Yoshiaki Yajima

Continuous removal of middle molecules by hemofiltration in patients with acute liver failure.

In patients with acute liver failure and hepatic coma, an increase in the abnormal “middle molecules” seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived >3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant.

Profiles of cytokines produced by CD4-positive T lymphocytes stimulated by anti-CD3 antibody in patients with chronic hepatitis C

Abstract: Helper T cells (Th) are classified as type 1 (Th1) and type 2 (Th2) according to the cytokines they produce; interferon-γ is produced by Th1, and interleukin-4 by Th2. We counted the circulating CD4-positive Th cells that produce interferon-γ or interleukin-4 with an enzyme-linked immunospot assay. CD4-positive T cells isolated from patients with chronic hepatitis B (n = 10), chronic hepatitis C (n = 16), and healthy subjects (n = 10) were stimulated with anti-CD3 antibody in vitro. The number of interferon-γ-producing Th cells was significantly lower in patients with chronic hepatitis C than in healthy subjects (P = 0.0024), whereas in patients with chronic hepatitis B, the number was similar to that in healthy subjects (P = 0.8530). The number of interleukin-4-producing Th cells was significantly higher in patients with chronic hepatitis C (P = 0.0010) and chronic hepatitis B (P = 0.0089) than in healthy subjects. In chronic hepatitis C, the number of interferon-γ-producing Th cells was increased after incubation of the cells with interferon-α (P = 0.008) or with recombinant interferon-γla (P = 0.024), but not with interferon-β (P = 0.051). The number of interleukin-4-producing Th cells was decreased after incubation with interferon-α (P = 0.0004), with interferon-β (P = 0.003), and with recombinant interferon-γla (P = 0.0004). Changes in the numbers of interferon-γ- or interleukin-4-producing Th cells in vitro were more evident in sustained responders to interferon therapy than in non-responders. These results suggest that Th2 cells are the predominant cell type in chronic hepatitis C, and that their activity may be suppressed by the administration of interferon.

Non-septic endotoxemia in cirrhotic patients

SummaryWe have found that endotoxemia detected by conventional LCT (limulus colorimetric test) in patients with liver diseases could not be detected by endotoxin-specific LCT at all, and proposed that this β-glucan like activity (BGLA) should be termed as non-septic endotoxemia, distinguishing it from septic endotoxemia seen in gram-negative sepsis. In this study, we investigated non-septic endotoxemia through the clinical course of 8 cirrhotic patients. Non-septic endotoxemia appeared at the onset of DIC but tended to decline in level in the late terminal stage. This phenomenon cannot be consistent with the “spillover” theory which explains the mechanism of endotoxemia without sepsis in liver disease. We think it is an urgent problem to elucidate the nature of BGLA in liver disease, without recourse to the “spillover” theory.

Abstracts of selected papers presented at the 74th general meeting of the Japanese Society of Gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 74TH GENERAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY March 24-26, 1988 Sendai, Japan Chairman: Toshio SATO, M.D.