Yasutake Yamamoto

Exacerbation of primary biliary cirrhosis during interferon-α2b therapy for chronic active hepatitis C

SummaryA 60-year-old woman with chronic active hepatitis C was treated with 6 million units of rIFN-α2b daily for two weeks and subsequently three times weekly for several months. Histological examination proved a severe form of chronic active hepatitis C unexpectedly complicated with primary biliary cirrhosis (PBC). Before treatment, levels of serum alkaline phosphatase (ALP) or gammaglutamyltranspeptidase (GGT) had remained within normal limits over six months, although anti-mitochondrial antibody (AMA) was shown to be positive. After eight weeks of therapy, the daily dose of rIFN was reduced to 3 million units because of a marked increase of ALP and GGT, although the serum alanine aminotransferase (ALT) was normalized. Four months later, IFN treatment was suspended because of continuous elevation of ursodeoxycholic acid was substituted. Two months later, the ALP and GGT levels returned to the normal range, although ALT was not normalized and HCV-RNA remained positive.This is the first report case that demonstrates IFN treatment potentially exacerbates PBC associated with chronic active hepatitis C. It is important for treating physicians to keep this association in mind.

T cell autoreactivity against a 28 kD biliary protein (B1-p28) in primary biliary cirrhosis

BACKGROUND/AIMSnCellular immune responses against biliary epithelial cells are important in understanding the pathogenesis of primary biliary cirrhosis. We previously reported a biliary antigen B1 which stimulated peripheral T lymphocytes of primary biliary cirrhosis as a possible, non-mitochondrial target of biliary epithelial cells. Further characterization of B1 was performed.nnnMETHODSnTo confirm localization of B1 in biliary epithelial cells, a mouse monoclonal antibody was raised against B1. As B1 could be separated into two main components by SDS-PAGE under reducing condition, these components were individually cut out from Western blots and converted into antigen-bearing particles for a proliferation assay to detect the antigenic component responsible for stimulating lymphocytes. The relation of this proliferation to HLA DR antigens was also analyzed.nnnRESULTSnImmunohistochemically, B1 was shown to be specifically expressed on biliary epithelial cells of human liver tissue. Of two components from B1 under reducing condition, prominent proliferation against B1-p28, a 28 kD component of B1 was detected in primary biliary cirrhosis. The reactivities were significantly higher than chronic liver diseases (p < 0.001) or normal controls (p < 0.001). Furthermore, high responders to B1-p28 were observed frequently in primary biliary cirrhosis patients with HLA DR8 (p < 0.02), which was susceptible to the development of primary biliary cirrhosis.nnnCONCLUSIONSnThese data suggest B1-p28 expressed on biliary epithelial cells is a candidate for the target antigen of primary biliary cirrhosis in addition to mitochondrial autoantigens. Further characterization of B1-p28 may provide new insight into the autoimmune mechanisms of primary biliary cirrhosis.

Longitudinal characteristic curve of liver disease

A longitudinal characteristic curve of chronic liver disease (LCC-LD) is derived for the first time by a new method of time series data analysis, where a hospital information system is utilized as a clinical research application of the database. It describes a typical pattern of development of disease from the beginning of chronic hepatitis to the final stage of cirrhosis. The LCC-LD is obtained by effectively using patient data with various stages of developments of liver disease and the present method is applicable to derive the LCC of other diseases. The obtained LCC-LD may be useful for a clinical decision making support such as the prospective assessment (for example, the onset time of cirrhosis) of liver disease in individual patients, an evaluation of drug effect, etc.