No abstract

During liver fibrogenesis, Ito cells are regarded as the principal matrix synthesizing cells and transforming growth factor beta 1 (TGF-beta 1) appears to be the main fibrogenic mediator. This study analyzed the effects of TGF-beta 1 on Ito cell activation, proliferation, and on the expression of a set of matrix proteins, antiproteases, and TGF-beta receptors both in "early cultured" and "culture-activated" Ito cells. Rat liver Ito cells at day 2 of primary culture ("early cultured" cells) were mainly smooth muscle alpha actin (SMA)-negative, whereas cells at day 6 were judged as "activated" cells (SMA-positive). Following 24-hour exposure to 1 ng/mL TGF-beta 1, total protein synthesis, cell proliferation, and expression of the "activation" marker SMA were not significantly changed. In addition to previously described stimulatory effects on collagen types I and III, fibronectin, undulin, and proteoglycan-gene expression, TGF-beta also dose-dependently increased synthesis and secretion of tenascin, laminin, entactin, collagen type IV, and alpha 2-macroglobulin, but decreased C1-esterase inhibitor production by Ito cells, as revealed by immunoprecipitation of endogenously labeled proteins and by Northern blot analysis. The stimulatory effect of TGF-beta was evident both in "early cultured" as well as "culture-activated" Ito cells. By reverse-transcription polymerase chain reaction (RT-PCR) analysis, TGF-beta type II, III, and TGF-beta/activin type I receptors were present in Ito cells, and their expression pattern was not changed upon TGF-beta exposure. Northern blot analysis demonstrated that type I TGF-beta/activin receptor was induced during in vitro activation and that TGF-beta exposure resulted in a slight increase of type I and III receptor messenger RNAs. In summary, the data illustrate that TGF-beta is an important fibrogenic mediator acting both on "early cultured" as well as "culture-activated" Ito cells, rather than a mitogenic or morphogenic mediator. The differential regulation of TGF-beta/activin receptors during in vitro activation and their up-regulation by TGF-beta 1 might represent a mechanism by which the receptor complex regulates TGF-beta signalling in Ito cells.

The long-term results of liver transplantation for Budd-Chiari syndrome (BCS) and timely indication for the procedure are still under debate. Innovations in interventional therapy and better understanding of underlying diseases have improved therapy strategies. The aim of this study was the analysis of patient and disease characteristics, outcome, and specific complications. Between September 1988 and December 2006 we performed 42 orthotopic liver transplantations (OLTs) in 39 patients with BCS. A total of 29 (74%) women and 10 men (26%) had a median age of 35 years; the median follow-up period was 96 months. Etiologically, 27 patients had a preoperative diagnosis of hematologic disease, including myeloproliferative disorders (MPD), followed by factor V Leiden mutation and antiphospholipid syndrome. The actuarial 5-year and 10-year survival rates were 89.4% and 83.5%, respectively, compared to 80.7% and 71.4%, respectively, for other indications (n ϭ 1742). Retransplantation was necessary in 3 patients (7.1%) with portal vein thrombosis or recurrent BCS. Although the number of bleeding events was similar, incidence of vascular complications was significantly higher in patients with BCS. Thrombosis of the portal vein was observed in 4.8% versus 0.8% of the patients, whereas liver veins were affected in 7.1% versus 0.2%. Our data shows that severe acute or chronic forms of BCS with liver failure can be successfully treated by OLT. Despite higher rates of vascular complications, patient and graft survival are similar or even better compared to other indication groups. In conclusion, patients with reversible hepatic damage should be treated by combined strategies, including medical therapy and surgical or interventional shunting.

No abstract