Hepatocellular carcinoma in chronic hepatitis B patients under antiviral therapy

Table 1 Summary of meta-analyses evaluating the effect of antiviral treatment on the incidence of hepatocellular carcinoma in patients with chronic hepatitis B

1st author, year	No. of studies, total (used1)	Total No. of patients, treated/untreated	Treatment regimen	HCC cases, total n	HCC incidence	RD or RR	95%CI	P value
Cammà et al[22], 2001	7	853/652	IFN-α	122	Overall	RD = -6.4	-2.8--10	< 0.001
	(5)				European studies	RD = -4.8	-11.1-1.5	NS
	(2)				Oriental studies	RD = -8.0	-1.4--14.6	< 0.001
Sung et al[23], 2008	12	1292/1458	IFN-α	190	Overall	RR = 0.66	0.48-0.89	0.006
	(6)				Cirrhotics	RR = 0.53	0.36-0.78	0.001
	(3)				Non-cirrhotics	RR = 0.72	0.16-3.15	NS
	(4)				Virological responders	RR = 0.76	0.08-7.23	NS
	(4)				Non-virological responders	RR = 0.64	0.33-1.26	NS
Yang et al[24], 2009	11	1006/1076	IFN-α	178	Overall	RR = 0.59	0.43-0.81	0.001
Miyake et al[25], 2009	8	553/750	IFN-α	100	Overall	RD = -5.0	-9.4--0.5	0.028
	(3)				European studies	RD = -0.5	-4.9-4.0	NS
	(5)				Asian studies	RD = -8.5	-13.6--3.6	0.001
	(5)				Incidental rate of HCC ≥ 10%	RD = -9.4	-14.2--4.6	< 0.001
	(3)				Incidental rate of HCC < 10%	RD = -0.2	-4.3-4.7	NS
	(4)				HBeAg positive ≥ 70%	RD = -6.0	-11.8--0.2	0.043
	(3)				HBeAg positive < 70%	RD = -5.4	-15.4-4.6	NS
Sung et al[23], 2008	5	1267/1022	LAM	152	Overall	RR = 0.22	0.10-0.50	< 0.001
	(3)				Cirrhotics	RR = 0.17	0.04-0.79	0.020
	(2)				Non-cirrhotics	RR = 0.21	0.10-0.47	< 0.001
	(3)				Drug resistance	RR = 0.52	0.28-0.97	0.040
	(3)				Without drug resistance	RR = 0.37	0.17-0.77	0.008
	(3)				HBeAg positive	RR = 0.21	0.10-0.44	< 0.001
	(3)				HBeAg negative	RR = 0.25	0.06-1.06	NS
Papatheodoridis et al[38], 2010	21 (3)	3881/534	LAM	202	Treated vs untreated	2.8% (22/779) vs 6.4% (34/534)		0.003
	(3)				Treated in remission vs untreated	2.5% (9/353) vs 6.4% (34/534)		0.015
	(3)				Treated without remission vs untreated	2.8% (12/426) vs 6.4% (34/534)		0.016
	(10)				Treated in remission vs treated without remission	2.3% (23/982) vs 7.5% (64/852)		< 0.001
	(14)				Treated in remission under initial therapy vs treated in remission under rescue therapy	2.3% (23/982) vs 5.9% (19/320)		0.003
Singal et al[49], 2013	49 (6)	10025/3571	LAM or Other NAs3	808	LAM2vs untreated	RR = 0.48	0.38-0.61	< 0.001
	(49)				No difference between NAs3	Pooled HCC incidence rate: 1.3 (1.1-1.6) per 100 person-years

¹Number of studies included in each analysis;

²In 6 studies including both LAM treated (n = 3306) and untreated patients (n = 3571);

³In the 49 studies, there were 5946 patients treated with LAM, 1929 patients treated with adefovir, 879 patients treated with entecavir, 616 patients treated with telbivudine and 657 patients treated with tenofovir. IFN-α : Interferon-α; LAM: Lamivudine; NS: Non-significant.