Aberrant Expression of Keratin 7 in Hepatocytes as a Predictive Marker of Rapid Progression to Hepatic Failure in Asymptomatic Primary Biliary Cirrhosis.

A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patients' hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis.

[1]  Maylee Hsu,et al.  Application and Validation of a New Histologic Staging and Grading System for Primary Biliary Cirrhosis , 2013, Journal of clinical gastroenterology.

[2]  M. Smith,et al.  Keratin 19 Demonstration of Canal of Hering Loss in Primary Biliary Cirrhosis: “Minimal Change PBC”? , 2013 .

[3]  Kazuhide Yamamoto,et al.  Prevalence and associated factors with esophageal varices in early primary biliary cirrhosis , 2012, Journal of gastroenterology and hepatology.

[4]  Kazuhide Yamamoto,et al.  Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population , 2009, Journal of Gastroenterology.

[5]  Masahiro Ito,et al.  Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis , 2007, Hepatology.

[6]  M. Kaplan,et al.  The natural history of PBC: has it changed? , 2005, Seminars in liver disease.

[7]  A. Chetwynd,et al.  Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort , 2004, Gut.

[8]  E. Dickson,et al.  Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis) , 1978, Virchows Archiv A.

[9]  T. Roskams,et al.  Progenitor cells in diseased human liver. , 2003, Seminars in liver disease.

[10]  O. James,et al.  The epidemiology of primary biliary cirrhosis. , 2003, Clinics in liver disease.

[11]  M. Abe,et al.  Esophagogastric varices as a prognostic factor for the determination of clinical stage in patients with primary biliary cirrhosis , 2003, Journal of Gastroenterology.

[12]  Kazuhide Yamamoto,et al.  Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis. , 2001, Liver.

[13]  K. O'rourke,et al.  Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis , 1999, American Journal of Gastroenterology.

[14]  Y. Nakanuma,et al.  Semiquantitative assessment of cholestasis and lymphocytic piecemeal necrosis in primary biliary cirrhosis: a histologic and immunohistochemical study. , 1990, Journal of clinical gastroenterology.

[15]  V. Desmet,et al.  A cytokeratin immunohistochemical study of cholestatic liver disease: Evidence that hepatocytes can express “bile duct‐type” cytokeratins , 1989, Histopathology.

[16]  F. Schaffner,et al.  Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas. , 1989, Archives of pathology & laboratory medicine.

[17]  P. van Eyken,et al.  The development of the intrahepatic bile ducts in man: A keratin‐immunohistochemical study , 1988, Hepatology.

[18]  S. Sherlock,et al.  Is copper hepatotoxic in primary biliary cirrhosis? , 1981, Journal of clinical pathology.