Volume 137, Issue 5, Pages 1687-1697 (November 2009) Hepatitis B Virus Core Variants Modify Natural Course of Viral Infection and Hepatocellular Carcinoma Progression  Feng–Yu Sung, Chun–Ming Jung, Chih–Feng Wu, Chih–Lin Lin, Chun–Jen Liu, Yun–Fan Liaw, Keh–Sung Tsai, Ming–Whei Yu  Gastroenterology  Volume 137, Issue 5, Pages 1687-1697 (November 2009) DOI: 10.1053/j.gastro.2009.07.063 Copyright © 2009 AGA Institute Terms and Conditions

Figure 1 Study design and subject selection flowchart. *Sixty-five cases and 30 controls in the longitudinal viral load study were also included in the nested case-control study. A total of 7706 samples (627 from HBV carriers who progressed to HCC and 7079 from nonprogressors) were included for the analysis of longitudinal series of plasma viral load during follow-up. GECC, government employee central clinics; CGMH, Chang Gung Memorial Hospital; HCV, hepatitis C virus. Gastroenterology 2009 137, 1687-1697DOI: (10.1053/j.gastro.2009.07.063) Copyright © 2009 AGA Institute Terms and Conditions

Figure 2 Core variants and other viral features at baseline in the nested case-control study. Subjects were classified based on their core gene polymorphisms belonging to wild types (open squares or bars) or variant types (solid squares or bars). Error bars shown in (A) indicate means and 95% confidence intervals. P value for trend is from the Cochran–Armitage trend test. *P < .05; **P < .005; ***P < .0001. Gastroenterology 2009 137, 1687-1697DOI: (10.1053/j.gastro.2009.07.063) Copyright © 2009 AGA Institute Terms and Conditions

Figure 3 Influence of T1938C and T2045A on dynamics of plasma viral load and risks of liver disease in the longitudinal viral load study. (A) All data are estimated means from the linear mixed-effects models adjusting for age at entry, HBV genotype, and time at visit. Data are presented as the mean ± SEM. (B) Disease-modifying effects of T1938C and T2045A. The plots show the odds ratio (OR, diamond) and 95% confidence interval (CI, error bars) for the risk of elevated aspartate aminotransferase (AST), liver cirrhosis (LC), and HCC according to a core gene polymorphism. Results are derived from an unconditional logistic regression model adjusting for age at entry and number of visits. During follow-up, high-resolution, real-time ultrasonography was performed routinely for the detection of LC since 1993, and serum AST levels were routinely examined after August 1994. Subjects with missing data were excluded from analysis. Gastroenterology 2009 137, 1687-1697DOI: (10.1053/j.gastro.2009.07.063) Copyright © 2009 AGA Institute Terms and Conditions

Figure 4 Trajectory patterns of plasma viral load and their associations with liver disease during 16 years of follow-up in the longitudinal viral load study. (A) Expected (gray lines) and observed (black lines) trajectories of viral load estimated by a 3-group trajectory analysis. (B and C) Frequency of liver biochemical abnormality and major liver disease according to trajectory classes of viral load. During follow-up, high-resolution, real-time ultrasonography was performed routinely for the detection of liver cirrhosis (LC) since 1993, ALT and aspartate aminotransferase (AST) levels were routinely examined after August 1994, and γ-glutamyltransferase (GGT) levels were routinely examined after August 1996. Subjects with missing data were excluded from analysis. P values presented are from Fisher exact test. S, single elevation; M, multiple elevations. (D) Odds ratios and 95% confidence intervals for risks of liver abnormalities by trajectory classes of viral load. Results are derived from unconditional logistic regression model adjusting for age at entry and number of visits. Subjects with missing data were excluded from analysis. **P < .005; ***P < .0001. Gastroenterology 2009 137, 1687-1697DOI: (10.1053/j.gastro.2009.07.063) Copyright © 2009 AGA Institute Terms and Conditions