BACKGROUND AND GOALS: Reliable noninvasive biomarkers to assess the histologic activity of nonalcoholic fatty liver disease (NAFLD) have not been established. As the frequency of Mallory bodies is known to be closely associated with the disease severity, we hypothesized that serum levels of Mallory body-related proteins were correlated with NAFLD histologic activity and evaluated this possibility. STUDY: Serum levels of total and fragmented cytokeratin (CK) 18, heat shock protein (Hsp) 70, Hsp90alpha, ubiquitin+1, and p38alpha at the time of liver biopsy were measured in 118 NAFLD patients and their association with histologic findings and NAFLD histologic activity score (NAS) was investigated. RESULTS: Serum levels of both forms of CK18 and Hsp90alpha were markedly higher in patients having nonalcoholic steatohepatitis (NASH) compared with non-NASH ones. Both forms of CK18 significantly correlated with degree of steatosis, lobular inflammation, and ballooning, and showed stronger positive correlations with NAS than serum aspartate and alanine aminotransferase (AST and ALT). Multiple regression analysis further revealed that fragmented CK18 and AST were effective predictors of NAS, with the former being the more definitive of the two (P<0.001 vs. 0.005). In 20 NAFLD patients who received a follow-up biopsy, changes in fragmented CK18 levels, but not AST or ALT levels, closely paralleled those in NAS. CONCLUSIONS: These results establish the usefulness of fragmented CK18 measurement for assessing and monitoring the histologic activity of NAFLD.
BACKGROUND AND GOALS: Reliable noninvasive biomarkers to assess the histologic activity of nonalcoholic fatty liver disease (NAFLD) have not been established. As the frequency of Mallory bodies is known to be closely associated with the disease severity, we hypothesized that serum levels of Mallory body-related proteins were correlated with NAFLD histologic activity and evaluated this possibility. STUDY: Serum levels of total and fragmented cytokeratin (CK) 18, heat shock protein (Hsp) 70, Hsp90alpha, ubiquitin+1, and p38alpha at the time of liver biopsy were measured in 118 NAFLD patients and their association with histologic findings and NAFLD histologic activity score (NAS) was investigated. RESULTS: Serum levels of both forms of CK18 and Hsp90alpha were markedly higher in patients having nonalcoholic steatohepatitis (NASH) compared with non-NASH ones. Both forms of CK18 significantly correlated with degree of steatosis, lobular inflammation, and ballooning, and showed stronger positive correlations with NAS than serum aspartate and alanine aminotransferase (AST and ALT). Multiple regression analysis further revealed that fragmented CK18 and AST were effective predictors of NAS, with the former being the more definitive of the two (P<0.001 vs. 0.005). In 20 NAFLD patients who received a follow-up biopsy, changes in fragmented CK18 levels, but not AST or ALT levels, closely paralleled those in NAS. CONCLUSIONS: These results establish the usefulness of fragmented CK18 measurement for assessing and monitoring the histologic activity of NAFLD.
Authors: Raj Vuppalanchi; Ajay K Jain; Ross Deppe; Katherine Yates; Megan Comerford; Howard C Masuoka; Brent A Neuschwander-Tetri; Rohit Loomba; Elizabeth M Brunt; David E Kleiner; Jean P Molleston; Jeffrey B Schwimmer; Joel E Lavine; James Tonascia; Naga Chalasani Journal: Clin Gastroenterol Hepatol Date: 2014-05-17 Impact factor: 11.382
Authors: Bryan D Maliken; James E Nelson; Heather M Klintworth; Mary Beauchamp; Matthew M Yeh; Kris V Kowdley Journal: Hepatology Date: 2013-03-14 Impact factor: 17.425
Authors: Manuela G Neuman; Samuel W French; Barbara A French; Helmut K Seitz; Lawrence B Cohen; Sebastian Mueller; Natalia A Osna; Kusum K Kharbanda; Devanshi Seth; Abraham Bautista; Kyle J Thompson; Iain H McKillop; Irina A Kirpich; Craig J McClain; Ramon Bataller; Radu M Nanau; Mihai Voiculescu; Mihai Opris; Hong Shen; Brittany Tillman; Jun Li; Hui Liu; Paul G Thomes; Murali Ganesan; Steve Malnick Journal: Exp Mol Pathol Date: 2014-09-11 Impact factor: 3.362