Incidence Of Hepatitis B Virus Reactivation Research Articles

Hepatitis B Virus Infection Status and Reactivation Analysis in Multiple Myeloma in China

Background: China is a highly endemic area for Hepatitis B virus (HBV) infection and HBV reactivation is an event of concern in treating patients with hematologic malignancy. However, there were very few reports regarding HBV reactivation in patients with multiple myeloma (MM) in China. Since the approval of novel agents, especially immunotherapy such as monoclonal antibody and chimeric antigen T cell immunotherapy, the risk of HBV reactivation has increased. Therefore, the study aimed to evaluate the HBV infection status in MM and explore the incidence and risk factors of HBV reactivation in MM patients in China. Methods: Newly diagnosed MM patients with available serologic assays for HBV infection were retrospectively enrolled between June 30, 2008 and December 30, 2022 in West China Hospital, Sichuan University. Demographic and clinical data were obtained from the “HemaTank” Chinese Multiple Myeloma Database (HCMMD). Meanwhile, patients diagnosed with Waldenstrom Macroglobulinemia (WM) at the same time were enrolled as the control group. HBV reactivation was defined as the occurrence of one of the following: ≥ 2 log increase in HBV-DNA levels from baseline level, detection of HBV-DNA with level > 100 IU/ml in a person with undetectable HBV DNA at baseline or HBsAg-negative becoming positive. The penalized maximum likelihood logistic regression for rare events was applied to identify independent risk factors related to HBV reactivation. Results: The study recruited 3040 MM patients with a median age of 62 (range 14~98) and 240 WM patients with a median age of 63 (range 25~92). The HBsAg-positive rates were similar between MM and WM (9.4% vs 10.8%, P=0.49), but both the HBcAb-positive rates and HBeAb-positive rates in WM were significantly higher than MM (76.3% vs 60.7%, P<0.001; 37.5% vs 25.1%, P<0.001). The analysis of co-expression of HBV markers shows that the prevalence of HBsAg-/Anti-HBs+/anti-HBC- in MM was significantly higher than WM (16.7% vs 8.3%, P<0.001) and HBsAg-/Anti-HBs-/anti-HBC+ in MM was significantly lower than WM (18.3% vs 27.1%, P<0.001). However, he prevalence of HBsAg+/ HBeAg+/anti-HBC+ and HBsAg+/ anti-HBeAb+/anti-HBC+ were similar between MM and WM (0.5% vs 1.3%, P=0.158; 8.6% vs 8.8%, P=0.503). The baseline characteristics of HBsAg-positive MM and HBsAg-negative MM were summarized in Table 1. The rates of HBsAg-positive MM were significantly increased in young male patients (P<0.05). The level of ALT and AST, and the incidence of HBV reactivation, liver cirrhosis and pulmonary disease were significantly higher in HBsAg-positive MM than in HBsAg-negative MM (P<0.05). Of the 2147 MM patients who have received at least one line of chemotherapy (Table 1), 924 (43%) MM patients received bortezomib-containing or lenalidomide-containing regimens as the frontline therapy, while only 21 (1.0%) received a daratumumab-containing regimen as the frontline therapy. During hospital-documented follow-up visits, 26 (1.21%) MM patients have experienced HBV reactivation. According to the multivariate analysis of risk factors for HBV reactivation in MM, liver cirrhosis (OR 8.63, 95%CI 2.95-25.24, P<0.001), autologous stem cell transplantation (OR 6.03, 95%CI 2.47-14.72, P<0.001) and HBsAg-positive (OR 14.45, 95%CI 6.50-32.14, P<0.001) were independent risk factors associated with high prevalence of HBV reactivation. The ROC curve of the model integrating the three factors is shown in Figure 1, and the AUC was 0.8584. Conclusions: Among Chinese MM patients with multiple myeloma, a high proportion of MM patients presented with resolved hepatitis B virus infection, whereas HBV reactivation was pretty rare. However, long-term HBV DNA levels monitoring is still needed for MM patients at high risk for HBV reactivation.

HBV reactivation and its effect on survival in HBV-related hepatocarcinoma patients undergoing transarterial chemoembolization combined with tyrosine kinase inhibitors plus immune checkpoint inhibitors.

This study aimed to access hepatitis B virus (HBV) reactivation and its effect on survival in HBV-related hepatocarcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs). In this single-center retrospective study, we enrolled 119 HBV-related unresectable advanced HCC patients receiving TACE combined with TKIs plus ICIs. Risk factors for HBV reactivation were analyzed by logistic regression. Kaplan-Meier method was applied to draw the survival curve, and log-rank test was used to compare survival between patients with and without HBV reactivation. A total of 12 patients (10.1%) encountered HBV reactivation in our study, of which only 4 patients received antiviral prophylaxis. The incidence of HBV reactivation was 1.8% (1/57) in patients with detectable baseline HBV DNA and 4.2% (4/95) in patients with antiviral prophylaxis respectively. Lack of prophylactic antiviral treatment (OR=0.047, 95%CI 0.008-0.273, P=0.001) and undetectable HBV DNA (OR=0.073, 95%CI 0.007-0.727, P=0.026) were independent risk factors for HBV reactivation. The median survival time (MST) for all patients was 22.4 months. No survival difference was observed in patients with or without HBV reactivation. (MST: undefined vs 22.4 months, log-rank test: P=0.614). HBV reactivation could occur in HBV-related HCC patients who treated with TACE in combination with TKIs plus ICIs. Before and during the combination treatment, it is necessary to routinely monitor HBV DNA and to take effective prophylactic antiviral therapy.

The Impact of b/tsDMARD Dose Reduction on Chronic Hepatitis B in Rheumatoid Arthritis Patients: A Two-Center Long-Term Safety Analysis

We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). This two-center analysis retrospectively investigated the virological and biochemical evidence of HBVr in RA patients who underwent b/tsDMARD dose reduction. Serum levels of viral loads were determined using real-time PCR. Serum levels of alanine transaminase (ALT) were determined using spectrophotometry. Among a total of 40 HBsAg+ RA patients who tapered b/tsDMARDs, 14 (35%) used tocilizumab; 12 (30%) used tumor necrosis factor (TNF)-α inhibitors; and the rest used either abatacept or tofacitinib. We found that patients who had detectable HBV DNA before tapering achieved a one-log reduction in HBV DNA levels, in contrast to the findings in the other 12 patients who did not taper b/tsDMARDs (no change in HBV DNA levels with time). The incidence of HBVr (increased viral loads with hepatitis) was 4.62 (95%CI: 2.08, 10.28) and 2.26 (95%CI: 0.56, 9.02) events per 100 person-years before and after b/tsDMARD tapering, respectively. The HBV viral load decreased after the tapering of b/tsDMARDs in RA patients with detectable HBV DNA. Dose reduction in b/tsDMARDs might be beneficial.

Risk of HBV reactivation in relapsed or refractory diffuse large B-cell lymphoma patients receiving Bruton tyrosine kinase inhibitors therapy.

BackgroundBruton tyrosine kinase inhibitors (BTKis) interrupt B-cell receptor signaling and thereby could potentially reactivate hepatitis B virus (HBV). However, data about the risk for HBV reactivation (HBVr) of BTKis in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) patients are sparse.MethodsA total of 55 R/R DLBCL patients receiving BTKis therapy in the Tongji Hospital of Tongji University were enrolled. Patient clinical characteristics, treatment outcomes and details of HBVr were collected and analyzed, aiming to demonstrate the risk of HBVr in R/R DLBCL patients post BTKis therapy and the efficacy of BTKis in HBV-associated R/R DLBCL patients.ResultsOf 55 R/R DLBCL patients treated with ibrutinib (N=38) and zanubrutinib (N=17), 4 were with chronic HBV infection (HBsAg positive), 26 with resolved HBV infection (HBsAg negative and HBcAb positive) and 25 without HBV infection (HBsAg negative and HBcAb negative). In resolved HBV infection group, 2 patients developed HBVr after the use of ibrutinib and zanubrutinib respectively. Neither of them developed HBV-related hepatitis. Our finding showed that the incidence of HBVr in resolved HBV infection group was 7.69% (95% CI, 0.9-25.1%). In this study, Overall response rate (ORR) was 70.9%. 1-year overall survival (OS) rate was 80.0%. Median progression-free survival (PFS) was 4 months (95% CI, 3-5 months). In addition, HBV infection was not associated with response rates or survival among R/R DLBCL patients post BTKis treatments.ConclusionOur study suggested that HBV infection do not affect the efficacy of BTKis’ treatment. However, R/R DLBCL patients with resolved HBV infection are at a moderate risk of developing HBVr throughout BTKis treatment. Patients should be screened for HBVr during BTKis therapy.

Drugs and hepatitis B virus reactivation

Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.

Abstract P1-15-02: Low incidence of hepatitis B reactivation after chemotherapy in Japanese breast cancer patients with resolved HBV

Abstract Background: Recently, chemotherapy-induced reactivation of hepatitis B virus (HBV) has been reported not only in patients with HBV surface antigen positive (HBsAg+) but also in patients with resolved HBV (HBsAg-, anti-HBV-core antibody positive (anti-HBc+). The incidnce of HBV reactivation after adjuvant/neo-adjuvant chemotherapy for breast cancer in patients with resolved HBV infection remains unclear. In this study, we surveyed the incidence of HBV reactivation in Japanese breast cancer patients who received adjuvant/neo-adjuvant chemotherapy. Methods: A total of 3042 breast cancer patients who received neoadjuvant and/or adjuvant chemotherapy from June 2008 to December 2016 were included in this study. HBsAg, anti-HBc and anti-HBV-surface antibody (anti-HBs) were tested before chemotherapy. Serum HBV-DNA levels were subsequently measured and monitored for one year after the completion of adjuvant/neo-adjuvant chemotherapy if the patient exhibited a resolved HBV infection. Results: Of the 3042 patients (pts), 32 (1.05%)cases were positive for HBsAg and 2992 pts were negative for HBsAg. 301 pts (9.9 %) were revealed resolved HBV infection; 221 pts were with anti-HBc+ and anti-HBs+, 40 pts were with anti-HBc+ and anti-HBs-, and 130 pts were with anti-HBc- and anti-HBs+. Of the 130 pts with anti-HBc- and anti-HBs+, 77 pts were previously vaccinated for hepatitis B. The antibody-positive rate by age group was 2.7% (1/37) for patients in their 20s, 4.1% (14/344) for those in their 30s, 6.5% (67/1037) for those in their 40s, 9.4% (77/817) for those in their 50s, 16.6% (109/655) for those in their 60s, 20% (30/150) for those in their 70s, and 0% (0/2) for those in their 80s. Among the 301 pts with resolved HBV infection, 71 pts were monitored for one year after the completion of their chemotherapy. The median monitoring period was 579 days (386-3458). In our monitoring period, only one patient (1.4%) was diagnosed with HBV reactivation based on a slightly elevated HBV-DNA level at 1-year-test. No death or hepatitis due to HBV reactivation occurred during the monitoring period. Conclusions: The prevalence of resolved HBV infection in Japan showed an increasing trend with age. Adjuvant/neoadjuvant chemotherapy for breast cancer patients with resolved HBV infection has a risk of HBV reactivation. Our study suggested the risk of reactivation was low and the risk of a flare of HBV disease could be controlled with screening and carefully monitoring. Citation Format: Takayo Fukuda, Masaya Hattori, Yukinori Ozaki, Lina Inagaki, Mari Hosonaga, Ippei Fukada, Kokoro Kobayashi, Fumikata Hara, Takayuki Kobayashi, Sachiyo Yoshio, Takayuki Ueno, Toshimi Takano, Shinji Ohno. Low incidence of hepatitis B reactivation after chemotherapy in Japanese breast cancer patients with resolved HBV [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-15-02.

905. Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National VA Cohort

BackgroundIbrutinib, a bruton tyrosine kinase inhibitor was approved by Food and Drug Administration (FDA) in 2013 and became the first-line treatment for chronic lymphocytic leukemia in 2014. The risk Hepatitis B Virus (HBV) reactivation after initiation of ibrutinib is unclear. Here, we report the results of national Veterans Health Administration (VHA) pharmacy database review estimating the incidence of HBV reactivation after initiation of ibrutinib.MethodsVeterans who received ibrutinib between Feb 1, 2014 through October 31, 2019 were included in our study. Possible reactivations were identified by change of Hepatitis B Virus surface antigen (HBV sAg), HBV core antibody (Ab) or HBV viral load from no data or negative to positive after starting ibrutinib. Individual chart review was conducted to verify HBV reactivation due to ibrutinib. Cumulative incidence was calculated by identifying HBV reactivation cases among at risk patients, which was defined as prior exposure by positive HBV core Ab regardless of HBV sAg or HBV viral load status. For patients without any HBV serology, an estimated prevalence of HBV exposure in veterans from the literature is used. ResultsA total of 4130 veterans were on ibrutinib during the study period. Of 4130 patients, 1875 patients with HBV core Ab negative and 68 patients on antivirals against HBV prior to ibrutinib were excluded. Among the remaining 2187 patients, there were 170 patients with positive HBV core Ab and 2017 patients without HBV core Ab tested regardless of HBV sAg or HBV DNA status. We used the estimated 13.6% (95%CI 11.5-16.1) of HBV exposure in veterans and estimated that 274 (95%CI 232-325) out of 2017 patients would be at risk of HBV reactivation. Thirty-nine patients were identified to have HBV reactivation after ibrutinib. After detailed review, 7 HBV reactivations were attributable to initiation of ibrutinib. The cumulative incidence of HBV reactivation after ibrutinib was estimated as 1.5% (95% CI 1.4-1.7).ConclusionIn this large VHA study, we identified 7 cases of HBV reactivations among 444 at risk patients. The cumulative incidence of HBV reactivation after ibrutinib was 1.5% in patients with prior HBV exposure with positive HBV core Ab irrespective of HBV sAg or HBV DNA status, indicating a moderate risk of HBV reactivation.Disclosures All Authors: No reported disclosures

Rates and characteristics for hepatitis B reactivation of inactive hepatitis B carriers in rural communities

Objective: To analyze the intensity and epidemiological characteristics of hepatitis B virus (HBV) reactivation among inactive HBsAg carriers (IHC) of rural areas in Ji'nan. Methods: In 2018 and 2020, follow-up investigations were conducted on IHC identified in the population physical examination in Zhangqiu district of Ji'nan. The results of the two follow-up visits were compared to analyze the incidence and distribution characteristics of HBV reactivation in IHC at the community level. Results: A total of 424 IHC completed two follow-up visits, and 47 cases of HBV reactivation were found, the cumulative reactivation rate was 11.08%, and the incidence density was 5.46/100 person-years. Multivariate analysis showed that gender, age, smoking, drinking , family history of liver disease and chronic diseases were not associated with HBV reactivation (P>0.05), and baseline HBV DNA load was associated with reactivation (P<0.05), in the HBV DNA level ≥1 000 IU/ml group, the reactivation rate could reach 18.92%. After reactivation, the mean level of ALT increased from baseline and the abnormal rate increased, liver function tended to be abnormal in reactivated patients. 4 (8.51%) reactivators had hepatitis, and 1 (2.13%) had jaundice hepatitis. Conclusions: The incidence of HBV reactivation was higher among IHC in rural communities in Ji'nan. Most of the reactivators were asymptomatic or mildly reactivated. Follow-up of inactive HBsAg patients should be strengthened and changes in ALT and HBV DNA levels should be closely monitored.

The Incidence of HBV Reactivation in Patients Receiving First-Line R-CHOP Chemotherapy: Three-Year Follow-up Results from a Prospective, Observational Study

Background:Due to the high rate of chronic hepatitis B virus (HBV) infection in China, hepatitis B surface antigen (HBsAg) can be detected among 25-61% of patients with diffuse large B-cell lymphoma (DLBCL) and 20-40% with follicular lymphoma (FL), while HBsAg- negative (neg) /HBcAb-positive (pos) can be detected among 20-44% of patients with DLBCL (Chinese Society of Hematology, 2013). When these patients receive immune-suppressing treatment, they are at an increased risk of HBV reactivation which may lead to hepatic mortality and interrupt the rituximab-based chemotherapy. For patients and their physicians, HBV infection management plays a crucial role for achieving optimal survival outcomes without compromising safety. This multicenter, single-arm, prospective, non-interventional study was conducted at 24 centers in China between January 17, 2011 and October 31, 2016. Previously untreated CD20-positive DLBCL patients who were eligible to receive rituximab plus chemotherapy (R-chemo) (CHOP or non-CHOP) as first-line treatment were enrolled with no specific exclusion criteria. We investigated the risk of HBV reactivation in patients with CD20+ DLBCL or FL which received R-chemo as first-line treatment.Methods:Patients who received at least one dose of R-chemo were included in the analysis. Data were collected and analyzed from medical records for 3 years since the last R dose was administered. The evaluation of HBV infection management included HBV infection and liver function screening before R-chemo, viral replication monitoring during and after R-chemo, antiviral prophylaxis use and HBV reactivation rates. HBsAg-pos patients had HBV reactivation if HBV DNA increased ≥1 log10 from baseline, if HBV DNA appeared (above the lower limit of detection) or if HBeAg appeared in HBeAg- neg patients. HBsAg-neg/HBcAb-pos patients had HBV reactivation if there was appearance of either HBsAg or HBV DNA (above the lower limit of detection). The HBV reactivation was determined by SAP and investigator's judgment. This study was registered in clincialtrials.gov (NCT01340443).Results:In total, 282 DLBCL patients and 31FL patients were included in the analysis. HBV screening data were available from 271 enrolled patients. At baseline, 26 patients were HBsAg-pos, 79 were HBsAg- neg/HBcAb-pos and 166 were double neg. HBV infection status was undefined for 42 patients. During the study, HBV reactivation was detected in 8 patients, which was only in the DLBCL group. Seven cases were observed in treatment period, while 1 case occurred during 3-year follow-up. None of them led to study termination, temporary termination, or dose adjustment.Cox univariate regression analysis in DLBCL patients showed that baseline type of hepatitis B correlated with overall response rate (ORR) and complete response (CR) but had no effect on progression-free survival (PFS).In term of HBV infection management, in DLBCL group, 25 patients with HBsAg-pos or HBsAg-neg/ HBcAb-pos receiving antiviral prophylaxis. In FL group, only 3 patients received antiviral treatment. Lamivudine was mostly administered by Chinese investigators. Details on treatment, duration and infection status are listed in Table 1.Summary:In this prospective, observational study, we followed the patients with DLBCL or FL for 3 years to investigate the risk of HBV reactivation after they received R-chemo. Our study showed that, in real-world setting, the incidence of HBV reactivation in patients with a history of hepatitis, particularly those positive for HBsAg is acceptable, baseline type of hepatitis B had no effect on PFS. Close monitoring and antiviral prophylaxis would be beneficial to the patients with DLBCL or FL combined with hepatitis B infection while they receive R-chemo. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy.

BackgroundThis study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients.MethodsWe enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups.ResultsA total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36–0.91; p<0.05).ConclusionsHBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients.Name of the Trial RegisterHAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC.Clinical Trial Registration https://www.clinicaltrials.gov/, identifier NCT 02436044

Hepatitis B virus reactivation during temozolomide administration for malignant glioma.

The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. In one of two HBV carriers, HBV DNA turned positive 8months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections.

A prospective trial of vaccine to prevent hepatitis B virus reactivation after hematopoietic stem cell transplantation

Hepatitis B virus (HBV) reactivation reportedly occurs frequently after hematopoietic stem cell transplantation (HSCT) in resolved HBV-infected patients. Here, 50 patients with resolved HBV infections and scheduled to undergo HSCT were enrolled; all subjects were vaccinated with three doses of hepatitis B vaccine 12 months after HSCT and the incidence of HBV reactivation was monitored. The patients’ characteristics were: median age, 61 (34–72) years; male/female, 27/19; allogeneic/autologous, 40/6; bone marrow/peripheral blood stem cells/cord blood, 26/16/4. Of the 46 patients who underwent HSCT, 19 were excluded and did not make it to vaccination due to relapse of underlying disease, HBV reactivation within 12 months of HSCT, or transfer of patients. The remaining 27 were vaccinated 12 months after HSCT and monitored for 2 years. Six showed HBV reactivation, with a 2-year cumulative reactivation incidence of 22.2%; the same incidence was 27.3% only in allogeneic HSCT patients. Factors associated with HBV reactivation included the discontinuation of immunosuppressants (P = 0.0379) and baseline titers of antibody against hepatitis B surface antigen (P = 0.004). HBV reactivation with vaccination following HSCT could occur despite maintenance of serum anti-HBs at more than protective levels.

Optimal timing of antiviral therapy for patients with malignant tumor who presented with hepatitis B reactivation during chemotherapy and/or immunosuppressive therapy.

Background: Hepatitis B virus (HBV) reactivation may occur with chemotherapy and/or immunotherapy. Antiviral prophylaxis is recommended for all patients who are hepatitis B surface antigen (HBsAg)-positive during chemotherapy and/or immunosuppressive therapy. However, the optimal timing of antiviral therapy before chemotherapy and/or immunosuppressive therapy is not fully elucidated.Patients and methods: We retrospectively evaluated 446 HBsAg-positive patients who underwent chemotherapy and/or immunosuppressive therapy. The cumulative rates of HBV reactivation were evaluated using the Kaplan-Meier method and were compared using the log-rank test. The risk factors of HBV reactivation were examined via univariate and multivariate analyses using the Cox proportional hazards model.Results: The cumulative HBV reactivation rates of patients who received antiviral therapy before chemotherapy and/or immunosuppressive therapy were significantly lower than those of patients who received antiviral therapy after chemotherapy and/or immunosuppressive therapy (P = 0.002). The incidence of HBV reactivation was significantly different between patients who received antiviral therapy at least 1 day before chemotherapy and/or immunosuppressive therapy and those who did not (P = 0.006). No significant difference was observed in the HBV reactivation rates between patients who received antiviral therapy at least 2 days (P = 0.310), 3 days (P = 0.494), and 1 week (P = 0.655) before chemotherapy and/or immunosuppressive therapy and those who did not. The multivariate Cox proportional hazards model showed that women had a lower risk of developing HBV reactivation than men (P = 0.025). The use of the prophylactic antiviral agent entecavir, compared with lamivudine and telbivudine, was associated with the decreased risk of developing HBV reactivation (P = 0.002).Conclusion: HBsAg-positive patients who received preemptive antiviral therapy after chemotherapy and/or immunosuppressive therapy had a high risk of developing HBV reactivation. However, it is not necessary for patients to receive antiviral therapy at least 1 week before chemotherapy and/or immunosuppressive therapy.

Validity of administrative database detection of previously resolved hepatitis B virus in Japan.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person‐years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%‐89.3%). This study evaluated the PPV of the algorithm of HBV‐DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person‐years.

Incidence of hepatitis B reactivation during epidermal growth factor receptor tyrosine kinase inhibitor treatment in non–small-cell lung cancer patients

BackgroundReactivation of hepatitis B virus (HBV) is a documented risk during cytotoxic chemotherapy in patients with lung cancer. Cases of HBV reactivation in non–small-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment have been reported; however, the incidence of HBV reactivation in patients treated with EGFR TKIs has not yet been reported. Materials and methodsWe enrolled 171 patients who were diagnosed as having NSCLC from 2011 through 2017 and who also had positive hepatitis B surface antigen (HBsAg). All patients had received EGFR TKIs as anticancer treatment for at least 2 weeks during their treatment course. Reactivation of HBV is defined as one of the following: an increase in HBV DNA by at least 10-fold compared to baseline or an absolute increase to >10ˆ5 IU/mL with abnormal liver function. ResultsThe median duration of EGFR TKI treatment was 10.5 months (95% confidence interval: 8.2–12.8). Sixteen (9.36%) patients met the criteria of HBV reactivation during EGFR TKI treatment, with an annual incidence of 7.86%. HBV reactivation occurred during erlotinib treatment in 6 patients, followed by 5 patients with gefitinib treatments, 3 patients with osimertinib treatment and 2 with afatinib treatment. No independent risk factor for HBV reactivation was identified. ConclusionNSCLC patients receiving EGFR TKI treatment may have a clinically meaningful risk of HBV reactivation during the treatment period. Thus, monitoring liver function, HBV viral load and serology of HBV (i.e., HBeAg and anti-HBc) during EGFR TKI therapy is recommended for NSCLC patients with positive HBsAg.

PB2029 HEPATITIS B REACTIVATION DURING TREATMENT OF TYROSINE KINASE INHIBITORS—EXPERIENCE IN 175 ADULT PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Background:The cause of hepatitis B virus (HBV) reactivation in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) is unclear.Aims:Taiwan has a high prevalence of HBV infection, and this study aimed to investigate the epidemiology of HBV reactivation in patients with CML treated with TKIs.Methods:We retrospectively reviewed 175 adult patients with CML who were treated using TKIs at National Taiwan University Hospital between January 2008 and July 2018. HBV infection status and reactivation were reviewed during follow‐up.Results:A total of 99 men and 76 women with a median age of 46 years (range: 18–97) were enrolled in this study. Twenty‐one (12%) of 175 patients were carrying HBV when they were diagnosed with CML. Eight HBV carriers were prophylactically treated using an antiviral agent, and the others were closely followed‐up. At a median follow‐up period of 41 months (range 1–129 months), 6 (28.6%) of the 21 HBV carriers had 7 episodes of HBV reactivation. Two (1.3%) of the 154 negative hepatitis B surface antigen (HBsAg) patients had reverse seroconversion and became positive HBsAg, and both patients had acute blastic transformation and allogeneic transplantation. A univariate analysis revealed positive HBsAg and negative anti‐Hepatitis B surface antibodies (anti‐HBs Ab) significantly correlated with HBV reactivation. In this retrospective cohort study, the incidence of HBV reactivation was 0.5 per 100 person‐years in patients with CML carrying HBV who had been treated with TKIs and 0.076 per 100 person‐years in all patients with CML treated with TKIs.Summary/Conclusion:HBV reactivation could develop in patients with CML treated with TKI, especially in those who are HBV carriers. The incidence is lower than it is in hematological patients with HBV carrier status who have been treated with chemotherapy, immunotherapy and stem cell transplantation. We suggest that all patients with CML with positive HBsAg undergo prophylaxis with an antiviral agent. The cause of HBV reactivation in patients with resolved HBV infection and no allogeneic transplantation is unclear, and although the risk is low, further investigation is required.image

Management of anti-HBc-positive patients with rheumatic diseases treated with disease-modifying antirheumatic drugs-a single-center analysis of 2054 patients.

Hepatitis B virus (HBV) reactivation is a common complication of immunosuppressive treatment in high prevalence countries. Biological disease-modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than conventional immunosuppressants. The incidence of HBV reactivation during treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains open how to treat and monitor patients at risk during immunosuppressive therapy with bDMARDs. We examined 2054 patients from a German tertiary rheumatology center in order to analyze the prevalence of HBc-antibody-positivity and the incidence of HBV reactivation in German rheumatology patients treated with immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of HBV infection (anti-HBc positive). Only two patients were suffering from chronic infection (HBsAg positive). Three patients were treated pre-emptively with entecavir, and eight patients after HBV DNA reappearance. No liver failure occurred due to HBV reactivation. Compared to anti-HBc-positive patients without reactivation, the reactivation group included more patients exposed to three or more classes of bDMARDs (p= 0.017). The median HBs antibody titer was significantly lower in the reactivation group (15.0IU/l vs. 293.5IU/l; p= 0.001). This study shows that bDMARDs and csDMARDs can safely be administered to patients with a history of HBV, provided they are closely monitored. Low titers of anti-HBs antibodies and a history of ≥ 3 classes of immunosuppressants increase the risk of HBV reactivation. These data highlight major differences to high prevalence regions.

Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus reactivation in glomerulonephritis patients under immunotherapy: a real-life observation.

Antiviral prophylaxis is proved to be effective in reducing the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients under immunotherapy. But outcomes referring to discontinuation of antiviral prophylaxis in these patients are lacking. We performed a retrospective study of 105 HBsAg-positive patients under immunotherapy for glomerulonephritis and evaluated the incidence and risk factors for HBV reactivation. Among 105 patients, 55.24% completed antiviral prophylaxis, while 20.00% discontinued and 24.76% rejected antiviral prophylaxis. HBV reactivation was significantly different among completion, discontinuation, and rejection of antiviral prophylaxis: 5.17% versus 38.10% versus 15.38% in the incidence of HBV reactivation (P = 0.001), 3.45% versus 23.81% versus 11.54% in HBV DNA ≥ 5 Log copies/ml (P = 0.023), and 0 versus 14.29% versus 3.85% in hepatitis B e antigen seroconversion from negative to positive (P = 0.014). Survival curve showed the median occurrence time of HBV reactivation in discontinuation group was 32months (95% CI 24-39months), earlier than 69months (95% CI 65-72months) of completion group and 43months (95% CI 37-49months) of rejection group (χ2 = 13.780, P = 0.001). Univariate and multivariate analysis identified two independent risk factors for HBV reactivation: baseline HBV DNA detectable (OR 5.009, 95% CI 1.717-16.335, P = 0.012) and discontinuation of antiviral prophylaxis (OR 5.213, 95% CI 1.688-18.105, P = 0.011). Discontinuation of antiviral prophylaxis increased the risk of HBV reactivation in HBsAg-positive patients under immunotherapy for glomerulonephritis.

HBV reactivation in allogeneic stem cell transplant recipients: Risk factors, outcome, and role of hepatitis B virus mutations.

Hepatitis B virus (HBV) reactivation (HBVr) in recipients of allogeneic hematopoetic stem cells (aHSCs) appears heterogeneously with respect to its frequency, manifestation, and outcome. The aim of this study was to present data from a large German cohort of recipients of aHSC transplantation (aHSCT), focusing on the incidence of HBVr in antibody to hepatitis B core antigen (anti‐HBc)‐positive aHSCT recipients, its clinical outcome, and the role of mutations in HBV. Between 2005 and 2015, 1,871 patients received aHSCT at University Hospital Essen. A follow‐up of at least 6 months after transplant was available in 55 patients who were anti‐HBc‐positive; clinical and virologic data were analyzed. The HBV genome was sequenced with next generation technology from serum samples of 8 patients with HBVr. Thirteen out of 55 (23.6%) patients developed HBVr at a median of 26 months after aHSCT. After initiation of antiviral treatment, complete HBV DNA suppression was achieved in 7/10 (70%) patients 1 to 40 months after HBVr. Nine of 13 patients had increased alanine aminotransferase; 3 patients had compromised coagulation and model for end‐stage liver disease scores of 18‐27, and 1 of these patients died due to liver failure 5 weeks after HBVr. As a risk factor for HBVr, we identified anti‐HBc signal to cut‐off ration (S/CO) ≥7.5 before transplantation. Complete HBV DNA suppression was achieved in 7/10 patients; therapy‐relevant mutations were found in 1 patient. In 4/8 patients, immune escape mutations were detected either as majority or minority variants. Conclusion: HBVr is common in anti‐HBc‐positive aHRCT recipients and can lead to severe hepatitis with compromised coagulation. The level of anti‐HBc S/CO before transplantation is a risk factor for HBVr. Complete virologic response under adequate antiviral treatment could not be achieved in all patients. (Hepatology Communications 2017;1:1014–1023)

Hepatitis B virus reactivation and antiviral prophylaxis during lung cancer chemotherapy: A systematic review and meta-analysis.

BackgroundAntiviral drugs have been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV) infection in cancer patients undergoing chemotherapy. However, screening and antiviral prophylaxis for lung cancer remain controversial because of insufficient evidence.PurposeIn this study, we investigate the absolute risk for HBV reactivation and the prophylactic effects of antiviral drugs in hepatitis B surface antigen (HBsAg)-positive lung cancer patients during chemotherapy.MethodsWe searched Pubmed, Embase, Cochrane, Web of Science and SinoMed from inception until 28 November 2016, and identified all potential relevant references with or without prophylactic use of antiviral therapy in HBsAg-positive lung cancer patients during chemotherapy. The primary outcome was the incidence of HBV reactivation, the secondary outcomes were the incidence of hepatitis, chemotherapy disruption and mortality.ResultsEleven studies involving 794 patients were analyzed. The incidences of HBV reactivation in control group and antiviral prophylaxis group ranged from 0% to 38% (median, 21%, 95% CI: 0.17–0.25) and 0% to 7% (median, 4%, 95% CI: 0.02–0.06), respectively. Antiviral prophylaxis had significantly reduced the risk for HBV reactivation (RR, 0.22 [95% CI: 0.13–0.37], p< 0.0001), hepatitis (RR, 0.35 [95% CI: 0.22–0.56], p<0.0001) and chemotherapy disruption (RR: 0.29 [95% CI, 0.15–0.55], p<0.0002) compared to those without antiviral prophylaxis. There was no significant heterogeneity in the comparisons, and a fixed-model was used.ConclusionThe risks of HBV reactivation and relevant complications are high in HBsAg-positive lung cancer patients receiving chemotherapy, and available evidences support HBV screening for antiviral prophylaxis before initiation of chemotherapy for lung cancer patients.