Keratin 8 variants are infrequent in patients with alcohol-related liver cirrhosis and do not associate with development of hepatocellular carcinoma
1 Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
2 Department of Hepatology, AP-HP, Jean Verdier Hospital, Bondy, F-93140, France
3 University Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000, Bobigny, France
4 Centre de ressources biologiques - Jean Verdier Liver Biobank-GH Paris-Seine-Saint-Denis, APHP, Bondy and Université Paris 13, Sorbonne Paris Cité, UFR SMBH, Bobigny, FRANCE
5 Biostatistics unit, Pitié-Salpêtrière Hospital, AP-HP, Paris, France
6 Department of Biochemistry, AP-HP, Jean Verdier Hospital, F-93140, Bondy, France
7 Department of Internal Medicine III and IZKF, RWTH-University Hospital Aachen, Pauwelsstraße 30, D-52074, Aachen, Germany
BMC Gastroenterology 2012, 12:147 doi:10.1186/1471-230X-12-147Published: 18 October 2012
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.
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.
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.
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.