Real-World Experience of Telbivudine and Lamivudine as Antiviral Prophylaxis for Chemotherapy-Related Hepatitis B Reactivation

Lianda Siregar, Imelda Maria Loho, Agus Sudiro Waspodo, Siti Nadliroh, Rahmanandhika Swadari, Rizka Andalusia, Leovinna Widjaja

Abstract


Background: There is currently no data regarding the efficacy of prophylactic telbivudine in hepatitis B patients undergoing chemotherapy. This study aims to describe the results of preemptive telbivudine and lamivudine to prevent chemotherapy-related HBV reactivation.

Methods: The medical records of all patients with HBsAg positive or HBs-Ag negative, anti-HBc positive, who were referred to the hepatology clinic between May 2014 and December 2016, were retrospectively reviewed. As this is a descriptive study, no statistical analysis was done.

Results: A total of 52 patients with prophylactic telbivudine or lamivudine therapy were included, with 26 patients in each group. Rituximab-based treatment was given in nine and five patients in the telbivudine and lamivudine group, respectively. The number of patients who completed antiviral treatment up to six months after chemotherapy was 17 patients in each group. There was less incidence of HBV reactivation in the telbivudine group (2 of 17 patients, 11.8%) than in the lamivudine group (7 of 17 patients, 41.2%). Delayed reactivation was noticed in 1 of 2 patients in the telbivudine group and 3 of 7 patients in the lamivudine group. The median log10[HBV DNA] at reactivation was 4.52 (1.70 – 8.35) IU/mL. Severe hepatitis was observed in two patients in the lamivudine group and one patient in the telbivudine group. Of 34 patients who completed antiviral treatment, two patients died due to primary cancer. No interruption of chemotherapy or mortality due to hepatitis was noticed in both groups.

Conclusions: Preemptive telbivudine or lamivudine in HBsAg positive or HBsAg negative, anti-HBc positive patients seems to be a good treatment option.


Keywords


hepatitis B, lamivudine, prophylaxis, reactivation, telbivudine

References


Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, et al. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol. 2011;22(5):1170-80.

Mozessohn L, Chan KK, Feld JJ, Hicks LK. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving rituximab for lymphoma: a meta-analysis. J Viral Hepat. 2015;22(10):842-9.

Verma R, Foster RE, Horgan K, Mounsey K, Nixon H, Smalle N, et al. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Breast Cancer Res. 2016;18(1):10.

Lazdina U, Alheim M, Nystrom J, Hultgren C, Borisova G, Sominskaya I, et al. Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent. J Gen Virol. 2003;84(Pt 1):139-46.

Martin ST, Cardwell SM, Nailor MD, Gabardi S. Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation. Am J Transplant. 2014;14(4):788-96.

Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol. 2012;9(3):156-66.

Xunrong L, Yan AW, Liang R, Lau GK. Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy--pathogenesis and management. Rev Med Virol. 2001;11(5):287-99.

Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49(5 Suppl):S156-65.

Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1-98.

Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):215-9; quiz e16-7.

EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167-85.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370-98.

Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148(7):519-28.

Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125(6):1714-22.

Bang KB, Kim HJ. Management of antiviral drug resistance in chronic hepatitis B. World J Gastroenterol. 2014;20(33):11641-9.

Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357(25):2576-88.

Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661-2.

Tseng TC, Liu CJ, Chen CL, Wang CC, Su TH, Kuo SF, et al. Serum hepatitis B virus-DNA levels correlate with long-term adverse outcomes in spontaneous hepatitis B e antigen seroconverters. J Infect Dis. 2012;205(1):54-63.

Hsu C, Tsou HH, Lin SJ, Wang MC, Yao M, Hwang WL, et al. Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hepatology. 2014;59(6):2092-100.

Huang YH, Hsiao LT, Hong YC, Chiou TJ, Yu YB, Gau JP, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31(22):2765-72.

Loomba R, Liang TJ. Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology. 2017;152(6):1297-309.

Hou J, Yin YK, Xu D, Tan D, Niu J, Zhou X, et al. Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial. Hepatology. 2008;47(2):447-54.

Thompson AJ, Ayres A, Yuen L, Bartholomeusz A, Bowden DS, Iser DM, et al. Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors. J Gastroenterol Hepatol. 2007;22(7):1078-85.

Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, et al. 2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136(2):486-95.

Gane EJ, Deray G, Liaw YF, Lim SG, Lai CL, Rasenack J, et al. Telbivudine improves renal function in patients with chronic hepatitis B. Gastroenterology. 2014;146(1):138-46.e5.

Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148(1):221-44.e3.

Dong HJ, Ni LN, Sheng GF, Song HL, Xu JZ, Ling Y. Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients receiving rituximab-chemotherapy: a meta-analysis. J Clin Virol. 2013;57(3):209-14.

Loglio A, Vigano M, Grossi G, Labanca S, Goldaniga M, Pompa A, et al. Lamivudine prophylaxis prevents hepatitis B virus reactivation in anti-HBc positive patients under rituximab for non-Hodgkin lymphoma. Dig Liver Dis. 2019;51(3):419-24.

Chen WC, Cheng JS, Chiang PH, Tsay FW, Chan HH, Chang HW, et al. A Comparison of Entecavir and Lamivudine for the Prophylaxis of Hepatitis B Virus Reactivation in Solid Tumor Patients Undergoing Systemic Cytotoxic Chemotherapy. PLoS One. 2015;10(6):e0131545.

Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology. 2006;131(1):59-68.

Dai MS, Chao TY, Kao WY, Shyu RY, Liu TM. Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP. Ann Hematol. 2004;83(12):769-74.

Yeo W, Chan PK, Chan HL, Mo FK, Johnson PJ. Hepatitis B virus reactivation during cytotoxic chemotherapy-enhanced viral replication precedes overt hepatitis. J Med Virol. 2001;65(3):473-7.


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DOI: 10.33371/ijoc.v15i1.767

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