Published online Feb 14, 2013. doi: 10.3748/wjg.v19.i6.923
Revised: November 21, 2012
Accepted: December 5, 2012
Published online: February 14, 2013
AIM: To estimate hepatitis B virus (HBV) infection testing rate in cancer patients before chemotherapy with a focus on HBV reactivation.
METHODS: A retrospective study was conducted from January 1, 2009 to June 30, 2010. Inclusion required that patients be naïve to cancer chemotherapy but have indications for it. Patients who did not receive chemotherapy for any reason were excluded. Important clinical information, such as the levels of HBV DNA and serological markers were collected. HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline, or serum HBV DNA conversion from negative to positive. HBV DNA levels > 1000 copies/mL were defined as HBV DNA positive. The χ2 or Fisher’s exact test was used for analysis of categorized data. Multiple logistic regression analysis was used to estimate the odd ratio and 95%CI of the HBV screening rate.
RESULTS: Of 6646 patients, 5616 (84.5%) received chemotherapy. Only 17.1% of the cancer patients received pre-chemotherapy HBV testing (43.2% for hematological malignancies and 14.9% for solid tumors). Patients who had received rituximab therapy, had elevated aminotransferase levels, or had hematological malignancies were more likely to receive HBV testing. The prevalence of hepatitis B surface antigen (HBsAg) positivity was 13.4%. HBV reactivation (appearance of HBV DNA or an increase in HBV DNA levels by 1 log10) was observed in 33.1% (53/160) of the patients after chemotherapy. Among patients without prophylactic antiviral therapy, the reactivation rate was 43.9% (43/98) in the solid tumor group. Two reactivation cases occurred in patients who were HBsAg negative, but positive for hepatitis B core antibody. HBV reactivation was more likely to occur in patients with lymphoma, high levels of HBV DNA, or hepatitis B e antigen, and in men.
CONCLUSION: Less than 20% of patients received HBV testing before chemotherapy. HBV reactivation would have occurred in about 50% of infected patients with solid tumors without antiviral prophylaxis.
- Citation: Wang Y, Luo XM, Yang D, Zhang J, Zhuo HY, Zhang J, Jiang Y. Testing for hepatitis B infection in prospective chemotherapy patients: A retrospective study. World J Gastroenterol 2013; 19(6): 923-930
- URL: https://www.wjgnet.com/1007-9327/full/v19/i6/923.htm
- DOI: https://dx.doi.org/10.3748/wjg.v19.i6.923
Hepatitis B virus (HBV) infection is a global health problem. According to estimates of the World Health Organization, nearly 2 billion people worldwide have been infected with HBV, and > 350 million have chronic infection[1]. Hepatitis B is endemic in China, and the weighted prevalence of hepatitis B surface antigen (HBsAg) for the Chinese population is 7.2%[2]. Cancer patients receiving intensive chemotherapy may be at risk for HBV reactivation[3-8]. A previous study has reported that the reactivation rate of HBV infection after chemotherapy was as high as 73%[8]. It has been observed in a meta-analysis that the average reactivation rate of HBV infection was nearly 34% (162/475 patients), and the mortality rate was about 7% (27/394 patients)[9]. HBV reactivation might lead to a delay in chemotherapy, therefore, antiviral therapy should be administered immediately[3]. However, this might affect the efficacy of chemotherapy.
Corticosteroids, monoclonal antibodies (such as rituximab and alemtuzumab), and nearly all types of chemotherapeutic agents have been involved in HBV reactivation[5]. A diagnosis of lymphoma is another risk factor for HBV reactivation[4]. A multivariate analysis has revealed that patients with lymphoma or breast cancer are more likely to develop HBV reactivation after chemotherapy[10].
Recently, more attention has been paid to HBV testing before chemotherapy. Many clinical practice guidelines, such as the associated guidelines of the European Association for the Study of Liver Disease (EASL) and the American Association for the Study of Liver Diseases, advise HBV testing before starting chemotherapy[11,12]. The United States Centers for Disease Control and Prevention (CDC) also recommend testing for chronic HBV infection in cancer patients receiving chemotherapy[13]. It has been reported in recent years that the HBV infection testing rates before chemotherapy in Canada and the United States were 14%[14] and 16.7%[15], respectively. However, to the best of our knowledge, few studies have focused on this issue in a high endemic region of HBV infection such as China.
The aim of this study was to assess the rate of HBV serological testing prior to initiation of chemotherapy and the rate of HBV reactivation after chemotherapy in cancer patients in China.
From January 1, 2009 to June 30, 2010, all cancer patients who were seen in the Cancer Center of West China Hospital were analyzed. Inclusion in this study required that patients be naïve to cancer chemotherapy but have indications for it. Patients who did not receive chemotherapy for any reason were excluded. This study was approved by the Institutional Review Board of West China Hospital and carried out according to the provisions of the Helsinki Declaration.
A retrospective study of the chart information on cancer patients was undertaken. HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline, or serum HBV DNA conversion from negative to positive[16]. In our center, HBV DNA levels > 1000 copies/mL were defined as HBV DNA positive. Important clinical information, such as the levels of HBV DNA and serological markers [including HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), HBeAg antibody and hepatitis B core antibody (anti-HBc)], were collected and measured by a microparticle enzyme-linked immunosorbent assay (Santa Cruz Biotechnology, CA, United States). All hepatitis B serological marker results were reported as positive or negative. EASL guidelines recommend that all patients requiring chemotherapy be tested for HBsAg and anti-HBc prior to initiation of treatment[11], therefore, the presence of either HBsAg-positive or isolated anti-HBc-positive results was defined as positivity for an HBV serological marker (HBV-sm). HBV DNA levels were tested using a real-time polymerase chain reaction detection system (Applied Biosystems, Foster City, CA, United States). Individuals with chronically elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) should be routinely tested for HBV[12], and ALT and AST levels were analyzed using an automatic biochemistry analyzer (Olympus AU5400, Olympus Corporation, Tokyo, Japan). Values for ALT or AST above the upper limit of normal (58 IU/L in our hospital) were defined as elevated.
Frequencies and percentages were used for statistical descriptions. The χ2 or Fisher’s exact test was used for analysis of categorized data. A nonparametric Mann-Whitney/Wilcoxon test or t test was used for analysis of quantitative data. Multiple logistic regression analysis was used to estimate the odd ratio (OR) and 95%CI of the HBV screening rate. All statistical analyses were carried out using SPSS version 18.0 statistical software, and statistical significance was defined as P < 0.05.
From the beginning of January 2009 to the end of June 2010, a total of 6646 cancer patients were reviewed. Among these patients, 5616 (84.5%) received chemotherapy (Figure 1). Combined with other chemotherapeutic agents, rituximab was given to 49 patients (17.4%) and/or steroids were given to 203 (72.2%) patients with hematological malignancies. Patient characteristics are shown in Table 1.
| Characteristics | Hematological malignancy | Solid tumor | Total | |
| (n = 281) | HCC(n = 237) | Others(n = 5098) | (n = 5616) | |
| Age (yr), mean (range) | 50.5 (18-83) | 53.1 (39-67) | 54.4 (41-67) | 54.1 (29-79) |
| Sex | ||||
| Men | 176 (62.6) | 201 (84.8) | 2567 (50.4) | 2944 (52.4) |
| Women | 105 (37.4) | 36 (17.9) | 2531 (49.6) | 2672 (47.6) |
| Surgical history | 22 (7.8) | 6 (2.5) | 2157 (42.3) | 2185 (38.9) |
| History of HBV infection1 | 27 (9.6) | 126 (53.2) | 179 (3.5) | 332 (5.9) |
| Aminotransferase | ||||
| Normal (< 58 IU/mL) | 251 (89.3) | 144 (60.8) | 4816 (94.5) | 5211 (92.8) |
| Elevated | 30 (10.7) | 93 (39.2) | 282 (5.5) | 405 (7.2) |
As shown in Figure 1, 49.3% (2770/5616) patients were screened for HBV before initiation of chemotherapy. The testing rate for patients with hematologic malignancies and solid tumors was 47.7% (134/281) and 49.4% (2636/5335), respectively. However, the reason for HBV serological testing in 2185 patients was not in preparation for chemotherapy, but as a routine check before surgery. Only 17.1% (585/3431) of the cancer patients received pre-chemotherapy HBV testing. The exact pre-chemotherapy testing rate for hematological malignancies and solid tumors was 43.2% (112/259) and 14.9% (473/3172), respectively. As shown in Table 2, in univariate analysis, the characteristics of age > 50 years, male sex, history of HBV infection, rituximab use, elevated aminotransferases, and hematological malignancies were associated with HBV testing. In multiple logistic regression analysis, patients with rituximab therapy (OR: 1.96, 95%CI: 1.04-3.67, P < 0.05), elevated aminotransferase levels (OR: 10.88, 95%CI: 8.01-14.78, P < 0.001), and hematological malignancies (OR: 4.17, 95%CI: 3.10-5.61, P < 0.001) were more likely to have received pre-chemotherapy HBV serological testing.
| No. | Screening n (%) | P value | |
| Age (yr) | < 0.01 | ||
| ≤ 50 | 1215 | 240 (19.8) | |
| > 50 | 2216 | 345 (15.6) | |
| Sex | < 0.05 | ||
| Men | 2031 | 374 (18.4) | |
| Women | 1400 | 211 (15.1) | |
| Rituximab therapya | < 0.01 | ||
| Yes | 49 | 25 (51.0) | |
| No | 3382 | 560 (16.6) | |
| History of HBV infection | < 0.01 | ||
| Yes | 141 | 45 (31.9) | |
| No | 3290 | 540 (16.4) | |
| ALT and/or ASTb | < 0.01 | ||
| Abnormal | 205 | 128 (62.4) | |
| Normal | 3226 | 457 (14.2) | |
| Types of tumorc | < 0.01 | ||
| Hematological | 259 | 112 (43.2) | |
| Solid | 3172 | 473 (14.9) | < 0.05 |
| Liver cancer | 78 | 18 (23.1) | |
| Others | 3094 | 455 (14.7) |
The prevalence of HBsAg positivity was 13.4%. The prevalence of HBV-sm positivity was 23.7%. The prevalence of HBsAg positivity (P < 0.001) and HBsAg and/or anti-HBc positivity (P < 0.001) in the male patients were significantly higher than in the female patients. In patients < 20 years old, the rate of HBV-sm positivity was significantly lower than in patients in the older age group (P < 0.001) (Table 3).
| No. | HBsAg+ | HBsAb+ | HBeAg+ | HBeAb+ | Isolated HBcAb+ | HBV-sm positive1 | Screening HBV DNA2 | |
| Total | 2770 | 372 (13.4) | 1367 (49.4) | 43 (1.6) | 600 (21.7) | 284 (10.3) | 656 (23.7) | 177 (27.0) |
| Age (yr) | ||||||||
| ≤ 20 | 27 | 2 (7.4) | 14 (51.9) | 1 (3.7) | 2 (7.4) | 1 (3.7) | 3 (11.1) | 1 (33.3) |
| >20 | 2743 | 370 (13.5) | 1353 (49.3) | 42 (1.5) | 598 (21.8) | 283 (10.3) | 653 (23.8) | 176 (27.0) |
| Sex | ||||||||
| Women | 1495 | 144 (9.6) | 780 (52.2) | 15 (1.0) | 280 (18.7) | 146 (9.8) | 290 (19.4) | 52 (17.9) |
| Men | 1275 | 228 (17.9) | 587 (46.7 | 28 (2.2) | 320 (25.5) | 138 (10.8) | 366 (28.7) | 125 (34.2) |
| Types of tumor | ||||||||
| Hematological | 134 | 21 (15.7) | 51 (38.1) | 3 (2.2) | 26 (19.4) | 7 (5.2) | 28 (20.9) | 23 (82.1) |
| Solid | 2636 | 351 (13.3) | 1316 (49.9) | 40 (1.5) | 574 (21.8) | 277 (10.5) | 628 (23.8) | 154 (24.5) |
| Liver cancer | 177 | 114 (64.4) | 45 (25.4) | 17 (9.6) | 114 (64.4) | 27 (15.3) | 141 (79.7) | 68 (48.2) |
| Others | 2459 | 207 (8.4) | 1271 (41.7) | 23 (0.9) | 114 (64.4) | 250 (10.2) | 487 (19.8) | 84 (3.5) |
Among the 656 patients who were positive for HBV serological markers, 177 (27.0%) received HBV DNA testing and 160 (24.4%) underwent re-examination. The HBV DNA testing rate was significantly higher in the hematological cancer group (P < 0.001). Antiviral therapy (lamivudine) was given to 55.1% (49/89) of the patients who were positive for HBV DNA. All five HBV-DNA-positive patients with hematological malignancies received antiviral therapy, but only 52.4% (44/84) of the HBV-DNA-positive patients with solid tumors were given antiviral therapy (Figure 1 and Table 3).
Two cases of reactivation occurred in HBsAg-negative but anti-HBc-positive patients. One patient had diffuse large B-cell lymphoma while the other had breast cancer. As shown in Figure 1, HBV reactivation was observed in 33.1% (53/160) of patients after chemotherapy. Within the virus-untreated cohort (n = 113), the reactivation rate was 46.0% (52/113 patients). Among the 47 patients who received antiviral therapy, only one case of reactivation (2.1%) occurred. However, HBV reactivation was observed in 60.0% (9/15 patients) in the hematological malignancy group and 43.9% (43/98) in the solid tumor group who had not received any antiviral therapy. The median onset time of HBV reactivation was 11 wk (range: 3-25 wk) after initiation of chemotherapy. HBV reactivation developed earlier (P < 0.001) in patients with lymphoma (9 wk, range: 4-14 wk) than in those with other cancers (15 wk, range: 9-21 wk). HBV reactivation also developed earlier (P < 0.001) in patients receiving CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-like regimens (8 wk, range: 3-15 wk) compared to non-CHOP protocols. Baseline HBV status (positive or negative) was not significantly associated with the time interval between initiation of chemotherapy and onset of HBV reactivation. In multivariate analysis (Table 4), HBV reactivation was more likely to occur in patients with lymphoma, high levels of HBV DNA, HBeAg positivity, and male patients. It was also found that antiviral prophylaxis for patients who were positive for HBV DNA significantly reduced the incidence of chemotherapy-induced HBV reactivation (OR: 0.009, 95%CI: 0.001-0.073, P < 0.001).
| Patients developed HBV reactivation (n = 53) | Patients who did not develop HBV reactivation (n = 107) | P value | |
| Sexa | < 0.05 | ||
| Men | 43 (38.4) | 69 (61.6) | |
| Women | 10 (20.8) | 38 (79.2) | |
| Age (yr), median (range) | 51.5 (24.8-78.2) | 52.9 (27.8-77.9) | |
| Tumor typeb | < 0.05 | ||
| Lymphomas | 10 (55.6) | 8 (44.4) | |
| Solid tumor | 43 (30.3) | 99 (69.7) | |
| Liver cancer | 25 (35.7) | 45 (64.3) | |
| Others | 18 (25.0) | 54 (75.0) | |
| ALT levels, median (range) (normal < 58 IU/mL) | 69.1 (21.9-116.3) | 55.7 (18.2-93.2) | |
| HBeAg statusc | < 0.01 | ||
| Positive | 17 (73.9) | 6 (26.1) | |
| Negative | 36 (26.3) | 101 (73.7) | |
| HBV DNA statusd | < 0.01 | ||
| Positive | 47 (45.2) | 57 (54.8) | |
| Negative | 6 (10.7) | 50 (89.3) | |
| Use of rituximab | < 0.05 | ||
| Yes | 6 (60) | 4 (40) | |
| No | 47 (31.3) | 103 (68.7) | |
| Use of corticosteroids | < 0.05 | ||
| Yes | 8 (61.5) | 5 (38.5) | |
| No | 45 (30.6) | 102 (69.4) | |
| Receiving antiviral therapy | < 0.01 | ||
| Yes | 1 (2.1) | 46 (97.9) | |
| No | 52 (46.0) | 61 (54.0) |
Of the 160 patients who were re-tested for HBV, 13 had received corticosteroids (all patients had lymphoma) and 61.5% (8/13) developed HBV reactivation. In univariate analysis, HBV reactivation was more likely to occur in patients who had received corticosteroids (P = 0.023) and botanical chemotherapeutic drugs (P = 0.048). However, the components of the chemotherapy regimens (including corticosteroids) seemed not to be associated with HBV reactivation in multivariate analysis.
Of 5616 patients, 2679 (47.7%) were tested for hepatitis C virus (HCV). In this group, 305 and 12 patients were HBsAg positive and HCV RNA positive, respectively. Only four out of 305 patients (1.3%) were both HBsAg and HCV-RNA positive, and none of these patients developed HBV reactivation.
In recent years, many organizations have advocated that all chemotherapy candidates should receive HBV serological testing before starting treatment[11-13]. In the present study, it was observed that 49.3% of patients had received HBV serological testing prior to chemotherapy, which was much higher than reports from Canada (14%)[14] and the United States (16.7%)[15]. However, most of the patients were not for HBV infection because of impending chemotherapy, but as part of a preoperative routine (Figure 1). Therefore, only 17.1% of the cancer patients received pre-chemotherapy HBV testing, which is close to the testing rates in other published studies[14,15].
Patients with elevated aminotransferase levels prior to chemotherapy were more likely to be screened for HBV infection (OR: 10.88, P < 0.001). This is reasonable because elevated aminotransferase levels usually indicate liver inflammation, which may lead physicians to screen for HBV as a possible etiology. Guidelines have recommended that individuals with chronically elevated ALT or AST should be routinely screened for HBV infection[12]. However, not all patients with elevated aminotransferases receive HBV testing. It has been reported that only 30%-70% of oncologists screen for HBV infection before chemotherapy in patients with abnormal liver-associated enzymes[17,18]. The testing rate of only 62.4% in the current study is consistent with the data from other studies. The lack of HBV testing might be because some patients without a history of HBV infection had only slightly elevated aminotransferase levels that were insufficiently high to be a contraindication for chemotherapy.
In the current study, a relationship was found between the type of tumor and the rate of HBV serological testing. Patients with hematological malignancies (OR: 4.17, P < 0.001) were more likely to receive HBV testing before chemotherapy. The same phenomenon was also observed in an American study[19], which might be partly because lymphoma is a known risk factor for HBV reactivation[4,10]. Rituximab is a standard treatment for diffuse large B-cell lymphoma. Rituximab treatment was found to be an important indicator associated with HBV testing prior to chemotherapy (OR: 1.96, P = 0.038) in the present study. Testing for HBV infection before anticancer therapy is likely because of the known risk of HBV reactivation after rituximab administration[20].
In the current study, the HBV reactivation rate was found to be 33.1%, which was very close to the average reactivation rate (34%) observed in a prior meta-analysis[9].
The median onset time of HBV reactivation after initiation of chemotherapy was 11 wk (range: 3-25 wk), which was similar to that reported previously (16 wk, range: 4-36 wk)[21]. HBV reactivation was observed to occur earlier in patients with lymphoma and those receiving CHOP-like regimens in the current study. Previous studies have identified many risk factors related to HBV reactivation during anticancer therapy, such as male sex, younger age, absence of anti-HBs, HBeAg seropositivity, diagnosis of lymphoma or breast cancer, high pre-chemotherapy HBV DNA levels, and the use of steroids or rituximab[4,10,20,22]. In addition, it has also been reported that HBV DNA contains a glucocorticoid responsive element that stimulates HBV replication[23,24]. Multivariate analysis in the present study identified high baseline levels of HBV DNA, male patients, HBeAg positivity, and lymphoma to be predictive of HBV reactivation (Table 4). Further study is needed to determine the relationship between HBV reactivation and steroids (including their dose).
HBV reactivation rates were significantly higher in the non-lamivudine group compared with the lamivudine group (46.0% vs 2.1%). Moreover, multivariate analysis identified that antiviral prophylaxis significantly reduced the incidence of chemotherapy-induced HBV reactivation, which has also been reported previously[25-28]. Therefore, for patients with high baseline levels of HBV DNA, prophylactic lamivudine might be considered before chemotherapy. This is already recommended by EASL and CDC[11,13]. However, high baseline HBV viral loads are associated with the development of resistance to lamivudine (an antiviral agent with a low genetic barrier)[29]. After prophylactic administration of lamivudine, the rate of HBV reactivation was 5%-13.3% in previous studies[25,27,28]. It was observed in some small studies that none of the HBsAg-positive patients receiving chemotherapy or immunosuppressive therapy developed HBV reactivation after prophylactic entecavir[30,31]. Therefore, prophylactic administration of other antiviral agents with high genetic barriers to resistance, such as entecavir or tenofovir, might be considered suitable substitutes for lamivudine for HBV prophylaxis prior to chemotherapy.
In the current study, it was observed that 372 patients (13.4%) were HBsAg seropositive (Table 3). According to an epidemiological serological survey of hepatitis B[2], the weighted prevalence of HBsAg for the Chinese population aged 1-59 years was 7.2%. Therefore, the prevalence of HBsAg in the current study seems to be higher. This might be because most of the patients in our study were > 20 years old (Table 3), and therefore, born before the introduction of the universal vaccination program[32]. Another reason might be that our patients with a history of HBV or elevated aminotransferases were more likely to be tested for HBV infection (Table 2).
Previous studies have reported that 0.72%-3.3% of patients who were negative for HBsAg developed de novo HBV-related hepatitis after chemotherapy[33-35]. Therefore, it is not sufficient to test for the presence of HBsAg alone as a marker of HBV infection. This is consistent with the EASL recommendations that cancer patients should be tested for both HBsAg and anti-HBc before chemotherapy[11]. In the current study, 284 patients (10.5%) were HBsAg negative but anti-HBc positive (Table 3), and two of these had HBV reactivation; one with diffuse large-B lymphoma and the other with breast cancer.
As mentioned before, high baseline HBV DNA levels are an independent risk factor for HBV reactivation[10,22]. EASL has recommended that cancer patients who are HBsAg or anti-HBc positive should have their HBV DNA levels measured[11]. In the current study, of the 656 patients who were HBsAg positive and/or anti-HBc positive, only 177 patients (27.0%) had been tested for HBV DNA (Table 3). Oncology physicians should pay more attention to this problem.
A high prevalence of occult HBV infection has been observed in HCV-infected patients[36,37]. The HCV co-infection rate among HBsAg carriers ranged from 3% to 18%[38,39], depending on the geographic location and selection of patients. In the current study, 4 patients (1.3%) were positive for both HBsAg and HCV RNA, and none developed HBV reactivation. This might have been because HCV replication is suspected to suppress HBV replication strongly[40].
The limitations of this study include the fact that it was a single-institution, retrospective study. Some important information was not recorded, such as the reasons why physicians made decisions regarding testing for HBV infection. This limitation may be resolved by a prospective study in the future.
In conclusion, only 17.1% of cancer patients received complete HBV testing prior to chemotherapy. Patients who were to receive rituximab therapy, had elevated aminotransferase levels, or had hematological malignancies were more likely to receive HBV testing. Only 27% of the patients who were positive for HBsAg and/or anti-HBc received testing for HBV DNA. HBV reactivation was observed in 33.1% of the patients, and was more likely to occur in patients with lymphoma, high levels of HBV DNA, HBeAg positivity, and male patients. Prophylactic antiviral therapy for patients with positive HBV DNA can significantly reduce the incidence of chemotherapy-induced HBV reactivation.
Cancer patients receiving intensive chemotherapy may be at risk for hepatitis B virus (HBV) reactivation. Recently, more attention has been paid to HBV testing before chemotherapy. Many clinical practice guidelines advise HBV testing before starting chemotherapy. However, few studies have focused on this issue in regions of high HBV endemicity, such as China.
Authors demonstrated that only 17.1% of cancer patients received pre-chemotherapy HBV testing (43.2% for hematological malignancies and 14.9% for solid tumors). Patients who had received rituximab therapy, had elevated aminotransferase levels, or had hematological malignancies were more likely to receive HBV testing. HBV reactivation was more likely to occur in patients with lymphoma, high levels of HBV DNA, hepatitis B e antigen positivity, and male patients.
In recent years, more organizations have advocated that all chemotherapy candidates should receive HBV serological testing before starting treatment. This is believed to be the first study to report the exact pre-chemotherapy HBV testing rate in China; a region of high endemicity for HBV infection. The rate of HBV reactivation after chemotherapy and the median onset time are also reported.
Many clinical practice guidelines advise HBV testing before starting chemotherapy. However, the results in this study showed that only 17.1% of cancer patients received pre-chemotherapy HBV testing.
HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline, or serum HBV DNA conversion from negative to positive.
In this retrospective analysis, the authors assessed the rate of HBV serological testing prior to the initiation of chemotherapy and the rate of HBV reactivation after chemotherapy in Chinese patients with cancer. The authors concluded that < 20% of patients received HBV testing before chemotherapy, and HBV reactivation would have occurred after chemotherapy in nearly half of these infected patients who did not receive pre-emptive antiviral therapy.
P- Reviewer Chen DY S- Editor Wen LL L- Editor A E- Editor Li JY
| 1. | World Health Organization. Hepatitis B: World Health Organization Fact Sheet 204. Available from: http: //www.who.int/mediacentre/factsheets/fs204/en/. [Cited in This Article: ] |
| 2. | Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27:6550-6557. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 633] [Cited by in F6Publishing: 678] [Article Influence: 45.2] [Reference Citation Analysis (0)] |
| 3. | Liu CJ, Chen PJ, Chen DS, Kao JH. Hepatitis B virus reactivation in patients receiving cancer chemotherapy: natural history, pathogenesis, and management. Hepatol Int. 2011;Jun 14; Epub ahead of print. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 33] [Cited by in F6Publishing: 43] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
| 4. | Yeo W, Chan PK, Zhong S, Ho WM, Steinberg JL, Tam JS, Hui P, Leung NW, Zee B, Johnson PJ. Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol. 2000;62:299-307. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 2] [Reference Citation Analysis (0)] |
| 5. | Manzano-Alonso ML, Castellano-Tortajada G. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy. World J Gastroenterol. 2011;17:1531-1537. [PubMed] [DOI] [Cited in This Article: ] |
| 6. | Niitsu N, Hagiwara Y, Tanae K, Kohri M, Takahashi N. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol. 2010;28:5097-5100. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 64] [Cited by in F6Publishing: 68] [Article Influence: 4.9] [Reference Citation Analysis (1)] |
| 7. | Yeo W, Lam KC, Zee B, Chan PS, Mo FK, Ho WM, Wong WL, Leung TW, Chan AT, Ma B. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Ann Oncol. 2004;15:1661-1666. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 129] [Cited by in F6Publishing: 132] [Article Influence: 6.6] [Reference Citation Analysis (0)] |
| 8. | 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] [Cited in This Article: ] [Cited by in Crossref: 217] [Cited by in F6Publishing: 217] [Article Influence: 10.3] [Reference Citation Analysis (0)] |
| 9. | 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] [Cited in This Article: ] |
| 10. | Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, Lam KC, Johnson PJ. Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer. 2004;90:1306-1311. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 231] [Cited by in F6Publishing: 248] [Article Influence: 12.4] [Reference Citation Analysis (0)] |
| 11. | European Association For The Study Of The Liver. EASL clinical practice guidelines. Management of chronic hepatitis B. Gastroenterol Clin Biol. 2009;33:539-554. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 19] [Cited by in F6Publishing: 25] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
| 12. | Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-539. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1794] [Cited by in F6Publishing: 1731] [Article Influence: 101.8] [Reference Citation Analysis (0)] |
| 13. | Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20. [PubMed] [Cited in This Article: ] |
| 14. | Lee R, Vu K, Bell CM, Hicks LK. Screening for hepatitis B surface antigen before chemotherapy: current practice and opportunities for improvement. Curr Oncol. 2010;17:32-38. [PubMed] [Cited in This Article: ] |
| 15. | Hwang J, Fisch M, Zhang H, Kallen M, Routbort M, Lal L. S, Vierling J and Suarez-Almazor M. Reactivation of hepatitis B infection among patients with cancer. J Clin Oncol. 2011;29 Suppl 15:9056. [Cited in This Article: ] |
| 16. | Lau GK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int. 2008;2:152-162. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 79] [Cited by in F6Publishing: 75] [Article Influence: 4.7] [Reference Citation Analysis (0)] |
| 17. | Tran TT, Rakoski MO, Martin P, Poordad F. Screening for hepatitis B in chemotherapy patients: survey of current oncology practices. Aliment Pharmacol Ther. 2010;31:240-246. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3] [Cited by in F6Publishing: 20] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 18. | Khokhar OS, Farhadi A, McGrail L, Lewis JH. Oncologists and hepatitis B: a survey to determine current level of awareness and practice of antiviral prophylaxis to prevent reactivation. Chemotherapy. 2009;55:69-75. [PubMed] [Cited in This Article: ] |
| 19. | Hwang J, Fisch M, Zhang H Kallen, M . Routbort, L. Lal, J. Vierling, M. Suarez-Almazor. Hepatitis B screening and positivity prior to chemotherapy. J Clin Oncol. 2010;28 Suppl 15:9008. [Cited in This Article: ] |
| 20. | 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] [Cited in This Article: ] [Cited by in Crossref: 486] [Cited by in F6Publishing: 473] [Article Influence: 31.5] [Reference Citation Analysis (0)] |
| 21. | Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS, Cheung M, Zhang HY, Lie A, Ngan R. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003;125:1742-1749. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 340] [Cited by in F6Publishing: 312] [Article Influence: 14.9] [Reference Citation Analysis (0)] |
| 22. | Lau GK, Leung YH, Fong DY, Au WY, Kwong YL, Lie A, Hou JL, Wen YM, Nanj A, Liang R. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood. 2002;99:2324-2330. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 170] [Cited by in F6Publishing: 183] [Article Influence: 8.3] [Reference Citation Analysis (0)] |
| 23. | Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA. 1986;83:1627-1631. [PubMed] [Cited in This Article: ] |
| 24. | Liaw YF. Hepatitis viruses under immunosuppressive agents. J Gastroenterol Hepatol. 1998;13:14-20. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 54] [Cited by in F6Publishing: 54] [Article Influence: 2.1] [Reference Citation Analysis (0)] |
| 25. | Lau GK, He ML, Fong DY, Bartholomeusz A, Au WY, Lie AK, Locarnini S, Liang R. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation. Hepatology. 2002;36:702-709. [PubMed] [Cited in This Article: ] |
| 26. | Keam B, Lee JH, Im SA, Yoon JH. Why, when, and how to prevent hepatitis B virus reactivation in cancer patients undergoing chemotherapy. J Natl Compr Canc Netw. 2011;9:465-477. [PubMed] [Cited in This Article: ] |
| 27. | Chen XQ, Peng JW, Lin GN, Li M, Xia ZJ. The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy. Med Oncol. 2012;29:1237-1241. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 34] [Cited by in F6Publishing: 36] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
| 28. | Yeo W, Ho WM, Hui P, Chan PK, Lam KC, Lee JJ, Johnson PJ. Use of lamivudine to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2004;88:209-215. [PubMed] [Cited in This Article: ] |
| 29. | Zoulim F, Poynard T, Degos F, Slama A, El Hasnaoui A, Blin P, Mercier F, Deny P, Landais P, Parvaz P. A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine. J Viral Hepat. 2006;13:278-288. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 57] [Cited by in F6Publishing: 54] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
| 30. | Watanabe M, Shibuya A, Takada J, Tanaka Y, Okuwaki Y, Minamino T, Hidaka H, Nakazawa T, Koizumi W. Entecavir is an optional agent to prevent hepatitis B virus (HBV) reactivation: a review of 16 patients. Eur J Intern Med. 2010;21:333-337. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 21] [Cited by in F6Publishing: 29] [Article Influence: 2.1] [Reference Citation Analysis (0)] |
| 31. | Mimura N, Kojima H, Tsujimura H, Ise M, Sakai C, Fukai K, Yokosuka O, Kumagai K. [Prevention of hepatitis B virus reactivation in B-cell lymphoma patients receiving chemotherapy with rituximab]. Rinsho Ketsueki. 2010;51:213-215. [PubMed] [Cited in This Article: ] |
| 32. | Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y. Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China. J Infect Dis. 2009;200:39-47. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 203] [Cited by in F6Publishing: 219] [Article Influence: 14.6] [Reference Citation Analysis (0)] |
| 33. | Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, Leung N, Luk JM, Lie AK, Kwong YL. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology. 2006;131:59-68. [PubMed] [Cited in This Article: ] |
| 34. | Koo YX, Tay M, Teh YE, Teng D, Tan DS, Tan IB, Tai DW, Quek R, Tao M, Lim ST. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis. Ann Hematol. 2011;90:1219-1223. [PubMed] [Cited in This Article: ] |
| 35. | Sugauchi F, Tanaka Y, Kusumoto S, Matsuura K, Sugiyama M, Kurbanov F, Ueda R, Mizokami M. Virological and clinical characteristics on reactivation of occult hepatitis B in patients with hematological malignancy. J Med Virol. 2011;83:412-418. [PubMed] [Cited in This Article: ] |
| 36. | Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002;2:479-486. [PubMed] [Cited in This Article: ] |
| 37. | Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160-170. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 359] [Cited by in F6Publishing: 389] [Article Influence: 22.9] [Reference Citation Analysis (0)] |
| 38. | Semnani S, Roshandel G, Abdolahi N, Besharat S, Keshtkar AA, Joshaghani H, Moradi A, Kalavi K, Jabbari A, Kabir MJ. Hepatitis B/C virus co-infection in Iran: a seroepidemiological study. Turk J Gastroenterol. 2007;18:20-21. [PubMed] [Cited in This Article: ] |
| 39. | Gaeta GB, Stornaiuolo G, Precone DF, Lobello S, Chiaramonte M, Stroffolini T, Colucci G, Rizzetto M. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol. 2003;39:1036-1041. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 107] [Cited by in F6Publishing: 122] [Article Influence: 5.8] [Reference Citation Analysis (0)] |
| 40. | Raimondo G, Cacciamo G, Saitta C. Hepatitis B virus and hepatitis C virus co-infection: additive players in chronic liver disease? Ann Hepatol. 2005;4:100-106. [PubMed] [Cited in This Article: ] |