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The fetal alcohol syndrome is a clinical condition that affects newborns from alcoholic mothers. It is not clear, however, whether ethanol consumption during gestation can affect liver functions of fetuses and newborns. In this study, we aimed to assess the effects of ethanol administration on body weight, liver energy level, and antioxidant status of mothers, fetuses, and newborns. Pregnant rats were exposed to ethanol during the third week of gestation. Body weight, survival, and liver concentration of gluthatione (GSH) and adenosintriphosphate (ATP) were measured. No differences were observed in body weight or in liver ATP and GSH between mothers exposed to ethanol and control animals. Conversely, fetuses from rats exposed to ethanol showed a marked decrease in GSH, ATP, and body weight when compared to those from control rats. Newborns exposed prenatally to ethanol were no different from those born to control mothers. This study suggests that an amount of ethanol that is not sufficient to determine a significant effect on mothers can, nevertheless, cause a marked decrease in growth and in liver antioxidant and energy status in fetuses. These parameters, however, return to control value one week after ethanol discontinuation.

The prevalence of liver cell membrane antibodies (LMA) was evaluated in the sera of 124 untreated patients with various chronic liver diseases, in 17 acute hepatitis patients and in 40 normal controls by indirect immunofluorescence on rabbit hepatocytes, isolated by non-enzymatic method. The presence of LMA was compared with the presence of HBs Ag, anti-HBc and non-organ specific autoantibodies (anti-nuclear antibody, ANA; smooth muscle antibody, SMA; anti-mitochondrial antibody, AMA; liver-kidney microsomal antibody, LKM). LMA was found in 83% of autoimmune chronic active liver disease (CALD), in 47% of cryptogenic CALD and in 42% of primary biliary cirrhosis (PBC). LMA prevalence both in HBsAg positive and HBsAg negative/anti-HBc positive CALD was 11%, significantly lower than in the other three groups. In the cryptogenic group the prevalence of non-organ specific autoantibodies was significantly lower than LMA prevalence. The 35 LMA positive sera were titred to end point dilution. Autoimmune cases presented titres higher than those of all the other groups. Adsorption experiments showed that in autoimmune cases LMA fluorescence is not blocked by pre-incubation with liver antigens LSP and LP2, while a mild blocking effect was observed in some HBsAg positive cases or PBC sera. No cross-reaction with mitochondrial antigens was observed in PBC sera. LMA can still be considered a marker of autoimmune CALD only when present at high titre and without cross-reactivity with other liver antigens.

The presence of immunoglobulins (Ig) G, A, and M and of complement fractions (C3-C4) on the liver cell surface was investigated by direct immunofluorescence in 40 patients with alcoholic liver disease. IgG was detected on the liver cell membrane with a linear staining pattern in 29 patients. The percentage of IgG-positive hepatocytes correlated with transaminase activities, independently of the histological findings. IgA was demonstrable with a coarse granular staining pattern in 11 of the 14 cases with established cirrhosis. The finding of IgG bound to the hepatocyte surface in patients with alcohol-induced liver damage suggests that alcohol could be responsible for antigenic modifications of hepatocyte membrane with consequent triggering of a humoral immune response.

The presence, in chronic active hepatitis (CAH) patients, of an inflammatory infiltrate basically composed of T lymphocytes suggested the hypothesis that these lymphocytes could play a role in the pathogenesis of the disease. The aim of this study has been to characterize, in a group of carefully selected CAH patients, the liver-infiltrating T lymphocyte, utilizing commercial monoclonal antibody (anti-Leu 1, anti-Leu 2a, anti-Leu 3a) and 5/9 monoclonal antibody that recognizes a further lymphocyte subset within T4 cells. Our data show that both T4 positive subpopulation and T8 positive subpopulation are represented in the infiltrate in the same ratio; furthermore the distribution of 5/9 positive lymphocytes is prevalent where the infiltrate is mainly composed of T8 positive lymphocytes. Moreover, there is a positive correlation between 5/9 positive cells in the liver and GPT and the patients with high percentages of infiltrating 5/9 positive lymphocytes show a low T4/T8 ratio with respect to patients with low percentages of 5/9 positive cells. These data support the hypothesis that 5/9 positive lymphocytes may present an inducer role on cytotoxic cells.

"In vivo" and "in vitro" action of 2 MPG on lymphocytotoxic activity was evaluated in 22 patients with CAH, 14 were HBsAg positive and 8 were negative. The test was performed with and without 2 MPG in the colture medium, and before and after treatment. HBsAg+ patients received 2 MPG treatment, while HBsAg- ones received immunosoppressive therapy and 4 of these were on 2 MPG treatment as well. Cytotoxic Index was reduced non-significantly by addition of 2 MPG in colture medium in both groups. 2 MPG treatment does not modify cytotoxic activity which is reduced by immunosoppressive therapy. These findings suggest a positive effect of 2 MPG on liver-cell metabolism with an increased resistence of the epatocyte to the "in vitro" lymphocytes aggression. Hence it may be suggested an association treatment with immunosoppressive agents and 2 MPG.

Sera from 42 patients with acute viral hepatitis (AVH), 97 patients with chronic active liver disease (CALD) and 89 controls were tested by radioimmunoprecipitation for the presence of antibodies against human liver-specific protein (LSP). Anti-LSP were found in all but one patient with AVH type A (93%) and in a smaller percentage of AVH type B (55%). In non-A, non-B cases, anti-LSP were found in low percentages: 27% in acute cases, 10% in chronic cases. Furthermore, in CALD, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, both in anti-LSP prevalence (21%, 67%; P less than 0.005) and in anti-LSP titre (1:154 +/- 170, 1:316 +/- 186; P less than 0.005). In HBsAg-negative/anti-HBc-positive CAH, three of 15 patients were anti-LSP positive. Anti-LSP were found only in three of 57 patients with various non-hepatic diseases with autoimmune features. None of the 12 healthy HBsAg carriers was positive. Hence there is evidence for a considerable heterogeneity in anti-LSP response in acute and in chronic inflammatory HBsAg-negative liver diseases. These data suggest that anti-LSP antibodies do not play a prominent role in the process of transition to chronicity of acute viral hepatitis particularly in non-A, non-B cases, whereas these antibodies may be important in the mechanism of ongoing liver cell injury in patients with 'autoimmune' CAH, and can represent a useful diagnostic marker of this type of hepatitis.

The relative distribution of T lymphocyte subsets, as defined by the monoclonal antibodies OKT, was determined by cytofluorimetric analysis in peripheral blood and in cells isolated from liver biopsies of 31 patients with chronic active hepatitis (CAH). The percentage of peripheral blood lymphocytes binding OKT8 (directed against cytotoxic/suppressor T cells) was found to be elevated in patients with HBsAg and HBeAg positive chronic active hepatitis. Patients with CAH who had seroconverted to anti-HBe, had an increased number of OKT3-positive cells in their blood, which was directed against a common T cell surface antigen, associated with a decreased number of OKT8 positive cells. Lymphocytes isolated from liver biopsies of patients with CAH presented a general increase of OKT8-positive cells associated with a decreased number of OKT4-positive (helper/inducer) T cells. It is likely that OKT8-positive cells found in liver biopsies represent cytotoxic T cells directed against either viral or liver cell determinants.

We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated" and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction.