A Non-invasive Model for Predicting Liver Inflammation in Chronic Hepatitis B Patients With Normal Serum Alanine Aminotransferase Levels

Abstract

Background and Aims: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are at risk of disease progression. Currently, liver biopsy is suggested to identify this population. We aimed to establish a non-invasive diagnostic model to identify patients with significant liver inflammation.Method: A total of 504 CHB patients who had undergone liver biopsy with normal ALT levels were randomized into a training set (n = 310) and a validation set (n = 194). Independent variables were analyzed by stepwise logistic regression analysis. After the predictive model for diagnosing significant inflammation (Scheuer's system, G ≥ 2) was established, a nomogram was generated. Discrimination and calibration aspects of the model were measured using the area under the receiver operating characteristic curve (AUC) and assessment of a calibration curve. Clinical significance was evaluated by decision curve analysis (DCA).Result: The model was composed of 4 variables: aspartate aminotransferase (AST) levels, γ-glutamyl transpeptidase (GGT) levels, hepatitis B surface antigen (HBsAg) levels, and platelet (PLT) counts. Good discrimination and calibration of the model were observed in the training and validation sets (AUC = 0.87 and 0.86, respectively). The best cutoff point for the model was 0.12, where the specificity was 83.43%, the sensitivity was 77.42%, and the positive likelihood and negative likelihood ratios were 4.67 and 0.27, respectively. The model's predictive capability was superior to that of each single indicator.Conclusion: This study provides a non-invasive approach for predicting significant liver inflammation in CHB patients with normal ALT. Nomograms may help to identify target patients to allow timely initiation of antiviral treatment.

Presence of Liver Inflammation in Asian Patients With Chronic Hepatitis B With Normal ALT and Detectable HBV DNA in Absence of Liver Fibrosis

“…( 36,40‐42 ) However, other recent studies have found no significant association between age and liver inflammation activity in patients with CHB. ( 31,43‐45 ) Our results show that age was not associated with significant inflammation in either the univariate analysis or in the multivariate analysis. Different races, HBeAg levels, HBsAg levels, HBV DNA loads, as well as the discrepancy of scoring systems of liver inflammation may partially explain the inconsistent results on the association between age and liver inflammation activity among different studies.…”

“…Of note, the nonsignificant liver fibrosis group had a lower proportion of significant liver inflammation than the significant liver fibrosis group (5.8% vs. 32.8%). ( 31 ) Moreover, Wei et al found that 39.7% patients with significant liver fibrosis had significant liver inflammation, whereas the percentage was only 7.1% in patients without significant liver fibrosis in a cohort of 186 patients with CHB. ( 32 ) However, the levels of HBV DNA and ALT were not limited in these studies.…”

“…We included patients with detectable HBV DNA levels instead of HBV DNA > 2,000 IU/mL because low‐level viremia (<2,000 IU/mL) is associated with a relatively high risk of HCC. ( 31 , 35 ) Third, in the current study, only Asian patients with CHB were included. Asian ethnicity has been shown to be a risk factor for significant inflammatory activity compared with Caucasian patients.…”

“…(32) However, the levels of HBV DNA and ALT were not limited in these studies. (31,32) The discrepant findings may be interpreted in four aspects. First, not all of the patients were antiviral treatment-naïve in the study by Sonneveld et al, and antiviral treatment may have affected liver inflammation.…”

Correspondence on Letter regarding “Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune tolerant phase”

“…Our data showed that serum ALT levels alone do not fully reflect histological activity of IT phase. In the same vein, previous studies [9][10][11] found that ALT levels did not indicate the actual inflammation in the liver for the following reasons: i) ALT elevation is associated with the location of inflammation 12 , and ii) the changes in ALT levels occur faster than changes in histology. 13 One of the alternative is, as the authors mentioned 1 , different standards for normal alanine aminotransferase (ALT) levels might be applied according to age.…”