Mitochondrial Dysfunction in Patients with Alcoholic Liver Disease and Nonalcoholic Fatty Liver Disease

Introduction: Mitochondrial dysfunction is implicated in the pathogenesis of chronic liver diseases and is associated with metabolic disturbances and disease progression. This study aimed to investigate serum metabolite profiles reflective of mitochondrial dysfunction in patients with alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD).

Methods: Serum concentrations of carnitine and its 29 acylcarnitine derivatives were measured in patients with NAFLD (n=44) and ALD (n=40) at different disease stages, as well as in 14 healthy volunteers. Additionally, we compared acylcarnitine profiles between cirrhotic (irrespective of etiology) and non-cirrhotic individuals. Targeted metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry.

Results: Significant differences were found between liver disease groups and controls. The ALD and NAFLD groups differed significantly in C10:2 (p < 0.001) and C16:1 (p < 0.009). At the cirrhosis stage, compared to non-cirrhotic patients, increases were observed for C2, C5-DC, C14, C14-OH, C16, C16:1, C18:1, and C18:2 (p < 0.05 for all), while decreases were noted for C3, C4, C5, and C16-OH (p < 0.05 for all). Disease progression was associated with significant differences in Child-Pugh classes for C16 (p = 0.0014), C16:1 (p < 0.0001), and C18:1 (p < 0.0001). Statistically significant differences versus controls were observed from Child‑Pugh class B onward (p < 0.001), with C16:1 also showing a significant increase in class C.

Conclusion: According to our findings, acylcarnitine metabolism is closely associated with hepatic functional status. Differences between ALD and NAFLD are consistent with distinct pathogenic mechanisms. During cirrhosis progression, decreased C3, C4, and C5 indicate impaired mitochondrial fatty acid oxidation, while increased C2 may reflect restricted acetyl-CoA entry into the Krebs cycle. The rise in long-chain acylcarnitines (C16, C16:1, C18:1) with worsening Child–Pugh class supports accumulation of incomplete oxidation products. Taken together, these findings highlight the potential of serum acylcarnitine profiling as a non-invasive biomarker of mitochondrial dysfunction and disease severity in chronic liver diseases.