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04-04-2017 | HBV | News | Article

Host, viral factors associated with persistently elevated ALT in chronic HBV patients

medwireNews: Hepatic steatosis, hepatitis B e antigen (HBeAg) seropositivity, and age are independently associated with persistent increases in serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis B virus (HBV) infection receiving antiviral therapy, a study shows.

The researchers, led by Ira Jacobson (Mount Sinai Beth Israel Medical Center, New York, USA), explain that treatment with the “potent antivirals” tenofovir disoproxil fumarate (TDF) and entecavir leads to effective virologic suppression and improved liver histology in the majority of patients. However, “a substantial proportion” of treated patients do not achieve normalization of serum ALT levels, with reported rates ranging from 42% to 78%.

The current analysis included 471 participants of two phase III trials who remained in the studies up to the 5-year mark. They were randomly assigned to receive TDF 300 mg/day or adefovir 10 mg/day for the first year, after which patients could either continue with or switch to TDF, depending on the original allocation, for up to 10 years.

At 5 years, 18.5% of patients had persistent ALT, defined as levels that were higher than the upper limit of normal as per the reference values of the laboratory performing the analysis.

After adjusting for confounders, the presence of hepatic steatosis – defined as a score of at least 5% on the Nonalcoholic Steatohepatitis Clinical Research Network system – at baseline and year 5 was significantly associated with persistent ALT at the 5-year timepoint, with corresponding odds ratios (ORs) of 2.236 and 3.392 (p=0.042 and 0.002, respectively).

Just under a third (32.8%) of patients with baseline steatosis had persistent ALT at 5 years compared with 13.0% of those without steatosis, a significant difference (p=0.001).

HBeAg positivity also significantly predicted persistent ALT at 5 years, with an OR of 3.297 and 5-year rates of 26.3% and 13.9% for HBeAg-positive and -negative patients, respectively (p<0.001).

Jacobson et al note in Clinical Gastroenterology and Hepatology that half the HBeAg-positive patients with pre-treatment steatosis had persistent ALT at 5 years, compared with 9.1% of HBeAg-negative individuals without steatosis (p<0.001).

The final factor significantly associated with persistent ALT was age, such that participants aged 40 years or younger were significantly more likely to have elevated ALT levels after 5 years than those older than 40 years (OR=2.099, p=0.046).

The study authors highlight several limitations, such as the definition of persistent ALT being based on a single serum measurement and the preponderance of Caucasian participants (who tend to harbor HBV genotypes A or D), thus restricting the generalizability of the findings to other populations.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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