Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection: A case report

Table 1 Biochemical, serological, and virological data

Index	Normal range	December 2017	March 2018	April 2019	June 2019	August 2019	October 2019	June 2020	July 2021
ALT (U/L)	< 40	13	36	11	14	31	24	17	13
AST (U/L)	< 35	26	23	17	18	25	18	14	14
TBIL (μmol/L)	< 15	9.7	6.2	6.2	9.7	9.8	8.6	9	8.2
PT (s)	11-13	12.2	17.9						12.5
INR	0.8-1.5	1.01	1.55	0.97	1.09	0.96	0.93	0.93	1.06
FIB (g/L)	1.8-3.5	3.4	4.37						2.72
APTT (s)	25-31.3	24.6	30.8						22.9
TT (s)	14-21	18.5	16.3						17.8
AFP (ng/mL)	≤ 7	2.16	1.77	1.67	1.75	1.86	1.79	2	1.7
HBsAg (IU/mL)	< 1	0.650	0.377	0.287	0.330	0.371	0.288	0.394	0.397
Anti-HBs (mIU/mL)	< 10	> 1000	> 1000	> 1000	> 1000	> 1000	> 1000	> 1000	> 1000
HBeAg (S/Co)	< 1.0	60.64	134.4	62.69	27.9	17.72	12.79	10.4	11.82
Anti-HBe (S/Co)	> 1.0	1.3	1.39	1.1	0.994	1.01	1.06	1.09	1.03
Anti-HBc (S/Co)	> 1.0	0.009	0.007	0.007	0.008	0.008	0.007	0.007	0.006
HBV DNA (IU/mL)		3.82 × 104				6.82 × 105			2.72 × 104
HCV DNA (IU/mL)	< 50	< 50	< 50	< 50	< 50	< 50	< 50	< 50	< 50
HIV antibody	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative	Negative
HLA		HLA-A2				HLA-A2			HLA-A2
Hepatic steatosis on B-ultrasound		-	Yes	-	Yes	Yes	-	-	Yes

ALT: Alanine transaminase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; PT: Prothrombin time; INR: International normalized ratio; FIB: Fibrinogen; APTT: Activated partial thromboplastin time; TT: Thrombin time; AFP: Alpha fetoprotein; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B envelope antigen; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HLA: Human leukocyte antigen.

Table 2 Clinical characteristics and hepatitis B virus markers of occult hepatitis B infection patients positive for hepatitis B envelope antigen

Ref.	Case	Biochemical and virological characteristics	Serological characteristics	History of HBV infection history and treatment	Sequencing of the S gene
Han et al[4] 2015, China	Case 1: A 56-year-old man	ALT (U/L): Normal; AST (U/L): Normal; HBV DNA (IU/mL): 234-567	HBsAg: -	Assumed to have resolved HBV infection, treatment naive	Double mutations (A1762T and G1764A) in BCP; no mutations in the preC/C gene; the α determinant sequences were all mutant type
			HBsAb: +
			HBeAg: +
			HBeAb: -
			HBcAb: +
	Case 2: An 81-year-old man	ALT (U/L): Normal; AST (U/L): Normal; HBV DNA (IU/mL): 1130-135	HBsAg: -	Diagnosed with HCC with no known HBV infection history	Double mutations (A1762T and G1764A) in BCP; no mutations in the preC/C gene; three residue substitutions in the α determinant
			HBsAb: +
			HBeAg: +
			HBeAb: -
			HBcAb: +
Zhou et al[5] 2009, China	Case 1: A 50-year-old man	ALT (U/L): Normal; AST (U/L): Not done; HBV DNA: 370-491 copies/mL	HBsAg: -	Not known	The insertion is a perfect repeat of the preceding 15 nts. This insert resulted in an insertion of 5 amino acids between residues 128 and 129 in HBsAg, which is located in the α determinant. HBV variant had mutations both in preS2 and S proteins
			HBsAb: +
			HBeAg: +
			HBeAb: -
			HBcAb: +
Paparella et al[6] 2010, Italy	Case 1: A 76-year-old man	ALT(U/L): Normal; HBV DNA: < 40 IU/mL	HBsAg: -	Peritoneal dialysis since 2004 and regarded as naturally immune to HBV in 2007	Serotype adw2, one immune escape mutation (G145R), and no drug resistance mutations
			HBsAb: +
			HBeAg: +
			HBeAb: -
			HBcAb: -

ALT: Alanine transaminase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B envelope antigen; HCC: Hepatocelluar carcinoma; BCP: Basic core promoter; HBsAb: Hepatitis B surface antibody; HBeAb: Hepatitis B e antibody; HBcAb: Hepatitis B c antibody; nts: Nucleotides.