Chih-Lin Lin1,2, Tai-Chung Tseng3, Tung-Hung Su4, Chun-Jen Liu4,5,6, Pei-Jer Chen4,5, Ming-Yang Lai4,5, Ding-Shinn Chen4, Jia-Horng Kao7,8,9,10. 1. Department of Gastroenterology, Taipei City Hospital, Ren-Ai branch, Taipei, Taiwan. 2. Department of Psychology, National Chengchi University, Taipei, Taiwan. 3. Division of Hepatogastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan. 4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 5. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St, Taipei, 10002, Taiwan. 6. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan. 7. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw. 8. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St, Taipei, 10002, Taiwan. kaojh@ntu.edu.tw. 9. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw. 10. Department of Medical Research, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan. kaojh@ntu.edu.tw.
Abstract
PURPOSE: A significant portion of HBeAg-negative chronic hepatitis B patients have persistently normal serum alanine aminotransferase levels (PNALT). We thus investigated host genetic variants and virological features in HBeAg-negative hepatitis B carriers. METHODS: Baseline clinical and virological features of 133 HBeAg-negative hepatitis B carriers (77 with PNALT and 56 with chronic hepatitis activity) with follow-up for more than 5 years were investigated. Three single nucleotide polymorphisms (SNPs) located within or around human leukocyte antigen (HLA)-DPA1, HLA-DPB1, and interleukin (IL) 28B loci were genotyped. RESULTS: The genotype frequencies of these SNPs were comparable between hepatitis B carriers with PNALT and those with chronic hepatitis. Compared with hepatitis B carriers with PNALT, those with chronic hepatitis had significantly higher baseline serum HBV-DNA levels (4.96 vs. 4.04 log10 IU/ml, P = 0.001). Baseline serum HBV-DNA level > 2000 IU/ml (OR, 8.42; 95% CI, 2.74-25.90, P < 0.001) were the only independent factor associated with chronic hepatitis activity. Changes of serum HBV-DNA in 30 hepatitis B carriers with PNALT had showed a significant reduction of viral load from baseline to last visit (mean difference of paired HBV-DNA levels: -0.78 log10 IU/ml, 95% CI: -1.57 to -0.013, P = 0.047). In contrast, no significant reduction of viral load was found in 28 patients with chronic hepatitis. CONCLUSIONS: The results indicate that lower baseline serum HBV-DNA level and viral load reduction over time are associated with long-term biochemical remission in HBeAg-negative hepatitis B carriers.
PURPOSE: A significant portion of HBeAg-negative chronic hepatitis B patients have persistently normal serum alanine aminotransferase levels (PNALT). We thus investigated host genetic variants and virological features in HBeAg-negative hepatitis B carriers. METHODS: Baseline clinical and virological features of 133 HBeAg-negative hepatitis B carriers (77 with PNALT and 56 with chronic hepatitis activity) with follow-up for more than 5 years were investigated. Three single nucleotide polymorphisms (SNPs) located within or around humanleukocyte antigen (HLA)-DPA1, HLA-DPB1, and interleukin (IL) 28B loci were genotyped. RESULTS: The genotype frequencies of these SNPs were comparable between hepatitis B carriers with PNALT and those with chronic hepatitis. Compared with hepatitis B carriers with PNALT, those with chronic hepatitis had significantly higher baseline serum HBV-DNA levels (4.96 vs. 4.04 log10 IU/ml, P = 0.001). Baseline serum HBV-DNA level > 2000 IU/ml (OR, 8.42; 95% CI, 2.74-25.90, P < 0.001) were the only independent factor associated with chronic hepatitis activity. Changes of serum HBV-DNA in 30 hepatitis B carriers with PNALT had showed a significant reduction of viral load from baseline to last visit (mean difference of paired HBV-DNA levels: -0.78 log10 IU/ml, 95% CI: -1.57 to -0.013, P = 0.047). In contrast, no significant reduction of viral load was found in 28 patients with chronic hepatitis. CONCLUSIONS: The results indicate that lower baseline serum HBV-DNA level and viral load reduction over time are associated with long-term biochemical remission in HBeAg-negative hepatitis B carriers.
Authors: David L Thomas; Chloe L Thio; Maureen P Martin; Ying Qi; Dongliang Ge; Colm O'Huigin; Judith Kidd; Kenneth Kidd; Salim I Khakoo; Graeme Alexander; James J Goedert; Gregory D Kirk; Sharyne M Donfield; Hugo R Rosen; Leslie H Tobler; Michael P Busch; John G McHutchison; David B Goldstein; Mary Carrington Journal: Nature Date: 2009-10-08 Impact factor: 49.962