Hepatic ALT flares linked to HBsAg clearance

By Shreeya Nanda, Senior medwireNews Reporter

Hepatic alanine aminotransferase (ALT) flares are associated with rapid decline and greater annual reductions of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B virus (HBV) infection who achieve HBsAg seroclearance, say Japanese researchers.

Of the 392 HBsAg-positive chronic HBV patients included in this study, 50 achieved HBsAg seroclearance during the median follow-up of 14 years, reports the team from the Nagasaki University Graduate School of Biomedical Sciences in Hepatology Research.

When patients were categorised on the basis of rapidity of seroclearance, the 22 patients who achieved HBsAg seroclearance within 5 years of HBsAg levels reaching 2 log IU/mL had a significantly higher maximum ALT level than the 28 who achieved seroclearance more than 5 years after reaching this threshold, at 487 IU/L versus 146 IU/L (p=0.03).

Defining a flare as the elevation of ALT levels to 200 IU/L or higher, the team found that flares occurred significantly more often in the rapid decline group than in the slow decline group during the 10 to 20 years prior to HBsAg seroclearance, at 41.5% versus 8.1% (p<0.001).

And in the 5 to 10 years before HBsAg clearance, the percentage of years with at least one flare was also significantly greater in the rapid decline than in the slow decline group, at 21.6% versus 9.2% (p=0.02). But the groups were comparable in this respect during the 5 years immediately prior to seroclearance.

Moreover, during the 5 to 20 years before seroclearance, the annual decrease in HBsAg levels compared with the previous year was significantly greater in years with at least one occurrence of an ALT flare than in those without, at a median of 0.29 log IU/mL per year and 0.17 log IU/mL per year (p=0.003), respectively.

The researchers attribute their findings to “ALT flare being the host immune response to HBV-infected hepatocytes”.

“The fluctuating but sustained nature of host immune response within certain periods, represented by the number and the density of hepatic flares, is associated with rapid HBsAg seroclearance in the near future, independently with the magnitude and the proximity of flare”, observe Hiroshi Yatsuhashi and co-authors.

They conclude: “Transient hepatic flares without disease progression during immunomodulatory therapy, for instance, with IFN-based treatments or with a novel oral agonist of Toll-like receptor-7, may play an important role in achieving more frequent HBsAg seroclearance after treatment for chronic hepatitis B.”

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