S Lingala1, D T-Y Lau2, C Koh1, S Auh3, M G Ghany1, J H Hoofnagle1. 1. Liver Diseases Branch, Intramural Division, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA. 2. Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3. NIDDK, NIH, Bethesda, MD, USA.
Abstract
BACKGROUND: One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined. AIM: To describe outcomes of chronic hepatitis B with long-term lamivudine therapy. METHODS: Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease. RESULTS: Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis. CONCLUSIONS: Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy.
BACKGROUND: One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined. AIM: To describe outcomes of chronic hepatitis B with long-term lamivudine therapy. METHODS: Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease. RESULTS: Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis. CONCLUSIONS: Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy.
Authors: Michael T Pyne; Lauren Vest; Jennifer Clement; Jessica Lee; Jessica R Rosvall; Kevin Luk; Michael Rossi; Bryan Cobb; David R Hillyard Journal: J Clin Microbiol Date: 2012-04-25 Impact factor: 5.948
Authors: M G Ghany; J J Feld; X Zhao; T Heller; E Doo; Y Rotman; P Nagabhyru; C Koh; D E Kleiner; E C Wright; T J Liang; J H Hoofnagle Journal: Aliment Pharmacol Ther Date: 2012-03-26 Impact factor: 8.171
Authors: J L Dienstag; E R Schiff; M Mitchell; D E Casey; N Gitlin; T Lissoos; L D Gelb; L Condreay; L Crowther; M Rubin; N Brown Journal: Hepatology Date: 1999-10 Impact factor: 17.425
Authors: Patrick Marcellin; Edward Gane; Maria Buti; Nezam Afdhal; William Sievert; Ira M Jacobson; Mary Kay Washington; George Germanidis; John F Flaherty; Raul Aguilar Schall; Jeffrey D Bornstein; Kathryn M Kitrinos; G Mani Subramanian; John G McHutchison; E Jenny Heathcote Journal: Lancet Date: 2012-12-10 Impact factor: 79.321
Authors: J L Dienstag; E R Schiff; T L Wright; R P Perrillo; H W Hann; Z Goodman; L Crowther; L D Condreay; M Woessner; M Rubin; N A Brown Journal: N Engl J Med Date: 1999-10-21 Impact factor: 91.245
Authors: D T Lau; M F Khokhar; E Doo; M G Ghany; D Herion; Y Park; D E Kleiner; P Schmid; L D Condreay; J Gauthier; M C Kuhns; T J Liang; J H Hoofnagle Journal: Hepatology Date: 2000-10 Impact factor: 17.425
Authors: Norah A Terrault; Natalie H Bzowej; Kyong-Mi Chang; Jessica P Hwang; Maureen M Jonas; M Hassan Murad Journal: Hepatology Date: 2015-11-13 Impact factor: 17.425