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

Yang, Ke; Wang, Lin; Li, Le‐Qun; Zhong, Jian‐Hong

doi:10.4254/wjh.v6.i9.652

Cited by 14 publications

(16 citation statements)

References 44 publications

(125 reference statements)

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“…Nucleos(t)ide analogue‐based antiviral treatment has been reported to reduce the late‐stage recurrence rate and to improve survival after hepatectomy or liver transplantation . A systematic review found that the median 5‐year OS among NA‐treated patients with HBV DNA‐positive HCC was significantly higher (73%) than that among patients who did not receive NA treatment after resection (62%) . Thus, our findings that both the OS and RFS rates in the NA monotherapy group were significantly higher than those in the non‐antiviral group further support the benefit of antiviral treatment for HBV DNA‐positive HCC patients.…”

Section: Discussionsupporting

confidence: 70%

“…In clinical evaluation, combination therapy was superior to IFN monotherapy with regard to the loss of serum HBV DNA (risk ratio (RR)=1.55, 95% confidence interval (CI): 1.44‐1.66, P < .00001) as well as hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) positivity (RR = 1.38, 95% CI: 1.22‐1.56, P < .00001; RR = 1.69, 95% CI: 1.03‐2.78, P = .04, respectively) after 48 weeks of treatment . Another meta‐analysis showed significantly higher HBeAg loss (RR = 1.73, 95% CI: 1.32‐2.26, P < .001), HBV DNA negativity (RR = 1.58, 95% CI: 1.22‐2.04, P < .001), HBeAg seroconversion (RR = 1.68, 95% CI: 1.36‐2.07, P < .001) and HBsAg seroclearance (RR = 2.51, 95% CI: 1.32‐4.75, P < .001) in the combination therapy group compared with the NA monotherapy group . Because IFN also possesses antineoplastic potential, a combination of IFN with NAs may offer significant benefits for HBV DNA‐positive HCC patients.…”

Section: Introductionmentioning

confidence: 99%

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Peg‐interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti‐HBV efficacy and long‐term survival among HBV DNA‐positive hepatocellular carcinoma patients after hepatectomy/ablation

Zhang

et al. 2019

Journal of Viral Hepatitis

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Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA‐positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi‐centre trial enrolled HBV DNA‐positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg‐interferon [IFN]α‐2a co‐administration during year 1); late combination (addition of Peg‐IFNα‐2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non‐antiviral treatment. Primary endpoints included recurrence‐free survival and overall survival. A total of 447 patients were enrolled. The 2‐year and 8‐year recurrence‐free survival and 8‐year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P < .05). After 48‐week treatment, more patients achieved an HBsAg reduction >1500 IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P < .05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA‐positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48‐week treatment is associated with reduced mortality and disease recurrence of HBV DNA‐positive HCC patients after hepatectomy/ablation.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Peg‐interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti‐HBV efficacy and long‐term survival among HBV DNA‐positive hepatocellular carcinoma patients after hepatectomy/ablation

Zhang

et al. 2019

Journal of Viral Hepatitis

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“…However, these novel drugs are very expensive and unavailable in some countries; for example, tenofovir disoproxil fumarate became available in People’s Republic of China only in 2014. Moreover, these guidelines18,32–36 were developed for patients whose major disease is chronic hepatitis B, and it is unclear whether they are optimal for patients with HBV-related HCC 10. A recent retrospective study11 with a small sample size reported that LAM and entecavir were associated with similar antiviral efficacy, incidence of antiviral resistance, and overall survival in patients in advanced stages of HBV-related HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Five oral anti-HBV agents, all nucleos(t)ide analogues, are widely used in the clinic: lamivudine (LAM), adefovir dipivoxil (ADV), entecavir, telbivudine, and tenofovir disoproxil fumarate. Two randomized controlled trials,6,7 a nationwide cohort study8 and two systematic reviews,9,10 have shown that these analogues increase overall and recurrence-free survival in some patients with HBV-related HCC after radical resection. However, these findings are based on comparisons with placebo or no treatment, leaving open the question of how the analogues compare with one another.…”

Section: Introductionmentioning

confidence: 99%

Adefovir dipivoxil is less expensive than lamivudine and associated with similar prognosis in patients with hepatitis B virus-related hepatocellular carcinoma after radical resection

Zhong

Yang

Zhu

et al. 2016

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AimLamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients.MethodsWe retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n=155) or ADV (n=46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free, and overall survival, as well as antiviral medication costs.ResultsDespite significant improvement in HBV-DNA and alanine aminotransferase level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2, and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, and 56.4%) than in the ADV group (0%, 3.3%, and 14.5%; P<0.001). Overall survival at 1, 2, and 3 years after resection was similar for the LAM group (84.5%, 69.3%, and 64.6%) and the ADV group (84.1%, 77.8%, and 63.4%; P=0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, and 43.9%) and the ADV group (81.1%, 66.1%, and 53.0%; P=0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, and 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, and €5.6 per person per day) than in the ADV group (€2.2, €2.4, and €3.1 per person per day; all P<0.05).ConclusionADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.

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“…Moreover, it is unclear whether these guidelines are optimal or even appropriate for patients with HBVrelated HCC [36]. Since NA therapy cannot completely eradicate HBVand the treatment goal is to reduce HBV replication as much as possible to minimize the risk of reactivation, some investigators have advocated continuing antiviral treatment indefinitely, regardless of whether HBV DNA levels are undetectable or HBeAg seroconversion occurs [37,38].…”

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

Cited by 14 publications

References 44 publications

Peg‐interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti‐HBV efficacy and long‐term survival among HBV DNA‐positive hepatocellular carcinoma patients after hepatectomy/ablation

Peg‐interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti‐HBV efficacy and long‐term survival among HBV DNA‐positive hepatocellular carcinoma patients after hepatectomy/ablation

Adefovir dipivoxil is less expensive than lamivudine and associated with similar prognosis in patients with hepatitis B virus-related hepatocellular carcinoma after radical resection

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

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