers, is actually applied by only 70% of these practitioners.
AASLD Abstracts
†
S-832
M1899
AASLD Abstracts
The Efficacy of Interferon Treatment in HBeAg Positive Chronic Hepatitis B is Very Low in an Area With Exclusively D Genotype Hakan Senturk, Birol Baysal, Resat Ozaras, Hasan Zerdali, Fehmi Tabak, Ali Mert, Billur Canbakan, Ibrahim Hatemi, Omur Tabak, Gulsen Ozbay Background and aims: Previous studies reported encouraging results with interferon-based treatments in HBeAg positive chronic hepatitis B (CHB). The impact of genotype on response and relapse rate emerged very recently. Genotype D appeared as the least responsive. In this country the genotype is exclusively D. We report here very long-term results of interferonalfa treatment in HBe Ag positive CHB. Methods: We reviewed the data of HBeAg positive CHB patients treated with interferon-alfa 2b (IFN), 10 MU, subcutaneously 3 times per week for 6 months and were followed up for at least 120 months untreated as the response is going on were included. All patients had elevated ALT levels over 2X upper limit of normal for at least 6 months and had histological evidence of chronic hepatitis B (necroinflammatory activity >3, according to Knodell scoring) before therapy. At the admission serum HBV-DNA was detectable with molecular hybridization technique without amplification. The response to treatment was defined as HBeAg seroconversion with HBV-DNA undetectability and ALT normalization. The responders were followed- up 3-6 monthly intervals over ten years. Results: In a period of seven years, 71 patients with HBeAg positive chronic hepatitis B treated with IFN were eligible for inclusion. There were 10 females and 61 males, the mean age was 29±12 (range:16-62) years. After treatment twenty-eight patients (39.4%) achieved HBeAg seroconversion. While 25 developed seroconversion in the treatment period, 3 developed within 12 months after the end of the treatment. The responders were followed up with a median period of 152 months (range:123-181). In the follow-up period 21 of 28 responders relapsed (75%) 3 of them had e antigen reversion (14.3%). The sustained response (persistently normal ALT levels and serum HBV DNA level ≤ 2000 IU/ml) was present in 7 patient (9.8%). HBsAg disappeared in 2 patients, anti-HBs developed only in one patient . Serious side effects precluding completion of treatment occurred in three patients (4.2%). Conclusion: Although HBeAg seroconversion rate with IFN was relatively high in this study, relapse, especially with the so-called mutant type of infection, occurred in the majority and the sustained response rate was unacceptably low.
*
Multiple adverse events per individual patient are possible. laboratory parameter (reactive only).
No prospective testing for
M1902
M1900
Efficacy and Safety of Entecavir and/or Tenofovir in Hepatitis B Cirrhotic Patients Mireia Miquel, Oscar Nuñez Martinez, Maria Trapero-Marugan, Antonio Diaz-Sanchez, Miguel Jimenez, Juan I. Arenas, Antonio Palau
Screening and Prevention of Viral Hepatitis B Reactivation for Patients With Inflammatory Bowel Diseases (IBD): A Study on Practices at General Hospitals in France Stephane Nahon, Cécile Poupardin, Jean-Francois Cadranel, Claire Charpignon, Jacques Denis, Herve Hagege, Bruno Lesgourgues, Christophe Renou
AIMS: To investigate the efficacy and safety of Entecavir (ETV) and/or Tenofovir (TDF) in chronic hepatitis B (CHB) patients with compensated or decompensated cirrhosis. METHODS: Spanish, multi-centre, longitudinal and retrospective study of CHB cirrhotic patients who initiated ETV and/or TDF in clinical practice. 42 patients were included, 3 were excluded due to coinfection by HDV (2) and HCV (1). Analytical, virological and clinical variables (adverse events, liver decompensation, developing hepatocellular carcinoma (HCC), liver transplantation or death) were analysed in CHB decompensated (Child-Pugh ≥7) or compensated cirrhotic patients during treatment. The efficacy endpoint was determined by undetectability of HBV-DNA. RESULTS: 39 patients (34 males; mean age 56±13 years), caucasians (87%) were treated. HBeAg was negative in 31 (79.5%). Nine (28%) presented decompensated cirrhosis at the beginning of treatment. Before treatment, 8 patients had experienced ascites, 1 encephalopathy, 15 had esophageal varices, 1 had spontaneous bacterial peritonitis and two suffered variceal bleeding. ETV and/or TDF were the first line therapy in 59% of patients; the other 41% were experienced (4 LAM, 7 ADV and 5 LAM+ADV). In those patients, the main reason to switch therapy was suboptimal response in 7 (43.7%), resistance in 7 (43.7%) and renal insufficiency in 2 (12.5%). Patients received: ETV monotherapy in 29, TDF in 7 (2 added to LAM) and 3 ETV plus TDF. HBV-DNA was undetectable in 17 patients at 3 month and in 22 at 6 month. Mean basal HBV-DNA, at 3, 6 and 9 months were respectively: 9.7±7.5; 5.±4.6; 3.9±4.5; 2.8±3.4 logs UI/mL.. No statistically significant differences between compensated and decompensated cirrhotics were found regarding efficacy at 3 months (p<0.6) or 6 months (p<0.9), or if patients were naïve vs. experienced. No clinical relevant adverse events were found. Median of follow-up: 10.8 (0.67-31.2) months. At the end of follow-up, 5 patients presented decompensated cirrhosis, and 3 (decompensated at the beginning of therapy) developed clinical decompensation. Eight patients developed HCC (20.5%), 4 (10.3%) underwent liver transplantation (3 due to HCC), and 2 died (5%). CONCLUSIONS: In patients with CHB and decompensated cirrhosis, treatment with ETV and/or TDF seems to be effective and safe.
Introduction: EASL and ECCO recently stressed the importance of establishing patients' HBV status before initiating immunosuppressor treatment or prescribing pre-emptive treatment (PET) in the presence of AgHBs. The aim of this survey was to assess how hepatogastroenterologists working at general hospitals in France manage HBV in patients with IBD. Patients and Methods: A questionnaire was e-mailed to all the active members of the French National Association of General Hospital Practitioners. Volunteers responded to this computer-based questionnaire containing both simple and multiple-choice questions. Results: eighty-seven hospital practitioners answered all the questions in the survey. Their field of activity was gastorenterology in 34% of cases, hepatology in 15%, and mixed in 51%. Screening for HBV markers was carried out by 91% of the respondents, rarely at the diagnosis of IBD (28%) and more frequently before starting immunosuppressive treatment (72%). The screening was mostly based on serological tests (78%). Forty-nine percent of the practitioners systematically recommended HBV vaccination for seronegative patients, whereas 35% vaccinated only patients with a risk of viral infection. Detection of anti-HBs antibodies was carried out by 25% of the respondents after vaccination. PET was prescribed by 70% of the practitioners on inactive AgHBs carriers (HBV DNA levels <2000 UI/L). HBV DNA levels were determined by 75% of the respondents in patients with isolated anti-HBc. In this particular situation, PET was prescribed by 50% of them when the viral DNA was positive, and in 9% when it was negative. The PET prescribed consisted of lamivudine (22%), tenofovir (24.5%) and entecavir (31%). The PET was stopped 6 months after the end of immunosuppressor treatment in the case of inactive AgHBs carriers by 65.5% of the practitioners. Conclusion: The practices of hepato-gastroenterologists working at general hospitals in France are mostly in keeping with the current recommendations on the management of HBV in IBD patients. However, early HBV screening, which makes it possible to vaccinate non-immunised patients before starting treatment with immuno-suppressors, is carried out by only one quarter of the respondents. In addition, PET, which should be systematically proposed to inactive HBV carriers, is actually applied by only 70% of these practitioners.
AASLD Abstracts
†
S-832