Terry Cheuk-Fung Yip1, Grace Lai-Hung Wong2, Henry Lik-Yuen Chan2, Yee-Kit Tse1, Kelvin Long-Yan Lam1, Grace Chung-Yan Lui3, Vincent Wai-Sun Wong4. 1. Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. 2. Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. 3. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Division of Infectious Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. 4. Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: wongv@cuhk.edu.hk.
Abstract
BACKGROUND & AIMS: In treated patients with chronic hepatitis B (CHB) who have achieved complete viral suppression, it is unclear if functional cure as indicated by hepatitis B surface antigen (HBsAg) seroclearance confers additional clinical benefit. We compared the risk of hepatocellular carcinoma (HCC) and hepatic events in nucleos(t)ide analogue (NA)-treated patients with and without HBsAg seroclearance. METHODS: We performed a territory-wide retrospective cohort study on all patients with CHB who had received entecavir and/or tenofovir disoproxil fumarate (TDF) for at least 6 months between 2005 and 2016 from Hospital Authority, Hong Kong. Patients' demographics, comorbidities, and laboratory parameters were analyzed. The primary outcome was HCC. The secondary outcomes were hepatic events including cirrhotic complications, liver transplantation, and liver-related mortality. RESULTS: A total of 20,263 entecavir/TDF-treated patients with CHB were identified; 17,499 (86.4%) patients had complete viral suppression; 376 (2.1%) achieved HBsAg seroclearance. At a median (interquartile range) follow-up of 4.8 (2.8-7.0) years, 603 (3.5%) and 121 (4.4%) patients with and without complete viral suppression developed HCC; 2 (0.5%) patients with HBsAg seroclearance developed HCC. Compared to complete viral suppression, lack of complete viral suppression was associated with a higher risk of HCC (7.8% vs. 5.6% at 8 years, Gray's test, p <0.001) (adjusted hazard ratio [aHR] 1.69; 95% CI 1.36-2.09; p <0.001); patients who achieved functional cure had a lower risk of HCC (0.6% vs. 5.6% at 8 years, Gray's test, p <0.001) (aHR 0.24; 95% CI 0.06-0.97; p = 0.045) but not hepatic events (aHR 0.99; 95% CI 0.30-3.26; p = 0.991). CONCLUSIONS: Patients who achieved HBsAg seroclearance on top of complete viral suppression with entecavir/TDF treatment may have a lower risk of HCC but not hepatic events. LAY SUMMARY: We investigated 20,263 nucleos(t)ide analogue (NA)-treated patients with chronic hepatitis B. Patients with NA-induced hepatitis B surface antigen seroclearance on top of complete viral suppression have a lower risk of hepatocellular carcinoma but not hepatic events than those only achieving complete viral suppression under prolonged NA treatment.
BACKGROUND & AIMS: In treated patients with chronic hepatitis B (CHB) who have achieved complete viral suppression, it is unclear if functional cure as indicated by hepatitis B surface antigen (HBsAg) seroclearance confers additional clinical benefit. We compared the risk of hepatocellular carcinoma (HCC) and hepatic events in nucleos(t)ide analogue (NA)-treated patients with and without HBsAg seroclearance. METHODS: We performed a territory-wide retrospective cohort study on all patients with CHB who had received entecavir and/or tenofovir disoproxil fumarate (TDF) for at least 6 months between 2005 and 2016 from Hospital Authority, Hong Kong. Patients' demographics, comorbidities, and laboratory parameters were analyzed. The primary outcome was HCC. The secondary outcomes were hepatic events including cirrhotic complications, liver transplantation, and liver-related mortality. RESULTS: A total of 20,263 entecavir/TDF-treated patients with CHB were identified; 17,499 (86.4%) patients had complete viral suppression; 376 (2.1%) achieved HBsAg seroclearance. At a median (interquartile range) follow-up of 4.8 (2.8-7.0) years, 603 (3.5%) and 121 (4.4%) patients with and without complete viral suppression developed HCC; 2 (0.5%) patients with HBsAg seroclearance developed HCC. Compared to complete viral suppression, lack of complete viral suppression was associated with a higher risk of HCC (7.8% vs. 5.6% at 8 years, Gray's test, p <0.001) (adjusted hazard ratio [aHR] 1.69; 95% CI 1.36-2.09; p <0.001); patients who achieved functional cure had a lower risk of HCC (0.6% vs. 5.6% at 8 years, Gray's test, p <0.001) (aHR 0.24; 95% CI 0.06-0.97; p = 0.045) but not hepatic events (aHR 0.99; 95% CI 0.30-3.26; p = 0.991). CONCLUSIONS:Patients who achieved HBsAg seroclearance on top of complete viral suppression with entecavir/TDF treatment may have a lower risk of HCC but not hepatic events. LAY SUMMARY: We investigated 20,263 nucleos(t)ide analogue (NA)-treated patients with chronic hepatitis B. Patients with NA-induced hepatitis B surface antigen seroclearance on top of complete viral suppression have a lower risk of hepatocellular carcinoma but not hepatic events than those only achieving complete viral suppression under prolonged NA treatment.
Authors: Norah A Terrault; Abdus S Wahed; Jordan J Feld; Stewart L Cooper; Mark G Ghany; Mauricio Lisker-Melman; Robert Perrillo; Richard K Sterling; Mandana Khalili; Raymond T Chung; Philip Rosenthal; Robert J Fontana; Arif Sarowar; Daryl T Y Lau; Junyao Wang; Anna S Lok; Harry L A Janssen Journal: Hepatology Date: 2022-01-26 Impact factor: 17.425
Authors: Sara Ferrando-Martinez; Kelly Huang; Angie Snell Bennett; Patricia Sterba; Li Yu; JoAnn A Suzich; Harry L A Janssen; Scott H Robbins Journal: JHEP Rep Date: 2019-06-28