Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines

Abstract

Cardiac hepatopathy refers to acute or chronic liver damage caused by cardiac dysfunction in the absence of any other possible causative reasons of liver injury. There is a large number of evidence of the fact that cardiac hepatopathy is associated with poor clinical outcomes in patients with acute or actually decompensated heart failure (HF). However, the currently dominated pathophysiological background does not explain a role of metabolic regulative proteins secreted by hepatocytes in progression of HF, including adverse cardiac remodeling, kidney injury, skeletal muscle dysfunction, osteopenia, sarcopenia and cardiac cachexia. The aim of this narrative review was to accumulate knowledge of hepatokines (adropin; fetuin-A, selenoprotein P, fibroblast growth factor-21, and alpha-1-microglobulin) as adaptive regulators of metabolic homeostasis in patients with HF. It is suggested that hepatokines play a crucial, causative role in inter-organ interactions and mediate tissue protective effects counteracting oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and necrosis. The discriminative potencies of hepatokines for HF and damage of target organs in patients with known HF is under on-going scientific discussion and requires more investigations in the future.

Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases

“…As metabolic regulators, hepatokines provide a mechanistic link between liver function and metabolic disorders such as diabetes, obesity, CVDs, CKD, and sarcopenia. Some previous reports have reviewed these hepatokines excellently ( de Oliveira Dos Santos et al, 2021 ; Jensen-Cody and Potthoff, 2021 ; Khan et al, 2022 ; Berezin et al, 2023 ; Stefan et al, 2023 ). Few of the important hepatokines are summarized in Table 1 with their target organs, and their physiological roles.…”

Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function

“…Cardiogenic shock and hepatic circulation disorder are considered the causes of cardiogenic liver injury. However, Alexander E. Berezin et al [ 4 ] reviewed the current research on the regulatory role of hepatokines (including fetuin-a, alpha1-microglobulin, fibroblast growth factor-21 (FGF21), and selenoprotein P) in interorgan interactions, and proposed that hepatokines serve as adaptive regulators of metabolic homeostasis in heart failure patients by counteracting oxidative stress and promoting mitochondrial dysfunction, which may play an important role in the progression of cardiac hepatopathy. The authors also proposed that FGF21 and selenoprotein P may be potential therapeutic targets for cardiogenic liver injuries.…”