September 21, 2015
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Liver injury more frequent among chronic HBV with normal, minimally high ALT

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Researchers found that Chinese patients with chronic hepatitis B virus infection with persistent normal or minimally elevated alanine aminotransferase more frequently developed liver injury, such as fibrosis or necroinflammation, and may need increased surveillance.

“In this study, we present our analysis of liver histology in a large cohort of Chinese chronic hepatitis B patients with [persistent normal] ALT or minimally elevated ALT,” the researchers wrote. “Our analysis was focused on investigating mechanisms underlying normal or nearly normal alanine aminotransferase under conditions of liver injury and fibrosis.”

In a retrospective cross-sectional study, researchers evaluated 300 treatment-naive patients with chronic HBV admitted to the Hepatology Unit of Xiamen Hospital of Traditional Chinese Medicine, China, between January 2010 and October 2014. All patients had already undergone percutaneous liver biopsy, were positive for hepatitis B surface antigen (HBsAg) for at least 12 months, had HBV DNA levels greater than 500 IU/ml and persistent normal alanine aminotransferase (PNALT) or minimally elevated ALT.

Overall, 59% of patients were HBeAg-positive (n = 177). In the positive group, 28.2% of patients had PNALT levels (n = 50) and 71.8% of patients had minimally elevated ALT (n = 127). In the HBeAg-negative group, 51 patients were classified as having PNALT (41.5%) and 72 patients were categorized as having ALT slightly above the upper limit of normal (58.5%).

Approximately 42.9% of patients in the HBeAg-positive group showed changes in liver pathology compared with and 52.8% in the HBeAg-negative group. Fourteen-percent of the HBeAg-positive patients with PNALT (7/50) and 29.1% of patients with minimally elevated ALT showed significant necroinflammation. In the same group of HBeAg-positive patients, 24% with PNALT and 48% with minimally elevated ALT showed significant fibrosis. Fibrosis was detected more frequently compared with necroinflammation in the HBeAg-positive group of patients (P = .001).

Significant necroinflammation and fibrosis were found more frequently in patients with minimally elevated ALT compared with patients with normal ALT (P < .05).

The researchers concluded: “We detected significantly altered liver histology in almost 50% of chronic hepatitis B patients with persistent normal or minimally elevated ALT. We further elucidated the mechanisms of discordance between the appearance of normal or nearly normal ALT in the serum and the significant changes in liver pathology. We propose that small-scale liver injury, occurring intermittently is possibly responsible for such discordance.

“The fibrosis detected in the late HBeAg or in HBeAg-negative phase was possibly carried over from an early HBeAg phase, supporting therapeutic intervention in early HBeAg positive patients, as a priority. Lowering ALT [upper limit of normal] and increasing the frequency of ALT testing are recommended for management of patients with transiently elevated ALT.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.