Keratin 8 variants are infrequent in patients with alcohol-related liver cirrhosis and do not associate with development of hepatocellular carcinoma.
BACKGROUND
Keratins 8/18 (K8/K18) are established hepatoprotective proteins and K8/K18 variants predispose to development and adverse outcome of multiple liver disorders. The importance of K8/K18 in alcoholic liver disease as well as in established cirrhosis remains unknown.


METHODS
We analyzed the K8 mutational hot-spots in 261 prospectively followed-up patients with alcoholic cirrhosis (mean follow-up 65 months). PCR-amplified samples were pre-screened by denaturing high-performance liquid chromatography and conspicuous samples were sequenced.


RESULTS
67 patients developed hepatocellular carcinoma (HCC) and 133 died. Fourteen patients harbored amino-acid-altering K8 variants (5xG62C, 8xR341H). The presence of K8 variants did not associate with development of HCC (log-rank=0.5) or death (log-rank=0.7) and no significant associations were obtained for the single K8 variants after a correction for multiple testing was performed.


CONCLUSIONS
Keratin variants are expressed in a low percentage of patients with alcoholic cirrhosis and do not influence HCC development. Further studies conducted in larger prospective cohorts are needed to find out whether presence of K8 R341H variant predispose to non-HCC-related liver mortality.
Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany.
Valentyn
V
Usachov
Pierre
P
Nahon
Mariia
M
Lunova
Marianne
M
Ziol
Pierre
P
Rufat
Angela
A
Sutton
Michel
M
Beaugrand
Pavel
P
Strnad
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053533:Keratin-8 / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018709:Statistics, Nonparametric
D053533:Keratin-8