Abstract
Hepatitis is defined as cryptogenic only after exclusion of all known etiologies. Cryptogenic hepatitis has a worldwide prevalence of 5–15% in patients with chronic liver disease and is a frequent indication for liver transplantation. Keratin 8 (K8) and 18 (K18) are the cytoskeletal intermediate filament proteins of adult hepatocytes, and murine models indicate that mutations in the encoding genes predispose to liver disease. Moreover, numerous studies showed an association of K8/K18 variants with human acute and chronic liver disease. However, there is only little known about a putative association of K8/K18 variants with cryptogenic hepatitis/cirrhosis. Therefore, we analyzed whether K8 variants associate with cryptogenic hepatitis in a German cohort of 54 patients in comparison to 65 control blood bank donors. Genomic DNA isolated from liver biopsies of cryptogenic hepatitis patients or peripheral blood of healthy donors was analyzed for K8 variants in 3 of 8 exonic regions by PCR amplification and direct DNA sequencing, covering the 9 most common of 10 previously described variants (Ku et al.; Strnad et al.). Excluding published single nucleotide polymorphisms, we found amino acid altering K8 (mostly) heterozygous variants in 14 of 54 cryptogenic hepatitis patients (25.9%) and in 4 of 65 controls (6.2%). Notably, the most K8 variants were novel. In conclusion, previously described and novel K8 variants were identified in a German cohort and associate with cryptogenic hepatitis, possibly predisposing carriers to the development of liver disease.
Published Version
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