Treatment as a form of liver cancer prevention The clinical efficacy and cost effectiveness of treatment across Asia Prof. Henry LY Chan Head, Division of Gastroenterology and Hepatology Director, Institute of Digestive Disease Director, Center for Liver Health Assistant Dean, Faculty of Medicine The Chinese University of Hong Kong
HBV treatment prevent HCC HBeAg positive CHB Signposts! Goals of treatment Start Rx Start Rx Reduce HBV DNA Normal ALT HBeAg negative CHB Reduce HBV DNA Normal ALT HBeAg loss PCR nega9ve Ant-HBe Seroconversion PCR nega9ve HBsAg loss HBsAg loss Prevent cirrhosis Prevent liver failure Prevent HCC Improve survival Liver inflammation and fibrosis
HBV Treatment can reduce risk of cirrhotic complications and HCC Sustained remission by immune modulation PEG-IFN HBeAg seroconversion HBV DNA <2000 IU/ml Normal ALT HBsAg loss Maintained remission by continuous viral suppression Nucleos(t)ide analogue Undetectable HBV DNA Normal ALT? HBeAg seroconversion? HBsAg loss years
Interferon can reduce risk of HCC A meta-analysis of 12 studies Sung JJ, et al. Aliment Pharmacol Ther 2008;28:1067-77
Lamivudine to reduce HCC in early HBV cirrhosis Controversial in Asian randomized controlled trial Percentage with diagnosis P=0.047 10% Placebo Lamivudine 5% Time to diagnosis (months) Placebo (n=215) Lamivudine (n=436) Excluding 5 cases in yr1: HR=0.47; P=0.052 Liaw YF et al. N Engl J Med 2004; 351: 1521-31
Entecavir and Tenofovir are the first line NA treatment for CHB Drug Generation Not head- to- head trials; different pa2ent popula2ons and trial designs Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 1 st LAM 24% 38% 49% 67% 70% 2 nd ADV 0% 3% 11% 18% 29% LdT 4% 17% ETV 0.2% 0.5% 1.2% 1.2% 3 rd 0% 1.2% 1.2% TDF 0% 0% 0% 0% Adapted from 1. EASL. J Hepatol. 2009;50:227-42. 2. Tenney DJ, et al. EASL 2009. Oral presentation #20. 3. Marcellin P, et al. Hepatology 2009;50(4, Suppl.):532A-3A. 4. Heathcote EJ, et al. Hepatology 2009;50(4, Suppl.):533A-4A 5. Marcellin P, et al. Lancet 2013;381:468-75.
Estimated annual incidence of HCC in patients based on 5 year FU EsLmated annual incidence of HCC Entecavir/NA* Control 4% Adj HR 0.37 Adj HR 0.23 Adj HR 0.28 3.24% 3% 2.74% 2.26% 2% 1% 1.05% * 0.74% 0.54% 0% 21595 21595 316 316 117 Wu et al Hosaka et al Kumada et al 117 Propensity score matched Wu CY, et al. Gastroenterology 2014;147:143-51; Hosaka T, et al. Hepatology 2013;58:98-107; Kumada T, et al. J Hepatol 2013;58:427-33.
Estimated annual incidence of HCC in cirrhotic patients based on 5 year FU EsLmated annual incidence of HCC 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% Adj HR 0.55 2.76% 5.28% Entecavir/NA* Adj HR 0.72 3.90% Untreated control 4.94% HR N/A 1.40% Hong Kong Taiwan Japan * 7.78% 482 69 3016 2847 79 85 Wong GL, et al. Hepatology 2013;58:1537-47; Wu CY, et al. Gastroenterology 2014;147:143-51; Hosaka T, et al. Hepatology 2013;58:98-107
Treatment regimes evaluated in costeffectiveness analysis in Hong Kong PegIFN Peg IFN ETV Peginterferon (RGT) PegIFN Peginterferon ETV Entecavir TDF Tenofovir TBV Telbivudine TBV TBV TDF Telbivudine (roadmap) Lo AO, et al. Clin Gastroenterol Hepatol 2014 (in press)
Cost effectiveness analysis in Hong Kong HBeAg-positive patients ICER for peginterferon (RGT) = USD 1200 ICER for peginterferon 48 week = USD 9647 All other regimes dominated (lower QALY but higher cost than PegIFN RGT) 100000 Cost (USD) 80000 19.82 No treatment 60000 23.18 PegIFN (RGT) 23.11 PegIFN 40000 23.07 ETV 20000 23.12 TDF USD 35509 23.08 TBV 0 23.13 TBV (roadmap) 19.5 20 20.5 21 21.5 22 22.5 23 23.5 Quality Adjusted Life- Years Lo AO, et al. Clin Gastroenterol Hepatol 2014 (in press)
Sensitivity analysis for HBeAg-positive patients Lo AO, et al. Clin Gastroenterol Hepatol 2014 (in press)
Cost effectiveness analysis in Hong Kong HBeAg-negative patients ICER for entecavir = USD 34310 ICER for tenofovir = USD 357950; telbivudine roadmap = USD 715200 All other regimes dominated (lower QALY but higher cost than ETV) 100000 Cost (USD) 80000 20.38 No treatment 60000 21.48 PegIFN (RGT) 21.44 PegIFN 40000 21.55 ETV 20000 USD 33781 21.57 TDF 21.54 TBV 0 21.56 TBV (roadmap) 20.2 20.4 20.6 20.8 21 21.2 21.4 21.6 21.8 Quality Adjusted Life- Years Lo AO, et al. Clin Gastroenterol Hepatol 2014 (in press)
Summary Both interferon and nucleos(t)ide analogues can reduce risk of HCC development in chronic hepatitis B Most benefit of antiviral therapy among cirrhotic patients Annual incidence of HCC 1.4% - 3.9% In HBeAg-positive patients, peginterferon is cost-effective. But if price of entecavir/tenofovir can be reduced, it will become most cost-effective In HBeAg-negative patients, entecavir (or tenofovir if it is cheaper) is most cost-effective