A novel nomogram to predict evident histological liver injury in patients with HBeAg-positive chronic hepatitis B virus infection

Abstract

Background: HBeAg-positive chronic infection is a unique phase of chronic hepatitis B virus (HBV) infection. Current guidelines advise against starting antiviral treatment for HBeAg-positive chronic hepatitis B virus (HBV) infection patients, some data suggest treating such patients may reduce the risk of hepatocellular carcinoma. We aimed to explore whether these patients can have evident histological liver injury (EHLI), and develop a non-invasive model for identifying EHLI in such patients. Method: We assessed whether HBeAg-positive chronic HBV infection patients can have EHLI defined by Ishak fibrosis stage 3 and/or histologic activity index 9 in a prospective multicenter study. Logistic and Lasso regression was used to select the optimal predictors. We used Akaike information criterion, discrimination improvement, net reclassification improvement to develop and validate models predicting EHLI risk in training cohort and two external validation cohorts. Findings: Of these 336 patients met the inclusion criteria, 181(54%) were HBeAg-positive chronic HBV infection, of whom 60 patients (33%) had EHLI, the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, P < 0.001). Age, liver stiffness measurement, ALT, alkaline phosphatase, and albumin were identified as independent predictors for EHLI and used to develop a nomogram that have been demonstrated having a good performance in predicting EHLI with AUROCs of 0.92(95%CI: 0.86À0.99) in the training cohort (n = 233) and 0.90(95%CI: 0.84À0.95) in validation cohort 1(n = 103), significant correcting current guidelines recommendations overestimating insignificant or significant histological disease. After 72-weeks entecavir treatment for HBeAg-positive chronic HBV infection patients with EHLI identified by nomogram, histological improvement occurred in 40 of 49(82%), 38(78%) had fibrosis reversal, and 35(73%) no longer had EHLI.

Characterising the Intestinal Bacterial and Fungal Microbiome Associated With Different Cytokine Profiles in Two Bifidobacterium strains Pre-Treated Rats With D-Galactosamine-Induced Liver Injury

“…Similarly, Ishak score was greater in CP1_LI09 and CP1_LI10 cohorts than the corresponding cohorts with CP2. As lower Ishak score represented lower liver injury severity ( 34 , 35 ), it indicated that the cohorts with CP2 profile were with lower liver injury severity.…”

Early Treatment Consideration in Patients with Hepatitis B ‘e’ Antigen-Positive Chronic Infection: Is It Time for a Paradigm Shift?

“…In particular, among the 181 patients with HBeAg-positive chronic infection, 60 patients had EHLI; and the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, p < 0.001). In fact, the authors developed a nomogram to attempt to accurately identify HBeAg-positive chronic HBV infection patients with EHLI, which may respond well to antiviral therapy [ 31 ].…”

Current treatment of chronic hepatitis B: Clinical aspects and future directions

“…Patients infected with HBV but have normal ALT levels may exhibit manifestations of liver fibrosis and inflammation upon histological examination ( Chang et al, 2021 ; Liu et al, 2022 ). Previous studies have shown that people with normal ALT levels develop moderate liver tissue inflammation (16.8–40%) and moderate liver fibrosis (24.2–35.9%) ( Ormeci et al, 2016 ; Tan et al, 2017 ; Choi et al, 2019 ; Liu et al, 2022 ), which are associated with a high risk of progression to liver cirrhosis and cancer.…”

“…In 2018 AASLD guidelines, IT-CHB is defined by HBV DNA > 10 6 IU/mL and normal ALT, while in 2017 and 2019 China guidelines, IT-CHB is defined by HBV DNA > 10 7 IU/mL and normal ALT. However, the ULN of ALT remains controversial with limited value in distinguishing patients experiencing immune tolerance, as the patients are still at risk of liver inflammation or fibrosis when their ALT levels are defined as normal under the lowest ULN standard ( Ormeci et al, 2016 ; Tan et al, 2017 ; Choi et al, 2019 ; Chang et al, 2021 ; Duan et al, 2021 ; Liu et al, 2022 ). Hong et al (2015) speculated that innate immune cell maturation and helper T lymphocyte development existed before intrauterine exposure to HBV during infancy, while another study discovered HBV-specific T lymphocytes in that period ( Bertoletti and Ferrari, 2016 ).…”