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Interferon (IFN) receptor mRNA expression patterns in the liver have been shown to correlate with the effectiveness of IFN therapy in patients with hepatitis C virus (HCV) infection. However, it is not clear to what extent this factor contributes to the short (primary)- and long (sustained)-term results of IFN treatment with respect to biochemical and virological remission. Eighty-two patients who subsequently received lymphoblastoid IFN-alpha therapy underwent liver biopsies before IFN therapy. Possible factors that might correlate with IFN response were chosen and analyzed. The primary biochemical and virological responses at the end to treatment (24 weeks) were 63% and 43% vs. 46% and 32% for sustained biochemical and virological remission at the end of follow-up (48 weeks), respectively. In univariate analysis, the absence of HCV genotype 1b, a low titer of HCV RNA, and the expression of IFN receptor mRNA were significantly correlated with sustained biochemical and virological responses to IFN therapy. Multiple logistic regression analysis showed that IFN receptor mRNA expression and the absence of genotype 1b were significant predictors of the sustained biochemical and virological effectiveness of IFN therapy. IFN receptor mRNA expression predicted a sustained virological response to IFN therapy with a positive predictive value of 100% with genotype non-1b and had a negative predictive value of 97% with genotype 1b. It is concluded that expression of IFN receptor genes in the liver is a useful index for predicting the short- and long-term efficacy of IFN therapy in patients with chronic HCV infection.

A 62-year-old man was first found to have a gastric tumor in the fornix during a routine health examination 16 months previously. The case was not associated with von Recklinghausen's disease. Initially, the tumor was approximately 4 mm in diameter, but grew very rapidly to 20 mm in 13 months, and to 30 mm in the following month, without manifesting clinical symptoms. Malignancy was suspected because of the rapid growth and the endoscopic findings: a rough-granular elevated lesion with a wide stalk, and with erosions and mucus on its surface. Although endoscopic biopsy was done several times, the routine histological examinations were inconclusive. Endoscopic resection was therefore carried out. Examination of the resected specimen showed that the main elements consisted of wavy, long-spindled cells, which crossed irregularly, and whose interstitium was myxomatous. Immunohistochemically the specimen showed strongly positive reaction for S-100 protein and positive reaction for neuron specific enolase (NSE). Based on these immunohistochemical findings, a final diagnosis of gastric myxoid neurofibroma was made, which showed rapid growth due to myxomatous change. The patient showed a good postoperative course and no recurrence has been recognized by follow-up endoscopy.

PURPOSE This study investigated hemodynamic changes in the resistance index of the hepatic artery after mixed-meal ingestion. METHODS We used color Doppler sonography to measure hemodynamic changes in the right hepatic artery in response to mixed-meal ingestion (225 ml, 69 g, 300 kcal) in 9 healthy subjects, 15 patients with chronic hepatitis with low-grade fibrosis (no bridging), 10 patients with chronic hepatitis with moderate-grade (bridging) fibrosis, and 18 patients with cirrhosis. RESULTS After mixed-meal ingestion, the mean (+/-standard error) maximum increase in the resistance index of the right hepatic artery in healthy subjects was 31+/-2%. These changes were significantly greater than those in patients with chronic hepatitis with low-grade fibrosis (22+/-2%; p

Measurement of serum HCV-RNA is a useful index for evaluating the antiviral effect of interferon therapy in chronic hepatitis C. In the present study, we investigated whether the detection of hepatic HCV-RNA after interferon treatment, using a polymerase chain reaction assay, predicted long-term response to therapy in patients with chronic hepatitis C. Thirty-three patients underwent liver biopsies before and after interferon therapy. Histology and clinical courses were compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA became undetectable in samples from 22 (67%) patients ; however, in 10 of these patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA became undetectable in 14 patients after therapy and the serum aminotransferase concentration remained within normal limits during and following (24-92 weeks) therapy in 12 of these patients (86%). All 11 patients with detectable hepatic HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon treatment thus predicted a long-term complete response to therapy with a sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude that hepatic rather than serum HCV-RNA is a more useful index for the prediction of the long-term efficacy of interferon therapy.

Human hepatocellular carcinoma (HCC) is characterized by hypervascularity and tumor staining in angiograms, and tumor angiogenesis is considered indispensable for tumor growth. HCC is also characterized by an obvious multistage process of tumor progression. To find out in which stage of human hepatocarcinogenesis angiogenesis occurs, we have carried out a pathological study, of the phenotypic changes in tumor vessels taken from surgically resected liver tumors showing each step of the progression. Eleven early advanced HCCs (advanced HCC component in early HCC nodule, eAd HCC), seven early HCCs (eHCC) and six adenomatous hyperplasias (AH), the non-tumorous liver surrounding each and five normal livers were studied by lectin histochemistry and immunohistochemistry. The sinusoidal endothelial cells from the non-tumorous liver were shown to be negative for UEA-I (Ulex europaeus I), but the endothelial cells from the sinusoidal tumor vessels in advanced HCC components were strongly positive. In AH and eHCC, half the tumors were negative and the other half focally positive. In the early HCC lesion of eAdHCC, the rate of positivity for UEA-I was a little higher than in AH and eHCC but lower than in advanced HCC lesions in eAdHCC. Immunohistochemically, laminin was not detected in the sinusoids in the non-tumorous liver or in the sinusoidal tumor vessels in AH and eHCC. In eAdHCC, however, two early HCC lesions and four advanced HCC lesions were positive. An immunohistochemical examination for muscle actin revealed an increase in arterial tumor vessels in six advanced HCC lesions and one early HCC lesion of eAdHCC. The results indicate the emergence of UEA-I-positive sinusoidal tumor vessels to be most pronounced during the progression from eHCC to advanced HCC, and laminin-positive sinusoidal tumor vessels or actin-positive arterial tumor vessels to emerge mainly in advanced HCC.

The hepatic vagus nerve consists of mostly afferent fibers in the rat, and is a major afferent pathway between the liver and the medulla. The present study was carried out to examine the role of the hepatic branch of the vagus nerve in secretion of insulin and glucagon after intraperitoneal injection of arginine (1 g/kg body wt.) in rats. Measurements were made one week after section of this branch. Intraperitoneal arginine enhanced both plasma insulin and glucagon concentrations; more in hepatic-vagotomized than in sham-vagotomized rats. The results suggest that inhibition of the secretion of insulin and glucagon after arginine stimulation is mediated by the hepatic branch of the vagus nerve. The existence of ‘sensors’ in the liver for arginine, or its derivatives, is proposed as an explanation for the inhibition of the secretion of insulin and glucagon by the hepatic vagus nerve.