HBV re-activation is associated with increased mortality and dysregulation of oxidative and polyamine metabolism in pre-acute-on-chronic liver failure

Description

Background/Aims: Acute-on-chronic liver failure (ACLF) is one of the deadliest complications of chronic liver disease yet treatment options are sparse. In Asia, HBV-reactivation (HBVr) is one of the most common triggers. Recently, HBV-associated ACLF was associated with distinct changes in the metabolome. Here, metabolic impacts of HBVr were analysed in-depth in non-ACLF, pre-ACLF and ACLF. Methods: Clinical and metabolic data of 1024 Chinese patients (CATCH-LIFE studies) with chronic HBV mono-infection were analyzed. ACLF was diagnosed according to COSSH criteria. Metabolites in plasma were quantified using LC-MS, compared to non-ACLF and subjected to enrichment and pathway analyses using the database SMPDB via MetaboAnalyst v6. Results: In 1024 patients (611: non-ACLF, 72: pre-ACLF, 341: ACLF), HBVr was present in 20.2 % (ACLF) or 33.3 % (pre-ACLF) of patients. HBVr increased 28-day mortality in pre-ACLF patients (2.1 % in HBVnr vs. 25 % in HBVr). Energy metabolism generating reactive oxygen species (ROS) was highly induced in the absence of ROS-detoxifying pathways in pre-ACLF. Urea cycle, thus nitric oxide (NO) build-up, the polyamine metabolism and related pathways were highly increased in both HBVr pre-ACLF and ACLF, shifting pre-ACLF close to mature ACLF. Specific metabolites could be identified as putative markers and key-regulators herein. Conclusion: HBV reactivation induces inflammation, hepatic injury and mortality especially in pre-ACLF patients. Metabolic disruption in the ROS/NO/polyamine axis favors stress and hinders liver regeneration. Findings help identifying and alleviating HBVr-driven progression towards ACLF via pharmacological or biopharmaceutical intervention.

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Institutions

• Paul-Ehrlich-Institut

  Hessen, Langen
• Universitatsklinikum Munster Medizinische Klinik B fur Gastroenterologie und Hepatologie

  Nordrhein-Westfalen, Munster
• University Hospital Frankfurt

  Hesse, Frankfurt am Main
• Beijing Ditan Hospital

  Beijing, Beijing
• Tongji University

  Shanghai, Shanghai
• Taihe Hospital

  Hubei, Shiyan
• Jilin University

  Jilin, Changchun
• Fudan University

  Shanghai, Shanghai
• Nankai University

  Tianjin, Tianjin
• Shanghai Jiao Tong University

  Shanghai, Shanghai
• Hasso Plattner Institute

  Brandenburg, Potsdam

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