Clinical Application of HBs quantification

Transcription

1 Clinical Application of HBs quantification Hepatology on the Nile 2 Advances in Liver Disease 2014, "World Expert Review» Wednesday, September 24, 2014 Pr Tarik Asselah MD, PhD; Service d Hépatologie & INSERM UMR 1149 University Paris Diderot, Hôpital Beaujon, Clichy, France.

2 Agenda Introduction HBsAg quantification Why? When? Take home message The future

3 Treatment strategies Treatment goals as defined by EASL guidelines Sustained HBV DNA suppression, histologic improvement and HBsAg loss. Two treatment strategies recommended: Pegylated interferon (PEG-IFN): immune control and HBsAg clearance with 48 weeks therapy. Nucleos(t)ide analogues (NAs): viral suppression with unlimited treatment duration. Journal of Hepatology 2012

4 HBV epidemiology 360 millions carriers HBsAg prevalence 8% - High 2-7% - Intermediate <2% - Low Dienstag et al. NEJM 2008

5 Fibrosis evaluation: scores Fibrosis staging METAVIR 1 Score Knodell 2 Score Ishak 3 Score No fibrosis 0 No fibrosis 0 No fibrosis 0 Portal fibrosis without septa 1 Fibrosis portal expansion 1 Some portal tract fibrotic ± short fibrous septa 1 Most portal tract fibrotic ± short fibrous septa 2 Portal fibrosis with few septa 2 Bridging fibrosis (P-P or P-C) 3 Most portal tract fibrotic with occasional P-P bridging 3 Numerous septa without cirrhosis 3 Portal tract fibrotic with marked P-P and P-C bridging 4 Cirrhosis 4 Cirrhosis 4 Marked P-P and/or P-C bridging with occasional nodules (incomplete cirrhosis 5 Cirrhosis (probable or definite) 6 Asselah, Marcellin, Bedossa. Journal of Hepatology P-P: portal to portal; P-C: portal to central

6 Entecavir: Distribution of Ishak Fibrosis Scores at Baseline, Year 1, and Years 3 7 Number of Patients Ishak Fibrosis Score Missing n=57 Chang et al Hepatology, 2010

7 Regression of Fibrosis with Long-term Tenofovir p<0.001 p<0.001 Patients (%) Ishak score Baseline Year 1 Year 5 Marcellin et al. Lancet 2013 Reviewed in Marcellin and Asselah. J Gastroenterol Hepatol 2013;28:

8 Agenda Introduction HBsAg quantification Why? When? Take home message The future

9 HBsAg Loss is Associated with Improved Survival 309 cirrhotics with a mean follow-up of 6 years HBsAg loss P<0.001 No HBsAg loss Survival (%) Time (years) Fattowich et al. Am J Gastroenterology 1998

10 The Importance of HBsAg Loss - Ultimate goal of therapy - Closest to cure - Not HBV eradication but associated with improved prognosis

11 HBs : a surrogate marker of cccdna Association between HBs quantification and cccdna HBeAg positive 42 and HBeAg negative 77 HBeAg positive 71 and HBeAg negative 78 Volz T et al. Gastroenterolgy 2007;133:843 Thompson AJV et al. Hepatology 2010; 51: 1933-

12 The present: PEG-IFN therapy HBsAg titer in combination with HBV DNA enables on-treatment adjustments. Absence of decline combined with HBV DNA decline < 2 log IU/ml at week 12 is highly predictive of no response. NPV % Lau GK et al. Liver Int 2009 Brunetto MR et al., Hepatology 2009 Moucari R et al. Hepatology 2009 Sonneveld MJ et al. Hepatology 2010 Chan HL et al. Aliment Pharmacol Ther 2010 Liaw YF. Hepatology 2011 Piratvisuth T et al. Hepatol Int 2011

13 The present: NAs therapy Decline is lower than with PEG-IFN, more pronounced in HBe positive than in HBe negative patients. Low baseline titer and decline during the 24 first weeks of therapy predictive of HBe and HBs loss. Wursthorn K et al. Hepatology 2010 Reijinders JGP et l. J Hepatol 2011 Papatheodoridis G. et al. J Hepatol 2013 Shouval D et al. J Hepatol 2013 Tseng TC et al. J Gastroenterol 2013 Chevaliez S et al. J Hepatol 2013 Boglione L. et al. Liver International 2013

14 Why quantify HBsAg? Pegylated Interferon Therapy HBV DNA kinetics HBsAg kinetics Relapsers Relapsers SVR SVR Moucari M et al. Hepatology 2009 Brunetto MR et al., Hepatology 2009

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16 When: Baseline (PEG-IFN) Log UI/ml Predictive value of baseline HBsAg levels 4 Responders* Non responders 3 2 p<0.01 p<0.001 p< HBeAg positive HBeAg negative *ADN VHB <2000 IU/ml +HBeAg loss 6 months post-treatment *ADN VHB <2000 IU/ml 6 months post-treatment Tangkijvanich et al. J Clin Virol 2009 Piratvisuth T et al. Hepatol Int 2011 Marcellin et al. AASLD 2013T Takkenberg et al. Antiviral Therapy in Press.

17 When: during therapy (PEG-IFN) Real-world S-Collate study Predictive value of HBsAg levels at week HBeAg positive HBeAg negative UI/ml UI/ml > 1500 IU/ml Viral suppression HBs loss Viral suppression HBs loss > 1500 IU/ml Marcellin et al. APASL 2013

18 When: end of therapy (NAs) Prediction of outcome after NAs therapy discontinuation (APASL guidelines) % Cumulative probability of virologic relapse HBsAg >1000 IU/ml at end of therapy HBsAg IU/ml at end of therapy HBsAg 100 IU/ml at end of therapy Months Liaw YF et al. Hepatol Int 2008L Liang Y. AP&T 2011

19 Agenda Introduction HBsAg quantification Why? When? Take home message The future

20 When: during therapy (PEG-IFN) Week twelve stopping rule SVR HBsAg decline NO HBV DNA decline < 2 log 0% HBV DNA decline 2 log 24% HBsAg decline YES HBV DNA decline < 2 log 25% HBV DNA decline 2 log 39% Rijckborst V et al. Hepatology 2010

21 The present: summary (1) HBsAg kinetics during the 24 first weeks of Pegylated-interferon or nucleos(t)ides therapy, is highly predictive of HBeAg and HBsAg loss, independently from HBV genotypes.

22 The present: summary (2) qhbsag can complement HBV DNA levels to optimize the management of chronic hepatitis B patients. More data are needed, especially studies from Western countries to confirm these findings, mainly observed in Asian patients, and the role of HBV genotypes. There is needs for better definition of specific degree of HBsAg decline and identified time points with the best predictive fit for sustained virilogical response and evaluating the likelihood of HBsAg seroconversion.

23 Take home message The better use of this new tool is likely serial measurements of HBsAg concentration PEG-IFN therapy Baseline, weeks 12 and 24 to identify patients with high probability of non-response and switch. NAs therapy Baseline, week 24 to identify patients with high probability of HBeAg and HBsAg loss, before ending therapy to identify patients without risk of relapse.