Cytokeratin-18 increase as a signal for early liver cell changes in high-fat diet-induced obesity before overt steatohepatitis - Report - MDSpire

Cytokeratin-18 increase as a signal for early liver cell changes in high-fat diet-induced obesity before overt steatohepatitis

  • By

  • Özlem Özdemir

  • Çağrı Akalın

  • Fuat Ekiz

  • Pınar Naile Öğüten

  • Orhan Baş

  • Ahmet Bayrak

  • Yeliz Kaşko Arıcı

  • July 8, 2026

  • 0 min

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Elevation of Cytokeratin-18 as an Early Indicator of Hepatic Cellular Alterations

Overview

This study demonstrates that high-fat diet-induced obesity in rats leads to increased levels of cytokeratin-18 (CK-18). The findings indicate a relationship between CK-18 levels and liver histopathological changes, particularly ballooning, prior to the development of steatohepatitis.

Background

Obesity is a significant risk factor for non-alcoholic fatty liver disease (NAFLD), which has been redefined as metabolic dysfunction-associated steatotic liver disease (MASLD). The prevalence of NAFLD is increasing globally, closely linked with obesity and metabolic syndrome. Understanding early indicators of liver injury, such as CK-18, is important.

Data Highlights

ParameterHigh-Fat Diet (HFD)Normal-Fat Diet (NFD)p-value
Final Body Weight (g)335.8 ± 20.2291.5 ± 6.25<0.001
Glucose (mg/dL)186.4 ± 46.9130.0 ± 16.20.011
Insulin (IU/L)4.30 ± 0.702.23 ± 0.82<0.001
HOMA-IR2.03 ± 0.790.73 ± 0.340.003
ALT (U/L)72.34 ± 12.3555.43 ± 5.750.009
CK-18 (ng/mL)1.46 ± 0.180.88 ± 0.18<0.001
AST/ALT Ratio1.16 ± 0.091.32 ± 0.140.020

Key Findings

  • High-fat diet (HFD) led to significant increases in body weight, glucose, insulin, HOMA-IR, ALT, and CK-18 levels compared to normal-fat diet (NFD).
  • All HFD specimens exhibited ballooning, with half showing steatosis.
  • CK-18 levels correlated with higher ALT levels and ballooning formation in the HFD group.
  • NAFLD activity score remained ≤3 in all specimens despite the observed changes.
  • CK-18 is noted as an indicator of hepatocellular injury in obesity.

Clinical Implications

The elevation of CK-18 in the context of obesity may serve as a biomarker for hepatic cellular alterations.

Conclusion

The study highlights CK-18 as a biomarker for hepatic injury associated with obesity.

Related Resources & Content

  1. Journal of Gastroenterology, 2018 -- Association of Hepatic IRS1 and ß-catenin Levels with Histological Progression and Development of Diabetes in Patients with NAFLD
  2. Journal of Gastroenterology, 2013 -- Excess Lipid Accumulation During Liver Regeneration Impedes Hepatocyte DNA Replication by Elevating Endoplasmic Reticulum Stress in Mice with Simple Hepatic Steatosis
  3. conexiant -- Ultrasound Attenuation Imaging Tracks Hepatic Steatosis
  4. American Gastroenterological Association -- Clinical care pathway for the risk stratification and management of patients with MASLD
  5. Journal of Gastroenterology, 2026 -- Evidence-based clinical practice guidelines for metabolic dysfunction-associated steatotic liver disease (MASLD)
  6. Journal of Gastroenterology — Hepatocellular Carcinoma Among Individuals with Chronic Hepatitis C Virus Infection in the Asia-Pacific Area
  7. Clinical care pathway for the risk stratification and management of patients with MASLD  - American Gastroenterological Association
  8. Evidence-based clinical practice guidelines for metabolic dysfunction-associated steatotic liver disease (MASLD) 2026 | Journal of Gastroenterology | Springer Nature Link

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