Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2015; 7(6): 825-830
Published online Apr 28, 2015. doi: 10.4254/wjh.v7.i6.825
Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification
Wai-Kay Seto
Wai-Kay Seto, Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Wai-Kay Seto, Department of Medicine, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
Wai-Kay Seto, State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China
Author contributions: Seto WK solely contributed to this manscript.
Conflict-of-interest: Seto WK is an advisory board member of Gilead Sciences and received speaker’s fees from Bristol-Myers Squibb.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Wai-Kay Seto, Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. wkseto@hku.hk
Telephone: +852-2-2553994 Fax: +852-2-8162863
Received: January 13, 2015
Peer-review started: January 15, 2015
First decision: February 7, 2015
Revised: February 14, 2015
Accepted: March 5, 2015
Article in press: March 9, 2015
Published online: April 28, 2015


Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.

Key Words: Hepatitis B virus, Antibody to hepatitis B core antigen, Hepatitis B surface antigen, Rituximab, Antigen CD20, Hematopoietic stem cell transplantation, Antibody to tumor necrosis factor, Occult

Core tip: Hepatitis B virus (HBV) reactivation not only occurs in hepatitis B surface antigen (HBsAg)-positive, but also in HBsAg-negative, antibody to hepatitis B core antigen positive individuals. Immunosuppressive therapies with increased risk of HBV reactivation include corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor and hematopoietic stem cell transplantation. The decision between prophylactic antiviral therapy vs routine clinical monitoring would involve appropriate risk stratification for individual types of immunosuppressives regimes.

Citation: Seto WK. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification. World J Hepatol 2015; 7(6): 825-830

The introduction of nucleoside analogue therapy has revolutionized the management of chronic hepatitis B (CHB). The current first-line therapies of entecavir and tenofovir, if taken long-term, can bring about potent virologic suppression[1], improve liver histology[2,3], and reduce cirrhotic complications[4,5], with low risk of resistance development[6,7]. Nonetheless, the efficacy of nucleoside analogue therapy remains suboptimal in one distinct clinical entity: hepatitis B virus (HBV)-related acute-on-chronic liver failure[8], in which the 3-mo survival rates were only 40%-57%[9,10]. Reactivation of HBV during immunosuppressive therapy, if caught unaware, could present as acute-on-chronic liver failure, signifying the importance of management strategies directed towards preventing HBV reactivation.

The dangers of HBV reactivation are not only limited to hepatitis B surface antigen (HBsAg)-positive patients, but could also involve HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals. Unfortunately, despite the accumulating evidence in this field, the global oncology community remains divided on the need of routine screening of HBV serology prior to immunosuppressive therapy[11,12]. This editorial aims to provide a literature update as well as management recommendations for preventing and controlling HBV reactivation during immunosuppressive therapy.


Not all immunosuppressive therapies have been proven to be associated with HBV reactivation - the association is in fact limited to a selected few regimens. Corticosteroids is a well-known risk factor, in which the presence of prednisolone in chemotherapy regimens for HBsAg-positive lymphoma patients would increase the risk of HBV reactivation by 36%[13]. HBV reactivation is also possible in patients treated with steroids for non-malignant conditions, especially when the therapy duration is at least 3 mo or when the steroid dose is equivalent to 20 mg of prednisolone per day[14]. The monoclonal antibodies against B cell surface antigen CD20 (anti-CD20), rituximab and ofatumumab, could also enhance the chances of HBV reactivation, with rituximab resulting in more than five-fold increase[15]. More importantly, HBV reactivation could occur up to one year or more after cessation of rituximab[16,17].

Other biologics, including monoclonal antibodies against tumor necrosis factor (anti-TNF), e.g., infliximab, adalimumab and etanercept have been demonstrated to have a 35% HBV reactivation rate in HBsAg-positive patients with rheumatoid arthritis, inflammatory bowel disease and other non-malignant conditions[18]. Other agents proven to increase the risk for HBV reactivation

include transarterial chemo-embolization (TACE) for hepatocellular carcinoma[19], hematopoietic stem cell transplantation (HSCT)[20], methotrexate[21], anthracyclines[22], and other biologic agents including tyrosine kinase inhibitors[23] and ustekinumab[24] (Table 1).

Table 1 Immunosuppressive regimens known to increase risk of hepatitis B virus reactivation.
Anti-HBc positive
CorticosteroidsAnti-CD20 (e.g., rituximab)
Anti-CD20 (e.g., rituximab)HSCT
Anti-TNFTACE for hepatocellular carcinoma
TACE for hepatocellular carcinoma
Tyrosine kinase inhibitors

HBV reactivation is also possible in HBsAg-negative individuals who have occult HBV infection - defined as HBsAg-negativity but with detectable HBV DNA in serum or liver[25]. Such individuals could had CHB, achieved HBsAg seroclearance, but with intrahepatic HBV DNA remaining[26]. They may or may not possess serum antibody to the hepatitis B surface antibody (anti-HBs), with the only positive serologic marker being anti-HBc, indicating past HBV exposure.

HBV reactivation in HBsAg-negative, anti-HBc positive patients has been extensively reported in rituximab-containing chemotherapy (Table 2). Previous retrospective studies reported a reactivation rate of 8.9% to 23.8%[17,27,28]. This large variability could be due to the lack of regular serologic and virologic monitoring, with only HBV reactivation noted when biochemical hepatitis (a late event) occurred. Two recent prospective studies described the risk of HBV reactivation in better detail. The first, when using multiple virologic endpoints, found the rate of reactivation to vary from 11.3% to 18.9%[29]. The second, when defining detectable HBV DNA (> 10 IU/mL) as HBV reactivation, found the cumulative 2-year reactivation rate to be 41.5%. This second study also found patients with negative anti-HBs to have a higher cumulative rate of reactivation than those with positive anti-HBs (68% vs 34% at 2 years respectively)[16]. Patients with detectable HBV DNA all responded well to entecavir, with no cases of hepatitic flares.

Table 2 Rates of hepatitis B virus reactivation during rituximab-containing chemotherapy in hepatitis B surface antigen-negative, antibody to hepatitis B core antigen positive individuals as described by various studies.
Study regionStudy natureNo. of patientsHBV reactivation rateDefinition of HBV reactivation
Hong Kong[17]Retrospective2323.8%HBsAg seroreversion
Japan[27]Retrospective568.9%HBsAg seroreversion
Asia-Pacific[28]Retrospective1789.6%HBsAg seroreversion
Taiwan[29]Prospective15011.3%-18.9%Multiple virologic endpoints
Hong Kong[16]Prospective6341.5%Detectable HBV DNA

HBV reactivation has also been reported in HBsAg-negative anti-HBc-positive patients undergoing HSCT. Retrospective studies again found variable rates of reactivation (8.9% to 19.7%)[30-32], again limited by the lack of routine clinical monitoring. Nonetheless, HBV reactivation could occur many months (up to 47 mo) after HSCT, indicating prolonged clinical monitoring would be needed post-HSCT to ensure early detection of HBV reactivation. The preliminary results of an ongoing prospective study found HBsAg-negative, anti-HBc positive HSCT recipients developing graft-vs-host disease to have an increased chance of HBV reactivation[33] - these results would need further validation.

Anti-TNF therapy could also increase the risk of HBV reactivation in HBsAg-negative, anti-HBc positive patients, although when compared to HBsAg-positive patients, reactivation rates were much lower (1.7% to 5%)[18,34]. Other regimens known to be associated with HBV reactivation among HBsAg-negative, anti-HBc positive patients include TACE for hepatocellular carcinoma[35] and methotrexate[21] (Table 1).

Screening for HBsAg and anti-HBc prior to immunosuppressive therapy

Despite the lack of consensus among the global oncology community[11,12], current guidelines from international liver societies[36,37] recommend mandatory screening for serum HBsAg and anti-HBc prior to all forms of immunosuppressive therapy. Screening would be particularly important in HBV-endemic regions, and is cost-effective[38].

Prophylactic nucleoside analogue therapy for HBsAg-positive individuals

The provision of concomitant nucleoside analogue therapy at the commencement of immunosuppression has been demonstrated to be effective in reducing the risk of HBV reactivation for both hematological malignancies and solid-organ tumors[39]. For most immunosuppressive regimes, nucleoside analogue therapy should be kept until at least 6 mo after the last dose of immunosuppressive therapy. The exception is rituximab, with nucleoside analogue therapy continued until at least 12 mo after completion of rituximab-containing chemotherapy[15].

In terms of the choice of nucleoside analogue for prophylactic therapy, lamivudine has been used most extensively, achieving a 79% risk reduction on HBV reactivation[40]. The disadvantage of lamivudine is its low genetic barrier to resistance[4], such that it is no longer a recommended first-line treatment for CHB. Hence, the two first-line therapies, i.e., entecavir or tenofovir, both with a high genetic barrier to resistance should be used instead[6,7]. This is supported by a recent randomized controlled trial demonstrating entecavir to be superior to lamivudine in the prevention of HBV reactivation among HBsAg-positive individuals undergoing rituximab-containing chemotherapy[41].

Prophylactic nucleoside analogue therapy with a finite therapy duration should be only for CHB patients with quiescent disease, as indicated by baseline HBV DNA < 2000 IU/mL. For CHB patients with baseline HBV DNA ≥ 2000 IU/mL, long-term nucleoside analogue therapy should be considered to reduce the risk of liver-related complications associated with high viral loads[42,43].

Monitoring HBsAg-negative, anti-HBc positive individuals

Defining the optimal management strategy for HBsAg-negative, anti-HBc positive individuals is more difficult. A randomized controlled trial did demonstrate the efficacy of prophylactic nucleoside analogue therapy during rituximab-containing chemotherapy[44]. Nonetheless, within the HBsAg-negative anti-HBc positive population, HBV reactivation seemed to occur only among specific immunosuppressive regimes (Table 1). The risk of HBV reactivation among certain therapies is also low (e.g., < 5% during anti-TNF therapy). Another factor to consider is the seroprevalence of anti-HBc, which could be > 40% among HBV-endemic regions in East Asia[45,46]. Hence, the universal provision of prophylactic nucleoside analogue therapy for all immunosuppressive regimens might not be cost-effective.

Currently, the regular monitoring of serum HBV DNA would probably be the preferred strategy. The optimal interval of monitoring is uncertain - a suggestion would be for every 1-3 mo[36], although there is no high-quality data to support this. Prophylactic nucleoside analogue therapy can still be considered for specific population groups, e.g., anti-HBs negative patients undergoing rituximab-containing chemotherapy[16].


More studies would be needed for risk stratification. Can the current data in HBsAg-positive patients be extrapolated to all forms of immunosuppressive therapy? There is a paucity of data concerning HBV reactivation among traditional immunomodulators, e.g., azathioprine, thalidomide or methotrexate. Other immunosuppressive agents lacking HBV reactivation data include non-steroid or anthracycline-containing chemotherapeutic regimens, monoclonal antibodies other than anti-CD20 or anti-TNF, epidermal growth factor receptor inhibitors and proteasome inhibitors. If current guidelines continue to emphasize prophylactic HBV therapy for all forms of immunosuppression, then cost-effective studies would be needed to justify their usage.

For HBsAg-negative, anti-HBc positive individuals undergoing rituximab-containing chemotherapy, the discrepancies in reactivation rates from previous studies (Table 2) could indicate not all cases of HBV reactivation, when defined as detectable serum HBV DNA, would end up being clinically relevant. In addition, prospective data is still needed to clearly define the risk of HBV reactivation among HSCT and anti-TNF therapy, as well as to identify additional risk factors besides anti-HBs status.

Hopefully, future studies in these directions would help in stratifying the risk of HBV reactivation among different immunosuppressive regimes and improve disease outcomes of HBV-infected individuals undergoing immunosuppressive therapy.


P- Reviewer: Tamori A S- Editor: Ji FF L- Editor: A E- Editor: Liu SQ

1.  Yuen MF, Seto WK, Fung J, Wong DK, Yuen JC, Lai CL. Three years of continuous entecavir therapy in treatment-naïve chronic hepatitis B patients: VIRAL suppression, viral resistance, and clinical safety. Am J Gastroenterol. 2011;106:1264-1271.  [PubMed]  [DOI]
2.  Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Schall RA. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-475.  [PubMed]  [DOI]
3.  Chang TT, Liaw YF, Wu SS, Schiff E, Han KH, Lai CL, Safadi R, Lee SS, Halota W, Goodman Z. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886-893.  [PubMed]  [DOI]
4.  Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai CL. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12:1295-1303.  [PubMed]  [DOI]
5.  Wong GL, Chan HL, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Lai JW, Lo AO. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013;58:1537-1547.  [PubMed]  [DOI]
6.  Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology. 2009;49:1503-1514.  [PubMed]  [DOI]
7.  Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P, Borroto-Esoda K, Miller MD. No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B. Hepatology. 2014;59:434-442.  [PubMed]  [DOI]
8.  Seto WK, Lai CL, Yuen MF. Acute-on-chronic liver failure in chronic hepatitis B. J Gastroenterol Hepatol. 2012;27:662-669.  [PubMed]  [DOI]
9.  Cui YL, Yan F, Wang YB, Song XQ, Liu L, Lei XZ, Zheng MH, Tang H, Feng P. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci. 2010;55:2373-2380.  [PubMed]  [DOI]
10.  Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology. 2011;53:774-780.  [PubMed]  [DOI]
11.  Tan D, Tan SY, Lim ST, Kim SJ, Kim WS, Advani R, Kwong YL. Management of B-cell non-Hodgkin lymphoma in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14:e548-e561.  [PubMed]  [DOI]
12.  Artz AS, Somerfield MR, Feld JJ, Giusti AF, Kramer BS, Sabichi AL, Zon RT, Wong SL. American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol. 2010;28:3199-3202.  [PubMed]  [DOI]
13.  Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF. Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology. 2003;37:1320-1328.  [PubMed]  [DOI]
14.  Lai CL, Yuen MF. Systemic corticosteroid and reactivation of chronic hepatitis B. Respirology. 2010;15:1017-1018.  [PubMed]  [DOI]
15.  Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, Dai MS, Chiu BC, Fintel B, Cheng Y. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol. 2011;22:1170-1180.  [PubMed]  [DOI]
16.  Seto WK, Chan TS, Hwang YY, Wong DK, Fung J, Liu KS, Gill H, Lam YF, Lie AK, Lai CL. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol. 2014;32:3736-3743.  [PubMed]  [DOI]
17.  Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, Chan HL, Hui EP, Lei KI, Mok TS. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605-611.  [PubMed]  [DOI]
18.  Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, Lopez-Roses L, Brito-Zerón P, Pérez-de-Lis M, Retamozo S, Bové A, Bosch X, Sanchez-Tapias JM. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90:359-371.  [PubMed]  [DOI]
19.  Jang JW, Choi JY, Bae SH, Kim CW, Yoon SK, Cho SH, Yang JM, Ahn BM, Lee CD, Lee YS. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma. J Hepatol. 2004;41:427-435.  [PubMed]  [DOI]
20.  Locasciulli A, Bruno B, Alessandrino EP, Meloni G, Arcese W, Bandini G, Cassibba V, Rotoli B, Morra E, Majolino I. Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation. Bone Marrow Transplant. 2003;31:295-300.  [PubMed]  [DOI]
21.  Tamori A, Koike T, Goto H, Wakitani S, Tada M, Morikawa H, Enomoto M, Inaba M, Nakatani T, Hino M. Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts. J Gastroenterol. 2011;46:556-564.  [PubMed]  [DOI]
22.  Ling WH, Soe PP, Pang AS, Lee SC. Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours. Br J Cancer. 2013;108:1931-1935.  [PubMed]  [DOI]
23.  Lai GM, Yan SL, Chang CS, Tsai CY. Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor. World J Gastroenterol. 2013;19:1318-1321.  [PubMed]  [DOI]
24.  Navarro R, Vilarrasa E, Herranz P, Puig L, Bordas X, Carrascosa JM, Taberner R, Ferrán M, García-Bustinduy M, Romero-Maté A. Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting. Br J Dermatol. 2013;168:609-616.  [PubMed]  [DOI]
25.  Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160-170.  [PubMed]  [DOI]
26.  Yuen MF, Wong DK, Fung J, Ip P, But D, Hung I, Lau K, Yuen JC, Lai CL. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology. 2008;135:1192-1199.  [PubMed]  [DOI]
27.  Matsue K, Kimura S, Takanashi Y, Iwama K, Fujiwara H, Yamakura M, Takeuchi M. Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Cancer. 2010;116:4769-4776.  [PubMed]  [DOI]
28.  Kim SJ, Hsu C, Song YQ, Tay K, Hong XN, Cao J, Kim JS, Eom HS, Lee JH, Zhu J. Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: analysis from the Asia Lymphoma Study Group. Eur J Cancer. 2013;49:3486-3496.  [PubMed]  [DOI]
29.  Hsu C, Tsou HH, Lin SJ, Wang MC, Yao M, Hwang WL, Kao WY, Chiu CF, Lin SF, Lin J. Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hepatology. 2014;59:2092-2100.  [PubMed]  [DOI]
30.  Hammond SP, Borchelt AM, Ukomadu C, Ho VT, Baden LR, Marty FM. Hepatitis B virus reactivation following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1049-1059.  [PubMed]  [DOI]
31.  Ceneli O, Ozkurt ZN, Acar K, Rota S, Aki SZ, Yeğin ZA, Yağci M, Ozenirler S, Sucak GT. Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients. World J Gastroenterol. 2010;16:1765-1771.  [PubMed]  [DOI]
32.  Viganò M, Vener C, Lampertico P, Annaloro C, Pichoud C, Zoulim F, Facchetti F, Poli F, Scalamogna M, Deliliers GL. Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011;46:125-131.  [PubMed]  [DOI]
33.  Seto WK, Chan TS, Hwang YY, Choi O, Wong DK, Fung J, Lie AK, Lai CL, Kwong YL, Yuen MF. Interim analysis of hepatitis B reactivation in patients with prior HBV exposure undergoing hematopoietic stem cell transplant: a prospective study (abstract). Hepatology. 2013;58:650A.  [PubMed]  [DOI]
34.  Lee YH, Bae SC, Song GG. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol. 2013;31:118-121.  [PubMed]  [DOI]
35.  Peng JW, Lin GN, Xiao JJ, Jiang XM. Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy. Asia Pac J Clin Oncol. 2012;8:356-361.  [PubMed]  [DOI]
36.  European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167-185.  [PubMed]  [DOI]
37.  Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661-662.  [PubMed]  [DOI]
38.  Zurawska U, Hicks LK, Woo G, Bell CM, Krahn M, Chan KK, Feld JJ. Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis. J Clin Oncol. 2012;30:3167-3173.  [PubMed]  [DOI]
39.  Yeo W, Chan PK, Ho WM, Zee B, Lam KC, Lei KI, Chan AT, Mok TS, Lee JJ, Leung TW. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol. 2004;22:927-934.  [PubMed]  [DOI]
40.  Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519-528.  [PubMed]  [DOI]
41.  Huang H, Li X, Zhu J, Ye S, Zhang H, Wang W, Wu X, Peng J, Xu B, Lin Y. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312:2521-2530.  [PubMed]  [DOI]
42.  Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.  [PubMed]  [DOI]
43.  Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678-686.  [PubMed]  [DOI]
44.  Huang YH, Hsiao LT, Hong YC, Chiou TJ, Yu YB, Gau JP, Liu CY, Yang MH, Tzeng CH, Lee PC. 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;31:2765-2772.  [PubMed]  [DOI]
45.  Shen LP, Zhang Y, Wang F, Zhang S, Yang JY, Fang KX, Yu T, Wang XY, Zhang WY, Bi SL. Epidemiological changes in hepatitis B prevalence in an entire population after 20 years of the universal HBV vaccination programme. Epidemiol Infect. 2011;139:1159-1165.  [PubMed]  [DOI]
46.  Zhang H, Li Q, Sun J, Wang C, Gu Q, Feng X, Du B, Wang W, Shi X, Zhang S. Seroprevalence and risk factors for hepatitis B infection in an adult population in Northeast China. Int J Med Sci. 2011;8:321-331.  [PubMed]  [DOI]