Plasma levels of cyclic GMP, immune parameters and depressive status during interferon therapy. A prospective study in Japan.

In this report, we investigated the relationship between depressive symptoms and plasma interferon (IFN)-alpha-like immunoreactivity, cyclic GMP (cGMP) and soluble interleukin-2 receptor (sIL-2R) levels during IFN therapy. An altered mood state was observed in 5 of 26 patients. IFN-alpha-like immunoreactivity in the depressed group tended to be elevated. cGMP levels of depressed patients were significantly greater than those of control subjects before and 6 weeks after IFN therapy. However, sIL-2R levels were not different between the two groups. These results suggest that a number of patients suffered from depression during IFN therapy and that patients had greater concentrations of cGMP levels.

Hepatitis C virus RNA and hepatitis C virus antibody in the serum of patients with abnormal liver function.

In order to elucidate the relation between hepatitis C virus (HCV) RNA and antibody to HCV (anti-HCV) in serum, we examined samples of serum collected from 228 HBsAg-negative patients, with abnormal alanine aminotransferase (ALT) values, for HCV-RNA by nested polymerase chain reaction (PCR) assay and for anti-HCV using C100 protein as the antigen. HCV-RNA was detected in 99 (92.5%) of 107 anti-HCV-IgG-positive samples, regardless of ELISA optical density cut-off value (ELISA ratio), and in 34 (28.1%) of 121 anti-HCV-IgG-negative samples in which the frequency of the presence of HCV-RNA became higher in proportion to the ELISA ratio. Among 42 discordant cases (34 anti-HCV-IgG-negative, RNA-positive cases and eight anti-HCV-IgG-positive, RNA-negative cases), 10 were positive for anti-HCV-IgM (8/34 and 2/8, respectively) irrespective of clinical status. These findings suggest that in patients with abnormal ALT values, even if they are anti-HCV-IgG negative, HCV infection cannot be excluded. Furthermore, PCR assay for detecting HCV-RNA may be more suitable for identifying patients with infectious virus than is detection of anti-HCV-IgG. Detection of anti-HCV-IgM may also be useful.

A long-term follow-up of five patients with hepatitis delta virus in Japan.

From 1973 to 1989 five patients with hepatitis delta virus having anti-hepatitis delta antibodies continuously in the serum for more than 5 years were identified among 1019 hepatitis B virus carriers who were being followed-up for more than 3 years (mean 8.9 years). Of the five patients with antibodies, three had a history of blood transfusion, in two cases the transfusion was massive, and one patient had been addicted to narcotics given intravenously 35 years before. In the remaining patient, the route of superinfection could not be determined. Hepatitis delta antigen was detected in hepatocyte nuclei of one of the three patients in whom liver biopsies were performed and there was chronic persistent hepatitis detected by an indirect immunoperoxidase technique. During the follow-up, hepatocellular carcinoma developed in one case but the clinical prognosis was favourable in the remaining four cases.

[Clinical analysis of ascitic fluid in patients with liver cirrhosis and hepatocellular carcinoma].

To investigate the clinical significance of ascitic fluid in patients with a malignancy, an abdominal paracentesis to evaluate the ascitic fluid was performed in 10 patients with a hepatocellular carcinoma (HCC) and in 7 patients with liver cirrhosis (LC). The AFP levels in the ascitic fluid and in the serum of the HCC patients was found be significantly higher than that of the LC patients. In addition, the ratio of albumin/total protein in ascitic fluid was also higher in the HCC patients. However, no significant findings were uncovered with regard to the concentration of lipid in ascitic fluid, in either type of patient although 2 HCC patients were found to have a very high concentration of total cholesterol. The cytological findings provided no reliable marker because of significant number of false negatives in the HCC patients. Also, there was no significant difference between the fibronectin levels in the ascitic fluid of either type of patients. This finding differs from previous studies, and suggests that the fibronectin levels in the ascitic fluid may not be a useful marker in determining a malignancy.

[A clinical study of complements as a marker of a hepatocellular carcinoma].

Serum complement C3, C4, and C3 proactivator (C3PA) have been evaluated for their diagnostic power in detecting a hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). It was found that serum complement levels were lower in LC patients than in HCC patients and that difference of the serum C4 and C3PA levels between LC patients and HCC patients were statistically significant. In addition, serum C3 PA levels were found to correlate significantly with the serum gamma-GTP levels in HCC patients. Thus, using the cutoff values of C4 and C3PA as the mean values for HCC patients, examination of serum complement levels enabled the detection of 38% of the HCC patients with low AFP levels. These findings suggest that the examination of the serum complements may be a useful a tool for the detection of HCCs in LC patients.

[The ornithine decarboxylase activity of the gastric remnant mucosa: the effect of the duodenal juice with bile on the gastric mucosa].

Using male Wister rats, the ornithine decarboxylase (ODC) activity in the fundic mucosa has been determined from the duodenal juice with bile of a reflux model. The activity at 24 hours postoperatively presented a value approximately 18 times higher than the preoperative level. Though this level declined subsequently, it still was approximately two times higher four weeks later. The ODC activity in the corporal mucosa of humans was compared in 25 normal persons, in 21 patients with a gastric adenoma in 29 patients with a gastric cancer, in 20 patients who had undergone a Billroth I operation and in 20 patients who had undergone a Billroth II operation. No differences in ODC activity were observed among those with a gastric adenoma, a gastric cancer, and normal cases but significantly higher values were seen in cases with a remnant stomach, particularly those who had undergone Billroth II reconstructive surgery. Further, this activity tended to be especially high from 5 to 15 years postoperatively in cases with a gastric remnant.

[A clinical study of serum erythropoietin concentrations in patients with liver cirrhosis and hepatocellular carcinomas].

We have measured the serum erythropoietin concentrations in 14 patients with liver cirrhosis and in 14 patients with a hepatocellular carcinoma. Among these patients, 2 with liver cirrhosis (14.3%) and 7 with a hepatocellular carcinoma (50.0%) were found to have raised serum erythropoietin concentrations, ranging up to 40 mU/ml. Negative correlations were found between erythropoietin and the RBC, and the Hb and Ht in the cases with liver cirrhosis. In contrast, a positive correlation which was not significant was found only between the erythropoietin and the RBC in cases involving a hepatocellular carcinoma. This has suggested that the relationship between the erythropoietin and the RBC in cases of a hepatocellular carcinoma differs from the relationship seen under the usual physiological circumstances of those with liver cirrhosis.

[Clinical analysis of patients with hepatocellular carcinoma with non-A, non-B hepatitis virus].

An analysis of 242 patients with a hepatocellular carcinoma (HCC) has shown that 65 patients without a hepatitis B virus (HBV), alcohol abuse, or a transfusion history and 17 posttransfusion patients had a mean death age of 65.5 +/- 10.2 and 62.1 +/- 8.4 years respectively. The average age of 65 patients was 8.5 years older than those with a HBV and without a alcohol abuse history. Of 17 patients, 3 with a HBV had a mean death age of 55.3 +/- 10.8 years and the interval time from transfusion to a HCC was significantly shorter than in other post-transfusion patients.

Effect of neonatal thymectomy on experimental autoimmune hepatitis in mice.

Using an autoimmune hepatitis model of A/J mice which was prepared with immunization by syngeneic crude liver proteins, various influences of neonatal thymectomy were studied by observations of histological liver changes, autoantibody to liver-specific membrane lipoprotein (LSP), delayed-type hypersensitivity (DTH) to LSP, and purified protein derivative (PPD), and suppressor activity to LSP. The liver changes in the thymectomized mice were more intense than those in the non-thymectomized controls. Production of the anti-LSP autoantibodies and positive DTH to syngeneic LSP could be recognized in both groups of the thymectomized mice and the non-thymectomized controls, but the levels of those were higher in the former. In the level of DTH to PPD the thymectomized mice were lower than the non-thymectomized controls. Adoptive transfer experiments showed that suppressor activity to LSP was reduced in the spleen cells of neonatally thymectomized mice. This experiment suggests that neonatal thymectomy is apt to abolish tolerance to LSP on account of depressed suppressor activity to autoantigen, and accordingly liver damage is increased.