Effect of Antiviral Treatment With Nucleotide/Nucleoside Analogs on Postoperative Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma: A Two-Stage Longitudinal Clinical Study

Yin, Jianhua; Li, Nan; Han, Yaling; Xue, Jie; Deng, Yang; Shi, Jie; Guo, Wei-Xing; Zhang, Hongwei; Wang, Hongyang; Cheng, Shuqun; Cao, Guangwen

doi:10.1200/jco.2012.48.5896

Cited by 264 publications

(294 citation statements)

References 38 publications

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“…Several retrospective studies and a RCT [27,33,35,39] support this idea. However, the other RCT [38] in our review found that NA therapy significantly decreased early HCC recurrence, while it did not report outcomes on late HCC recurrence. NA therapy may inhibit early HCC recurrence, which usually arises due to diffusion of the primary tumor, by reducing high HBV load and HBV mutations, all of which are associated with HCC metastasis and growth [40][41][42] , as well as by inhibiting HBxAg, which promotes HCC invasiveness and metastatic potential [43,44] .…”

Section: Recurrence-free Survivalmentioning

confidence: 55%

“…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%

“…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%

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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: 55%

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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“…However, the therapy fails to provide obvious clinical benefits for reducing early tumor recurrence or improving short-term overall survival (18)(19)(20)(21). This may reflect the fact that the majority of patients in these trials (19,20) were in the early stages of HCC. A longer follow-up of these patients suggested certain clinical benefit.…”

Section: Indications For Nucleos(t)ide Analog (Na) Therapy After Hepamentioning

confidence: 90%

“…The only two randomized trials (19,20) that we identified in literature searches, as well as large cohort studies (18,19,21) examining NA therapy, found that it significantly reduced late HCC recurrence and improved long-term overall survival in patients with HBV-associated HCC following curative hepatectomy. However, the therapy fails to provide obvious clinical benefits for reducing early tumor recurrence or improving short-term overall survival (18)(19)(20)(21). This may reflect the fact that the majority of patients in these trials (19,20) were in the early stages of HCC.…”

Section: Indications For Nucleos(t)ide Analog (Na) Therapy After Hepamentioning

confidence: 99%

Feasibility of combining adjuvant transarterial chemoembolization with nucleos(t)ide analog therapy for patients with HBV-associated hepatocellular carcinoma after hepatectomy

Gong

Zhong

Xiang

et al. 2016

Molecular and Clinical Oncology

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Abstract. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortalities, and its prevalence is expected to increase in future decades. Hepatitis B virus (HBV) infection is the leading cause of HCC. Although hepatectomy is the preferred curative treatment for HCC, tumor recurrence is common, which is the most frequent cause of mortality in patients with HCC. HCC recurrence may originate from the primary tumor or be associated with remnant liver tissue, and include high viral load and hepatic inflammatory activity. Adjuvant transarterial chemoembolization and postoperative nucleos(t)ide analogs therapy are the two corresponding therapies. Following systematic searching of the PubMed database, the indications for adjuvant transarterial chemoembolization and nucleos(t)ide analog therapies for HBV-related HCC after hepatectomy were acquired. Additionally, the feasibility of combining these two therapies were also reviewed.

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Tenofovir vs Entecavir Among Patients With HBV-Related HCC After Resection

Li,

Wang,

et al. 2023

JAMA Netw Open

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ImportanceTenofovir disoproxil and entecavir are both commonly used first-line antiviral treatments, but their comparative recurrence and overall survival (OS) benefits remain unclear.ObjectiveTo explore differences of tenofovir disoproxil vs entecavir in recurrence-free survival (RFS) and OS after liver resection with curative intent in patients with hepatocellular cancer (HCC) related to hepatitis B virus (HBV).Design, Setting, and ParticipantsThis retrospective cohort study was conducted at Eastern Hepatobiliary Surgery Hospital, a tertiary referral hospital in Shanghai, China, between January 4, 2015, and April 1, 2023. Participants included patients with HBV-related HCC who underwent liver resection with curative intent from January 2015 to December 2018. Patients who received tenofovir disoproxil were matched with patients who received entecavir in a 1:1 ratio using propensity score matching. Data were analyzed from April 3 to May 31, 2023.ExposuresReceiving tenofovir disoproxil or entecavir as antiviral treatment for HBV.Main Outcomes and MeasuresPrimary end points were RFS and OS rates.ResultsAmong 4451 patients (mean [SD] age, 58.1 [10.0] years; 3764 male [84.6%]; median [range] follow-up, of 51 [3 to 91] months), 989 patients in each of the groups were selected in propensity score matching. Baseline characteristics were comparable. In propensity score–matched groups, OS rates were 92.2% at 1 year, 70.9% at 3 years, and 54.2% at 5 years in the entecavir group, compared with 90.9% at 1 year, 75.2% at 3 years, and 64.0% at 5 years in the tenofovir disoproxil group. RFS rates were 83.9% at 1 year, 50.0% at 3 years, and 43.3% at 5 years in the entecavir group, compared with 85.3% at 1 year, 55.6% at 3 years, and 51.4% at 5 years in the tenofovir disoproxil group. Patients in the tenofovir disoproxil group had better OS (hazard ratio, 0.82; 95% CI, 0.72 to 0.94; P = .004) and RFS rates (hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) compared with the entecavir group. Restricted mean survival time differences of entecavir vs tenofovir disoproxil groups were −0.05 (95% CI, −0.18 to 0.08) months at 1 year (P = .45), 0.20 (95% CI, −0.62 to 1.03) months at 3 years (P = .63), and 1.82 (95% CI, 0.14 to 3.51) months at 5 years (P = .03).Conclusions and RelevanceThese findings suggest that in patients undergoing curative liver resection for HBV-related HCC, tenofovir disoproxil was associated with better long-term OS and RFS rates compared with entecavir, providing insights for antiviral treatment.

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Effect of Antiviral Treatment With Nucleotide/Nucleoside Analogs on Postoperative Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma: A Two-Stage Longitudinal Clinical Study

Abstract: Although it might not affect the HCC-promoting potential of Ct-HBx, NA treatment is effective in normalizing liver function, decreasing HBV-HCC recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III RCT.

Cited by 264 publications

References 38 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

Feasibility of combining adjuvant transarterial chemoembolization with nucleos(t)ide analog therapy for patients with HBV-associated hepatocellular carcinoma after hepatectomy

Tenofovir vs Entecavir Among Patients With HBV-Related HCC After Resection

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