Risk factors for de novo hepatitis B during solid cancer treatment

Table 1 Primary disease in all hepatitis B surface antigen-negative, hepatitis B core antibody- and/or hepatitis B surface antibody-positive patients

Primary disease	Cases, n
Head and neck cancer	137
Pharyngeal cancer	64
Oral cancer	23
Pharynx cancer	23
Thyroid/parotid/submandibular gland cancer	18
Tongue cancer	7
Nasal cancer	2
Colon cancer	133
Lung cancer	129
Gynecologic cancer	111
Uterine cancer	73
Ovarian cancer	38
Gastric cancer	104
Breast cancer	100
Liver cancer	89
Esophageal cancer	81
Pancreatobiliary cancer	66
Pancreas cancer	33
Bile duct cancer	33
Urological cancer	42
Renal cancer	17
Bladder cancer	14
Prostate cancer	10
Testicular cancer	1
Others	48
Unknown	19
Sarcoma	8
Neuroendocrine tumor	7
GIST	6
Malignant melanoma	4
Rare cancer	4

GIST: Gastrointestinal stromal tumor.

Table 2 Number of patients with hepatitis B virus DNA expression and frequency of hepatitis B virus DNA expression by primary disease in hepatitis B core antibody-positive patients

Primary disease	n (%)
Liver cancer	9/87 (10.3%)
Pancreatobiliary cancer	6/62 (9.6%)
Esophageal cancer	5/72 (6.9%)
Unknown	3/43 (6.9%)
Gastric cancer	5/97 (5.1%)
Head and neck cancer	6/122 (4.9%)
Lung cancer	4/119 (3.3%)
Colon cancer	4/123 (3.2%)
Gynecologic cancer	1/86 (1.1%)
Breast cancer	1/89 (1.1%)
Urological cancer	0/38 (0%)

Table 3 Comparison of viral-related factors between the hepatitis B virus reactivation group and the nonreactivation group

	Reactivation (n = 44)	Nonreactivation (n = 894)	P value
HBcAb titer	9.00 ± 0.45, 95%CI: 8.12-9.89	7.22 ± 0.100, 95%CI: 7.02-7.43	< 0.0001
HBsAb+ (%)	59.0	67.8	0.1490
HBsAb ≤ 10 (mIU/mL) (%)	43.1	35.2	0.1785
HBsAb titer	395.5	473.1	0.059
HBeAb+ (%)	52.0	43.0	0.2540
HCVAb+ (%)	9.0	10.3	0.9417

HBcAb: Hepatitis B core antibody; HBsAb: Hepatitis B surface antibody; HBeAb: Hepatitis B e antibody; HCVAb: Hepatitis C virus antibody.

Table 4 Comparison of background factors, including the type and status of underlying disease, between the hepatitis B virus reactivation group and the nonreactivation group

	Reactivation (n = 44)	Nonreactivation (n = 894)	Fisher P value
Age (75 yr or over) (%)	27.2	23.5	0.3314
Double cancer (%)	25.0	21.8	0.3592
Stage (3, 4) (%)	77.2	72.4	0.2936
HCC (%)	20.9	8.8	0.0150
Digestion and absorption organ (%)	79.0	58.7	0.0051
Bone marrow suppression (%)	30.2	33.4	0.7293

HCC: Hepatocellular carcinoma.

Table 5 Comparison of treatment regimens between the hepatitis B virus reactivation group and the nonreactivation group

	Reactivation (n = 44)	Nonreactivation (n = 894)	Fisher P value
Steroid (%)	65.9	73.1	0.8844
Chemotherapy (%)	86.3	88.4	0.8831
TKI (%)	20.4	23.9	0.7580
IO (%)	6.8	3.7	0.2109
RT (%)	43.1	42.9	0.5466
Operation (%)	52.2	60.9	0.9039

TKI: Tyrosine kinase inhibitor; IO: Immune checkpoint inhibitor; RT: Radiation therapy.

Table 6 Univariate and multivariate analysis of factors contributing to hepatitis B virus reactivation

	Univariant analysis	Odds ratio (95%CI)	Multivariate analysis	Odds ratio (95%CI)
Primary disease in digestion and absorption organs	0.0051	2.65 (1.255-5.595)	0.0095	2.523 (1.24-5.67)
HBcAb titer	< 0.0001	1.263 (1.122-1.439)	0.0002	1.244 (1.10-1.41)
HBsAb titer	0.1580	0.999 (0.998-1.001)
HBsAb negative	0.2490	1.464 (0.789-2.71)

CI: Confidence interval; HBcAb: Hepatitis B core antibody; HBsAb: Hepatitis B surface antibody.

Table 7 Comparison of time to reactivation in the reactivation cases with or without hepatitis B surface antibody

	HBsAb positive (n = 633)	HBsAb negative (n = 305)	Fisher P value
Time to reactivation	197 (93-320)	38.5 (7-178)	0.1281
Reactivation rate within 6 mo (%)	2.05	4.26	0.0459

HBsAb: Hepatitis B surface antibody.