Role of occult hepatitis B virus infection in chronic hepatitis C

Table 1 The studies evaluating the role of anti-HBc in the development of cirrhosis in HBsAg-negative patients with chronic hepatitis C

First author, year	No. of patients	Country	Type of study	Cirrhosis, positive/tested, n/n (%)		P value
				HBcAb+	HBcAb-
Verbaan 1998[63]	99	Sweden	Cross-sectional	10/44 (22.7)	10/55 (18.2)	NS
De Maria 2000[37]	285	United States	Cross-sectional	29/90 (32.2)	41/195 (21.0)	< 0.05
Sagnelli 2000[24]	174	Italy	Case-control	9/76 (11.8)	6/98 (6.1)	< 0.005
Giannini 2003[38]	119	Italy	Cross-sectional	20/48 (41.6)	15/71 (21.0)	0.020
Dinis-Ribeiro 2005[59]	129	Portugal	Cross-sectional	14/30 (46.6)	32/99 (32.3)	HR:1.35 (1.01-2.69)1
Helmy 2006[64]	169	Saudi Arabia	Cross-sectional	14/85 (16.5)	45/84 (53.6)	0.0001
Laguno 2008[65]	238	Spain	Cross-sectional	78/142 (55)2	49/96 (51)2	0.720
Carvalho-Filho 2009[60]	111	Brazil	Cross-sectional	24/31 (77.4)3	40/80 (50.0)3	0.017
El-Sherif 2009[61]	100	Egypt	Cross-sectional	68/71 (95.8)	23/29 (79.3)	0.009
Levast 2010[66]	140	France	Cross-sectional	5/45 (11.1)	16/95 (16.8)	NS
Coppola 2014[62]	222	Italy	Cross-sectional	21/77 (27.3)	12/145 (8.3)	< 0.009

¹Hazard ratio for progression to cirrhosis in HBsAb/HBcAb⁺ patients;

²Advanced fibrosis (Scheuer score > 2);

³Advanced fibrosis (Metavir score F2-F4). NS: Not significant.

Table 2 The studies evaluating the role of hepatitis B virus DNA in serum and/or liver tissue in the development of cirrhosis in surface antigen of hepatitis B virus-negative patients with chronic hepatitis C

First author, year	No. of patients	Country	Type of study	Liver disease	Sample for HBV-DNA detection	Cirrhosis, positive/tested, n/n (%)		P value
						OBI+	OBI-
Cacciola 1999[31]	200	Italy	Cross-sectional	CH/cirrhosis	Liver	22/66 (33.3)	26/134 (19.4)	0.040
Fukuda 1999[35]	65	Japan	Cross-sectional	CH/cirrhosis	Serum	5/34 (14.7)	3/31 (9.7)	NS
Giannini 2003[38]	119	Italy	Cross-sectional	CH/cirrhosis	Serum	2/8 (25.0)	32/111 (28.8)	NS
Silva 2004[71]	59	Brazil	Cross-sectional	CH/cirrhosis	Serum	2/10 (20.0)	6/49 (12.0)	NS
Toberson 2004[70]	180	United States	Cross-sectional	CH/cirrhosis	Serum	8/81 (9.9)1	11/99 (11.1)1	NS
Hui 2006[72]	74	United States	Cohort	CH/cirrhosis	Serum	6/31 (19.4)2	8/43 (18.6)2	NS
Hui 2006[73]	118	United States	Cohort	Liver transplantation	Serum	8/41 (19.5)2	13/77 (16.9)2	NS
Mrani 2007[67]	203	France	Cross-sectional	CH/cirrhosis	Serum	28/47 (60.0)	52/156 (33.3)	< 0.001
Laguno 2008[65]	90	Spain	Cross-sectional	CH/cirrhosis	Serum	8/15 (53.3)3	37/75 (49.3)3	NS
Matsuoka 2008[68]	468	Japan	Cross-sectional	CH/cirrhosis	Serum	37/204 (18.1)	28/264 (10.6)	0.002
Sagnelli 2008[44]	89	Italy	Cohort	CH/cirrhosis	Serum/PBMC/liver	10/37 (27.0)3	19/52 (36.5)3	NS
Emara 2010[74]	155	Egypt	Cross-sectional	CH/cirrhosis	Serum	0/6 (0.0)	4/149 (2.7)	0.020
Squadrito 2013[69]	326	Italy	Cohort	CH/cirrhosis	Liver	30/128 (23.4)	25/198 (12.6)	< 0.01

¹Advanced fibrosis (Ishak score 3-6);

²Severe fibrosis (Metavir score F3-F4);

³Advanced fibrosis (Scheuer score > 2); ⁴Severe fibrosis (Scheuer score 3-4). CH: Chronic hepatitis; PBMC: Peripheral blood mononuclear cells; NS: Not significant; HBV: Hepatitis B virus; OBI: Occult HBV infection.

Table 3 The studies evaluating the role of anti-hepatitis B core in the development of hepatocellular carcinoma in surface antigen of hepatitis B virus-negative patients with chronic hepatitis C

First author, year	No. of patients	Country	Type of study	Liver disease	HCC, positive/tested, n/n (%)		P value
					Anti-HBc+	Anti-HBc-
Takano 1995[84]	61	Japan	Cohort	CH	9/36 (25.0)	2/25 (8.0)	NS
Chiba 1996[76]	412	Japan	Cohort	CH/cirrhosis	47/198 (23.7)	16/214 (7.5)	0.020
Chiba 1996[77]	204	Japan	Cross-sectional	cirrhosis	92/128 (71.9)	36/76 (47.4)	0.0005
Shiratori 1997[86]	502	Japan	Case-control	CLD	111/263 (42.2)	81/239 (33.9)	NS
IIHCSG 1998[85]	451	Italy	Cohort	CLD	34/206 (16.5)	32/245 (13.1)	NS
Dutta 1999[78]	51	Australia	Case-control	CH/cirrhosis	10/17 (58.8)	7/34 (20.6)	0.010
Marusawa 1999[34]	2366	Japan	Cross-sectional	CH/cirrhosis	363/1047 (34.7)	248/1319 (18.8)	< 0.01
Hiraoka 2003[48]	202	Japan	Case-control	CLD	109/250 (43.6)	93/342 (27.2)	NS
Imazeki 2003[79]	459	Japan	Cohort	CH/cirrhosis	37/160 (23.1)	26/299 (8.7)	< 0.05
Hasegawa 2005[87]	140	Japan	Cohort	CH/cirrhosis	9/64 (14.0)	9/76 (11.8)	NS
Tanaka 2006[80]	74	Japan	Cohort	CLD	13/53 (24.5)	0/21 (0.0)	0.012
Bruno 2007[49]	160	Italy	Cohort	Cirrhosis	29/86 (33.7)	25/74 (33.8)	0.390
Ikeda 2007[81]	846	Japan	Cohort	CH/Cirrhosis	130/392 (33.1)	107/454 (23.6)	IRR: 1.03 (0.66-1.56)1
							IRR: 1.58 (1.12-2.22)2
Adachi 2008[82]	123	Japan	Cohort	Cirrhosis	57/96 (59.3)	10/27 (37.0)	0.0039
Alencar 2008[89]	50	Brazil	Cross-sectional	Cirrhosis	5/12 (41.7)	12/38 (31.6)	NS
Miura 2008[94]	141	Japan	Cohort	CH	22/83 (26.5)	11/58 (19.0)	0.700
Ramia 2008[88]	3364	Lebanon	Cross-sectional	CH/cirrhosis/healthy controls	7/408 (1.7)	2/2956 (0.07)	0.507
Stroffolini 2008[47]	693	Italy	Cohort	Cirrhosis	44/303 (14.5)	57/390 (12.0)	0.900
Ohki 2010[90]	1262	Japan	Cohort	CLD	160/522 (30.6)	179/740 (24.2)	0.630
Lok 2011[43]	273	United States	Case-control	CH/Cirrhosis	38/121 (31.4)	53/152 (35.0)	0.540
Reddy 2013[83]	459	United States	Case-control	CLD	95/229 (41.5)	27/230 (11.7)	0.010
Tsubouchi 2013[91]	400	Japan	Cohort	CLD	24/213 (11.3)	14/187 (7.5)	0.280

¹Incidence Rate Ratio for HCC in patients with chronic hepatitis;

²Incidence Rate Ratio for HCC in patients with cirrhosis. CH: Chronic hepatitis; CLD: Chronic liver disease; NS: Not significant; HCC: Hepatocellular carcinoma; HBc: Hepatitis B core.

Table 4 The studies evaluating the role of hepatitis B virus DNA in serum and/or liver tissue in the development of hepatocellular carcinoma in surface antigen of hepatitis B virus-negative patients with chronic hepatitis C

First author, year	No. of patients	Country	Type of study	Liver disease	Sample for HBV-DNA detection	HCC, positive/tested, n/n (%)		P value
						OBI+	OBI-
Pollicino 2004[39]	226	Italy	Case-control	CH/cirrhosis/ HCC	Liver	45/101 (44.5)	28/125 (22.4)	< 0.001
Tanaka 2004[80]	93	Japan	Cross-sectional	CH/cirrhosis/ HCC	Serum	25/32 (78.1)	25/61 (41.0)	< 0.001
Hasegawa 2005[87]	140	Japan	Cohort	CH/cirrhosis	Serum	2/11 (18.2)	16/129 (12.4)	NS
Squadrito 2006[40]	134	Italy	Cohort	CH/cirrhosis	Liver	8/53 (15.1)	1/81 (1.2)	0.002
Branco 2007[93]	66	Brazil	Cross-sectional	CH/HCC/health controls	Serum/liver1	7/10 (70.0)	13/56 (23.2)	0.029
Adachi 2008[82]	123	Japan	Cohort	Cirrhosis	Serum	6/14 (42.9)	60/109 (55.0)	NS
Matsuoka 2008[68]	468	Japan	Cohort	CH/cirrhosis	Serum/liver1	29/204 (14.2)	9/264 (3.4)	0.0001
Miura 2008[94]	141	Japan	Cohort	CH	Serum	4/8 (50.0)	29/133 (21.8)	0.0036
Obika 2008[41]	167	Japan	Cohort	CLD	Liver	2/25 (8.0)	10/142 (7.0)	NS
Shetty 2008[42]	44	United States	Cross-sectional	cirrhosis	Liver	12/22 (54.5)	8/22 (36.3)	NS
Lok 2011[43]	83	United States	Case-control	CH/Cirrhosis	Liver	3/16 (18.7)	25/67 (37.3)	NS
Squadrito 2013[69]	94	Italy	Cohort	CH/cirrhosis	Liver	13/37 (35.1)	5/57 (8.1)	< 0.01

¹OBI assessed with immunochemistry for HBsAg and/or HBcAg. OBI: Occult HBV infection; CH: Chronic hepatitis; CLD: Chronic liver disease; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma.