Prophylactic Lamivudine Research Articles

A CASE OF THYROTOXIC PERIODIC PARALYSIS AND MODERATE TO SE- VERE GRAVE’S OPHTHALMOPATHY REQUIRING INTRAVENOUS STEROID THERAPY WITH A COMORBIDITY OF CHRONIC HEPATITIS B INFECTION

Grave’s disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Grave’s ophthalmopathy, an inflammatory disease in the orbital area, is the primary extrathyroid manifestation of Grave’s disease. About 5% of Grave’s ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Grave’s disease also has a few complications, one of which is thyrotoxic periodic paralysis characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (e.g., Grave’s ophthalmopathy). The need for a high dose of corticosteroid therapy in treating Grave’s ophthalmopathy is a risk of reactivation in hepatitis B-infected patients. This paper presented a Grave’s disease patient complicated with Grave’s ophthalmopathy who developed limb muscle weakness. The patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

A Case of Thyrotoxic Periodic Paralysis and Graves’ Ophthalmopathy Patient in Coincidence with Chronic Hepatitis B Infection

Graves' disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Graves' ophthalmopathy, an inflammatory disease in the orbital area, is the main extrathyroid manifestation of Graves' disease. About 5% of Graves' ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Graves' disease also has few complications, one of which is thyrotoxic periodic paralytic characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (eg Graves ophthalmopathy). The need of high dose of corticosteroid therapy in treating Graves’ ophthalmopathy is a risk of reactivation in hepatitis B infection patient. This paper presented a Graves' disease patient complicated with Graves’ ophthalmopathy who developed limb muscle weakness. Patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

Real-World Experience of Telbivudine and Lamivudine as Antiviral Prophylaxis for Chemotherapy-Related Hepatitis B Reactivation

Background: There is currently no data regarding the efficacy of prophylactic telbivudine in hepatitis B patients undergoing chemotherapy. This study aims to describe the results of preemptive telbivudine and lamivudine to prevent chemotherapy-related HBV reactivation.Methods: The medical records of all patients with HBsAg positive or HBs-Ag negative, anti-HBc positive, who were referred to the hepatology clinic between May 2014 and December 2016, were retrospectively reviewed. As this is a descriptive study, no statistical analysis was done.Results: A total of 52 patients with prophylactic telbivudine or lamivudine therapy were included, with 26 patients in each group. Rituximab-based treatment was given in nine and five patients in the telbivudine and lamivudine group, respectively. The number of patients who completed antiviral treatment up to six months after chemotherapy was 17 patients in each group. There was less incidence of HBV reactivation in the telbivudine group (2 of 17 patients, 11.8%) than in the lamivudine group (7 of 17 patients, 41.2%). Delayed reactivation was noticed in 1 of 2 patients in the telbivudine group and 3 of 7 patients in the lamivudine group. The median log10[HBV DNA] at reactivation was 4.52 (1.70 – 8.35) IU/mL. Severe hepatitis was observed in two patients in the lamivudine group and one patient in the telbivudine group. Of 34 patients who completed antiviral treatment, two patients died due to primary cancer. No interruption of chemotherapy or mortality due to hepatitis was noticed in both groups.Conclusions: Preemptive telbivudine or lamivudine in HBsAg positive or HBsAg negative, anti-HBc positive patients seems to be a good treatment option.

Reactivation of Hepatitis B Virus in Cancer Patients Receiving Chemotherapy

Reactivation of Hepatitis B Virus in Cancer Patients Receiving Chemotherapy

Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation

Introduction and aim. Studies suggest that entecavir and lamivudine are useful as prophylactics against hepatitis B virus (HBV) reactivation in patients undergoing chemotherapy or immunosuppressive therapy, but which drug is more effective is unclear. Here we meta-analyzed available evidence on relative efficacy of prophylactic entecavir or lamivudine therapy in patients with chronic or resolved hepatitis B infection who were undergoing chemotherapy or immunosuppressive therapy.Material and methods. Two reviewers searched PubMed, EMBASE and Google Scholar as well as reference lists in relevant articles to find studies published between January 2005 and May 2015 that met inclusion and exclusion criteria. Data on HBV reactivation, HBV-related hepatitis and all-cause mortality were extracted from the studies and meta-analyzed.Results. A total of eight studies involving 593 patients were included in the meta-analysis, which was performed using a fixed-effect model since no significant heterogeneity was found. Entecavir was associated with significantly lower risk of HBV reactivation than lamivudine (RR 0.29, 95% CI 0.17 to 0.52) as well as lower risk of HBV-related hepatitis (RR 0.11, 95% CI 0.03 to 0.40). The two drugs were associated with similar risk of all-cause mortality (RR 1.12, 95% CI 0.54 to 2.35). Egger’s test suggested no significant publication bias in the meta-analysis.Conclusions. The available evidence suggests that entecavir is more effective than lamivudine for preventing HBV reactivation and HBV-related hepatitis in patients with chronic or resolved HBV infection who are undergoing chemotherapy or immunosuppressive therapy.

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

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

Hepatitis B reactivation characterized by HBsAg negativity and anti-HbsAg antibodies persistence in haematopoietic stem cell transplanted patient after lamivudine withdrawal

BackgroundHBV reactivation is associated with high mortality rates in hematopoietic stem cell transplantation (HSCT) and prophylactic lamivudine (LMV) treatment is suggested to prevent this phenomenon. However, the duration of LMV treatment in HSCT patients is not fully defined and the time of immune recovery is considered the best parameter for a drug to be safely interrupted. In patients undergoing allogeneic HSCT, the time of immune recovery is not easy to define and may take years after transplantation and prolonged LMV treatments, which can lead to drug-resistant viral strains.Case presentationAn anti-HBc-positive hematological patient who was undergoing prolonged immunosuppression and who experienced HBV reactivation 3 months after the suspension of a prolonged LMV prophylaxis is described. HBV-DNA matching an atypical serological profile characterized by HbsAg negativity and anti-HBs positivity was detected in the patient. The genotypic analysis of the HBV strain identified T127P, F170FL and S204R mutations of HbsAg, which can hinder HBsAg recognition in a diagnostic assay.ConclusionsHBV reactivation in the HSCT host can be sustained by HBsAg viral variants with characteristics of altered immunogenicity that cannot be detected by usual laboratory tests. This clinical case description suggests the importance of screening for serum HBV-DNA levels in the diagnosis of HBV reactivation and monitoring HBV-DNA after prophylaxis suspension, particularly in HSCT subjects who have undergone prolonged periods of LMV treatment.

Prevention of Hepatitis B Virus Reactivation With Lamivudine in a Patient With Advanced Renal Cell Carcinoma Treated With Everolimus

Anticancer agents may trigger reactivation of hepatitis B virus infection ensuing in asymptomatic to severe liver damage. Preemptive administration of antiviral agents such as lamivudine to patients receiving cytotoxic chemotherapy has been shown to inhibit viral replication and prevent such events. No data are available so far concerning the coadministration of antiviral agents and everolimus, an oral mammalian target of rapamycin inhibitor recently approved for the treatment of advanced renal cell carcinoma. We present in this study the first case to our knowledge of a hepatitis B surface antigen-positive patient with metastatic renal cell carcinoma who has been successfully treated with prophylactic lamivudine and everolimus. Long-term depletion of viral replication was obtained along with stabilization of lung and bone metastases. Hepatitis B surface antigen positivity may be found in up to 10% of cancer patients but should not be considered a contraindication to treatment with everolimus.

Antiviral prophylaxis in patients with solid tumours and haematological malignancies--update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Reactivation of viral infections is common in patients with solid tumour or haematological malignancy. Incidence and severity depend on the extent of cellular immunosuppression. Antiviral prophylaxis may be effective to prevent viral reactivation. In 2006, the Infectious Diseases Working Party of German Society for Hematology and Medical Oncology (DGHO) published guidelines for antiviral prophylaxis in these patient populations. Here, we present an update of these guidelines for patients with solid and haematological malignancies undergoing antineoplastic treatment but not allogeneic stem cell transplantation. Relevant literature for reactivation of different viruses (herpes simplex virus (HSV), varicella zoster virus (VZV), hepatitis B virus (HBV) and respiratory viruses) is discussed to provide evidence-based recommendations for clinicians taking care of this patient population. We recommend a risk-adapted approach with (val)acyclovir against HSV and VZV in patients treated with alemtuzumab, bortezomib or purine analogues. Seasonal vaccination against influenza is recommended for all patients with solid or haematological malignancies regardless of antineoplastic therapy. Hepatitis B screening is recommended in lymphoproliferative disorders, acute leukaemia, and breast cancer, and during treatment with monoclonal anti-B-cell antibodies, anthracyclines, steroids and in autologous stem cell transplantation. In those with a history of hepatitis B prophylactic lamivudine, entecavir or nucleotide analogues as adefovir are recommended to prevent reactivation.

Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: A systematic review and meta-analysis

Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.

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.

Preventing hepatitis B reactivation in HBsAg-positive patients with untreated diffuse large B-cell lymphoma with R-CHOP chemotherapy: A prospective study to compare entecavir and lamivudine.

8503 Background: Hepatitis B reactivation is a serious complication in lymphoma patients treated with rituximab-contained chemotherapy despite lamivudine prophylaxis. The optimal prophylactic antiviral protocol is undetermined. This prospective study was designed to compare the efficacy of prophylactic entecavir and lamivudine in preventing hepatitis B reactivation in HbsAg-positive patients with untreated diffuse large B cell lymphoma (DLBCL) under R-CHOP treatment. Methods: HBsAg carriers with untreated DLBCL, normal liver function and low serum HBV DNA levels (less than 103copys/ml)were randomized to receive entecavir or lamivudine during R-CHOP treatment and for 6 months after completion of chemotherapy. HBsAg, HBsAb, HBeAg, HBeAb and HBcAb were performed prior to initiation of treatment. Serum alanine aminotransferase (ALT), and HBV-DNA levels were prospectively monitored before every cycle of chemo and every month after completion of chemotherapy. Results: Between February 2008 and December 2012, a total of 229 patients older than 18y with newly diagnosed DLBCL were included. The present analysis is based on 121 HBsAg-positive patients, including 61 patients randomly assigned to entecavir and 60 patients to lamivudine .The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end point was chemotherapy disruption due to hepatitis. Compared with the lamivadine group, the entecavir group had significantly lower rates of hepatitis(8.2% vs 23.3%,P=0.022), hepatitis B reactivation (0 vs 13.3%,P=0.003),HBV reactiviation(6.6% vs 30.0%,P=0.001), delayed HBV-related hepatitis (0 vs 8.3%,P=0.027) and disruption of chemotherapy (1.6% vs 18.3%,P=0.002). 7 of 8 patients with hepatitis B reactivation had advanced stage(III–IV) disease. Conclusions: In HBsAg-positive DLBCL patients undergoing R-CHOP chemotherapy, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy. Clinical trial information: CTR-TRC-11001687.

Long-term effects of prophylactic and therapeutic lamivudine treatments in hepatitis B surface antigen-positive renal allograft recipients

Among hepatitis B surface antigen (HBsAg)-positive renal allograft recipients, post-transplant immunosuppression is associated with the occurrence of hepatocellular carcinoma (HCC) and liver-related complications. Lamivudine has proven beneficial in short-term post-transplant follow-up. Between 2000 and 2009, 26 adult HBsAg-positive renal allograft recipients received lamivudine prophylaxis (Group 1) and another 28 patients received therapeutic lamivudine (Group 2) due to post-transplant hepatitis B reactivation. The historical control group included 43 HBsAg-positive renal allograft recipients who did not receive lamivudine therapy (Group 3). No subjects in Group 1 presented HCC or liver-related complications and the 10-year HCC incidence of Group 2 and Group 3 was 4.2 and 34 %, respectively. Furthermore, the HCC-free survival rates as well as the 10-year patient and graft survival rates of Group 1 and Group 2 were significantly higher than those of Group 3. However, the rates of liver-related complications and graft rejection of Group 2 and Group 3 were both higher than those of Group 1. Additionally, the HBV mutation-free rate of lamivudine was significantly higher in Group 1 than in Group 2. Lamivudine antiviral treatment, either on a prophylactic or therapeutic basis, provided long-term benefits for HBsAg-positive renal allograft recipients, in terms of reducing the occurrence of HCC and prolonging patient and graft survival. Furthermore, compared with therapeutic lamivudine, lamivudine prophylaxis appears to significantly reduce the incidence of liver-related complications, graft rejection, and lamivudine resistance.

Prophylactic Lamivudine to Improve the Outcome of Breast Cancer Patients With HBsAg Positive During Chemotherapy: A Meta-Analysis

ContextRaising the chemotherapy-induced HBV reactivation is parallel to the increment of chemotherapy treatments in breast cancer patients. This meta-analysis aims to evaluate the efficacy of prophylactic use of lamivudine in breast cancer patients with HBsAg positive during chemotherapy.Evidence AcquisitionMEDLINE, Pubmed, Ovid and Embase were used to search for clinical studies comparing with or without prophylactic use of lamivudine for HBV reactivation in breast cancer patients receiving chemotherapy. Outcomes of interest were the rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis attributable to HBV reactivation, severity of hepatitis and severity of hepatitis attributable to HBV reactivation, the rate of chemotherapy disruption, and the rate of chemotherapy disruption attributable to HBV reactivation, overall mortality, and mortality attributable to HBV reactivation.ResultsFour studies with 285 patients were included in this meta-analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis related to HBV reactivation were reduced by use of prophylactic lamivudine compared to control group. Pooled Odds Ratios (ORs) were 0.09 (95% confidence intervals [CI] 0.03-0.26; P < 0.0001), 0.23 (95% CI 0.06-0.92; P = 0.04), and 0.10 (95% CI 0.03-0.32; P < 0.0001) respectively. There was a reduction in chemotherapy disruption related to HBV reactivation by use of prophylactic lamivudine (pooled OR = 0.11; 95% CI 0.02-0.58; P = 0.01). Chemotherapy disruption, overall mortality, and mortality attributable to HBV reactivation were not significantly different between two groups. Pooled ORs were 0.42 (95% CI 0.11-1.58; P = 0.20), 0.37 (95% CI 0.07-2.04; P = 0.25), and 0.25 (95% CI 0.01-6.82; P = 0.41) respectively. Lamivudine was well-tolerated, and no additional toxicity was observed.ConclusionsUse of prophylactic lamivudine may have positive effect on the outcome of breast cancer patients with HBsAg positive during chemotherapy.

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

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

Efficacy of prophylactic lamivudine to prevent hepatitis B virus reactivation in B-cell lymphoma treated with rituximab-containing chemotherapy

Reactivation of hepatitis B virus (HBV) is a common complication in patients with HBV infection who receive cytotoxic chemotherapy. In rituximab-containing chemotherapy for B-cell lymphoma, severe hepatitis due to HBV reactivation occurred. The aim of this study is to estimate the effect of prophylactic lamivudine on the risk of HBV reactivation in patients with HBV infection who receive rituximab-containing chemotherapy. In this study, HBV markers and liver function tests were monitored in 268 consecutive patients with B-cell lymphoma, who received rituximab-containing chemotherapy between January 2008 and November 2011. Sixty-nine patients (25.7 %) with either chronic HBV infection or past HBV infection received prophylaxis with lamivudine 100 mg daily by oral intake. In the HBsAg-positive group, six (6/38) patients developed hepatitis, only one of which was attributed to HBV reactivation. In the HBsAg-negative and HBcAb-positive group, two (2/31) patients developed hepatitis, none of which was attributed to HBV reactivation. These results support that prophylactic lamivudine can prevent HBV reactivation for B-cell lymphoma with HBV infection who was receiving rituximab-containing chemotherapy.

Adherence to hepatitis B screening and prophylactic lamivudine for prevention of rituximab-associated hepatitis B reactivation

Treatment with rituximab can be associated with hepatitis B reactivation leading to fulminant hepatitis and sometimes fatal hepatitis. The manufacturer has recommended screening the high-risk patients and monitoring hepatitis B virus carriers during and several months after the therapy. Prophylaxis with lamivudine has been recommended to prevent reactivation in hepatitis B virus carriers receiving rituximab. An institutional guideline was developed and implemented. This study evaluated the adherence to these clinical guidelines of hepatitis B screening in patients receiving rituximab-based treatment, the use of lamivudine prophylaxis, and the prevalence of positive hepatitis B virus surface antigen in this patient population in southeast Michigan. A retrospective chart review of patients begun on rituximab therapy from January 2009 through June 2010 was conducted. Two hundred and eighty patients who received rituximab were identified. Approximately 70% of patients had hepatitis B virus surface antigen screening test prior to rituximab therapy. Antibody to hepatitis B virus core antigen was detected in 11.1% of patients, although the hepatitis B virus surface antigen positive rate was only 0.6%. One patient had hepatitis B virus reactivation despite lamivudine prophylaxis, but fully recovered after antiviral therapy was changed to tenofovir. The prevalence of hepatitis B virus surface antigen positivity is low in this study; however, antibody to hepatitis B virus core antigen positivity is high. Education to clinicians is warranted to increase awareness and further improve adherence to the clinical guidelines.

Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable

Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable

Cost-Effectiveness Analysis of Prophylactic Lamivudine Use in Preventing Vertical Transmission of Hepatitis B Virus Infection

As neonates born to mothers with positive hepatitis B e antigen may not be completely protected by hepatitis B vaccination, prophylactic lamivudine use in mothers with high viraemia has been proposed. However, the overall effectiveness and the balance between cost and benefit for such a prophylactic strategy have rarely been addressed. Using a review of recent literature, we aimed to assess the cost effectiveness, from the Taiwanese societal perspective, of administering prophylactic lamivudine to mothers to reduce vertical transmission of hepatitis B virus and its long-term sequelae in neonates. A meta-analysis of three randomized controlled trials was conducted to evaluate the efficacy of lamivudine versus placebo. A Markov decision model was constructed in which in both treatment arms infants received active and passive immunoprophylaxis. An economic evaluation was performed to calculate costs, acute infections averted, and QALYs gained. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve drawn. All these analyses were from the societal perspective. Costs ($US) were valued in year 2008 prices. Supplemental lamivudine use gained an additional 0.0024 QALYs and averted 0.23 acute infections per birth compared with the routine active-passive immunization without lamivudine. The cost-effectiveness analysis suggested that the use of additional prophylactic lamivudine dominated the routine strategy. The acceptability curve suggested that the probability of being cost effective under the willingness-to-pay threshold of $US20,000 was 94%. This analysis suggests that supplemental use of lamivudine in mothers with high hepatitis B viraemia is effective in reducing vertical transmission and may be cost effective, from a Taiwanese societal perspective, compared with the routine active-passive immunization without lamivudine.

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up