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

Table 1 Summary of controlled studies investigating the effect of nucleos(t)ide analogues on hepatocellular carcinoma risk among treated and untreated patients with chronic hepatitis B

Ref.	Country/region	Study type	Treatment	No. ofpatients (T/C)	Patient cohort	Follow-up (T/C), mean or median (yr)	Treatment outcome
Liaw et al[30]	Asia	RCT	Lamivudine (100 mg/d)	436/215	Advanced fibrosis or cirrhosis	2.7/2.7	Reduced HCC risk
Manolakopoulos et al[80]	Greece	Case-control	Lamivudine (100 mg/d)	30/30	Decompensated cirrhosis	1.5/1.8	No risk reduction
Matsumoto et al[33]	Japan	Retrospective cohort	Lamivudine (100 mg/d)	377/377	Chronic hepatitis B (any stage)	2.7/5.3	Reduced HCC risk
Papatheodoridis et al[40]	Greece	Retrospective cohort	Lamivudine (adefovir switch or add-on when required)	201/195	HBeAg-negative chronic hepatitis B	3.8/6.1	Better overall survival. Reduced risk of major events including HCC
Chan et al[32]	China	RCT	Lamivudine (100 mg/d)	89/47	HBeAg-negative chronic hepatitis B	2.5/2.5	No risk reduction
Yuen et al[34]	China	Prospective cohort	Lamivudine (25-100 mg/d)	142/124	HBeAg-positive chronic hepatitis B	7.5/9.0	Reduced cirrhosis/HCC risk
Lee et al[36]	South Korea	Retrospective cohort	Lamivudine (100 mg/d)	589/589	Chronic hepatitis B (any stage)	2.9/5.3	Reduced HCC risk
Ma et al[35]	China	Prospective cohort	Lamivudine (100 mg/d)	41/176	Cirrhosis	3.16/NS	Reduced HCC risk
Das et al[39]	India	Case-control	Lamivudine or adefovir	151/102	Decompensated cirrhosis	4.0/3.8	Less HCC rate in treated group
Eun et al[37]	South Korea	Retrospective cohort	Lamivudine (100 mg/d)	872/699	Chronic hepatitis B (any stage)	4.7/5.7	Reduced HCC risk in cirrhotic patients with SVS
Kim et al[38]	South Korea	Retrospective cohort	Lamivudine and/or adefovir, or entecavir	240/481	Cirrhosis	3.9/4.3	Better overall survival. Reduced HCC risk (borderline significance)
Hosaka et al[46]	Japan	Retrospective cohort	Entecavir (0.5 mg/d)	316/316	Chronic hepatitis B (any stage)	3.3/7.6	Reduced HCC risk
Wong et al[47]	China	Retrospective cohort	Entecavir (0.5 mg/d)	1446/424	Chronic hepatitis B (any stage)	3.0/9.5	Reduced HCC risk in cirrhotic patients
Kumada et al[81]	Japan	Retrospective cohort	Lamivudine ± adefovir, entecavir	117/117	Chronic hepatitis B (any stage)	12.3/11.6	Reduced HCC risk
Sievert et al[49]	Reg. trial (abstract)	Prospective cohort	Tenofovir (300 mg/d)	641	Chronic hepatitis B (any stage)	6	Reduced HCC risk compared to estimated risk (REACH-B model)
Su et al[48]	Taiwan	Prospective cohort	Entecavir (0.5 mg/d)	1123/503	Cirrhosis (HBVDNA > 2000 IU/mL)	3.6/6.8
Wu et al[44]	Taiwan	Retrospective nationwide cohort	Lamivudine, adefovir or entecavir	21595/21595	Chronic hepatitis B (any stage)	3.5/5.2	Reduced HCC risk
Gordon et al[82]	United States	Retrospective cohort	94% received NAs, remaining received IFNs	820/1851	Chronic hepatitis B (any stage)	5.2	Reduced HCC risk
Coffin et al[83]	United States	Retrospective cohort	NAs	322	Chronic hepatitis B (any stage)	3.2	Reduced HCC risk compared to estimated risk (REACH-B model)

NAs: Nucleos(t)ide analogues; HCC: Hepatocellular carcinoma; T: Treatment group; C: Control group; RCT: Randomized-controlled trial; HBeAg: Hepatitis B e antigen; SVS: Sustained virological suppression; IFNs: Interferons.