The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma

Chuma, Makoto; Hige, Shuhei; Kamiyama, Toshiya; Meguro, Takeshi; Nagasaka, Atsushi; Nakanishi, Koji; Yamamoto, Yoshiya; Nakanishi, M.; Kohara, Toshihisa; Sho, Takuya; Yamamoto, Keiko; Horimoto, Hiromasa; Kobayashi, Tomoe; Yokoo, Hideki; Matsushita, Michiaki; Todo, Satoru; Asaka, Masahiro

doi:10.1007/s00535-009-0093-z

Cited by 92 publications

(88 citation statements)

References 32 publications

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“…These references comprise 17 retrospective studies [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and 2 RCTs [38,39] . Most of studies come from Asia, including Chinese mainland, Japan, Hong Kong and Tai Wan, which reflects HBV epidemiology and the high incidence of HBV-related HCC in this region.…”

Section: Recurrence-free Survivalmentioning

confidence: 99%

“…Several retrospective studies [21][22][23][26][27][28][29]33,35] showed that NA treatment did not lead to significantly higher recurrence-free survival than non-NA treatment, while other retrospective studies [24,25,[30][31][32]34,36,37] and the RCTs [38,39] showed that NA therapy was associated with significantly higher recurrence-free survival than non-NA treatment.…”

Section: Recurrence-free Survivalmentioning

confidence: 99%

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Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Yang

Wang

et al. 2014

WJH

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Significant advances have been made in nucleos(t)ide analogue (NA) therapy to treat chronic hepatitis B, and this therapy reduces the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in some patients. However, whether NAs can also prevent recurrence after radical resection of HBV-related HCC remains controversial and is an important question, given that most patients will experience recurrence within a few years of curative surgery. Here we systematically reviewed the literature since 2004 on outcomes after administering NAs to patients with HBV-related HCC following radical resection. We focused on treatment indications, duration, effects on recurrence-free survival and overall survival, and the management of NA resistance. We find that patients with HCC should strongly consider NA therapy if they are positive for HBV-DNA, and that the available evidence suggests that postoperative NA therapy can increase both recurrence-free and overall survival. To minimize drug resistance, clinicians should opt for potent analogues with higher resistance barriers, and they should monitor the patient carefully for emergence of NA-resistant HBV.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Antiviral therapy; Hepatitis B virus; Hepatocellular carcinoma; Liver resection; Nucleos(t)ide analogue; Survival rate Core tip: Significant advances have been made in nucleos(t)ide analogue (NA) therapy to treat chronic hepatitis B. However, for patients undergoing radical resection for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), a number of important questions remain undefined, including when NA therapy should be initiated, how long the treatment should continue, and whether NAs can prevent recurrence after radical resection. Here we review the available evidence on these questions in the Medline database. We focus on NA treatment indications, duration, effects on recurrencefree survival and overall survival, and management of NA resistance in patients with HBV-related HCC.Ke Y, Wang L, Li LQ, Zhong JH. Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection. World J Hepatol 2014; 6(9): 652-659 Available from:

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Section: Recurrence-free Survivalmentioning

confidence: 99%

Section: Recurrence-free Survivalmentioning

confidence: 99%

Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Yang

Wang

et al. 2014

WJH

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“…In recent years, several reports from Japan have shown improved survival with lamivudine (LAM) therapy in patients following local treatment of HCC. [5][6][7][8] We report the effect of antiviral therapy on long-term survival (some patients approaching >10 years) of CHB patients whose initial HCC is locally ablated. This study was approved by the Institutional Review Board of Thomas Jefferson University.…”

Section: Dear Editormentioning

confidence: 99%

Prevention of new hepatocellular carcinoma with concomitant antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated

Hann¹,

Bergin²,

Coben³

et al. 2010

Intl Journal of Cancer

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“…High HBV load and replication are associated with greater risk of HCC incidence [3], and large studies with long follow-up have shown that NA therapy can dramatically reduce HCC incidence and death in patients with liver cirrhosis who are chronically infected with HBV [4,5]. NA therapy also appears to reduce risk of HCC recurrence after HR [6,7], suggesting that it may improve OS for patients with HBVrelated HCC after curative HR or RFA.Many retrospective studies have suggested that adjuvant NA therapy does reduce risk of HBV-related HCC recurrence after curative treatments [7][8][9][10][11][12][13][14][15][16][17][18][19]. Meta-analysis of these studies have concluded that NA therapy is associated with significantly lower tumor recurrence and liver-related mortality and significantly higher OS in patients with HBV-related HCC than no adjuvant therapy after curative treatments [20,21].…”

mentioning

confidence: 99%

“…Many retrospective studies have suggested that adjuvant NA therapy does reduce risk of HBV-related HCC recurrence after curative treatments [7][8][9][10][11][12][13][14][15][16][17][18][19]. Meta-analysis of these studies have concluded that NA therapy is associated with significantly lower tumor recurrence and liver-related mortality and significantly higher OS in patients with HBV-related HCC than no adjuvant therapy after curative treatments [20,21].…”

mentioning

confidence: 99%

Nucleos(t)ide analogue therapy for HBV-related HCC after hepatic resection: clinical benefits and unanswered questions

Zhong

2014

Tumor Biol.

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Hepatic resection (HR) and radiofrequency ablation (RFA) remain the most frequent curative therapies for hepatocellular carcinoma (HCC) because of strict indications for liver transplantation and shortages of donated livers. Nevertheless, recurrence occurs in up to 75 % of patients with intermediate or advanced HCC at 5 years after HR [1]; in these patients, 5-year recurrence-free survival (RFS) is lower than 25 %, and tumor recurrence is the main cause of death [2]. Therefore, inhibiting tumor recurrence is a key to improving HCC patients' overall survival (OS).Hepatitis B virus (HBV) is the most common cause of HCC around the world, which inspired clinicians to treat patients with HBV-related HCC using nucleos(t)ide analogues (NAs) to inhibit HBV replication and therefore reduce risk of HCC incidence. High HBV load and replication are associated with greater risk of HCC incidence [3], and large studies with long follow-up have shown that NA therapy can dramatically reduce HCC incidence and death in patients with liver cirrhosis who are chronically infected with HBV [4,5]. NA therapy also appears to reduce risk of HCC recurrence after HR [6,7], suggesting that it may improve OS for patients with HBVrelated HCC after curative HR or RFA.Many retrospective studies have suggested that adjuvant NA therapy does reduce risk of HBV-related HCC recurrence after curative treatments [7][8][9][10][11][12][13][14][15][16][17][18][19]. Meta-analysis of these studies have concluded that NA therapy is associated with significantly lower tumor recurrence and liver-related mortality and significantly higher OS in patients with HBV-related HCC than no adjuvant therapy after curative treatments [20,21]. Unfortunately, the retrospective design of these studies limits the strength of their evidence. The strongest evidence of whether NA therapy offers clinical benefits would come, in principle, from a randomized controlled trial (RCT). However, carrying out an RCT is ethically and logistically difficult because oral NA therapy has already proven effective at preventing disease progression in patients chronically infected with HBV and because such therapy is becoming more affordable and does not cause significant side effects. Therefore, few patients with HBV-related HCC would volunteer for an RCT.Despite these obstacles, Yin et al. managed to publish in 2013 the first RCT examining the efficacy of adjuvant NA therapy in 180 patients newly diagnosed with HBV-related HCC after curative HR [22]. All patients had serum HBV DNA levels greater than 100 IU/mL. After median follow-up of 39.9 months, per-protocol analysis revealed that patients receiving lamivudine (100 mg/day) showed significantly higher short-and long-term RFS and OS than patients receiving no adjuvant therapy. In 2014, Huang and coworkers [23] performed an RCT examining the efficacy of adjuvant adefovir therapy in 200 patients newly diagnosed with HBVrelated HCC after curative HR. In contrast to the earlier RCT, all patients in this study had serum HBV DNA levels greater t...

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The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma

Abstract: Background. Prediction and prevention of hepatitis B virus (HBV)-related

Cited by 92 publications

References 32 publications

Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Prevention of new hepatocellular carcinoma with concomitant antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated

Nucleos(t)ide analogue therapy for HBV-related HCC after hepatic resection: clinical benefits and unanswered questions

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