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Updated: Feb 2, 2026

Stabilizing Hepatocellular Phenotype Using Optimized Synthetic Surfaces
Published on: September 26, 2014
High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype
Nicole Golob-Schwarzl1, Kira Bettermann2, Anita Kuldeep Mehta3
1Institute of Pathology, Medical University of Graz, Graz, Austria; Center for Biomarker Research in Medicine, Graz, Austria.
Background & Aims:
Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, and fibrosis at late stage. Disturbance of the keratin cytoskeleton and aggregation of keratins (KRTs) are essential for MDB formation.
Methods:
We analyzed livers of aged Krt18-/- mice that spontaneously developed in the majority of cases SH-associated HCC independent of sex. Interestingly, the hepatic lipid profile in Krt18-/- mice, which accumulate KRT8, closely resembles human SH lipid profiles and shows that the excess of KRT8 over KRT18 determines the likelihood to develop SH-associated HCC linked with enhanced lipogenesis.
Results:
Our analysis of the genetic profile of Krt18-/- mice with 26 human hepatoma cell lines and with data sets of >300 patients with HCC, where Krt18-/- gene signatures matched human HCC. Interestingly, a high KRT8/18 ratio is associated with an aggressive HCC phenotype.
Conclusions:
We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC.
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