Lung-Yi Mak1,2, Qi Huang3, Danny Ka-Ho Wong1,2, Luisa Stamm3, Ka-Shing Cheung1,4, Kwan-Lung Ko1, Ran Yan3, Lea Ouyang3, James Fung1,2, Wai-Kay Seto1,2,4, Man-Fung Yuen5,6. 1. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, 4/F, Professorial Block, Pokfulam Road 102, Pok Fu Lam, Hong Kong. 2. State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong. 3. Assembly Biosciences, Inc., South San Francisco, USA. 4. Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. 5. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, 4/F, Professorial Block, Pokfulam Road 102, Pok Fu Lam, Hong Kong. mfyuen@hkucc.hku.hk. 6. State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong. mfyuen@hkucc.hku.hk.
Abstract
BACKGROUND: We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development. METHODS: This is a case-control study of 104 patients [52 HCC and 52 non-HCC (matched with age, gender, cirrhosis and treatment duration)] on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification [LLOQ] 20 IU/mL). Serial sera within 1, 1-2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively. RESULTS: Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients; P = 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424-5.468 & HR 4.544, 95% CI 1.07-19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients. CONCLUSIONS: More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC.
BACKGROUND: We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development. METHODS: This is a case-control study of 104 patients [52 HCC and 52 non-HCC (matched with age, gender, cirrhosis and treatment duration)] on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification [LLOQ] 20 IU/mL). Serial sera within 1, 1-2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively. RESULTS: Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients; P = 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424-5.468 & HR 4.544, 95% CI 1.07-19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients. CONCLUSIONS: More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC.
Authors: Roberto de Franchis; Antoine Hadengue; George Lau; Daniel Lavanchy; Anna Lok; Neil McIntyre; Alfonso Mele; Gustav Paumgartner; Antonello Pietrangelo; Juan Rodés; William Rosenberg; Dominique Valla Journal: J Hepatol Date: 2003 Impact factor: 25.083