Incidence Of Hepatitis B Virus Reactivation Research Articles

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.

Hepatitis B reactivation in psoriasis patients treated with anti-TNF agents: prevention and management.

The risk of hepatitis B virus (HBV) reactivation (HBVr) in chronic HBV carriers, in occult HBV patients or in acute HBV patients affected by psoriasis and treated with anti-tumor necrosis factor (TNF)-α agents is a clinical practice issue to face with, particularly if the treatment has a long-term maintenance finality. The aims of this review are to examine the current knowledge on HBVr incidence in chronic HBV carriers and potential occult carriers undergoing therapy with biologics for the treatment of psoriasis and psoriatic arthritis; analyze the prophylactic measure to prevent HBV reactivation and define how to manage HBVr in patients treated with biologics. We searched through PubMed, Google Scholar and Scopus databases and evaluated all published manuscripts concerning HBVr in psoriatic patients, both plaque-type and psoriatic arthritis, in treatment with any indicated anti-TNF-α. Although anti-TNFs are considered moderate immunosuppressive drugs, the incidence of HBVr in psoriatic patients is lower compared to patients affected by other immune-mediated diseases treated with TNF inhibitors. HBV prophylaxis should be probably reserved to anti-HBs+/anti-HBc+ patients with a viral load <2000 IU/mL and alterations in serum liver enzymes, in order to prevent HBVr.

A comparison of hepatitis B virus reactivation rates between liver resection and radiofrequency ablation for patients with tumor .LEQ.5 cm

Objective To investigate the value of liver resection and radiofrequency ablation (RFA) on reactivation rates of hepatitis B virus (HBV) in hepatocellular cancer (HCC) patients with tumor ≤5 cm and determine influential factors. Methods Retrospective analysis was performed in clinical data of hepatocellular cancer patients with tumor ≤5 cm from Shengli Oilfield Centeral Hospital between July 2007 and March 2012, 289 cases were assigned to liver resection group (n=157) and RFA group (n=132). Logistic regression was used to evaluate relative factors associated with HBV reactivation for univariate and multivariate analyses. The stratified χ2 test was utilized to assess clinical outcomes in HBV reactivation subgroup with or without antiviral treatment. CD3+ , CD4+ , CD8+ , CD4+ /CD8+ and NK cell proportions were comparatively analysized. Results (1) The univariate and multivariate logistic regression analyses showed antiviral therapy, Child-Pugh grade, vascular invasion and treatment (liver resection or RFA) were significant risk factors of HBV reactivation (P 0.05). (3) The proportions of CD3+ , CD4+ , CD4+ /CD8+ and NK cell after treatment for 7 days decreased in various degrees for both the liver resection and RFA groups regardless of patients with or without antiviral therapy (P 0.05). Conclusions For the patients with tumor ≤5 cm, the proportions of immunological cells decreased in liver resection when compared with RFA. Preoperative antiviral therapy may have partial response in immunological suppression, and lowered the incidence of HBV reactivation. Key words: Hepatocellular carcinoma; Hepatitis B virus; Antiviral therapy; Hepatic resection; Radiofrequency ablation

Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20–38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.

HBV activation after RCHOP-like immunochemotherapy in diffuse large B cell lymphoma patients: A retrospective multicenter study

Objective:To determine and compare the incidence of hepatitis B virus(HBV) activation in both hepatitis B surface antigen(HBsAg)-positive and HBsAg-negative patients who were diagnosed of diffuse large B cell lymphoma(DLBCL)and received rituximab-CHOP(RCHOP)-like immunochemotherapy and estimate the value of preventive anti-virus therapy.Methods:We retrospectively analyzed the clinical data from DLBCL patients who received RCHOP-like regimen in six grade 3 hospitals in Shanghai.The clinical characteristics of these patients and its correlation with HBV activation were analyzed.Results:A total of 234 patients including 29 HBsAg-positive patients and 205 HBsAg-negative patients fitted the inclusion criteria and were recruited in this study.Among the 29 HBsAg positive patients,11 received prophylactic antiviral therapy and none of them developed HBV reactivation;and in another 18 patients who did not receive antiviral prophylactic therapy,7(38.9%) cases developed HBV reactivation.Furthermore,3 out of the 7 patients who developed HBV reactivation died of liver failure.The incidence of HBV reactivation in non-prophylactic HBsAg-positive patients was significantly higher than that in the prophylactic patients(P=0.026).There was only 1 of the HBsAg-negative patients developed HBV reactivation and the incidence of HBV reactivation in HBsAg-negative patients was significantly lower than that in the HBsAg-positive ones(P=0.000).Conclusion:The present study revealed a high incidence and a bad prognosis of HBV reactivation in HBsAg-positive DLBCL patients after RCHOP-like therapy.Prophylactic antiviral therapy effectively reduced the risk of HBV reactivation in these patients.The incidence of HBV activation in HBsAg-negative DLBCL patients was relatively low and the role of antiviral prophylaxis in this population deserves further investigation.

Hepatitis B virus reactivation and hepatitis in gastrointestinal cancer patients after chemotherapy.

The objectives of this study were to investigate the incidences of hepatitis B virus (HBV) reactivation and hepatitis in gastrointestinal cancer patients with positive hepatitis B surface antigen (HBsAg) after chemotherapy and assess the effect of antiviral therapy on preventing HBV reactivation and hepatitis. The medical records of gastric or colorectal cancer patients with positive HBsAg undergoing chemotherapy in West China Hospital were reviewed from January 2009 to August 2014. One hundred and fifty-six patients were included. Seventy-six patients had no records of the baseline HBV DNA copy (bHDC) and received no antiviral therapy. Of 80 patients with known bHDCs, 39 patients received antiviral therapy. The incidence of HBV reactivation was 14.6% in the non-antiviral group with known bHDCs (n = 41), compared with 0% in the antiviral group (P = 0.039). Compared with 12.8% in the antiviral group (P = 0.034), 29.9% of patients suffered from hepatitis in the total non-antiviral group (n = 117). More patients with moderate/severe hepatitis were seen in the non-antiviral group (P = 0.027). Non-antiviral therapy was the only risk factor for hepatitis in multivariate analysis (HR 3.195, 95% CI 1.117-10.989; P = 0.043). HBV reactivation and hepatitis occurred in a significant proportion of gastrointestinal cancer patients with positive HBsAg who received chemotherapy. Antiviral therapy could reduce the incidences of HBV reactivation and hepatitis.

Hepatitis B virus reactivation in patients with multiple myeloma receiving bortezomib-containing regimens followed by autologous stem cell transplant

To investigate hepatitis B virus (HBV) reactivation and survival in patients with multiple myeloma (MM) receiving bortezomib-containing regimens, we analyzed 139 patients with MM receiving bortezomib-containing regimens in our hospital. Twenty-seven/139 patients were hepatitis B surface antigen positive (HBsAg+) with nine having DNA levels > 500 IU/mL, including four > 1000 IU/mL. All but five HBsAg+ patients were treated with lamivudine or entecavir before chemotherapy until at least 6 months after chemotherapy or autologous stem cell transplant (ASCT). HBV reactivation occurred in six HBsAg+ patients and two HBsAg− patients, including six who received ASCT. Overall survival and progression-free survival of HBsAg− patients were significantly longer than for HBsAg+ patients (both p < 0.01). From these results, we confirmed that the incidence of HBV reactivation was notable in patients with MM receiving bortezomib-containing regimens, especially those who underwent ASCT. HBsAg+ patients with MM had a poorer prognosis than HBsAg− patients. Prophylactic treatment should be prescribed to all patients with HBsAg+ MM for a minimum duration of 12 months.

O2-7-3 - Reactivation of Hepatitis B Virus (Hbv) in Hbv-Resolved Patients with Adult T-Cell Leukemia/Lymphoma

Background: Reactivation of hepatitis B virus (HBV) infection is generally known as a fatal complication in HBV-resolved patients with B-cell lymphoma who received rituximab-containing chemotherapy. However, there is little evidence regarding HBV reactivation in patients with adult T-cell leukemia/lymphoma (ATL). To evaluate the incidence and the characteristics of HBV reactivation in HBV-resolved patients with ATL, we performed this retrospective study in a single institution.Methods: Sixty-six patients who were diagnosed as ATL in our hospital between Jan 2005 and Jun 2013, were enrolled. Among HBsAg-negative patients at baseline, anti-HBc-positive and/or anti-HBs-positive were judged as having HBV-resolved infection. On regular HBV-DNA monitoring for HBV-resolved patients, HBV reactivation was defined as the detection of HBV-DNA levels.Results: Baseline HBV status was judged as follows: HBsAg-positive (3.0%, 2 of 66), HBsAg-negative (95.5%, 63 of 66), and no serological HBV assessment (1.5%, 1 of 66). Of 63 HBsAg-negative patients, 33 patients (52.4%) had HBV-resolved infection, and 26 of 33 patients underwent HBV-DNA monitoring. With median HBV-DNA follow-up of 238 days (range, 57 to 1420), HBV reactivation was observed in 3 (11.5%) of 26 HBV-resolved patients. All 3 reactivated patients were male, positive for both anti-HBc and anti-HBs at baseline, and received the LSG15 regimen as initial treatment. Anti-CCR4 monoclonal antibody, mogamulizumab was used in 2 patients before the occurrence of HBV reactivation. No hepatitis due to HBV reactivation occurred in those patients, who received antiviral drug immediately when HBV-DNA levels were detectable.Conclusions: The incidence of HBV reactivation was 11.5% among HBV-resolved patients with ATL. Regular monitoring of HBV-DNA is a reasonable strategy to prevent HBV-related hepatitis for those patients following systemic chemotherapy.

High risk of hepatitis B virus reactivation in nucleos(t)ide analogue-induced hepatitis B e antigen seroconverters older than 40 years.

A recent study showed that chronic hepatitis B virus (HBV) carriers with nucleos(t)ide analogue (NA)-induced hepatitis B antigen (HBeAg) seroconversion occurring before the age of 30 years have a higher risk of HBV reactivation. To compare the risk of HBV reactivation and HBeAg seroreversion between patients with spontaneous and NA-induced HBeAg seroconversion. A total of 135 and 251 non-cirrhotic patients with NA-induced and spontaneous HBeAg seroconversion, respectively, were analyzed. NA-induced HBeAg seroconverters faced higher risks of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (P < 0.001). In spontaneous HBeAg seroconverters, age at HBeAg seroconversion, sex, HBV DNA levels before HBeAg seroconversion, HBV genotype C, and pre-S deletions were independent predictors of HBV reactivation. In NA-induced HBeAg seroconverters, only age at baseline was an independent predictor of HBV reactivation. To determine whether the difference in the incidence of HBV reactivation or HBeAg seroreversion between two groups was age-specific, we analyzed these patients according to their age at HBeAg seroconversion (20-29, 30-39, and ≥40 years). Our data showed that NA-induced HBeAg seroconversion was an independent predictor of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconversion in patients older than 40 years at HBeAg seroconversion, but not in patients between 20-29 and 30-39 years of age. NA-induced HBeAg seroconverters are associated with higher risks of HBV reactivation and HBeAg seroreversion compared to spontaneous HBeAg seroconverters, especially in patients who are older than 40 years at HBeAg seroconversion.

Multicenter observational study of reactivation of hepatitis B virus (HBV) caused by chemotherapy for solid tumors (ST).

1590 Background: Reactivation of HBV has often been reported in patients (pts) with malignant lymphoma administered combination chemotherapy regimens containing rituximab. Recently, HBV reactivation has been reported even in pts with STs. However, the incidence of HBV reactivation in pts with STs and the treatment outcomes in pts with HBV reactivation have not yet been fully elucidated. Therefore, we prospectively investigated the incidence of HBV reactivation in pts with STs receiving first-line chemotherapy and the clinical outcomes of these patients. Methods: ST pts with seropositivity for HBsAg [sAg(+)], or seronegativity for HBsAg and seropositivity for HBcAb and/or HBsAb [c/sAb(+)], receiving first-line chemotherapy including neoadjuvant or adjuvant chemotherapy, were enrolled. HBV DNA was at least measured at the termination of the first-line chemotherapy, and at 3, 6, and 12 months after the termination of first-line chemotherapy. It was also measured in cases where HBV reactivation was suspected,...

Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: A prospective study

Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with "resolved" HBV infection (hepatitis B surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) can occur, but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10-fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year, respectively. Severe HBV-related hepatitis (ALT >10-fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P=0.003). In lymphoma patients with resolved HBV infections, chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092-2100).

Hepatitis B reactivation after treatment for HBV-related hepatocellular carcinoma: comparative analysis of radiofrequency ablation versus hepatic resection

To perform a comparative analysis of the reactivation rate of hepatitis B virus (HBV) infection and related risk factors after treatment of HBV-related hepatocellular carcinoma (HCC) by radiofrequency ablation (RFA) or hepatic resection. We retrospectively analyzed the HBV reactivation rate and related risk factors of a cohort of 218 patients treated for HBV-related HCC between August 2008 and August 2011; the study population consisted of 125 patients who received RFA and 93 patients who received hepatic resection. Comparisons were made using the unpaired Student's t-test for continuous variables and the x2-test and Fisher's exact test for categorical variables. Univariate and multivariate logistic regression analysis was used to assess risk factors. Twenty patients showed HBV reactivation following treatment, but the incidence was significantly lower in the RFA group than in the hepatic resection group (5.6% vs. 14.0%, 7/125 vs. 13/93, x2 = 4.492, P = 0.034). The univariate and multivariate analysis indicated that no antiviral therapy (OR = 11.7; 95% CI: 1.52-90.8, P = 0.018) and the treatment type (i.e. RFA or hepatic resection) (OR = 3.36; 95% CI: 1.26-8.97, P = 0.016) were significant risk factors of HBV reactivation. Subgroup analysis showed that the incidence of HBV reactivation was lower in patients who received antiviral therapy than in those who did not for both the RFA group and the hepatic resection group but the difference was not significant in the former group (1/68 vs. 19/150, x2=7.039, P = 0.008 and 0/33 vs. 7/92, x2 = 2.660, P = 0.188, respectively). However, the incidence of HBV reactivation in patients who did not receive antiviral therapy was higher than in those who did receive antiviral therapy in the hepatic resection group (12/58 vs. 1/35, x2 = 5.773, P = 0.027). The incidence of HBV reactivation was lower in patients who received RFA than in those who received hepatic resection to treat HBV-related HCC. Antiviral therapy prior to the hepatic resection treatment may be beneficial for reducing the incidence of HBV reactivation.

Hepatitis B Related Serological Events In Hematopoietic Stem Cell Transplant Patients and Efficacy Of Lamivudine Prophylaxis Against Reactivation

IntroductionRemote Hepatitis B Infection (RHBI) is an immunological stage in the life cycle of Hepatitis B virus (HBV). It is characterized by the persistence of HBV DNA at low level within the liver or blood of people infected in past. As a result HBsAg, HBeAg and HBV DNA in serum are negative while Anti-HBs and/or Anti-HBc IgG are positive with normal liver enzymes. In Hematopoietic stem cell transplant (HSCT) patients, reactivation of RHBI leads to increased HBV replication and increased HBV DNA titres in blood and/or HBsAg or HBeAg positivity. There may be loss or gain of Anti-HBs and/or Anti-HBc IgG. The importance of recognizing this stage with a potential for reactivation is highlighted by the fact that: 1) HBV reactivation can lead to fulminant hepatitis & 2) Anti-HBV therapy such as lamivudine can prevent HBV reactivation. In this study we have aimed to determine the incidence of RHBI and HBV reactivation in our patients, the role of lamivudine in preventing HBV reactivation and the pattern of change in serological markers after reactivation. MethodsAll patients undergoing HSCT from March 2010 to May 2013 were included. Pre transplant, all patients were tested by ELISA for HBsAg, Anti-HBs, Anti-HBc IgM and Anti-HBc IgG. Post transplant, at the time of deranged liver function, all patients were tested for HBsAg, Anti-HBs, Anti-HBc IgM, Anti-HBc IgG, Anti-HCV, Anti-HEV and Anti-HAV. HBV DNA and HCV RNA were tested by polymerase chain reaction. RHBI was defined as positive Anti-HBc IgG and/or Anti-HBs (without history of HBV vaccination) with negative HBsAg and Anti-HBc IgM and normal liver function. HBV reactivation was defined as increase in transaminases to more than 3 times the upper limit of normal with HBV DNA and/or Anti-HBs and/or Anti-HBc IgG positivity (HBsAg and Anti-Hbc IgM being negative) at the time of deranged liver function. Lamivudine at a dose of 100 mg/d or 3 mg/kg/d (children <12 years) was given to all but one patient with Anti-HBc IgG positivity pre transplant irrespective of Anti-HBs positivity (Prophylaxis Group). Patients who had only Anti-HBs positivity did not receive prophylaxis (No Prophylaxis Group). Data was analyzed to explore the role of prophylactic lamivudine in preventing HBV reactivation and to determine the pattern of change of HBV serological markers at the time of reactivation. The time to respond to lamivudine was calculated as the interval from start of prophylaxis to normalization of liver enzymes. ResultsTwo hundred five patients underwent HSCT (autologous - 103 and allogeneic - 102) from March 2010 to May 2013. Twenty-eight (14%) patients were diagnosed to have RHBI (autologous-9, allogeneic-19). Thirteen patients did not receive prophylactic lamivudine (No-Prophylaxis Group) while 15 patients received prophylactic lamivudine (Prophylaxis Group). Twelve (92%) patients in No-Prophylaxis Group developed HBV reactivation while none (0%) in the Prophylaxis Group (P<0.001). The incidence of HBV reactivation was 10% (21 of 205 patients) which included 11 (52%) with only Anti-HBs positive, 1 with only Anti-HBc IgG positive and nine (43%) with all HBV serological markers negative (i.e. no evidence of RHBI) pre transplant. Six of these 9 patients sero-converted (5 - Anti-HBc IgG and 1 - Anti-HBs positive) at the time of reactivation. Seven (33%) developed HBV viremia at the time of HBV reactivation, of which 6 were Anti-HBs negative pre transplant. In contrast, of the patients with undetectable HBV DNA at the time of reactivation (14 patients), only 4(29%) were Anti-HBs negative pre transplant (P=0.0237). Seven (33%) patients were on steroids and 9(43%) were on cyclosporine at the time of reactivation. All patients responded to lamivudine within a median time of 17 days. ConclusionsIncidence of RHBI in patients undergoing HSCT is high in our setting.Lamivudine prophylaxis protects against HBV reactivation post transplant. We would recommend lamivudine prophylaxis in patients with RHBI with isolated Anti-HBs positivity in addition to those with Anti-HBc IgG positivity given the high rate of HBV reactivation in these patients.All serological markers for Hepatitis B being negative pre transplant does not preclude HBV reactivation post transplant. Therefore, all serological markers for HBV should be repeated at the time of deranged liver functions post transplant.Anti-HBs positivity pre transplant decreases the risk of HBV viremia at the time of reactivation. Disclosures:No relevant conflicts of interest to declare.

Comparison of Clinical Outcomes in Hepatitis B Virus–Positive Kidney Transplant Recipients With or Without Pretransplantation Antiviral Therapy

BackgroundAntiviral agents have improved the outcomes of hepatitis B virus (HBV)–positive kidney transplant recipients (KTRs). Preemptive therapy has been the main approach to forestall HBV reactivation. We sought to compare prophylactic and preemptive approaches. MethodsWe divided the 69 HBV-positive KTRs into treatment and historical control groups, according to the time of starting pretransplantation antiviral therapy. The treatment group was further divided into prophylactic and preemptive therapy groups. ResultsThe treatment group showed a significant improvement in 10-year graft (82% vs 34%) and patient (91% vs 57%) survivals. Among the historical control group, the main causes of graft failure were patient deaths (68%), which were mostly caused by liver diseases. In contrast, there was no liver-related death in the treatment group. In addition, there was no difference in graft or patient survival between the prophylactic and preemptive groups, but the incidence of HBV reactivation was lower in the prophylactic group. Antiviral therapy was an independent factor for the improved patient survival (P = .005). ConclusionsPretransplantation antiviral therapy is essential to improve clinical outcomes. Prophylactic may be better than preemptive antiviral therapy to decrease HBV reactivation.

Hepatitis B virus reactivation after radiofrequency ablation or hepatic resection for HBV-related small hepatocellular carcinoma: A retrospective study

Reactivation of hepatitis B virus (HBV) happens after systemic chemotherapy, transarterial chemoembolization (TACE) or hepatic resection for HBV-related hepatocellular carcinoma (HCC) patients. The incidence and risk factors of HBV reactivation after radiofrequency ablation (RFA) are unclear. From August 2006 to August 2011, 218 consecutive patients with HBV-related small HCC treated with RFA (n=125) or hepatic resection (n=93) were retrospectively studied. The incidence of HBV reactivation and risk factors were analyzed. HBV reactivation developed in 20 (9.2%) patients after treatment. The incidence of HBV reactivation was significantly lower in the RFA group (5.6%, 7/125) than the hepatic resection group (14.0%, 13/93, P=0.034). On univariate and multivariate analyses, no antiviral therapy (OR 11.7; 95% CI 1.52-90.8, P=0.018) and treatment with RFA/hepatic resection (OR3.36; 95% CI 1.26-8.97, P=0.016) were significant risk factors of HBV reactivation. On subgroup analysis, the incidence of HBV reactivation was lower in patients who received antiviral therapy than those who did not receive antiviral therapy in both the hepatic resection group (2.9% vs. 20.7%, P=0.027) and the RFA group (0% vs. 7.6%, P=0.188), although the difference was not significant in the latter group. The incidence of HBV reactivation after RFA was relatively low when compared with hepatic resection. Prophylactic antiviral therapy is recommended, especially for patients who are going to receive hepatic resection for HBV-related HCC to decrease the incidence of post-treatment HBV reactivation.

Prospective Nationwide Observational Study of Hepatitis B Virus (HBV) DNA Monitoring and Preemptive Antiviral Therapy for HBV Reactivation in Patients with B-Cell Non-Hodgkin Lymphoma Following Rituximab Containing Chemotherapy: Results of Interim Analysis.

AbstractAbstract 2641▪▪This icon denotes a clinically relevant abstract INTRODUCTION:Since the introduction of the anti-CD20 monoclonal antibody rituximab, the outcomes of B-cell non-Hodgkin lymphoma (B-NHL) have improved markedly. However, fulminant hepatitis due to reactivation of hepatitis B virus (HBV) infection has emerged as a serious problem. Recently, rituximab plus corticosteroid containing chemotherapy (R-chemo) has been identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg)-negative B-NHL patients. Currently, there is no standard management to prevent HBV reactivation in HBV-resolved patients without HBsAg, but with antibodies against hepatitis B core antigen (anti-HBc) and/or HBsAg (anti-HBs). PATIENTS AND METHODS:We conducted a multicenter prospective observational study to estimate the incidence of HBV reactivation by serial monthly monitoring of HBV DNA in HBV-resolved patients with B-NHL during and just after R-chemo, and to establish preemptive antiviral therapy guided by this monitoring. The major eligibility criteria included previously untreated CD20-positive B-NHL with prior HBV-resolved infection, and planned treatment with 6 to 8 cycles of R-chemo defined by protocol. The baseline HBV status was evaluated on enrollment at each institute, comprising HBsAg, anti-HBc, and anti-HBs serology. Patients were excluded if they were seropositive for hepatitis C virus or human immunodeficiency virus. Plasma HBV DNA levels were measured independently at a central laboratory, using an automated real-time TaqMan polymerase chain reaction assay after enrollment. The primary end point was the incidence of HBV reactivation defined as HBV DNA levels of 1.8 log copies per mL or more. If HBV DNA levels of less than 1.8 log copies per mL were confirmed at baseline, the serial monitoring of HBV DNA (without prophylaxis of antiviral drugs) was performed with assessments every 4 weeks after enrollment for 1.5 years. Prompt antiviral treatment with an anti-HBV nucleoside analogue (entecavir, 0.5 mg per day) was highly recommended in patients with confirmed HBV reactivation. An ancillary study was conducted to identify risk factors for HBV reactivation using the preserved specimens. The protocol was approved by the Institutional Review Board of each participating institution. All patients gave written informed consent. The planned interim analysis was performed after the enrollment of 200 patients, using data available up to June 30, 2011. RESULTS:Between Sept. 2008 and Sept. 2010, a total of 187 patients (50.8% male) with a median age of 63 years (range, 26 to 79) from 45 institutes were analyzed. Histologic subtypes of B-NHL were diffuse large B-cell lymphoma (n=121, 64.7%), follicular lymphoma (n=57, 30.5%), MALT lymphoma (n=5, 2.7%) and other types (n=4, 2.0%). The number (%) of patients positive for both anti-HBc and anti-HBs was 132 (70.6%), 35 (18.7%) were positive for anti-HBc but negative for anti-HBs, and 19 (10.2%) were negative for anti-HBc but positive for anti-HBs. One patient was positive for anti-HBc but lacked anti-HBs measurement. 168 (89.8%) patients received 6 to 8 cycles of R-CHOP (n=151) or other R-chemo (n=17). With a median follow-up of 549 days (range, 35 to 939), HBV reactivation was observed in 16 out of 187 analyzed patients. The incidence of HBV reactivation at 1 year was 7.7% (95% confidence interval [CI], 4.7 to 12.7). HBV reactivation was diagnosed at a median time of 158 days (range, 33 to 490) after enrollment. No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were 1.8 to 3.1 log copies per mL. Multivariate analysis of the ancillary study showed that an anti-HBs baseline titer less than 10 mIU per mL was an independent risk factor for HBV reactivation, compared to a titer of 100 mIU per mL or more (adjusted hazard ratio, 5.3; 95% CI, 1.3 to 21.8; p=0.02). HBV mutations of precore (G1896A) or basal core promoter (A1762T/G1764A) that enhanced HBV replication were identified in 4 patients, two of whom had both mutations. Our strategy could inhibit such highly replicative clones and prevent hepatitis. CONCLUSIONS:Monthly monitoring of HBV DNA is highly effective for preventing hepatitis due to HBV reactivation in HBV-resolved B-NHL patients treated with R-chemo. (UMIN-CTR 000001299) (This study was supported by the Ministry of Health, Labour and Welfare of Japan.) Disclosures:Kusumoto:Bristol-Myers Squibb: Honoraria; Zenyaku Kogyo: Honoraria; Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Abbott: Honoraria. Tanaka:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria; Abbott: Honoraria. Tanaka:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Kinoshita:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria. Ogura:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria, Research Funding. Mizokami:Chugai Pharmaceutical Co., LTD.: Honoraria; Abbott laboratories: Honoraria. Ueda:Chugai Pharmaceutical Co., LTD.: Research Funding.

Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma

Reactivation of hepatitis B virus (HBV) replication happens in patients who receive transarterial chemoembolization or systemic chemotherapy for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV reactivation during the perioperative period in HCC patients receiving hepatic resection is unknown. Between May 2009 and November 2010, 164 consecutive patients with HBV-related HCC who underwent hepatic resection were prospectively enrolled in the study. Among these, 126 patients received antiviral treatment before the operation (the antiviral group) and 38 patients did not receive any antiviral treatment (the non-antiviral group). Ten patients (6.1%) developed HBV reactivation perioperatively (within 1 month after hepatectomy). The incidence of HBV reactivation in the antiviral group and non-antiviral group were 1.6% (2/126) and 21.1% (8/38), respectively (P < 0.001). On univariate analysis, preoperative HBV DNA < 1.0 × 10(3) copies/mL and non-antiviral therapy were significantly correlated with the occurrence of HBV reactivation (P = 0.044 and P < 0.001, respectively). Only non-antiviral therapy remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95% confidence interval, 2.80-85.46, P = 0.002). The recovery of liver function (defined as a decrease of alanine aminotransferase back to normal) was achieved in 86.8% (132/152) patients without HBV reactivation and in 37.5% (3/8) patients with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001). Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given.

Reactivation of resolved hepatitis B virus infection after immunosuppression: Is it time to adopt pre-emptive therapy?

New therapeutic options like monoclonal antibodies (anti-CD20/rituximab) and hematopoietic stem cell transplantation (HSCT) have increased both the effectiveness of therapies and the risk for reactivation of Hepatitis B virus (HBV). We describe two cases with serological evidence of resolved HBV infection (hepatitis B surface antigen (HBsAg) negative/antibody to hepatitis B core antigen (anti-HBc) and antibody to hepatitis B surface antigen (anti-HBs) positive), who developed reverse seroconversion (clearance of HBsAb/appearance of HBsAg) with active HBV infection after treatment with combination of conventional chemotherapy, rituximab and autologous HSCT for hematological malignancies. Review of the literature highlights the increasing incidence of HBV reactivation in patients with resolved infection and raises concerns as to whether current guidelines for pre-chemotherapy screening with sensitive HBV-DNA assays and serial monitoring for anti-HBs titres should be implemented also for patients with resolved infection. Future studies should aim at clarifying the cost-benefit from administration of nucleoside analogues in these patients.

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.

Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts

Screening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1 year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA. This was a prospective non-randomized, non-controlled study. We enrolled 50 patients with RA who had antibodies against hepatitis B core antigen (anti-HBc) and who had started treatment with disease-modifying anti-rheumatic drugs, including those who had additionally received anti-tumor necrosis factor-α (anti-TNF-α). HBV DNA levels were measured every 2-3 months by a real-time, polymerase chain reaction-based method. Entecavir was administered to patients with HBV DNA levels >2.1 log/ml. The mean observation period was 23 months (range 12-32 months). HBV reactivation occurred in 2 of 5 patients with HBV surface antigen (HBsAg) and in 1 of 45 patients without HBsAg. In patients who received anti-TNF-α therapy, antibodies against HBsAg decreased significantly. Entecavir therapy inhibited HBV amplification and prevented HBV-associated flares of hepatitis. The incidence of HBV reactivation was low in RA patients in whom HBV infection had been resolved. Screening for HBV reactivation and prophylactic therapy with entecavir were effective means of preventing HBV-associated hepatic failure in patients with HBsAg, as well as in those with only anti-HBc who received immunosuppressive therapy for RA.