Shigehiko Ueda

In vitro differentiation of hepatocyte-like cells from embryonic stem cells promoted by gene transfer of hepatocyte nuclear factor 3 β

We investigated the ability of a genetically altered embryonic stem (ES) cell line to promote endodermal differentiation toward hepatocytes in vitro by transfecting the hepatocyte nuclear factor-3beta (HNF-3beta) gene. Parental and HNF-3beta-transfected ES cells were initiated toward differentiation in embryoid bodies (EBs) for 5 days and the resulting EBs were transferred to an attached culture system. Albumin production was observed using an immuno-cytochemical method 7 days after induction of differentiation in almost all differentiating HNF-3beta-transfected ES cells, whereas scant immuno-reactivity against albumin was found on the same day in the cultures of differentiating parental ES cells. An analysis using a reverse transcriptase polymerase chain reaction revealed the HNF-4alpha expression in the HNF-3beta-transfected ES cells and also demonstrated that the expression of endodermal and hepatocyte-related markers, such as transthyretin, alpha-fetoprotein, albumin, alpha-1 antitrypsin, tryptophan-2,3-dioxygenase and phosphoenol-pyruvate carboxykinase, could be observed at an early stage in the outgrowths of HNF-3beta-transfected ES cells compared to the parental ES cells. These results suggest that HNF-3beta-transfected ES cells may be useful for the efficient induction of hepatocytes in vivo.

Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis C associated with autoimmune hepatitis-like serological manifestations

Abstract: We report a 70-year-old woman with chronic hepatitis C associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis C virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum γ-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.