Researchers associated hepatic steatosis, HBeAg seropositivity and age younger than 40 years with persistent increased levels of alanine aminotransferase in patients with chronic hepatitis B receiving suppressive antiviral treatment, according to data from a recently published study.
“Hepatic steatosis (nonalcoholic fatty liver disease) is common in the general population and in patients with [chronic HBV] and frequently is associated with an increase of serum transaminase levels. Consequently, the observed associations between persistent ALT level increase with steatosis and features of the metabolic syndrome despite effective antiviral therapy are not entirely surprising,” Ira M. Jacobson, MD, co-Chief Medical Editor of HCV Next, and colleagues wrote. “Our findings that younger age and HBeAg seropositivity are associated independently with failure to normalize ALT on therapy are novel and may relate to the intensity of the immune response.”
The researchers conducted two randomized studies, one with patients who were HBeAg-negative and the other with patients who were HBeAg-positive. A total of 471 patients remained in the study to year 5, 87 of whom had persistent ALT level increase at year 5. Patients received either Viread (tenofovir disoproxil fumarate, Gilead) or Hepsera (adefovir dipivoxil, Gilead).
Compared with patients with a normal ALT level at baseline, patients with persistent ALT level increase were more likely to be younger than 40 years (41.9% vs. 57.5%; P = .012), have a BMI of 25 kg/m2 or higher (46.3% vs. 63.2%; P = .006), diabetes (2.6% vs. 8.1%; P = .023), HBeAg-positivity (33.6% vs. 52.9%; P = .001), mean HBV DNA level (1.5% vs. 1.6%; P = .018), mean HBsAg level (0.7% vs. 0.8%; P = .005) and a steatosis score of 5% or higher (22.6% or 48.8%; P < .001) and of 34% or higher (1.1% vs. 14%; P < .001).
While self-reported hyperlipidemia and hypertension did not differ between the two groups, the number of metabolic risk factors was associated with the prevalence of persistent ALT level increase. There were 28 of 212 patients with zero risk factors, 38 of 186 patients with one risk factor, 17 of 59 patients with two risk factors, and 4 of 12 patients with three or more risk factors (P = .0123).
At 5 years, characteristics of patients with persistent ALT level increase compared with those who achieved normalization showed significant association for HBV DNA levels below 69 IU/mL (P < .001), fewer patients with cirrhosis regression (P < .007), more patients with a steatosis score of 5% or higher (P < .001) and more patients with a steatosis score of 34% or higher (P < .001).
On multivariate analysis, the characteristics associated with persistent ALT level increase at year 5 remained similar to previous analyses: HBeAg seropositivity at baseline (OR = 3.297; 95% CI, 1.653-6.576), steatosis score of 5% or higher at baseline (OR = 2.236; 95% CI, 1.031-4.852) and year 5 (OR = 3.392; 95% CI, 1.56-7.375), and age 40 years or younger (OR = 2.099; 95% CI, 1.014-4.342).
“In this analysis, we have shown that despite achievement of virologic suppression in nearly all patients and demonstration of fibrosis regression in the majority of those treated with [Viread] for 5 years, approximately 1 in 5 patients fail to achieve ALT normalization,” the researchers concluded. “Both host and viral factors, particularly hepatic steatosis and HBeAg seropositivity, are important contributors to this phenomenon.” – by Talitha Bennett
Disclosure: Jacobson is a consultant for and has received honoraria and received research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck; and is a consultant for Achillion, Alnylam and Enanta.