Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients

Hepatitis B virus (HBV) reactivation is a well-known complication of lymphoma treatment in the pre-rituximab era. This complication has not been as well studied, however, since monoclonal anti-CD20 antibody became the standard regimen for B cell lymphoma. In this retrospective study, 115 B cell lymphoma patients who received rituximab-containing therapy were analyzed. Of 15 hepatitis B surface antigen (HBsAg)-positive patients, five received lamivudine prophylaxis and did not develop HBV-related hepatitis during lymphoma treatment. Eight of ten HBV carriers without lamivudine prophylaxis experienced HBV-related hepatitis, including one fatal hepatic failure. Four (4.2%) of 95 HBsAg-negative patients developed de novo HBV-related hepatitis and two died of fulminant hepatitis. In conclusion, rituximab-based therapy may cause serious HBV-related complications and even death in both HBsAg-positive and HBsAg-negative patients.     

Prevention of hepatitis B flare-up during chemotherapy using lamivudine: case report and review of the literature

 Reactivation of chronic hepatitis B in patients receiving cytotoxic treatment for non-Hodgkin's lymphoma is well documented. We report a case of a patient with chronic hepatitis B who was treated by chemotherapy because of non-Hodgkin's lymphoma. After the second cycle of chemotherapy she developed a severe flare-up of hepatitis B. Liver biopsy revealed highly active hepatitis and confluent necroses. Within 3 weeks, the patient recovered spontaneously. Prophylactic treatment with lamivudine (Epivir,Glaxo-Wellcome, 150 mg b.i.d.) led to a decrease of HBV-DNA below the detection limit. Further chemotherapy was administered and autologous stem cell transplantation was successfully performed without another reactivation of hepatitis B. Antiviral treatment was stopped 16 weeks after stem cell retransfusion. So far, no further flare-up of hepatitis B has occurred and the patient's lymphoma has not relapsed. Thus, the case described here indicates a possible role of lamivudine in preventing hepatitis B flare-up during antineoplastic chemotherapy. We suggest that lamivudine be considered for prophylaxis against fulminant hepatitis in patients with chronic HBV infection undergoing high-dose antineoplastic therapy. Received: October 26, 1998 / Accepted: January 5, 1999     

Fatal Fulminant Hepatitis B after Withdrawal of Prophylactic Lamivudine in Hematopoietic Stem Cell Transplantation Patients

Hepatitis B virus (HBV) reactivation can give rise to acute hepatitis and even fatal fulminant hepatitis in patients receiving immunosuppressive or cytostatic treatment. Recently, the prophylactic use of lamivudine for HBV reactivation in HBV surface antigen-positive chronic-disease patients undergoing hematopoietic stem cell transplantation (HSCT) has been reported. However, the appropriate duration for this prophylactic therapy is unclear. Here, we report 2 cases of fatal fulminant hepatitis B reactivation in HSCT patients after lamivudine withdrawal. One patient with non-Hodgkin's lymphoma completed 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) and autologous peripheral blood SCT (PBSCT). Lamivudine was discontinued 3 months after transplantation. The second patient had acute myeloid leukemia. He received induction chemotherapy and postremission allogeneic PBSCT as late intensified consolidation therapy. Lamivudine treatment was discontinued 10 months after transplantation. In both patients, HBV reactivation 2 to 3 months following lamivudine cessation led to fatal fulminant hepatitis. We suggest that the duration of prophylactic use of lamivudine in chronic HBV carriers receiving HSCT be prolonged until the patient's immune system has been reconstituted.     

Hepatitis B virus reactivation in a patient undergoing steroid-free chemotherapy

A 62-year-old Japanese man who was positive for hepatitis B surface antigen (HBsAg) and anti-HBe antibody, underwent chemotherapy for non-Hodgkin‘s lymphoma (NHL). Mutations were detected in the precore region (nt1896) of HBV. Because steroid-containing regimen may cause reactivation of hepatitis B virus (HBV) and hepatitis may progress to be fulminant afcer its withdrawal, we administered CHO (CPA, DOX and VCR) therapy and the patient obtained complete response. However, he developed acute exacerbation of hepatitis due to HBV reactivation. Recovery was achieved with lamivudine (100 mg/d) and plasma exchange. The present case suggests that acute exacerbation of hepatitis can occur with steroid-free regimen. Because the efficacy of the prophylactic use of lamivudine has been reported and the steroid enhances curability of malignant lymphoma,the steroid containing regimen with prophylaxis of lamivudine should be evaluated further.     

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation

BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function. CONCLUSIONS: Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.     

Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab

A 59-year-old man developed acute hepatitis with reactivated hepatitis B virus (HBV) following administration of rituximab (anti-CD20 monoclonal antibody). The patient was diagnosed with malignant lymphoma in 1998, and virus marker testing indicated HBV surface antigen (HBsAg)-negative and anti-HBs antibody (anti-HBs)-positive results when chemotherapy including rituximab was started. Levels of aminotransferases were elevated, and HBsAg results turned positive. Despite therapy for late-onset hepatic failure, the patient died. Rituximab appears likely to have induced HBV reactivation in this case. Anti-viral agents should be administered for both HBsAg-positive and anti-HBs-positive patients who are scheduled to receive rituximab.     

Transient reactivation of occult hepatitis B virus infection despite lamivudine prophylaxis in a patient treated for non-Hodgkin lymphoma

A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months.     

Lamivudine for the treatment of hepatitis B virus reactivation following chemotherapy for non-Hodgkin's lymphoma

Chemotherapy for non-Hodgkin's lymphoma (NHL) patients with chronic hepatitis B virus (HBV) infection may be accompanied by severe hepatitis. Of 86 consecutive NHL patients, 11 (12.8%) exhibited a positive serum HBsAg. Six of these patients (54.5%) developed acute exacerbation of chronic HBV infection following chemotherapy and received lamivudine. Five of the six patients demonstrated a clinical improvement, one patient died from fulminant hepatic failure owing to delayed lamivudine therapy and poor compliance. These data suggest that HBsAg screening is necessary before commencing chemotherapy for NHL patients in a hyperendemic area and that lamivudine is effective in treating hepatitis B reactivation during chemotherapy.     

Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance

Lamivudine prophylaxis is an effective strategy in HbSAg-positive patients receiving cancer chemotherapy. Recent data indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates, though its effect on HBV-mortality remains equivocal. This report evaluates the benefits from this strategy among lymphoma patients and develops a management approach for patients with prolonged immunosuppression. A Medline search was conducted to retrieve published trials on HBsAg-positive lymphoma patients receiving prophylactic lamivudine during chemotherapy. Basic inclusion criterion was to report HBV-reactivation rates with and without lamivudine prophylaxis. A meta-analysis of the risk of HBV-reactivation and HBV-related mortality was conducted, and the pooled effect was calculated as risk ratio (RR). We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13–0.35) and a trend in reducing HBV-related mortality (RR 0.68, 95%CI 0.19–2.49). In order to study the long-term effects of anti-HBV prophylaxis when prolonged immunosuppression is needed, we used our findings to model a decision tree. Overall survival was the main outcome used in the analysis. Rituximab maintenance in B-cell lymphomas was used as a paradigm of prolonged immunosuppression. We found that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive patients. If 1,000 HBsAg-positive lymphoma patients receive prophylaxis, one will die from hepatitis B virus reactivation versus 25/1,000 if no prophylaxis is administered. This effect is probably mediated through a reduction of hepatitis B virus reactivation and HBV-related mortality. The ideal antiviral agent needs to be determined.     

Lamivudine therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in hepatitis B surface antigen carriers

Viral reactivation in hepatitis B surface antigen (HBsAg) carriers undergoing immunosuppressive therapy is well documented. To evaluate the role of lamivudine prophylaxis in Hepatitis B virus (HBV) carriers treated with immunosuppression for nonhepatic disorders, we reviewed our experience between 1997 and 2000 at Hadassah University Hospital (Jerusalem, Israel). Controls were patients who were HBV carriers and who, between 1990 and 1995, were treated for hematological malignancies but were not treated with lamivudine. Eighteen HBsAg-positive patients were treated with immunosuppression. Fourteen were males, with a mean age of 48 years. Eleven patients had lymphoma; 2 had colonic adenocarcinoma; and 5 had cryoglobulinemia, enophthalmitis, vasculitis, malignant histocytosis, or ulcerative colitis. Fourteen patients were treated with chemotherapy, and 4 with prolonged high-dose corticosteroids. All patients were HBsAg-positive; 4 had hepatitis B e antigen, and 10 had HBV DNA by polymerase chain reaction. Lamivudine was administered to 13 patients in the treatment group 1 to 60 days (mean, 15 days) before immunosuppressive treatment and continued 0.5 to 24 months (mean, 7 months) following initiation of immunosuppression. Mean follow-up after lamivudine administration was 21 months. Three patients died of lymphoma complications and 10 (77%) survived. None of the patients had clinical or serological evidence of HBV reactivation during or after lamivudine prophylaxis. Of 6 patients who presented with liver function test disturbances, 5 improved during combined lamivudine and immunosuppression treatment. At the end of follow-up, HBV DNA became undetectable in 2 of 10 patients. In 2 patients, seroconversion from HBsAg to anti-HBs was observed. In contrast, 2 of 5 control patients had HBV reactivation. Lamivudine prophylaxis in HBsAg carriers receiving immunosuppressive therapy may prevent HBV reactivation and hepatic failure.     

The effectiveness of lamivudine in preventing hepatitis B viral reactivation in rituximab-containing regimen for lymphoma

In rituximab-containing regimen for lymphoma, the role of lamivudine therapy has not been well established. Therefore, in this nonrandomized phase II clinical study, hepatitis B virus (HBV) carriers with B-cell lymphoma who received rituximab-containing regimen were treated with oral administration of lamivudine. The incidence and severity of hepatitis along with other adverse clinical outcomes were analyzed. Between January 2003 and March 2006, 29 consecutive patients were enrolled. Four of the 29 patients (13.8%) developed hepatitis during chemotherapy, none of which was attributed to HBV reactivation. According to WHO acute toxicity assessment criteria, the severity of hepatitis was grade I in two patients (6.9%) and grade II in two patients (6.9%). In these four patients, only one (3.5%) had interval delay in chemotherapy. No patient had total abnormal bilirubin. No patient had died as the result of hepatitis during the treatment. Interestingly, one of the 29 patients developed HBV activation 5.1 months after the withdrawal of lamivudine. This patient recovered after reinstallation of lamivudine therapy and is still alive. Consequently, our study confirmed previous reports that prophylactic lamivudine therapy can prevent HBV reactivation in HBV carriers who were receiving rituximab-containing regimen for lymphoma.     

Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.     

Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy

With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid‐containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.     

Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.     

Hepatitis B screening,prophylaxis and re‐activation in the era of rituximab‐based chemotherapy

Background: Hepatitis B re‐activation is a well‐described complication in patients with inactive chronic hepatitis B receiving chemotherapy. Screening for HBV and pre‐emptive therapy are recommended. However, the rates of HBV screening, prophylaxis and re‐activation during rituximab‐containing chemotherapy are unknown. Patients and methods: We performed a retrospective study of patients with non‐Hodgkin lymphoma (NHL) who received rituximab between August 1997 and September 2009. We evaluated patients for hepatitis B serologies, antiviral prophylaxis and hepatitis B re‐activation during or up to 6 months after chemotherapy. Results: One thousand four hundred and twenty‐nine patients underwent rituximab‐containing chemotherapy for NHL. Hepatitis B serologies were documented in 524 (36.6%) patients. Of these, 20 (3.8%) were HBsAg positive and 10 (50%) experienced HBV re‐activation. Only half (5/10) had HBV serology documented before re‐activation. Only 3/8 (37.5%) of patients with newly documented HBsAg positivity received antiviral prophylaxis. Virological breakthrough occurred in two of the patients on chronic therapy, in one of three inactive carriers on prophylaxis and in two of five patients not receiving prophylaxis. Re‐activation developed in another five patients not screened previously for hepatitis B. One patient developed ALF and died. Re‐activation did not occur in 25 patients with isolated positive core antibody. Conclusions: At tertiary care institutions hepatitis B serologies are infrequently assessed before rituximab‐based chemotherapy and prophylaxis is uncommon. Greater adherence to recommendations for screening and prophylaxis is necessary. This suboptimal screening rate could be even lower in community hospitals and could result in significant harm to unscreened and unprophylaxed patients.     

Low incidence of hepatitis B virus reactivation during chemotherapy among diffuse large B‐cell lymphoma patients who are HBsAg‐negative/ HBcAb‐positive: a multicenter retrospective study

Background: Reactivation of hepatitis B virus (HBV) is less common in lymphoma patients with prior resolved HBV infection [characterized by hepatitis B surface antigen (HBsAg)‐negative/hepatitis B core antibody (HBcAb)‐positive status] compared with chronic HBV infection (HBsAg positive) when receiving chemotherapy alone. The use of rituximab in chemotherapy regimen might increase the risk of HBV reactivation in patients with prior resolved HBV infection. However, the incidence of HBV reactivation is uncertain, and prophylactic antiviral treatment for this group of patients during rituximab‐containing chemotherapy is controversial. The objective of this study was to determine the incidence of HBV reactivation in HBsAg‐negative/HBcAb‐positive patients diagnosed of diffuse large B‐cell lymphoma (DLBCL) and treated with CHOP‐like or RCHOP‐like regimen. In addition, this study also aims to explore the relationship of HBV reactivation and HBV serology. Methods: Patients were identified using data from six university hospitals collected between January 1998 and November 2008. Four hundred and thirty‐seven patients with complete data were selected based on the diagnosis of CD20+ DLBCL, availability of HBV serum markers prior to initiation of chemotherapy and during the development of hepatitis, completion of at least four cycles of chemotherapy using CHOP‐like or RCHOP‐like regimen, and follow‐up for at least 6 months after completion of treatment. The characteristics of the HBsAg‐negative/HBcAb‐positive patients treated with CHOP‐like regimen were compared to those treated with RCHOP‐like regimen. Results: Eighty‐eight patients of the total 437 patients had pretreatment serology of prior resolved hepatitis B, with a prevalence of 20.1%. Among them, 45 patients received CHOP‐like regimen while 43 patients received RCHOP‐like regimen. Five patients developed hepatitis during treatment, two from CHOP group and three from RCHOP group. Only one patient treated with RCHOP had hepatitis associated with HBV reactivation, while the other four patients did not have evidence of HBV reactivation. Those four patients also demonstrated positive HBsAb at baseline, while the only patient who suffered from HBV reactivation had negative HBsAb status. This patient was successfully treated with antiviral medications. There were no statistically significant risk factors predictive of HBV reactivation. Conclusions: The present study revealed a low HBV reactivation rate of 2.3% in prior resolved hepatitis B among DLBCL patients undergoing RCHOP‐like therapy.     

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin’s lymphoma

Reactivation of hepatitis B virus(HBV)can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy.Prophylactic administration of lamivudine(LAM)reduces the morbidity and mortality associated with HBV reactivation.However,what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established.HBV reactivation may occur due to the cessation of prophylactic LAM,although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen(HBsAg)seroconversion,which is a satisfactory endpoint for the management of HBV infection.We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma.HBV reactivation developed following cessation of prophylactic LAM therapy.The patient subsequently received treatment with entecavir(ETV),which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion.We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients.A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients.We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy.     

Preemptive use of interferon or lamivudine for hepatitis B reactivation in patients with aggressive lymphoma receiving chemotherapy

The hepatitis B virus (HBV) reactivation rate among hepatitis B virus surface antigen (HBsAg)-positive patients undergoing chemotherapy ranges from 21 to 35% with a mortality rate of 4–41%. The risk is significantly evident in patients with aggressive lymphoma, which is highly responsive to standard chemotherapy with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP) achieving a complete response rate of 60–80% and 5-year survival rate of 30–50% with only 1% of treatment-related mortality. -Interferon and lamivudine were given as preemptive treatment for HBV reactivation in HBsAg-positive patients treated for aggressive lymphoma consecutively from 1994 to 1997 and 1998 to 2001, respectively, in our institution. The outcome of 77 HBsAg-positive patients treated for aggressive lymphoma at our institution from 1990 to 2001 was studied. Of these patients, 53 did not receive prophylaxis while 13 received subcutaneous -interferon 3×10⁶ U thrice weekly and 11 received oral lamivudine 100 mg/day simultaneously with chemotherapy. Seventeen patients in the non-prophylactic group experienced HBV reactivation (32%), seven of whom progressed to fatal fulminant hepatitis (41%), which is associated with 13.2% of the mortality rate among the non-prophylactic patients. None of the 24 patients in the prophylactic group had grade III or IV toxicity or elevated ALT level greater than fivefold exceeding 200 IU/l suggestive of clinical hepatitis that required dose reduction or delayed chemotherapy. Thus, preemptive use of -interferon or lamivudine in HBsAg-positive lymphoma patients undergoing chemotherapy may be a promising approach to prevent HBV reactivation that carries a risk of delayed treatment or even fatal outcome.     

Use of entecavir in hepatitis B virus reactivation of a patient with non-Hodgkin's lymphoma

We read with interest the case report by Liu et al and the correspondence by Tuna et al regarding this case. Liu et al described hepatitis B virus(HBV) reactivation in a patient with non-Hodgkin's lymphomaafter withdrawal of lamivudine prophylaxis. When HBV reactivation was observed three months after lamivudine withdrawal, entecavir 0.5 mg daily was started. HBV DNA level was moderately elevated(104 copies/m L) at that time. So, we could not understand why a potent antiviral like entecavir was required for this case. In addition to this, entecavir must be used at a dose of 1 mg in patients with prior prophylactic treatment with lamivudine. As stated by Tuna et al duration of lamivudine prophylaxis in this case might be insufficient and HBV reactivation might have occured for this reason. So, we suppose that resolution of HBV reactivation might also be achieved with lamivudine instead of entecavir in this case.