Role Of Antiviral Prophylaxis Research Articles

The Role of Antiviral Prophylaxis in Preventing HBV and HDV Recurrence in the Setting of Liver Transplantation.

Hepatitis B virus (HBV) is a prevalent underlying disease, leading to liver transplantation (LT) for both decompensated cirrhosis and hepatocellular carcinoma (HCC). The hepatitis delta virus (HDV) affects approximately 5-10% of HBsAg carriers, accelerating the progression of liver injury and HCC. The initial introduction of HBV immunoglobulins (HBIG), and then of nucleos(t)ide analogues (NUCs), considerably improved the survival of HBV/HDV patients post-transplantation, as they helped prevent re-infection of the graft and recurrence of liver disease. Combination therapy with HBIG and NUCs is the primary post-transplant prophylaxis strategy in patients transplanted for HBV- and HDV-related liver disease. However, monotherapy with high-barrier NUCs, such as entecavir and tenofovir, is safe and also effective in some individuals who are at low risk of HBV reactivation. To address the problems of organ shortage, last-generation NUCs have facilitated the use of anti-HBc and HBsAg-positive grafts to meet the ever-increasing demand for grafts.

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow‐up duration of 23 807 person‐years (py). Fifty‐seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab‐containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD‐free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.

Role of Antiviral Prophylaxis and Infection Control Measures in Elimination of Influenza -A- Nosocomial Infection among Unvaccinated Patients and Healthcare Workers

Role of Antiviral Prophylaxis and Infection Control Measures in Elimination of Influenza -A- Nosocomial Infection among Unvaccinated Patients and Healthcare Workers

Antiviral prophylaxis during chemotherapy or immunosuppressive drug therapy to prevent HBV reactivation in patients with resolved HBV infection: a systematic review and meta-analysis.

Until recently, the role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation during immunosuppressive therapy or chemotherapy in patients with resolved HBV infection was unclear. The aim of the study reported here was to compare the efficacy of antiviral prophylaxis versus that of non-prophylaxis in resolved HBV-infected patients undergoing chemotherapy or immunosuppressive therapy. PubMed, the Cochrane library, and the ClinicalTrials.gov website were searched from inception until December 2017. Studies comparing reactivation in prophylaxis versus non-prophylaxis in patients undergoing immunosuppressive therapy or chemotherapy were included. The meta-analysis was performed to calculate the relative risk (RR) and the pooled estimates. A meta-analysis was conducted of 13 studies (2 randomized controlled trials [RCTs] and 11 cohort studies). The summary RR for HBV reactivation was 0.47 (95% confidence interval [CI] 0.13-1.69) for antiviral prophylaxis versus non-prophylaxis. Both of the RCTs included in the meta-analysis enrolled patients treated with rituximab. Subgroup analyses showed that the two RCTs ± high-quality cohort studies showed a decreased risk of HBV reactivation among the antiviral prophylaxis groups (RCT 1: RR 0.13, 95% CI 0.02-0.70; P = 0.02; RCT 2: 0.28, 95% CI 0.08-0.98; P = 0.05). Subgroup analyses further showed that the cohort studies did not support an association between the antiviral prophylaxis groups and HBV reactivation (RR 0.62, 95% CI 0.14-2.83; P = 0.54); adjusting for confounding factors, such as detectable anti-HBs antibodies, failed to produce a significant association (RR,0.29, 95% CI 0.07-1.28; P = 0.10). Our meta-analyses did not show an association between antiviral prophylaxis use and risk of HBV reactivation. As using only the RCTs ± high-quality cohort studies data rendered this association significant, clinicians can consider providing antiviral prophylaxis to patients with resolved HBV infection who are undergoing rituximab-based therapy.

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 reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure.

Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.

The risk of hepatitis B virus reactivation and the role of antiviral prophylaxis in hepatitis B surface antigen negative/hepatitis B core antibody positive patients with diffuse large B-cell lymphoma receiving rituximab-based chemotherapy

The risk factors and the role of prophylactic antiviral therapy of hepatitis B virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg) negative/hepatitis B core antibody (HBcAb) positive disease remain controversial. We reviewed 629 patients with diffuse large B-cell lymphoma (DLBCL). Among 629 patients, 150 of 246 patients with resolved HBV (HBsAg negative and HBcAb positive) were treated with rituximab-combined therapy. Among these 150 patients, none of 104 patients (0.0%) who were hepatitis B surface antibody (HBsAb) positive experienced HBV reactivation versus four of 46 patients (8.7%) who were HBsAb negative (p = 0.008). One of 113 patients (0.9%) with International Prognostic Index (IPI) 0–2 suffered HBV reactivation versus three of the remaining 37 patients (8.1%) with IPI 3–5 (p = 0.047). HBsAb and IPI are potential risk factors for HBV reactivation. The use of prophylactic agents may not be recommended for these patients until the occurrence of HBV reactivation.

Risk of Hepatitis B Virus (HBV) Reactivation and the Role of Anti-Viral Prophylaxis in Multiple Myeloma Patients with HBV Infection in the Era of Novel Therapies.

Abstract 3882Poster Board III-818 IntroductionPatients with hepatitis B virus (HBV) infection, defined by the presence of HBV surface antigen (HBsAg), have an increased risk of HBV reactivation when they are on immunosuppressive treatment for multiple myeloma (MM). Although there is no guideline for MM patients with HBV infection, current lymphoma guidelines do recommend that these patients should receive antiviral prophylaxis during and after chemotherapy. Of late, the advent of bortezomib in the management of MM has resulted in a high reported incidence of variecella-zoster reactivation. The risk of HBV reactivation in MM patients with HBV infection undergoing treatment has not been previously studied. As HBV infection is endemic in Asia, we sought to evaluate the prevalence of HBV infection in our patients, the incidence of its reactivation especially in patients receiving bortezomib and the role of anti-viral prophylaxis. MethodsPreviously untreated MM patients diagnosed from 2000-2008 who were tested for HBsAg in our institution were included. Hepatitis attributable to HBV reactivation was defined as an increase in HBV DNA levels of tenfold, or an absolute increase greater than105 copies/ml in the HBV DNA level. HBV infected patients were prospectively followed. 33% of all patients have been exposed to bortezomib, while 26% received high dose therapy with autologous stem cell transplantation (HDT/ASCT). Results243 untreated MM patients were identified. The prevalence of HBV infection is 5.8% (14/243). 6 (43%) HBV infected patients had detectable HBV DNA viral load (>3 log) at baseline. All 6 patients had normal baseline liver function tests and received lamivudine prophylaxis. All 14 HBV infected patients went on to receive systemic therapy for MM, with continual monitoring of HBV DNA viral load and liver enzymes for viral reactivation. 4 patients with undetectable HBV DNA load did not receive anti-viral prophylaxis. Of these 14 patients, 3 (21%) who had been on lamivudine prophylaxis had reactivation of the virus, with 1 dying from it, and 1 having emergence of a mutant viral strain. Two of them had no detectable viral load at presentation. Two patients reactivated 3 and 5 months after HDT/ASCT, while 1 reactivated immediately after a bortezomib/ doxil salvage regimen. ConclusionThe risk of HBV reactivation appeared to be commonest during the immune reconstitution phase after HDT/ASCT. Although the majority of patients with HBV infection and not receiving HDT/ASCT do not reactivate, the risk may not negligible when bortezomib is used (7%). Undetectable HBV DNA and the use of anti-viral prophylaxis do not appear to preclude reactivation. The optimal use of anti-viral prophylaxis, particularly if bortezomib is given, should be further evaluated. This is particularly relevant in the current era where bortezomib plays a dominant role in the treatment of MM, and especially in endemic regions where the incidence of HBV infection is high. Disclosures:No relevant conflicts of interest to declare.

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

Individuals who had past hepatitis B virus (HBV) infection appeared to clear their serum hepatitis B surface antigen (HBsAg) while producing antibody to the hepatitis B core antigen (HBcAb), which is detectable in their serum. Currently, it is uncertain whether patients with past HBV infection require routine antiviral prophylaxis during chemotherapy, although some cancer agencies recommend its routine use. The objective of the current study was to determine the prevalence of past HBV infection in patients with lymphoma and its relevance in terms of HBV-related complications. The authors reviewed 430 patients with lymphoma from May 2006 to May 2008. Among the 430 patients, 233 had both the HBsAg and HBcAb tests performed, whereas 197 had only the HBsAg test performed. Among those with both tests performed, 34.3% (80 of 233) were HBcAb positive only. Of these 80 patients, 58 had a concomitant HBV DNA level test, which was positive in 3 (5.2%). Of the 67 patients with past and 26 with chronic HBV infection who received chemotherapy, HBV reactivation occurred in 1.5% and 42.3% of patients, respectively (P<.0001). Prophylactic lamivudine was administered in 7 (10.4%) patients with past HBV infection and in 18 (69.2%) with chronic HBV infection. The low rate of HBV reactivation reported in our study coupled with the high prevalence of past HBV infection in an endemic area suggests that routine usage of antiviral prophylaxis may not be required for all patients with past HBV infection. Close surveillance remains a reasonable and viable option for the majority of patients.

Risk of Hepatitis B Virus (HBV) Reactivation and Role of Anti-Viral Prophylaxis in Lymphoma Patients with Past HBV Infection (HBV Antigen negative but anti-Hepatitis B core antibody positive) Receiving Chemo-Immunotherapy

Hepatitis B virus (HBV) infection, defined by the presence of HBV surface antigen (HBsAg), increases the risk of HBV reactivation and current guidelines recommend that patients who are HBV-infected should receive antiviral prophylaxis during and after chemotherapy. As HBV infection is endemic in Asia, a proportion of patients may have had past HBV infection unknowingly. These patients have cleared HBsAg and are HBsAg negative but anti-Hepatitis B core antibody (anti-HBc) positive. The risk of HBV reactivation in lymphoma patients with past HBV infection undergoing immunochemotherapy has not been previously studied. We accrued 430 consecutive patients from our prospectively maintained data-base and an ongoing prospective epidemiological study from May 2006 to May 2008. All patients were tested for HBsAg. Prior to May 2006, anti-HBc test was performed at the discretion of the treating physician. After May 2006, anti-HBc test was performed for all patients. Stored sera from consented patients were genotyped for HBV DNA. Hepatitis attributable to HBV reactivation was defined as an increase in HBV DNA levels of tenfold, or an absolute increase greater than 105 copies/ml in the HBV DNA level. At presentation, characteristics of lymphomas and baseline liver function test in patients with HBV infection were similar to those with past HBV infection. Among the 430 patients tested for HBsAg, the prevalence of HBV infection is 7.2% (31/430). Overall, 233 patients had both tests performed and 80 (34%) were anti-HBc positive only. Among the 80 patients with past HBV infection, 67 patients received systemic treatment. Of these 67 patients, 58 had a HBV DNA test, which was positive in three (5.2%). 46 patients with past HBV infection were treated with rituximab immunochemotherapy. Of these 46 patients, one reactivated and died (1/46; 4.3%); this patient did not receive anti-viral prophylaxis and had undetectable HBV DNA at time of lymphoma diagnosis. Of the 26 patients with HBV infection receiving systemic treatment, 11 (42.3%) reactivated (p<0.0001). 90% of patients with HBV infection received antiviral prophylaxis compared to 10% with past HBV infection. Of note, all 4 patients with HBV infection with mutant HBV on genotyping reactivated despite prophylactic lamivudine usage. The incidence of past HBV infection (34%) is unexpectedly high and a small proportion (5.2%) had occult infection (detectable HBV DNA). These findings have further implications in terms of HBV screening in endemic regions. Our data is the first to suggest that although majority of patients with past infection do not reactivate, the risk is not negligible when rituximab is used (4%). Undetectable HBV DNA does not appear to preclude reactivation. This data is also provocative and suggests that anti-HBc should be routinely tested and those with past infection, with or without detectable HBV DNA, be monitored closely for reactivation. The optimal use of anti-viral prophylaxis, particularly if immunotherapy is given, should be further evaluated. This is particularly relevant in endemic regions where the incidence of past infection is likely to be high. Given the observation that all patients with mutant HBV reactivated despite lamivudine prophylaxis, the optimal anti-viral agents chosen should be further evaluated.Past HBV infection (n=67)HBV–carrier (n=26)p=Prophylactic lamivudine7 (10.4%)18 (69.2%)<0.0001ALT(Baseline) (median/range)20 (5–118)21 (6–338)-Received Rituximab46 (68.7%)17 (65.4%)0.8073Hepatic decompensation22 (32.8%)10 (38.5%)0.633HBV reactivation1 (1.5%)11 (42.3%)<0.0001