A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy

Shuyan Chen; Bingqiong Wang; Jialing Zhou; Xiaoning Wu; Tongtong Meng; Hui Liu; Tailing Wang; Xinyan Zhao; Shanshan Wu; Yuanyuan Kong; Xiaojuan Ou; Jidong Jia; Aileen Wee; Hong You; Yameng Sun

doi:10.1002/jmv.28555

A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy

J Med Virol. 2023 Feb;95(2):e28555. doi: 10.1002/jmv.28555.

Authors

Shuyan Chen¹, Bingqiong Wang¹, Jialing Zhou¹, Xiaoning Wu¹, Tongtong Meng¹, Hui Liu², Tailing Wang³, Xinyan Zhao¹, Shanshan Wu⁴, Yuanyuan Kong⁴, Xiaojuan Ou¹, Jidong Jia¹, Aileen Wee⁵, Hong You¹, Yameng Sun¹

Affiliations

¹ Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China.
² Department of Pathology, Beijing You-an Hospital, Capital Medical University, Beijing, China.
³ Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
⁴ Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China.
⁵ Department of Pathology, National University Hospital, Singapore, Singapore.

PMID: 36738235
DOI: 10.1002/jmv.28555

Abstract

Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GS_PT ) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GS_HV ) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GS_HV /(GS_HV + GS_PT ), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fibrosis (Ishak stage ≥4). Posttreatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (interquartile range [IQR]: 0%-23%) at baseline to 36% (IQR: 20%-57%) at Week 78 (p < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index_78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (median value of ∆/Baseline in ALT: restored vs. nonrestored was 79.1% vs. 48.8%, p = 0.018; median value of ∆/Baseline in AST: restored vs. nonrestored was 69.1% vs. 32.5%, p = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. nonrestored was 25.0% vs. 0%, p = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.

Keywords: Ishak stage; P-I-R score; hepatic vein; portal tract; regression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine Transaminase
Antiviral Agents / therapeutic use
Biopsy
Fibrosis
Glutamate-Ammonia Ligase*
Hepatitis B, Chronic* / drug therapy
Humans
Liver / pathology
Liver Cirrhosis / pathology

Substances

Glutamate-Ammonia Ligase
Alanine Transaminase
Antiviral Agents