Nucleos(t)ide analogs in the prevention of hepatitis B virus related hepatocellular carcinoma

Table 3 Summary of controlled studies investigating the efficacy of nucleos(t)ide analogues in prevention of hepatocellular carcinoma recurrence after curative treatments

Ref.	Country	Study type	Antiviral treatment	No. ofpatients (T/C)	HCCtreatment	Follow-up (T/C),mean/median (yr)	Treatment outcome
Piao et al[69]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	30/40	Resection or ablation/TACE	Not specified	No risk reduction for HCC recurrence
							Better overall survival
Shuqun et al[70]	China	Retrospective cohort	Lamivudine (100 mg/d) + thymosin α1	17/16	Resection	1-3	Reduced HCC recurrence (NS)
Kuzuya et al[71]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	16/33	Resection or RFA	3.2/2.7	No risk reduction
Kubo et al[72]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	14/10	Resection	2.1	Higher tumor-free survival
Yoshida et al[84]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	33/71	RFA	2.8/3.9	No risk reduction
Hung et al[85]	China	Retrospective cohort	Lamivudine (100 mg/d)	10/62	Resection	1.6	Reduced HCC recurrence
Koda et al[86]	Japan	Retrospective cohort	Lamivudine or entecavir	30/20	Resection or ablation/TAE	2.4/3.0	No risk reduction for HCC recurrence
							Better overall survival
Chuma et al[87]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	39/64	Resection or RFA	2.9/4.4	Reduced HCC recurrence
Li et al[74]	China	Prospective cohort	Lamivudine ± adefovir	43/36	Resection	1.0	No risk reduction
Chan et al[73]	China	Retrospective cohort	Lamivudine or entecavir	42/94	Resection	Not specified	Reduced HCC recurrence
Urata et al[88]	Japan	Retrospective cohort	Not specified	46/242	Resection	3.1	Tumor-free survival is better vs patients with high viral load
Yang et al[89]	China	Prospective cohort	Lamivudine, adefovir or entecavir	142/188	Resection	4.0	Reduced HCC recurrence
Wu et al[75]	Taiwan	Retrospective nationwide cohort	Nucleoside analogue(s)	518/4051	Resection	2.6/2.2	Reduced HCC recurrence
Huang et al[90]	China	Prospective cohort	Lamivudine, adefovir or entecavir	865/175	Resection (HBVDNA > 2000 IU/mL)	3.5	Better disease-free survival (borderline significance)
							Better overall survival
Huang et al[68]	China	Retrospective cohort	Lamivudine, adefovir or entecavir	150/1459	Resection (HBVDNA < 2000 IU/mL)	2.9-3.3	Better disease-free survival
Ke et al[91]	China	Retrospective cohort	Lamivudine (100 mg/d)	141/337	Resection	2.0/1.9	No risk reduction for HCC recurrence
							Better overall survival
Su et al[92]	Taiwan	Retrospective cohort	Lamivudine, entecavir or pegylated interferon	62/271	Resection	3.8	Reduced HCC recurrence
							Better overall survival
Yin et al[76]	China	2 cohorts (RCT and NRC)	Lamivudine1 (100 mg/d)	RCT: 81/82; NRC: 215/402	Resection	RCT: 3.3; NRC: 1.98	Reduced HCC recurrence and better overall survival in both cohorts
Yeh et al[93]	Taiwan	Retrospective cohort	Entecavir, lamivudine, telbivudine, or combination	490/3369	Resection, RFA, PEI	3.3/3.3	No benefits for HCC progression or overall survival
Zhang et al[94]	China	Retrospective cohort	Entecavir (0.5 mg/d)	40/47	Resection	2.6	Reduced recurrence if HCC ≤ 3 cm
Hann et al[95]	United States	Retrospective cohort	NAs	16/9	Resection, RFA, PEI, TACE	5.0	Reduced HCC recurrence
							Better overall survival
Nishikawa et al[96]	Japan	Retrospective cohort	Lamivudine, adefovir or entecavir	99/32	Resection, RFA, PEI	3.5/4.0	No risk reduction for HCC recurrence
							Better overall survival
Huang et al[77]	China	RCT	Adefovir (10 mg/d)	100/100	Resection	5.0	Reduced HCC recurrence
			Switch to entecavir (18 patients)				Better overall survival
Chong et al[97]	China	Retrospective-prospective cohort	Nucleoside analog(s)	254/150	Resection	3.3/3.6	No risk reduction for HCC recurrence
							Better overall survival

¹Adefovir ± lamivudine or entecavir for drug resistance;

²13 patients with high viral load, 11 patients with low viral load. HCC: Hepatocellular carcinoma; T: Treatment group; C: Control group; NS: Not significant; TACE: Transarterial chemoembolization; TAE: Transarterial embolization; RFA: Radiofrequency ablation; PEI: Percutaneous ethanol injection; NAs: Nucleos(t)ide analogues; RCT: Randomized-controlled trial; NRC: Non-randomized cohort.