Prophylactic Lamivudine Administration Prevents Exacerbation of Liver Damage in HBe Antigen Positive Patients with Hepatocellular Carcinoma Undergoing Transhepatic Arterial Infusion Chemotherapy

Nagamatsu, Hiroaki; Itano, Satoshi; Nagaoka, Sakae; Akiyoshi, Junji; Matsugaki, Satoru; Kurogi, Junichi; Tajiri, Nobuyoshi; Yamasaki, Sanki; Koga, Hironori; Torimura, Takuji; Kumashiro, Ryukichi; Sata, Michio

doi:10.1111/j.1572-0241.2004.40069.x

Cited by 54 publications

(52 citation statements)

References 34 publications

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“…This finding is in agreement with the findings of a retrospective study in which lamivudine prophylaxis prevented a deterioration in hepatic functions in HBeAg-positive HCC patients undergoing intraarterial infusion chemotherapy. 21 The beneficial effects of preemptive therapy on the severity of hepatitis most probably result from an elimination of any potential risk arising from viral reactivation. Whether preemptive antiviral therapy would reduce hepatic adverse events during TACL irrespective of viral reactivation remains an issue that should be evaluated further.…”

Section: Discussionmentioning

confidence: 99%

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

Jang¹,

Choi²,

Bae³

et al. 2006

Hepatology

186

211

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Reactivation of hepatitis B virus (HBV) during chemotherapy is well documented. However, there are limited data on this complication in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemotherapy. The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization (TACL) and to seek predictors of this event. A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m 2 and cisplatin 60 mg/m 2 at monthly intervals were prospectively and randomly assigned to receive lamivudine 100 mg daily from the start of TACL (preemptive group) or not (control group). During the study, 11 (29.7%) of 37 patients in the control group and 1 (2.8%) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation (P ‫؍‬ .002). In addition, there were significantly more incidences of overall hepatitis (P ‫؍‬ .021) and severe grade of hepatitis (P ‫؍‬ .035) in the control group. With multivariate Cox regression model, a baseline HBV DNA level of more than 10 4 copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization (P ‫؍‬ .046). In conclusion, preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL. Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10 4 copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia. (HEPATOLOGY 2006;43:233-240.)

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Section: Discussionmentioning

confidence: 99%

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

Jang¹,

Choi²,

Bae³

et al. 2006

Hepatology

186

211

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“…Almost all these patients had intense marrow suppression with a drastic reduction of white cell count, and the rebound of the white cell with immune recovery correlates with the initiation of liver damages [56]. Severe hepatitis due to HBV reactivation has also been reported in HBV-infected patients treated with chemotherapy for other malignancies such as breast cancer [10][11][12], hepatocellular carcinoma [18,57,58], small-cell lung cancer [59], and nasopharyngeal cancer [60]. The relative lack of report in other type of malignancy is probably related to their lower incidence in HBV endemic area, such as the Asia-Pacific region.…”

Section: Chemotherapy or Immunosuppressive Therapy Related To Hbv Reamentioning

confidence: 99%

“…On the other hand, prolonged therapy with nucleos(t)ide analogues is associated with an increased likelihood of developing lamivudine-resistant mutants. Hence, most cancer centers would aim at discontinuing or withdrawing preemptive lamivudine as soon as possible to limit the duration of antiviral therapy [57,85,86,[111][112][113][114][115][116][117][118][119]127]. However, at the moment there is no available consensus on the optimal duration of lamivudine therapy.…”

Section: Preemptive Use Of Nucleoside Analoguesmentioning

confidence: 99%

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Lau

2008

Hepatol Int

102

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Hepatitis due to hepatitis B virus reactivation after cytotoxic or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. With the characterization of the underlying pathogenesis, much progress in the management of this important clinical problem has been made in the past 2 decades. By year 2008, it is mandatory to screen for hepatitis B surface antigen status before initiating intensive chemotherapy or immunosuppressive therapy. All those who are hepatitis B surface antigen positive should be started on preemptive nucleos(t)ide analogues. However, there remains important issues, such as the type and duration of nucleos(t)ide analogue therapy, which need to be understood. As not all hepatitis B surface antigen-positive patients will suffer from HBV reactivation, it is therefore useful to identify risk factors related to HBV reactivation so that patients will not be treated unnecessarily with nucleos(t)ide analogues. To date, a high baseline level of viral replication, as reflected by high serum HBV DNA level, positive serum hepatitis B e antigen, and a high intrahepatic covalently closed circular DNA level, is the most important predictor for HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, such as the Asia-Pacific region. Careful epidemiological study will be needed to clarify the impact of occult hepatitis B infection in patients treated with cytotoxic or immunosuppressive therapy. How important is the problem?Over the past 20 years of clinical practice at Queen Mary Hospital, we have seen a lot of progress in the management of hepatitis due to HBV reactivation in hepatitis B surface antigen carriers [1][2][3][4][5]. In the past, we saw patients who died of fulminant hepatic failure after being administered a few courses of cytotoxic therapy to treat their life-threatening lymphoma [6][7][8][9] and breast cancer [10][11][12] if they were also hepatitis B surface antigen positive. At that time, the literature report of this important clinical issue was scanty. The first report in the field was published by Wand et al. [13] who studied the effects of antitumor chemotherapeutic agents on hepatitis antigen (HBAg) and antibody (HBAb) in 25 patients with myeloproliferative and in 60 patients with lymphoproliferative disorders. This elegant study was performed at the time when only antigen and antibody associated with viral hepatitis could be semiquantified [14]. In those patients who had HBAg at the time of initiation of chemotherapy, bone marrow suppression by chemotherapeutic agents was associated with a marked increase in HBAg titer, which was then followed by hepatocellular damage, as manifested by an elevation in serum transaminase enzymes [13]. Since then, this important observation was further confirmed in other studies [8,15,16], with the rate of HBV reactivation ranging from 19% to 48%. Among them, one-quarter to half would be complicated, with severe hepatitis...

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“…[110][111][112][113][114][115][116][117][118] Table 4 lists reports that compared patients who did and did not receive prophylactic lamivudine; all of these reports demonstrated that the prophylactic antiviral reduced HBV reactivation.…”

Section: Prevention Of Hbv Reactivationmentioning

confidence: 99%

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

2006

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It is estimated conservatively that more than one third of the world's population has been infected with the hepatitis B virus (HBV) and that there are 350 million people with chronic infection, 75% of whom live in Southeast Asia and the Western Pacific regions. [1][2][3] Reactivation of HBV infection is now a well-recognized complication in infected patients who undergo cytotoxic chemotherapy for cancer. The condition ranges from asymptomatic self-limiting anicteric hepatitis to severe, potentially fatal progressive decompensated hepatitis. With the increasing use of potent cytotoxic chemotherapy, reactivation of hepatitis B in endemic regions is becoming a common clinical problem. This adversely affects advances made in various forms of cancer therapy. In this review, we consider the diagnosis, prevention, and management of HBV reactivation in association with chemotherapy and hematopoietic stem cell transplantation, particularly in light of the availability of effective prophylactic antiviral therapy.Reactivation of HBV was first described by Wands et al., 4 who in 1975 reported the condition in 20 patients with lympho-and myeloproliferative disorders. Most of the cases reported since were similar in patients with hematological malignancies-in particular, lymphomas. [4][5][6][7][8][9][10][11][12][13][14][15][16] The skewed observations may be due to the fact that these patients are often subjected to intense myelosuppressive treatment regimens, the malignancies per se are often associated with an immunocompromised state, and the patients have been consistently reported to have a higher rate of hepatitis B surface antigen (HBsAg) seropositivity than the normal population. 9,[17][18][19] Over the past decade, HBV reactivation has been increasingly observed in patients with solid tumors. [18][19][20][21][22] In patients with hepatocellular carcinoma (85% of whom have chronic HBV infection in Southern China 3,23 ), hepatitis following systemic chemotherapy has been reported in 60% 20,24 ; this is mostly attributed to HBV reactivation, which has a 30% mortality rate. 20 In other cancer subpopulations, the incidence of HBV reactivation ranges between 25% and 40%. 10,15,18,21,25 In the setting of hematopoietic stem cell transplantation (HSCT) for various hematological and oncological conditions, HBV reactivation has been reported in over 50% of patients. [26][27][28] This is related to the intense chemotherapy with or without total body irradiation, and the coexistence of acute graft-versus-host disease. 28 Although the frequency of viral reactivation among HBsAg-positive patients with cancer would be expected to be the same irrespective of geographical area, the prevalence of HBV infection varies between different populations from 10% to 25% in endemic areas to less than 1% in others. 3,10,29 As a result, there would be proportional difference in the incidence of viral reactivation in a given population. Definitions and DiagnosisIn early reports, the diagnosis of HBV reactivation was based on HBsAg and hepatitis B ...

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Prophylactic Lamivudine Administration Prevents Exacerbation of Liver Damage in HBe Antigen Positive Patients with Hepatocellular Carcinoma Undergoing Transhepatic Arterial Infusion Chemotherapy

Abstract: These results indicate that prophylactic lamivudine administration reduces HBV-DNA levels and prevents exacerbation of liver damage throughout the period of chemotherapy in HBe antigen positive patients with hepatocellular carcinoma.

Cited by 54 publications

References 34 publications

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy

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