| Summary: | 博士 === 臺灣大學 === 流行病學研究所 === 98 === Background
The determination of viral load is becoming of greater importance in the management of chronic hepatitis B virus infected persons. The implication of the viral load on liver disease progression for chronic hepatitis B virus infection remains incomplete.
Methods
Four HBsAg-positive-anti-HCV-negative subsets were selected from the prospective cohort in Taiwan enrolled in 1991-1992. 1) Inactive HBV carrier subcohort, characterized by HBeAg-negative, a viral load <10000 copies/mL and normal serum ALT level, free of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), was selected at baseline. An HBsAg-negative-anti-HCV-negative control subcohort with similar clinical liver feature was selected for comparison. 2) Persons with persistently serum ALT levels, free of LC and HCC through 1991-1999, were selected as the persistently normal serum ALT (PNALT) subcohort. 3) Chronic hepatitis (CH) subcohort comprised persons who developed chronic hepatitis from the persons with PNALT, free of LC and HCC in the first two years of cohort enrollment. 4) Liver cirrhosis (LC) subcohort included persons who developed liver cirrhosis from the persons with PNALT, free of liver cirrhosis and HCC in the first two years of cohort enrollment. HBV DNA levels were determined through follow-up serum samples at each subcohort entry. The outcomes included CH, LC, HCC, liver-related death (LD), and end-stage liver disease (ESLD, defined as at least one event of LC, HCC and LD). They were determined through follow-up tests and data-linkage with the computerized National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. Multivariate-adjusted hazard ratios (HRa) of risk predictors were derived by the Cox regression models.
Results
1) During a mean (±std) follow-up of 13.1 (±1.8) years, there were 51 HCC and 62 LD cases－the incidence rates (/100 person-years) of HCC and LD were 0.06, 0.04 for inactive HBV carriers, and 0.02, 0.02 for controls. The HRa (95%CI) for the inactive HBV carriers, compared to controls, to develop HCC and LD were 4.6 (2.5–8.3) and 2.1 (1.1–4.1). Older age and an alcohol drinking habit were additional independent predictors of HCC. 2) In PNALT subcohort, there were 96 CH cases during a mean (±std) follow-up of 4.9 (±0.3) years, the incidence rates of CH (/100 person-years) by viral load (copy/mL) were 3.0 (<105), 10.0 (105-<108) and 11.8 (≥108) for HBeAg- positive persons and 2.0 (<300), 1.8 (300-<104), 4.4 (104-<106), and 11.3 (≥106) for HBeAg-negative persons. The HRa (95% CI) by viral load (copy/mL) of developing CH for HBeAg-positive persons were 2.6 (0.9-7.3) (105-<108) and 3.3 (2.6-6.5) (≥108) (<105 copies/mL as reference); while for HBeAg-negative persons, they were 0.9 (0.5-1.6) (300-<104), 2.1 (1.2-3.5) (104-<106) and 4.8 (2.1-11.0) (≥106) (<300 copies/mL as reference). 3) In the CH subcohort, there were 21 newly developed ESLD cases during a mean (±std) follow-up of 5.1 (±2.1) years. The overall incidence rates (/100 person-years) of ESLD for HBeAg-negative and HBeAg-positive persons were 1.5 and 3.6. A viral load above 105 copies/mL (vs. <103 copies/mL) overall predicted ESLD with a HRa of 9.2 (1.2-70.8). Older age was an additional risk predictor. 4) In the LC subcohort, there were 25 HCC and 23 LD cases during a mean (±std) follow-up of 6.1 (±3.7) years. The incidence rates (/100 person-years) of HCC (LD) for HBeAg- negative and HBeAg-positive persons were 3.1 (2.5), and 3.0 (2.9). Older age was the only important risk predictor of HCC. Independent of HCC, a viral load above 104 copies/mL (vs. <104) remained important in predicting LD with a HRa of 5.6 (1.6-2.6).
Conclusions
Carriers of inactive HBV, compared with controls, have a substantial risk of HCC and LD, which risk would be diminished after loss of HBsAg. High viral loads lead to more rapid liver disease progression, state by state, throughout the natural history of chronic hepatitis B virus infection.
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