Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients

Table 1 Characteristics of included studies

Ref. (first author, year)	Country/region	Type of study	Sample size/LLV/MVR	Age (year)/sex (male%)	Definition of LLV	Baseline ALT (U/L)	HBeAg positive (n)	Diabetes (%)	Duration of follow-up	Outcomes reported (HR, 95%CI)	Adjustments for confounders
Huang et al[11], 2023	Korea, Singapore, Japan	Retrospective cohort study	1075/742/333	LLV: 55.1/67.8%; MVR: 59.1/72.1%	With ≥ 1 detectable serum HBV-DNA (20-2000 IU/mL)	LLV: 38.5; MVR: 31.2	LLV: 109; MVR: 46	LLV: 16.3; MVR: 19.2	LLV: 62.8 months; MVR: 64.2 months	HCC: MVR Ref LLV 1.20 (0.79, 1.82); Hepatic decompensation: MVR Ref LLV 1.10 (0.66, 1.82)	Sex, diabetes, positive HBeAg, FIB-4 index, Albumin, eGFR, recruitment centers
Lee et al[20], 2020	Korea	Retrospective cohort study	440/110/330	LLV: 51.1/80.6%; MVR: 52.9/61.5%	With ≥ 1 detectable serum HBV-DNA (12-2000 IU/mL)	138.31	6.4%1	NA	132 months	HCC: MVR Ref LLV 2.64 (1.10, 6.34); Hepatic decompensation: MVR Ref LLV 2.75 (1.39, 5.45)	NA
Lee et al[23], 2022	Korea	Retrospective cohort study	567/391/176	54.8/67.9% (LLV: 54.0/66.5%; MVR: 56.7/71.0%)	With ≥ 1 detectable serum HBV-DNA (20-2000 IU/mL)	30.0 (LLV: 30.3; MVR: 29.3)	81 (LLV: 50; MVR: 31)	LLV: 15.1; MVR: 14.8	71.9 months	HCC: MVR Ref LLV 1.42 (0.69, 2.91); Liver-related clinical events: MVR Ref LLV 1.82 (0.84, 3.91)	Age, sex, alcohol consumption, HBeAg, AST, ALT, total bilirubin, albumin, platelet count, and eGFR no. of LLV episodes
Sinn et al[21], 2015	Korea	Retrospective cohort study	246/175/71	51.8/66%1	With ≥ 1 detectable serum HBV-DNA (12-2000 IU/mL)	24 (median)1	111	NA	5.6 years (median)	HCC: MVR Ref LLV 4.79 (1.11, 20.50)	Age
Yang et al[9], 2023	Korea	Retrospective cohort study	627/386/241	54.7/64.4% (LLV: 52.2/65.8%; MVR: 58.7/62.2%)	With ≥ 1 detectable serum HBV-DNA (20-2000 IU/mL)	24 (LLV: 25; MVR: 23)	22 (LLV: 19; MVR: 3)	LLV: 16.4; MVR: 23.7	3.9 years	HCC: MVR Ref LLV 2.36 (1.36, 4.11); liver-related clinical events: MVR Ref LLV 1.14 (0.77, 1.70)	Age, AST, ALT, albumin, platelet, total cholesterol, total bilirubin, creatinine, PT, INR, HBeAg, family history, diabetes, hypertension, alcohol drinking, fatty liver
Zhang et al[10], 2021	China	Retrospective cohort study	200/60/140	44/72.4%1	With ≥ 1 detectable serum HBV-DNA (100-2000 IU/mL)	801	56.7%1	NA	42 months	HCC: MVR Ref LLV 3.64 (1.61, 8.20); Hepatic decompensation: MVR Ref LLV 5.11 (1.02, 25.55); Liver-related clinical events: MVR Ref LLV 3.59 (1.66, 7.63)	NA

¹This data is extracted from the total sample of the article.

LLV: Low-level viremia; MVR: Maintained virological response; Ref: reference; HBeAg: Hepatitis B e antigen; HR: Hazard ratio; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; FIB-4 index: Fibrosis 4 Score index; eGFR: Estimated glomerular filtration rate; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; NA: Not available.