Intracellular cytokine analysis of CD4-positive T cells predictive of sustained response to interferon therapy for patients with chronic hepatitis C.

We investigated whether the measurement of serum interleukin 18 (IL-18) and intracellular cytokine analysis of peripheral blood CD4-positive T cells (ICA-CD4+ Tc) of chronic hepatitis C (CH-C) patients before and two weeks after interferon (IFN) administration are useful for predicting sustained response to IFN. Twenty-nine CH-C patients received IFN every day for two weeks and three times a week for 22 weeks. Patients were divided into two groups: responders, in whom serum HCV-RNA was undetectable at the end of the follow-up (week 48), and nonresponders, in whom any other patterns were seen. Before and two weeks after IFN administration, serum IL-18 and ICA-CD4+ Tc as described by Jung et al were measured. Serum IL-18 and the relative prevalence of IFN-gamma+ and IL-4+, IFN-gamma+ and IL-4 (Th-1), and IFN-gamma- and IL-4+ cells in the responders were significantly increased, but only the relative prevalence of Th-1 cells in the nonresponders was increased two weeks after IFN therapy. In conclusion, ICA-CD4+ Tc and the measurement of serum IL-18 might be useful for predicting IFN therapy by comparing the results between before and two weeks after IFN.

Heterochronous development of intrahepatic cholangiocellular carcinoma following hepatocellular carcinoma in a hepatitis B virus carrier.

A 68-year-old Japanese woman was admitted to our hospital in September 1995, because of a mass detected by ultrasonography during a follow-up examination for chronic hepatitis B. Hepatocellular carcinoma (HCC) in the right liver lobe was diagnosed based on imaging studies and elevated alpha-fetoprotein (AFP). Percutaneous ethanol injection therapy (PEIT) was performed. PEIT was repeated in November 1998, because the tumor had enlarged and serum AFP was re-elevated. Follow-up ultrasonography (US) demonstrated low echoic mass in the left liver lobe in August 1999; serum AFP was normal, but serum carbohydrate antigen 19-9 (CA19-9) was elevated to 420 U/ml. In October 1999, radiofrequency interstitial tissue ablation (RITA) was performed after tumor biopsy. Pathological findings revealed adenocarcinoma and pathological diagnosis was made as intrahepatic cholangiocellular carcinoma (ICC). Three weeks later, her serum CA19-9 was remarkably decreased (180 U/ml). The patient has been well for 5 months. Her latest AFP and CA19-9 in the serum were 2 ng/ml and 89 U/ml, respectively. The incidence of double cancer in the liver is rare. This is also the first case report to discuss ICC treated with RITA.

[Clinical evaluation of hepatic bruit audible in patients with alcoholic hepatitis].

It is well accepted that many patients with alcoholic hepatitis have an audible bruit over the liver (hepatic bruit) in western countries. However, this sign has not been discussed in Japan. The aim of this study was to assess the significance of the hepatic bruit in Japanese patients with alcoholic hepatitis. Hepatic bruit was specifically searched for on auscultation by two physician in consecutive patients (6 alcoholic hepatitis, 58 other alcoholic liver disease, 128 nonalcoholic liver disease including 16 hepatocellular carcinoma). Hepatic bruit was detected in 5 of 6 (83%) patients with alcoholic hepatitis, and in 1 of 16 (6%) patients with hepatocellular carcinoma. In any of other liver diseases, hepatic bruit was not detected. We conclude that hepatic bruit may be an important diagnostic finding in Japanese patient with alcoholic hepatitis as it is in western countries.

Chronic splanchnic hemodynamic effects of spironolactone with unrestricted sodium diet in patients with compensated cirrhosis.

The purpose of this study is to determine the hemodynamic effects of spironolactone administration associated with an unrestricted sodium diet (salt 10 g) in patients with compensated cirrhosis and portal hypertension. We studied the hemodynamic changes following eight weeks of administration of either placebo (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No significant changes were observed after the administration of the placebo. Spironolactone induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P < 0.05). There was no significant change in hepatic blood flow and there was no significant correlation between the change in the HVPG and the change in circulating plasma volume. A decrease in the HVPG greater than 10% was observed in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six (100%) grade A patients and two of six (33%) grade B patients responded. This study demonstrated that spironolactone with an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease the HVPG in grade B patients.

Oral administration of nipradilol and the acute and chronic splanchnic hemodynamic effects of a new beta-blocker with nitrovasodilating properties in patients with liver cirrhosis.

OBJECTIVES: We studied the effects of nipradilol, which has both a nonselective beta-blocker action and a vasodilating action similar to nitroglycerin, on portal hypertension. METHODS: We measured hepatic venous pressure gradient and splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14) or of a placebo (n = 6) in 20 cirrhotic patients. RESULTS: No significant changes were observed after the administration of the placebo. Oral nipradilol induced a significant reduction in the hepatic venous pressure gradient (base line: 14.8 +/- 3.2 mm Hg vs 2 h: 12.3 +/- 3.4 mm Hg, p < 0.01; 6 mo: 12.5 +/- 3.2 mm Hg, p < 0.05) without a significant change in the free hepatic venous pressure. The hepatic vascular resistance decreased significantly (base line: 1811 +/- 778 dyn.sec.cm-5 vs 2 h: 1540 +/- 701 dyn.sec.cm-5, p < 0.05; 6 mo: 1564 +/- 693 dyn.sec.cm-5, p < 0.05) without a significant change in hepatic blood flow. A decrease in the hepatic venous pressure gradient greater than 10% was observed in nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at 6 months. The reduction of mean heart rate and hepatic venous pressure gradient in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months, respectively. CONCLUSIONS: We found that in some cirrhotic patients, at the doses used in this study, long term oral nipradilol administration produces a reduction in the hepatic venous pressure gradient with both a beta-blocking and a nitrovasodilating action.

Intrahepatic arteriovenous shunting due to hepatocellular carcinoma and cirrhosis, and its change by transcatheter arterial embolization.

OBJECTIVES: To investigate intrahepatic arteriovenous shunt rate due to cirrhosis and hepatocellular carcinoma (HCC), complicated by cirrhosis, and its change after transcatheter arterial embolization. METHODS: The shunt rate was measured by hepatic artery infusion of labeled macroaggregated albumin. Counts were taken over the liver and both lungs for calculation of the shunt rate: cpm in lungs divided by (cpm in liver and lungs) x 100%. RESULTS: The intrahepatic arteriovenous shunt rate of cirrhosis ranged from 6.8% to 16.6% (12.6% +/- 3.4%, mean +/- SD). In HCC, it ranged from 7.2% to 27.1% (16.0% +/- 4.9%, mean +/- SD). The difference between the groups was statistically significant (p < 0.05). When the liver was more than 20% replaced by tumor, the intrahepatic arteriovenous shunt rate was higher than when less than 20% occupied (n = 6, 20.1% +/- 4.8% vs. n = 15, 14.4% +/- 4.0%; p < 0.05). Although the former was significantly different from liver cirrhosis, the latter was not significantly different from the shunt rate observed in liver cirrhosis without HCC. After transcatheter arterial embolization, excluding one patient who developed a visible hepatofugal arterioportal shunt, the mean change in shunt rate between the effective treatment group (n = 9, -2.1% +/- 2.8%, mean +/- SD) and the ineffective treatment group (n = 5, 3.0% +/- 3.3%, mean +/- SD) was statistically significant (p < 0.05). CONCLUSIONS: We found that intrahepatic arteriovenous shunt rate more sensitively detects intrahepatic arteriovenous shunting due to HCC than does angiography alone. Measuring intrahepatic arteriovenous stunt rate may provide useful information regarding response to treatment.

Noncardiac chest pain due to acute gastric anisakiasis.

This paper described the first confirmed case of acute anginalike chest pain caused by gastric anisakiasis. A 55-year-old male, with a history of a sudden onset of chest pain and also a history of eating raw mackerel and tuna 9 hr prior to the onset of chest pain, was found upon endoscopy to have an imbedded parasite in the mucosal lining of his stomach. The chest pain disappeared after the endoscopic removal of larva. Endoscopy is highly recommended at the earliest possible time for patients who are suspected to have acute gastric anisakiasis.

Incidence of ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy.

This is a prospective study in which 120 patients with diffuse liver disease undergoing liver biopsy were followed by serial ultrasounds to determine the incidence of postbiopsy intrahepatic hematoma formation. Forty-five of the patients had a blind biopsy, while the remaining 75 patients had a biopsy performed during laparoscopy. In both groups a 2.0-mm Tru-cut needle was employed. The overall incidence of postbiopsy hematoma formation was 18.3%, with approximately the same results occurring in blind biopsy patients (20%) and laparoscopy-guided biopsy patients (17%). Only two patients had significant pain associated with the hematoma formation (one from each group), one of whom had evidence of intraperitoneal bleed and rebleed. Our results suggest that postbiopsy asymptomatic hematomas occur more frequently than had been generally thought and that laparoscopy-guided biopsy is not safer than blind biopsy.