Although the mainstay of treatment of patients with nasopharyngeal carcinoma (NPC) had been radiotherapy, chemotherapy has increasingly been adopted in conjunction with radiation and in advanced disease. In parts of Asia where NPC is prevalent, it is also known that around 10% of the population has chronic hepatitis B virus (HBV) infection. Cancer patients who are HBV carriers are frequently complicated by HBV reactivation during chemotherapy. This may result in liver damage, which disrupts anticancer therapy and compromises the patients' prognosis. In its most severe form, fatal hepatic failure may occur. With the increasing use of chemotherapy in NPC, the occurrence of HBV reactivation is likely to increase further. Although recent reports have suggested that the antiviral agent lamivudine may reduce HBV reactivation and its associated morbidity, there has been no data on this aspect in NPC patients. This study assessed the role of lamivudine in preventing HBV reactivation and its associated morbidity in NPC patients who have chronic HBV infection and are undergoing chemotherapy.
Two groups were studied. One group consisted of 16 patients who received prophylactic lamivudine prior to and until 8 weeks after discontinuing chemotherapy. The other comprised 21 historical control subjects who underwent chemotherapy without prophylactic lamivudine. The outcomes were compared.
With prophylactic lamivudine, there were significantly fewer incidences of hepatitis (6.7% vs 33.3%, P = 0.047) and HBV reactivation (0% vs 28.6%, P = 0.027), and less disruption of chemotherapy (18.8% vs 67.7%, P = 0.045).
Prophylactic lamivudine significantly reduces the incidence and morbidity of HBV reactivation in NPC patients undergoing chemotherapy.
"Whilst no uniform definition of reactivation exists one that is commonly used is the presence of hepatitis (as suggested by an ALT > 3ULN) in combination with either a 10-fold rise in HBV DNA viral load or an absolute value greater than 20,000 IU/ml. The risk of reactivation for HBsAg-positive patients undergoing chemotherapy for haematological malignancy is between 33% and 67% (Lok et al., 1991; Nakamura et al., 1996; Markovic et al., 1999; Yeo et al., 2005), with regimes containing high dose steroid or rituximab independently increasing risk (Cheng, 1996; Takai et al., 2005; Hui et al., 2006). Patient factors conferring increased risk include high serum HBV DNA pre-chemotherapy (Lau et al., 2002; Yeo et al., 2004), male sex and high levels of ALT. "
[Show abstract][Hide abstract] ABSTRACT: Patients with chronic hepatitis B virus (HBV) infection have a substantial risk of reactivation and jaundice following the use of immunosuppressant therapy. A single topic conference was convened to discuss the management of HBV patients undergoing chemotherapy for haematological malignancy, liver and renal transplantation and with HIV co-infection. In advance of the meeting a draft guideline was prepared and circulated to a participating expert panel. Presentations and consensus views were obtained on the day of conference to allow pragmatic algorithms to be established on each of these topics. Use of lamivudine prophylaxis for HBV patients undergoing chemotherapy and renal transplantation is strongly supported with good evidence. Patients with HBV cirrhosis who are candidates for transplantation should be started on nucleos(t)ide therapy prior to surgery and, in addition, hepatitis B immune globulin given from the time of transplantation onward. Co-infection with HBV and HIV offers unique challenges. If the patient is a candidate for highly active retroviral therapy then dual nucleos(t)ide analogues which are also active against HBV must be used to prevent immune reconstitution hepatitis. In all these conditions, awareness of possible HBV resistance to therapy must be kept in mind and HBV DNA levels monitored.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) reactivation is a common but preventable complication of immunosuppression. With the advent of new
therapies that provide efficient and prolonged immunosuppression, the incidence of HBV reactivation is likely to increase.
The clinical presentation can range from mildly elevated aminotransferase values to fatal fulminant hepatitis. Despite prompt
antiviral therapy, the mortality rates remain high, and it can adversely affect the outcome of immunosuppressive therapy for
the underlying hematological disease. Over the past decade, several studies evaluated the risk of HBV reactivation, role of
serological tests, and effectiveness of antiviral therapies in preventing severe hepatic dysfunction among patients undergoing
immunosuppressive therapy. Studies show that HBV antiviral therapy given prior to chemotherapy may prevent HBV replication,
and reduce the risk of HBV reactivation during the immunosuppression period. This article reviews the current literature and
society guidelines on HBV reactivation, risk factors, and prophylaxis for HBV reactivation in patients undergoing chemo-/immunosuppressive
KeywordsHepatitis B virus-Hepatitis B virus reactivation-Bone marrow transplantation-Chemoprevention-Immunosuppression
Current Hepatitis Reports 08/2010; 9(3):178-186. DOI:10.1007/s11901-010-0048-0
[Show abstract][Hide abstract] ABSTRACT: Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized.
To review current randomized-controlled trials, randomized trials and prospective case series to provide a clinically applicable, evidence-based recommendation.
The published literature was identified using a MEDLINE/PubMed search with secondary review of cited publications, and inclusion of all prospective studies.
In nine prospective trials and one randomized-controlled trial, the rate of hepatitis among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173, 9.2%), compared with 33-67% among controls. Of patients receiving prophylaxis, 0-24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29-56% of controls. Three reactivation-related mortalities were reported (one receiving prophylaxis, two controls). No patients withdrew secondary to toxicity or development of lamivudine-resistant mutations.
The available data show a four- to sevenfold decrease in the rate of hepatitis and hepatitis B virus reactivation in patients who receive lamivudine prophylaxis. It is thus recommended that all hepatitis B surface antigen carriers receive lamivudine, or a comparable anti-viral agent, as prophylaxis from the initiation of chemotherapy until at least 1 year following its completion.
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