Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients

In parts of Asia, about 10% of the population have chronic hepatitis B virus (HBV) infection, and cancer patients who are HBV carriers are frequently complicated by HBV reactivation while receiving cytotoxic chemotherapy. The condition may result in varying degrees of liver damage, causing disruption in chemotherapy and compromising the patients prognosis. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Recent reports have suggested that the anti-viral agent, lamivudine, may reduce HBV reactivation and its associated morbidity. However, most studies are based on small series of lymphoma patients, while information on the other high risk population, namely breast cancer patients, has been lacking. In this study, we studied the role of lamivudine in preventing HBV reactivation and its associated morbidity in breast cancer patients with chronic HBV infection who were planned for chemotherapy. Two groups were studied. One group consisted of 31 patients who received prophylactic lamivudine prior to and until 8 weeks after discontinuing chemotherapy. The other comprised of 61 historical controls who underwent chemotherapy without prophylactic lamivudine. The outcomes, in terms of the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity during chemotherapy were compared. The results revealed that in the prophylactic lamivudine group, despite a significantly higher proportion receiving anthracyclines, there was significantly fewer incidences of hepatitis (12.9 vs. 59.0%, p < 0.001), less HBV reactivation (6.5. vs. 31.1%, p=0.008), and less disruption of chemotherapy (16.1% vs. 45.9%, p=0.006). We conclude that prophylactic lamivudine significantly reduces the incidence of HBV reactivation and the overall morbidity of breast cancer patients undergoing chemotherapy.     

A single-center, prospective and randomized controlled study: Can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy?

Over the past four decades, chemotherapy has played an important role in prolonging survival in breast cancer patients. However, it may also result in undesirable side effects such as hepatitis B virus (HBV) reactivation seen in this study. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Several strategies use lamivudine to deal with this problem. Initially, lamivudine had been used to treat patients who developed alanine transaminase elevation attributable to HBV reactivation during chemotherapy. However, using this strategy, fatal reactivation has also been reported. Later studies have suggested that prophylactic lamivudine significantly reduces HBV reactivation and its associated morbidity. However, these studies were based mainly on patients with lymphoma, whereas studies on breast cancer patients were few. Moreover, these studies were retrospective. Recently, a prospective study has recommended that deferred preemptive lamivudine could be a comparable alternative to the prophylactic strategy. However, it was not a randomized controlled study. In this study, it was examined the efficacy of the prophylactic strategy in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy using a prospective, randomized controlled study. Two groups were studied. One group consisted of 21 patients who were treated with prophylactic lamivudine, the other group consisted of 21 patients who were not treated with prophylactic lamivudine. The results showed that the prophylactic lamivudine strategy significantly decreased the incidence of HBV reactivation (0 vs. 28.6%, P = 0.021). It was conclude that the prophylactic lamivudine strategy significantly reduces the incidence of HBV reactivation for hepatitis B s-antigen seropositive breast cancer undergoing chemotherapy.     

Lamivudine prophylaxis reduces the incidence and severity of hepatitis in hepatitis B virus carriers who receive chemotherapy for lymphoma

BACKGROUND: Hepatitis B virus (HBV) infection is a common disease in China. Severe hepatitis is a well recognized complication in HBV carriers with malignant disease who receive cytotoxic chemotherapy. The objective of the current study was to assess the value of antiviral lamivudine for reducing the incidence and severity of hepatitis in HBV carriers with lymphoma who receive chemotherapy. METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group was comprised of 40 patients who received oral lamivudine at a dose of 100 mg daily before and until at least 8 weeks after they discontinued chemotherapy. The historic control group was comprised of 116 patients who received chemotherapy without lamivudine. The incidence and severity of hepatitis and other adverse clinical outcomes were compared between the two groups. Significant prognostic factors for the development of hepatitis were determined based on data derived from the control group. RESULTS: The two groups were comparable in most clinical baseline characteristics, including gender distribution, age, tumor types, primary treatment, hepatitis Be antigen status, and the use of anthracyclines or/and prednisone. In the prophylactic lamivudine group, there was significantly less incidence of hepatitis (17.5% vs. 51.7% in the control group; P = 0.000); less severe hepatitis (according to World Health Organization [WHO] criteria) (10% with Grade 1, 5% with Grade 2, and 2.5% with Grade 3 hepatitis vs. 3.4% with Grade 1, 12.1% with Grade 2, 12.9% with Grade 3, and 23.3% with Grade 4 hepatitis in the control group; P = 0.000); and less disruption of chemotherapy (10.0% vs. 37.1% in the control group; P = 0.001). The overall mortality as a result of hepatitis in the prophylactic lamivudine group was lower compared with that in the control group, but the difference was not statistically significant (0.0% vs. 5.2%; P = 0.163). In the control group, the factor associated with a greater risk of developing hepatitis was the use of prednisone. In the prophylactic lamivudine group, 1 of 40 patients (2.5%) developed hepatitis that was attributable to HBV reactivation. Further examination demonstrated that this single patient had a variation of HBV with YMDD mutations after the use of lamivudine for 9.2 months. CONCLUSIONS: The results of the current study confirmed previous reports that lamivudine prophylaxis significantly reduced the incidence and severity of hepatitis in HBV carriers who were receiving chemotherapy for lymphoma. The chemotherapy disruption rate as a result of severe hepatitis also was decreased significantly.     

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy

Background:

With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy.

Methods:

The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed.

Results:

From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14% P=0.04), and less severe hepatitis (0 vs 17% P=0.002).

Conclusion:

Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.     

拉米夫定对HBV—DNA阳性恶性肿瘤患者化疗所致HBV再激活的预防作用评价

目的：探讨拉米夫定对HBV—DNA阳性恶性肿瘤患者化疗所致HBV再激活的预防作用。方法：选择HBV—DNA阳性恶性肿瘤患者60例,分成两组,即试验组与对照组各30例。试验组在化疗前2周给予拉米夫定（100mg口服,qd,直至化疗结束后8周）。预防性治疗,观察化疗前后HBV—DNA水平变化情况,并与对照组比较。结果：试验组化疗后出现肝功能损害12例（40％）,HBV—DNA均〈10^4copies／ml,仅有1例HBV再激活。对照组肝功能损害23例（76．7％）,HBV—DNA〉10^4copies／ml22例（73．3％）,〉10^9copies／ml8例（26．7％）,其中有7例（23．3％）HBV再激活。试验组HBV再激活率明显低于对照组（3．3％VS23．3％,P〈0．05）,且肝功能损害率亦较低（40％VS76．7％,P〈0．05）。结论：拉米夫定可以有效预防和治疗HBV再激活,对防治HBV—DNA阳性的恶性肿瘤患者化疗所致肝损害有较好的效果。     

拉米夫定预防B细胞非霍奇金淋巴瘤患者利妥昔单抗化疗后乙型肝炎病毒再激活的临床分析

 【摘要】　目的　研究利妥昔单抗联合化疗治疗B细胞非霍奇金淋巴瘤（B-NHL）合并乙型肝炎病毒（HBV）携带患者的安全性,探讨拉米夫定预防性治疗的价值。方法　回顾性分析含利妥昔单抗联合化疗前后B-NHL患者乙型肝炎五项、HBV-DNA和肝功能指标变化。将39例HBV核心抗体（HBcAb）（+）／HBV表面抗体（HBsAb）（-）的B-NHL患者分为拉米夫定预防组和对照组,比较两组化疗后HBV再激活、肝功能损害等指标。结果　108例接受利妥昔单抗联合化疗的B-NHL患者中,15例患者为HBV表面抗体（HBsAg）（+）,占所有患者的13.89 %;39例为HBsAg（-）／HBcAb（+）患者,占所有患者的36.11 %。15例HBsAg（+）的患者中HBV再激活率为13.3 %,13例拉米夫定预防患者中1例（7.7 %）HBV再激活,2例未预防的患者中1例HBV再激活。39例HBsAg（-）／HBcAb（+）患者中HBV再激活率为7.7 %（3例）,14例拉米夫定预防组HBV再激活率为0,25例未预防的患者中3例（12 %）HBV再激活。结论　B-NHL合并HBV携带患者在利妥昔单抗联合化疗导致HBV再激活的风险是可控的,预防性使用拉米夫定能明显降低HBV再激活。     

The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy

The association of prolonged rituximab therapy and hepatitis B virus (HBV) reactivation in diffuse large B-cell lymphoma (DLBCL) and the role of lamivudine prophylaxis remain undefined. The prevalence and mortality of HBV reactivation in HBsAg-positive patients with DLBCL undergoing rituximab-based treatment, who received prophylactic treatment with or without lamivudine, were retrospectively analyzed. From January 2003 to December 2009, there were 50 patients enrolled in the study, among of which 30 received the prophylactic treatment of lamivudine and 20 without prophylactic treatment of lamivudine. Among of the 50 patients, seven patients received further rituximab maintenance, once every 3 months for 2 years. Compared with lamivudine treatment group, it showed that there was significantly higher prevalence of HBV reactivation (60.0% vs 13.3%, P = .001), severe hepatitis (45.0% vs 6.7%, P = .004), and mortality (25.0% vs 3.3%, P = .032) in non-lamivudine prophylactic group; however, there was no statistically significant difference in the HBV DNA levels at reactivation (3.94 × 10⁶ vs 8.30 × 10⁵ copies/ml, P = .47) and the time from first dose of rituximab to HBV reactivation(207 vs 386 days, P = .28). For patients undergoing further rituximab maintanence treatment, the prevalence and mortality of HBV reactivation were 71.4 and 28.6%, respectively. The prevalence and mortality of HBV reactivation are 66.7% vs 75.0% (P = 1.00) and 0 vs 50.0% (P = .43) in lamivudine prophylactic and non-lamivudine prophylactic groups, respectively. The effect of lamivudine prophylaxis on preventing HBV reactivation was found to be less in patients undergoing longer duration of rituximab treatment. A longer duration of rituximab treatment contributed to higher morbidity and mortality of HBV reactivation in HbsAg-positive patients with DLBCL. Further study is warranted for the optimal management of hepatitis caused by HBV reactivation     

Why, when, and how to prevent hepatitis B virus reactivation in cancer patients undergoing chemotherapy

Hepatitis B virus (HBV) reactivation is a serious clinical problem in HBV carriers undergoing chemotherapy. The clinical course of HBV reactivation can be separated into 2 phases: 1) an increase in HBV replication and 2) hepatic injury. Patients with resolved HBV infections (negative for hepatitis B surface antigen [HBsAg], and positive for both hepatitis B core antibody [anti-HBc] and/or hepatitis B surface antibody) can experience HBV reactivation, and Western guidelines recommend that not only HBsAg but also anti-HBc be screened before initiation of chemotherapy or immunosuppressive therapy. Several meta-analyses have repeatedly confirmed the prophylactic role of lamivudine in preventing HBV reactivation. In conclusion, screening for HBV is required before chemotherapy, and prophylactic antiviral therapy can reduce not only the incidence of HBV reactivation but also HBV-related morbidity and mortality.     

拉米呋定预防化疗中乙型肝炎活动的临床分析

目的:分析研究合并乙型肝炎病毒(HBV)感染的肿瘤患者预防应用拉米呋定是否减少化疗中乙型肝炎病毒再活化。方法:回顾性分析本科2000年2月～2005年8月收治的39例合并HBV感染的需化疗的乳腺癌、非小细胞肺癌、非霍杰金淋巴瘤(NHL)和骨肉瘤患者的治疗方法,按是否从化疗前1周开始口服拉米呋定分为:治疗组18例,对照组21例。前者口服拉米呋定,至化疗后6个月。比较化疗后肝功能损害、急性肝炎、HBV再活化和化疗延迟等指标的变化。结果:两组比较,治疗组肝功能损害发生率无显著性差异(55.6%vs.42.9%,P=0.429),急性肝炎发生率明显下降(11.1%vs.57.1%,P=0.006),HBV再活化发生率下降(5.6%vs.38.1%,P=0.023),而化疗延迟发生率下降(16.7%vs.61.9%,P=0.008)。结论:预防性口服拉米呋定可能可以有效抑制HBV复制和肝炎活动,值得进一步研究。     

Prophylactic effect of lamivudine on chemotherapy‐induced hepatitis B virus reactivation in patients with solid tumour: A meta‐analysis

Hepatitis B virus (HBV) reactivation is a remarkable risk during the chemotherapy for solid tumour patients. Nucleos(t)ide analogues (NAs) are recommended as prophylaxis for the reactivation of HBV infection in some cancer patients prior to systemic chemotherapy. Therefore, we performed a meta‐analysis aiming to determine the efficacy of prophylactic lamivudine on prevention of HBV reactivation and its related negative outcomes among solid tumour patients with chronic HBV infection receiving systemic chemotherapy. The primary outcome was HBV reactivation, and the secondary outcomes were HBV‐related hepatitis, chemotherapy disruption, mortality and tyrosine‐methio‐nine‐aspartate‐aspartate (YMDD) mutations. Twelve original researches involving 1,101 patients were analysed in this study. The relative risk of HBV reactivation in patients with lamivudine prophylaxis was significantly lower than that without prophylaxis (RR = 0.17, 95% CL: 0.10‐0.29, p < .00001). Lamivudine prophylaxis reduced the relative risk of hepatitis (p < .00001), chemotherapy disruptions (p = .01) and mortality (p = .08) due to HBV reactivation. Lamivudine prophylaxis is effective in reducing HBV reactivation and its related negative outcomes, such as hepatitis and chemotherapy disruption and mortality among chemotherapeutic solid tumour patients with chronic HBV infection. Future studies should lay more emphasis on the early HBV screening, mode of treatment and duration of NAs prophylaxis among solid tumour patients receiving chemotherapy.     

乙肝病毒感染与肺癌患者化疗后肝功能损害的相关性研究

  目的  探讨化疗引起的肺癌患者肝功能损害与乙肝病毒感染的相关性及抗病毒治疗在预防化疗引起的HBV再激活中的作用。  方法  收集2008年1月至2009年12月在中山大学附属肿瘤医院经病理确证的肺癌患者636例, 比较HBsAg阴性(466例)和HBsAg阳性(170例)患者化疗后肝功能损害的发生情况, 并分析在HBsAg阳性患者中, 预防性使用(33例)与未预防性使用(43例)抗病毒药物拉米夫定后乙肝病毒再激活率的差异。  结果  化疗后出现肝功能损害的肺癌患者中, HBsAg阳性(29.4%)与HBsAg阴性患者(15.2%)所占比例的差异有统计学意义(P < 0.001)。化疗前预防性使用(3.0%)与未预防性使用(20.9%)拉米夫定, 患者出现HBV再激活率的差异亦有统计学意义(P=0.022)。  结论  肺癌患者化疗后, HBsAg阳性患者较HBsAg阴性患者更易出现肝功能损害, 预防性使用核苷类似物抗病毒药物拉米夫定, 可明显降低肺癌合并乙肝患者化疗后HBV再激活肝炎的发生。      

An optimized antiviral modification strategy for prevention of hepatitis B reactivation in patients undergoing prophylactic lamivudine and chemotherapy: a pilot study

In patients receiving prophylactic lamivudine (LAM) and chemotherapy, hepatitis B virus (HBV) reactivation cannot be eliminated without knowing the latent causes and optimal management. In our previous study, virus breakthrough and relapse were highly suspected as potential virologic causes for HBV reactivation. Therefore, we reviewed 24 previous studies and 447 patients who underwent chemotherapy and prophylactic LAM, with an incidence of 7.2 % HBV reactivation. Virus breakthrough and relapse were seldom investigated in these studies. In addition, 72 patients that underwent prophylactic LAM and chemotherapy at our centers were also analyzed. Among them, eight patients developed virus breakthrough, with another nine developing virus relapse after discontinuation of LAM. Eight patients received antiviral modification, which included administration of adefovir for patients with virus breakthrough or resumption of LAM for patients with virus relapse and none of them developed HBV reactivation. In contrast, of the nine patients who did not receive antiviral modification, six developed HBV reactivation and two died. In conclusion, this study demonstrated that virus breakthrough and relapse were the critical causative factors of HBV reactivation in patients receiving chemotherapy and prophylactic LAM. An optimized antiviral modification strategy could effectively prevent HBV reactivation in patients with virus breakthrough or relapse.     

Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriers: a review of the problem.

In places where hepatitis B virus (HBV) infection is endemic, it is often necessary to give chemotherapy to or perform bone marrow transplantation for cancer patients who are also chronic HBV carriers. When standard chemotherapy was given to lymphoma patients, elevation of liver transaminases was observed in nearly half of those who were chronic HBV carriers. Ten percent of them became jaundiced, and the overall liver-related mortality was about 5%. There is currently no reliable way to predict the severity of HBV reactivation after chemotherapy. The risk is probably higher when the chemotherapy used is significantly immunosuppressive and the viral load in the liver is high. Different strategies have been used in an attempt to reduce the risk of HBV reactivation after chemotherapy, but they have not been very successful. Further studies will be required to determine the impact of newly available antiviral agents that are active against HBV. Recipients who are carriers of HBV or who receive hepatitis B surface antigen (HBsAg)-positive marrow are at increased risk of hepatitis B-related morbidity and mortality after bone marrow transplantation (BMT). There is evidence to suggest that prophylactic use of an active antiviral agent, such as famciclovir, may result in a significant decrease in the incidence and severity of HBV reactivation after BMT. Sustained serologic clearance of chronic HBV infection has also been reported in many HBsAg-positive marrow recipients receiving hepatitis B surface antibody-positive marrow from their allogeneic donors. There seems to be a transfer of both humoral and cellular immunity against HBV from donors to recipients. Further prospective studies are required to define the best approach to manage HBsAg-positive cancer patients receiving chemotherapy or BMT. It is recommended that all cancer patients be checked for their hepatitis B status before receiving chemotherapy or a bone marrow transplant, especially if they reside in or come from endemic areas of HBV infection.     

长、短疗程口服抗病毒药预防急性髓系白血病患者乙型肝炎病毒再激活的观察研究

背景与目的：乙型肝炎病毒(hepatitis B virus,HBV)再激活是急性髓系白血病(acute myeloid leukemia,AML)合并HBV感染的患者接受诱导和巩固化疗期间严重并发症之一,核苷类抗HBV药物(包括拉米夫定和恩替卡韦等)已成为预防和抢先治疗HBV再激活主要抗病毒药物。该研究观察并探究AML合并HBV感染患者化疗前后长疗程和短疗程口服核苷类抗HBV药物预防病毒再激活的临床疗效和安全性。方法：回顾性分析29例AML合并HBV感染并接受至少4个疗程化疗患者的临床资料。根据患者口服核苷类抗HBV药物预防治疗前HBV表面抗原(hepatitis B surface antigen,HBsAg)含量以及抗HBV药物持续服用时间分为4个亚组,系统分析和比较不同亚组患者HBV再激活情况和药物不良反应。结果：长疗程预防(long course prophylaxis group,LCP)组,即口服抗HBV药物持续至化疗结束后6个月以上,该组患者的HBV再激活率和HBV相关性肝炎发生率分别为5.56%(1/18)和0%(0/18),明显低于短疗程预防(short course prophylaxis group,SCP)组患者(即口服抗HBV药物持续至化疗结束后1个月以内)的45.45%(5/11)和36.36%(4/11),差异有统计学意义(P=0.018和P=0.014),而LCP和SCP组患者的HBV原发耐药率分别为11.11%(2/18)和9.09%(1/11),差异无统计学意义(P>0.05)。进一步亚组分析显示,预防治疗前HBsAg阳性患者(HBsAg大于等于0.05 IU/mL)经长疗程预防,其HBV再激活率和HBV相关性肝炎发生率分别为8.33%(1/12)和0%(0/12),明显低于SCP组,66.67%(4/6)和66.67%(4/6),差异有统计学意义(P=0.022和P=0.005);同时,LCP和SCP组中HBsAg(+)患者的HBV原发耐药率分别为8.33%(1/12)和16.67%(1/6),差异无统计学意义(P>0.05)。此外,LCP组中HBsAg阴性患者(HBsAg小于0.05 IU/mL)的HBV再激活率、肝炎发生率和原发耐药率与SCP组中HBsAg(-)患者比较,差异无统计学意义(P>0.05)。LCP和SCP组患者均未发生3级以上药物毒性反应。结论：长疗程口服核苷类抗HBV药物是降低AML合并HBsAg(+)感染患者化疗后病毒再激活以及病毒相关事件发生率有效而且安全性良好的预防治疗方案。     

Hepatitis B virus reactivation and role of antiviral prophylaxis in lymphoma patients with past hepatitis B virus infection who are receiving chemoimmunotherapy

BACKGROUND:

Individuals who had past hepatitis B virus (HBV) infection appeared to clear their serum hepatitis B surface antigen (HBsAg) while producing antibody to the hepatitis B core antigen (HBcAb), which is detectable in their serum. Currently, it is uncertain whether patients with past HBV infection require routine antiviral prophylaxis during chemotherapy, although some cancer agencies recommend its routine use. The objective of the current study was to determine the prevalence of past HBV infection in patients with lymphoma and its relevance in terms of HBV‐related complications.

METHODS:

The authors reviewed 430 patients with lymphoma from May 2006 to May 2008.

RESULTS:

Among the 430 patients, 233 had both the HBsAg and HBcAb tests performed, whereas 197 had only the HBsAg test performed. Among those with both tests performed, 34.3% (80 of 233) were HBcAb positive only. Of these 80 patients, 58 had a concomitant HBV DNA level test, which was positive in 3 (5.2%). Of the 67 patients with past and 26 with chronic HBV infection who received chemotherapy, HBV reactivation occurred in 1.5% and 42.3% of patients, respectively (P<.0001). Prophylactic lamivudine was administered in 7 (10.4%) patients with past HBV infection and in 18 (69.2%) with chronic HBV infection.

CONCLUSIONS:

The low rate of HBV reactivation reported in our study coupled with the high prevalence of past HBV infection in an endemic area suggests that routine usage of antiviral prophylaxis may not be required for all patients with past HBV infection. Close surveillance remains a reasonable and viable option for the majority of patients. Cancer 2010. © 2010 American Cancer Society.     

The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients with diffuse large B‐cell lymphoma

We performed a retrospective study to analyse the characteristics and clinical outcomes of diffuse large B‐cell lymphoma (DLBCL) patients with hepatitis B virus (HBV) infection and compare with those without HBV infection. The occurrence of hepatitis after withdrawal of prophylactic antiviral treatment on completion of chemotherapy was also assessed. The HBsAg‐positive patients were given prophylactic antiviral treatment until 6 months after finishing chemotherapy. A total of 81 patients were recruited with 16 in the HBsAg‐positive group and 65 in the HBsAg‐negative group. The clinical characteristics were similar in both groups of patients. There was no significant difference in complete remission rate between the two groups (63% in HBsAg‐positive group vs. 54% in HBsAg‐negative group, P = 0.59). There was also no statistically significant difference in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg‐positive patients (25%) had hepatitis after cessation of chemotherapy and prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after stopping lamivudine. In conclusion, HBV infection did not appear to affect the prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to consider prophylactic antiviral therapy to extend to at least one year on completion of chemotherapy.     

Lamivudine prophylaxis for hepatitis B virus carrier patients with breast cancer during adjuvant chemotherapy

Background

This study aimed to assess the efficacy of lamivudine prophylaxis on hepatic complications in HBsAg-positive patients with breast cancer undergoing adjuvant chemotherapy and to describe the temporal trend in HBV surveillance and prophylaxis during the last decade.

Methods

Patients with stage I–III curatively resected invasive breast cancer who received adjuvant and/or neoadjuvant chemotherapy between 2000 and 2009 were eligible for this study. Patients with positive HBsAg and normal liver function were enrolled. Hepatotoxicity, defined as alanine aminotransferase (ALT) ≥100 IU/ml, and HBV reactivation were compared according to lamivudine prophylaxis. Annual trends in HBV surveillance and use of lamivudine prophylaxis were also reviewed.

Results

One hundred sixty-five HBsAg-positive patients with breast cancer were enrolled. After the year 2004, surveillance of HBV infection status and use of lamivudine prophylaxis increased significantly (2.5 vs. 57.6 %, P < 0.001). Seventy-three (44.2 %) patients received lamivudine prophylaxis and 92 (55.8 %) patients did not. The incidence of hepatotoxicity was significantly lower in the group receiving prophylaxis (2.7 vs. 14.1 %, P = 0.011) with fewer premature terminations of planned adjuvant chemotherapy (0 vs. 10.9 %, P = 0.004) in the prophylaxis group. Among the patients for whom the baseline HBV DNA titer was available, the HBV reactivation rate was lower, albeit not significantly, in the prophylaxis group (0 %) compared with the no prophylaxis group (20 %) (P = 0.104). Lamivudine-withdrawal hepatitis was not detected; however, one case of breakthrough HBV reactivation during lamivudine treatment was observed in this study.

Conclusions

Over the past decade, there has been an increase in the awareness of HBV reactivation and in the use of lamivudine during cytotoxic chemotherapy. Lamivudine prophylaxis reduced hepatic complications during adjuvant chemotherapy in patients with breast cancer. Lamivudine prophylaxis should be considered in HBsAg-positive patients with breast cancer who are candidates for adjuvant chemotherapy.     

Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer

Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with hematologic malignancies and those who undergo hematopoietic stem-cell transplantation. Reported rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14-72%. In these patients, mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation and is usually associated with a good outcome and low mortality. However, once severe hepatitis develops, as a result of viral reactivation, mortality rates seem to be similar among patients infected with HBV or HCV. Liver damage owing to viral reactivation frequently leads to modifications or interruptions of chemotherapy, which can negatively affect patients' clinical outcome. Risk factors for the development of severe HBV or HCV reactivation need to be better defined to permit identification of patients who may benefit from preventive measures, early diagnosis, and therapy. In this article, we review the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with reactivation of HBV and HCV during immunosuppressive therapy. We also discuss strategies for the prevention and treatment of viral reactivation, including the management of reactivation with new antiviral agents.     

Lamivudine and glycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma

We report a chronic hepatitis B virus (HBV) carrier with non-Hodgkin lymphoma (NHL) who developed HBV hepatitis following conventional dose chemotherapy and was successfully treated with lamivudine and glycyrrhizin. A 55 year-old male patient with primary testicular NHL (diffuse large B-cell type) relapsed. During the salvage chemotherapy, the patient showed elevated serum levels of transaminase and HBV-DNA due to HBV reactivation. Treatment with lamivudine, an antiviral nucleoside analog, was started at a dose of 100mg/day. Shortly after the treatment the HBV-DNA level was suppressed, and sustained elevation of transaminase levels were normalized after additional treatment with glycyrrhizin. This experience suggests that lamivudine combined with glycyrrhizin may be effective for controlling HBV replication and treating chemotherapy-induced HBV hepatitis in chronic HBV carriers with NHL.     

HBsAg阴性HBcAb阳性肿瘤患者化疗后HBV再激活3例报道并文献复习

目的：探讨乙肝表面抗原（HBsAg）（-）核心抗体（HBcAb）（+）肿瘤患者化疗后引起乙型肝炎病毒（HBV）再激活的治疗与监控。方法：报道3例HBsAg（-）HBsAg（+）的肿瘤患者化疗过程中出现HBV再激活的病例,针对可行的治疗监控措施进行文献复习。结果：1例最初乙肝表面抗体（HBsAb）（+）、HBcAb（+）的非霍奇金淋巴瘤（NHL）患者经过多次化疗后转变为HBsAg（+）、e抗原（HBeAg）(+)、HBcAb（+）;1例乙肝e抗体（HBsAb）（+）、HBcAb(+)的霍奇金淋巴瘤（NL）患者化疗后乙肝模式未改变,乙肝病毒载量（HBV-NDA）定量结果增高;1例HBsAb(+)、HBeAb(+)、HBcAb(+)的肝癌患者性肝动脉化疗栓塞术（TACE）后出现HBV-DNA定量结果增高。3例HBsAg(-)患者化疗后均出现HBV再激活,经抗病毒治疗后获得良好转归。结论：不仅对于HBsAg（+）的患者,对于即使处于康复期的既往有急性或慢性乙肝病史的HBsAg(-)、HBcAb（+）患者,在应用化疗或免疫抑制剂治疗时均需严密监测血清HBsAg、肝功能及HBV-DNA定量的动态变化,必要时实施预防性抗病毒治疗,以免中止原有治疗计划延误病情。