Relationship Between Level of Hepatitis B Virus DNA and Liver Disease: A Population-based Study of Hepatitis B e Antigen-Negative Persons With Hepatitis B.

McMahon BJ1, Bulkow L2, Simons B3, Zhang Y4, Negus S3, Homan C3, Spradling P5, Teshale E5, Lau D4, Snowball M3, Livingston SE6.

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Abstract

BACKGROUND & AIMS:

There is little information on the proportion of persons with chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to determine the proportion of persons with hepatitis B e antigen-negative chronic HBV infection who develop immune-active HBV infection over time and the relationship between demographic and viral factors on severity of disease on liver biopsy.

METHODS:

We performed a longitudinal population-based cohort study of 754 Alaska Native patients with chronic HBV infection. Levels of alanine aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were measured at study entry and whenever ALT levels exceeded the upper limit of normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT ≥30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more time points from 2001-2008. Liver biopsies were scored by using the modified histology activity index score of Knodell and the Ishak fibrosis score.

RESULTS:

Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56% of these initially and 44% later during follow up. Of the 38 patients with liver biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and 1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT > twice ULN (P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA >20,000 IU/mL (P < .001), had moderate or severe hepatitis or fibrosis.

CONCLUSIONS:

In a cohort of Alaska Natives with chronic HBV infection, 25% met criteria for immune-active HBV. There is a low probability of advanced fibrosis if levels of HBV DNA never exceed 20,000 IU/mL.