[A study of hypertriglyceridemia occurring in patients with chronic hepatitis C during administration of interferon beta].

The prevalence and risk factors of hypertriglyceridemia during the administration of interferon (IFN) were examined in 78 patients with chronic hepatitis C who were treated with 6 MU of IFN-beta once or 3 MU of IFN-beta twice a day for 6 weeks. Hypertriglyceridemia (serum triglyceride (TG) above 150 mg/dl) was found before the start of IFN treatment in 9% of the patients. During the administration of IFN, elevation of serum TG above 150 mg/dl was found in 82% of patients. In addition, serum TG level exceeded 500 mg/dl at least once during the administration of IFN in 13% of patients. On stepwise multiple regression analysis, three risk factors, high serum TG value before the administration of IFN, high ALT value before the administration of IFN, and divided administration of IFN-beta twice daily were found to be associated with hypertriglyceridemia during IFN administration.

Prediction of esophageal varices in cirrhosis by per-rectal portal scintigraphy.

Portal circulation in patients with chronic liver disease was evaluated by per-rectal portal scintigraphy, and per-rectal portal shunt indices were calculated to estimate the extent of the portosystemic shunt. The purpose was to identify patients with cirrhosis at special risk of developing esophageal varices. The cumulative incidence of varices in 3 years of the study in patients whose shunt index was originally 20% or over, was significantly higher than that in patients whose shunt index was originally under 20%. The cumulative survival rate in 7 years of the study in patients whose shunt index was originally under 70% was significantly higher than that in patients whose shunt index was originally 70% or over. The information obtained by calculating the shunt index could be used by physicians in out-patient clinics when deciding the schedule with which to monitor patients using barium esophagogram or endoscopy, and choosing the examination method.

Changes in interferon receptors on peripheral blood mononuclear cells from patients with chronic hepatitis B being treated with interferon.

We studied the binding of 125I-labeled human interferon-alpha to peripheral blood mononuclear cells and the activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis B who were treated with human interferon-alpha or interferon-beta. Fourteen patients were given interferon daily for 4 wk. Interferon receptors per cell decreased to about 50% of baseline but increased to baseline by 2 wk after therapy ended. The activity of 2',5'-oligoadenylate synthetase rose about fivefold during therapy, decreasing to baseline by 1 wk after the end of therapy. The seven other patients were given interferon daily for 2 wk, no interferon for 2 wk and then interferon daily for 2 wk more. During both periods of therapy on this schedule, interferon receptors decreased to about 50% but returned to baseline 1 wk after the interferon was stopped. The activity of 2',5'-oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped. Close negative correlation existed between the number of interferon receptors and the 2',5'-oligoadenylate synthetase activity. The results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy.

Portal circulation in monkeys and humans studied after ingestion of a capsule containing a radionuclide.

Capsules (8 x 30 mm) of technetium-99m pertechnetate were designed for measurement of portal blood flow. Most of the radionuclide entered the superior mesenteric vein. The capsule was taken orally and monitored with a collimator for scintigraphy until it reached the small intestine, when a magnetic field completed an electrical circuit in a sensor, burning a thread, releasing a spring, and discharging the preparation. A study in crab-eating monkeys (Macaca fascicularis) showed that the radionuclide in the small intestine circulated through the superior mesenteric vein to the portal vein and liver. Portal scintigraphy through the small intestine could be analysed in the same way as per-rectal portal scintigraphy, in which blood flow mostly from the inferior mesenteric vein is evaluated. A study of four volunteers showed that, after the radionuclide was released, it circulated through the superior mesenteric vein to the portal vein and liver. Use of a capsule enclosing a radioisotope was possible, and the procedure seemed to be safe. The use of the per-small intestine method plus the per-rectal method should give more accurate results than either method used alone, because the haemodynamics of both the superior and inferior mesenteric vein would be reflected.

[Interferon-alpha/beta receptors in patients with chronic HBV infection].

We analyzed the binding of 125I-labelled IFN-alpha to peripheral blood mononuclear cells in 19 healthy controls, 25 asymptomatic HBV carriers (AsC), and 69 patients with HBs antigen positive chronic liver disease (CLD). Histological examination showed that of the 69 patients with CLD, 14 had chronic persistent hepatitis (CPH), 46 had chronic active hepatitis (CAH), 9 had liver cirrhosis (LC). The mean number of IFN-alpha/beta receptor sites per cell totaled 1270 +/- 340 in the healthy controls, 1440 +/- 290 in AsC, and 1600 +/- 480 in CLD (with 1770 +/- 480 in CPH, 1580 +/- 490 in CAH, and 1420 +/- 410 in LC). HBV carriers had more IFN-alpha/beta receptor sites than the healthy controls (AsC: P less than 0.1, CLD: P less than 0.01). In CLD, patients with LC tended to have fewer IFN-alpha/beta receptor sites than those with CPH or CAH. The number of IFN-alpha/beta receptor sites in CLD was correlated with the HBe antigen titer (P less than 0.01), and activity of HBV-DNA polymerase (P less than 0.05). These results were suggested that IFN-alpha/beta receptor sites was higher at the HBV carrier state, and correlated with viral replication.

Diagnosis of hepatocellular carcinoma by factor analysis.

We examined the usefulness of factor analysis for the diagnosis of hepatocellular carcinoma by analysis of the data obtained by radionuclide angiography. The data could be separated into two factors, a hepatic phase (hepatic artery and portal vein) and an arterial phase (aorta and kidney). In patients with hepatocellular carcinoma, the factor of the tumor is included in the arterial phase, so that the cancerous region could be differentiated from the noncancerous region. The ratio of the radioactivity of the cancerous region to the noncancerous region was used to estimate the blood flow of the tumor region.

Interferon receptors during treatment of chronic hepatitis B with interferon.

The in vitro binding of 125I-labelled human alpha-interferon to peripheral blood mononuclear cells from 13 patients with chronic hepatitis B during interferon therapy was assayed in order to identify changes in the number of interferon receptors during treatment. Nine patients were treated with human alpha-interferon (Hu alpha-IFN) or human beta-interferon (Hu beta-IFN) daily for 4 weeks. During therapy, receptor sites per cell decreased by 40%. Two weeks after therapy ceased, this number had returned to the pretreatment level. The other four patients were given Hu alpha-IFN daily for 2 weeks, no injections for 2 weeks, and daily injections for 2 weeks. During both periods of therapy, receptor sites decreased by 40%. The number increased to 94% of the pretreatment level 1 week after the first period and to 101% 2 weeks later. It was 80% 1 week after the second period of injections and 108% 2 weeks later.

Portal circulation by technetium-99m pertechnetate per-rectal portal scintigraphy.

Portal circulation in patients with chronic liver diseases was evaluated by [99mTc]pertechnetate per-rectal scintigraphy. Technetium-99m pertechnetate (10 mCi) was instilled into the upper rectum, and serial scintigrams were taken. Radioactivity curves for the liver and heart were then recorded sequentially. Through analysis of these curves, the per-rectal portal shunt index (Sl) was calculated for six healthy subjects and 228 patients, 59 with chronic hepatitis, seven with idiopathic portal hypertension, six with primary biliary cirrhosis, and 156 with cirrhosis. In the healthy subjects, the Sl was 1.9-5.2% (mean 4.1%). In hepatitis, the mean Sl was 7.1%, and in cirrhosis, 52.9%. The Sl was higher in cirrhotic patients with esophageal varices than in those without (p less than 0.001), and in cirrhotic patients with encephalopathy than in those without (p less than 0.01). For some patients with portal hypertension, portal collateral circulation could be depicted, and images of changes in the portal collateral circulation after vascular anastomosis were seen.