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Objective: We aimed to clarify the time course of the Helicobacter pylori stool antigen (HpSA) level during and after eradication therapy and to determine the appropriate time of measurement of HpSA to evaluate eradication., Methods: The subjects were 47 patients who were positive for H. pylori. The patients underwent a 1-wk regimen of triple therapy. The outcome of the eradication therapy was judged by urea breath test, culture, and histology 6 wk after the end of treatment. The HpSA level was serially measured nine times from before therapy until 12 wk after the end of therapy., Results: In the group with successful eradication, HpSA became negative immediately after the end of therapy and the negativity persisted. In contrast, in the noneradication group HpSA became negative immediately after therapy, but became positive again within 2 wk after the end of therapy. The mean absorbance value of the HpSA test on the 4th day after the initiation of eradication therapy was significantly higher in the noneradication group than in the group with successful eradication. The diagnostic accuracy of the HpSA test increased to > or = 90% 2 wk after therapy and thereafter. Comparison of the diagnostic accuracy at 4 wk after the end of therapy showed no significant differences with that at 2, 6, 8, and 12 wk after the end of therapy., Conclusions: The course of the HpSA levels during and after eradication therapy in patients with successful eradication was quite different from that in noneradication patients. Measurement of HpSA was useful to evaluate eradication, and the appropriate evaluation of the outcome of treatment could be made as early as 2 wk after the end of therapy.

Objective: Des-gamma-carboxy prothrombin (DCP), also called protein induced by vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available immunoassays for DCP are not sensitive enough to detect HCC at an early stage. Recently, two new immunoassays with enhanced sensitivity were developed. The aim of this study was to assess the diagnostic values of the new methods in patients with small-sized HCC., Methods: Coded serum samples obtained from 36 patients with small-sized and single-nodular HCC (< or = 3 cm in diameter) and 49 patients with posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were determined in three different ways: 1) conventional EIA; 2) a new immunoassay using the electrochemiluminescence (ECLIA) detection system; and 3) a new immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were also determined., Results: In 36 patients with small-sized HCC, the rates of abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%, 27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%., Conclusions: Compared with the conventional method, the sensitivity in detecting small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA). The overall performance as evaluated by an ROC analysis was significantly better in ECLIA than in IRMA.

Objectives: Currently available enzyme immunoassays for des-gamma-carboxy prothrombin (DCP) are not sensitive enough to detect hepatocellular carcinoma (HCC) at an early stage. Therefore, the objectives of this study were to enhance the sensitivity of the currently available enzyme immunoassay (EIA) for DCP and to assess the diagnostic values of the new methods compared with those of alpha-fetoprotein (AFP) in patients with small-sized HCC., Methods: Coded serum samples obtained from a total of 128 patients with chronic liver diseases, including 27 patients with small-sized HCC, were analyzed. DCP levels were determined in three different ways: 1) conventional EIA, 2) the overnight method, similar to the conventional EIA but the first reaction (immunoreaction of DCP with the monoclonal antibody) was proceeded overnight, and 3) the avidin-biotin complex (ABC) method., Results: In 27 patients with HCC ( < or = 3 cm in diameter), the rates of abnormal values obtained by the conventional, the overnight, and the ABC methods were 14.8, 25.9, and 29.6%, respectively. The overnight and the ABC methods comparably increased the sensitivity, whereas the ABC method gave the highest false-positive value in patients with chronic liver diseases (cirrhosis and chronic hepatitis) without HCC. The negative predictive value was 84.9% when AFP and the overnight DCP assays were combined, whereas the true positive rate by the combination assay of the ABC method for DCP and AFP (cut-off level at 200 ng/ml) was 33.3%., Conclusions: Two modifications of the conventional EIA for DCP comparably increased the sensitivity, but the overnight method may be of more practical value in terms of specificity and ease. The rate of detection of small-sized HCC by tumor markers alone, however, is not satisfactory even when the modified DCP and AFP measurements are combined.

To assess the effect of interferon therapy on posttransfusion non-A, non-B acute hepatitis, we examined the appearance of serum hepatitis C virus antibody (anti-HCV) and abnormal serum aminotransferase levels after the onset of hepatitis in 12 patients treated with interferon and in 46 patients treated conservatively. Eleven patients were given 3 million units of human fibroblast beta-interferon three times weekly for 4 wk and 1 was given one million units of human lymphoblastoid alpha-interferon daily for 3 months. In the interferon-treated patients, the effect of therapy on hepatic histology was also assessed. Detection of anti-HCV within 6 and 12 months after the onset of hepatitis was less common in interferon-treated patients than in control patients (6/12 vs 35/46 and 5/12 vs 35/46, both p = NS). At 24 months after the onset of hepatitis, anti-HCV levels were significantly lower in interferon-treated patients (0/10, p less than 0.05), but had not changed significantly in control patients (34/46). Abnormal serum aminotransferase levels at 6, 12, and 24 months after the onset of hepatitis were significantly less common in interferon-treated patients than in controls (25% vs 78.3%, p less than 0.005; 25% vs 71.7%, p less than 0.01; and 0% vs 67.4%, p less than 0.001). The percentage of abnormal serum aminotransferase levels at 6, 12, and 24 months after onset of hepatitis was also less in interferon-treated patients than in control patients, both among anti-HCV-positive patients (50% vs 85.7%, p = NS; 50% vs 80%, p = NS; and 0% vs 77.1%, p less than 0.01) and among anti-HCV-negative patients (0% vs 54.5%, p = NS; 0% vs 45.5%, p = NS; and 0% vs 27.3%, p = NS). Immediately after interferon therapy, the histological activity index dropped from 6.0 +/- 4.2 to 4.8 +/- 2.5 in anti-HCV-positive patients (p = NS) and from 4.2 +/- 4.3 to 2.6 +/- 1.7 in anti-HCV-negative patients (p = NS). Biopsy specimens obtained from four patients 12-23 months after interferon therapy revealed normal histology in one anti-HCV-positive patient and two anti-HCV-negative patients, and marked improvement in the other anti-HCV-positive patient. These results indicate that short-term, low-dose interferon therapy may be effective for posttransfusion non-A, non-B acute hepatitis (both anti-HCV-positive and anti-HCV-negative).

Extrahepatic lymph node metastases are not uncommon in advanced cases of hepatocellular carcinoma (HCC). This is the account of a HCC case in which intrahepatic lymphatics running toward the hepatic hilus were clearly opacified during hepatic arteriography. The patient was treated by hepatic artery embolization followed by selective embolization of the portal branches, but lymph node metastases at the hepatic hilus were later found during follow-up. The clinical course of this case suggests that the communication between the tumor and the lymphatics was responsible for the lymph node metastasis.

Three patients with proven Budd-Chiari syndrome were examined with a duplex sonograph consisting of a real-time ultrasonograph and a pulsed Doppler flowmeter. In these cases, the pulsed Doppler analysis associated with the real-time imaging showed abnormalities in the direction of flow in the hepatic vein, communicating vessel between hepatic veins, and/or retrohepatic inferior vena cava, which were consistent with obstruction of hepatic venous outflow. With these findings, duplex sonography can be used to diagnose Budd-Chiari syndrome.

Effects of two histamine H2 receptor antagonists, cimetidine and ranitidine, on systemic and splanchnic hemodynamics were studied in patients with chronic liver disease by simultaneous catheterization of the portal vein and the right hepatic vein and measurement of portal venous flow using the ultrasound doppler system or cineangiography. Neither infusion of 200 mg of cimetidine nor 50 mg of ranitidine reduced cardiac output, portal venous pressure, the gradient between wedged hepatic venous pressure and free hepatic venous pressure, hepatic blood flow, and portal venous flow. It is unlikely that histamine is an important modulator of flow via the H2 receptor.

A comparative study of portal hemodynamics was made in 79 cirrhotics (24 cirrhotics with a large spleen greater than or equal to 500 cm3 in volume, 55 cirrhotics with a spleen less than 500 cm3 in volume), 22 patients with idiopathic portal hypertension, and 63 healthy adults who served as the control for portal and splenic venous flows. Portal and splenic venous flows were significantly increased in the group order of the cirrhosis without splenomegaly group, the cirrhosis with splenomegaly group, and idiopathic portal hypertension group. Intrahepatic shunt index was significantly greater in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly group, and it was negligible in the idiopathic portal hypertension group. Portal vein pressure was significantly elevated in the cirrhosis with splenomegaly group than in the cirrhosis without splenomegaly and idiopathic portal hypertension groups. Postsinusoidal resistances were significantly greater in the two groups of cirrhosis than in the idiopathic portal hypertension group, whereas presinusoidal resistance was significantly greater in the idiopathic portal hypertension group than in the two groups with cirrhosis. It is concluded that these differences are inconsistent with the view that cirrhosis with splenomegaly comes from idiopathic portal hypertension.

We treated five patients with posttransfusion non-A, non-B chronic active hepatitis and six patients with posttransfusion non-A, non-B acute hepatitis with 3 million units of human fibroblast beta-interferon three times weekly for 4 wk. Initiation of interferon therapy was followed by a prompt and marked decrease in serum aminotransferase activity in five patients with chronic active hepatitis and five patients with acute hepatitis; the exception was one patient with acute hepatitis in whom serum aminotransferase levels fluctuated during treatment. Biopsy specimens obtained immediately after therapy showed improvement in hepatic histology in two of four patients with chronic active hepatitis and three of four patients with acute hepatitis. Cessation of interferon therapy was followed by a prompt increase in serum aminotransferase levels in five patients with chronic active hepatitis and in one patient with acute hepatitis, although re-elevated serum aminotransferase levels returned gradually to the normal range in the patient with acute hepatitis, but did not do so in five patients with chronic active hepatitis. In another patient with acute hepatitis whose serum aminotransferase levels fluctuated during interferon therapy, serum aminotransferase levels reached normal range after discontinuation of therapy. At 6 months and 12 months after discontinuation of interferon therapy, all five patients with chronic active hepatitis showed elevated serum aminotransferase levels, and all six patients with acute hepatitis showed normal serum aminotransferase levels. These results suggest that short-term and low doses of beta-interferon therapy has an only temporal effect on controlling the disease activity in patients with posttransfusion non-A, non-B chronic active hepatitis, and it might become an effective therapy for posttransfusion non-A, non-B acute hepatitis.

To elucidate the mechanism by which propranolol reportedly affects portal hemodynamics, we investigated the effect of propranolol on systemic and splanchnic hemodynamics in 15 patients with portal hypertension and esophageal varices by simultaneous catheterization of the portal vein and the right hepatic vein and measurement of portal venous flow using an ultrasound doppler system. Infusion of 5 mg of propranolol significantly decreased pulse rate (-12.6%), cardiac output (-24.5%), portal venous flow (-22.3%), portal venous pressure (-13.3%), and gradient between portal venous pressure and free hepatic venous pressure (-24.8%). Thus, propranolol seems to decrease portal venous pressure by reducing portal venous flow, at least in part, as a result of reduction of cardiac output due to its beta 1 adrenergic receptor blocking action.

Spontaneous disappearance of limy bile is extremely rare, and only four cases have so far been reported. This is the account of the fifth case, a 42-year-old woman, who spontaneously lost a stone incarcerated in the neck of the gallbladder and all of the limy bile, after symptoms suggestive of a transient obstructive jaundice. Various investigations including ultrasound, computed tomography, and percutaneous transhepatic cholangiography suggested spontaneous passage of the stone through the cystic duct and the papilla of Vater, followed by limy bile. Apparently the patient's gallbladder had a contracting capacity. The literature on this subject is briefly reviewed.

To assess the role of intrahepatic portal-systemic shunts in the reduction of portal blood supply to the liver cells in cirrhosis, we measured portal venous flow (blood flow in the portal trunk) by the pulsed Doppler flowmeter and intrahepatic portal-systemic shunt index from the counts over the lungs and liver in both the anterior and posterior projections after instillation of 99mTc-macroaggregated albumin in the portal vein, and calculated portal sinusoidal flow (blood flow into the sinusoids via the portal vein), using the equation, (sequence; see text) in 47 patients with posthepatitic cirrhosis, and measured portal venous flow in 63 healthy adults in whom portal sinusoidal flow should be comparable to portal venous flow. Portal sinusoidal flow was significantly reduced in cirrhotics with an intrahepatic portal-systemic shunt index averaging 24%, whereas portal venous flow was similar in the cirrhotics and control. There was a significant inverse correlation between intrahepatic portal-systemic shunt index and portal sinusoidal flow. When cirrhotics were divided into three stages, based on Child's grading, intrahepatic portal-systemic shunt index was significantly increased in the group order of Child's A (8 +/- 9%), Child's B (27 +/- 22%), and Child's C patients (46 +/- 19%), and portal sinusoidal flow was decreased in the same order. Portal sinusoidal flow was significantly reduced in Child's B and Child's C patients, but not in Child's A patients, compared with the control. In conclusion, intrahepatic portal-systemic shunts may play a role, at least in part, in the reduction of portal blood supply to the liver cells in patients with advanced stage of posthepatitic cirrhosis when large intrahepatic portal-systemic shunts develop.

On the premise that extensive intrahepatic portal-venous anastomoses known to occur in cirrhosis would be demonstrated by contrast medium directly placed in the portal vein, percutaneous transhepatic portograms were analyzed in 82 patients with liver cirrhosis in relation to the estimated degree of shunting. The degree of intrahepatic shunt was measured during transhepatic portography using 99mTc-macroaggregated albumin. Hepatic veins began to opacify at 4 to 10 s after the start of injection of contrast medium during portography in 20 patients with cirrhosis who had intrahepatic shunt indices of 58.5 +/- 18.5%, but it was not visualized in 62 patients with cirrhosis whose shunt indices were 19.9 +/- 14.1%. Anomalous large anastomoses of 1 or 2 mm in size between the right portal vein and the right hepatic vein were clearly visualized during portography in 18 of 20 patients in whom the hepatic vein was opacified. Frequency and time of beginning opacification of the hepatic vein were closely correlated with the degree of intrahepatic shunt. Thus, opacification of the hepatic vein and abnormal anastomoses between the portal and hepatic vein systems in an early phase of portography indicates extensive intrahepatic shunts.

The interrelationship between the type and degree of spontaneous portal systemic shunting, and portal vein pressure was studied in 155 patients with liver disease by catheterizing the portal vein. The degree of portal vein shunting was measured in 100 patients and that of splenic vein shunting in 50 and that of total portal systemic shunting in 52, using macroaggregated radioalbumin. Increasing portal vein pressures were associated with progressively higher indices of portal vein shunt, splenic vein shunt, and total portal systemic shunt up to a certain level. Beyond this level, portal vein pressure did not increase further, and rather it decreased with further increasing degrees of splenic vein shunt and total portal systemic shunt. These results indicate that spontaneous portal systemic shunt keeps the portal vein pressure within certain limits or decreases it.

Of 66 patients with hepatocellular carcinoma, 32 were treated by intraarterial injection of mitomycin C microcapsules (group A) and 34 patients by intraarterial injection of mitomycin C microcapsules followed by transcatheter hepatic artery embolization (group B). Measurable tumor regression greater than 50% in area on liver image occurred in 28% of group A and 57% of group B (p less than 0.05). A decrease of serum alpha-fetoprotein to less than half the initial level was demonstrated in 59% of group A and 91% of group B (p less than 0.05). The survival rate was better in group B compared with group A (p less than 0.05). These results indicate that arterial chemoembolization with mitomycin C microcapsules plus transcatheter hepatic artery embolization will be an improvement over arterial chemoembolization with mitomycin C microcapsules alone in the treatment of hepatocellular carcinoma.

The diagnostic value of plasma abnormal prothrombin (PIVKA-II) measurements in detecting relatively small hepatocellular carcinomas (HCC), less than 5 cm in diameter, was compared with that of serum alpha-fetoprotein (AFP) determinations. Among 18 patients with relatively small hepatocellular carcinoma (HCC), abnormal PIVKA-II values were found in only three (16.6%). Highly elevated serum AFP levels (greater than 200 ng/ml) relatively specific for HCC were seen also in three patients. However, nonspecific elevation of PIVKA-II in patients with liver cirrhosis not accompanied by HCC was much less than that of AFP. Although complementary, both tests appear to be of limited value in early detection of HCC, indicating that searches for other markers are necessary, to allow early detection of small HCC.

We studied the effects of endoscopic sclerotherapy with transhepatic variceal obliteration on portal hemodynamics in 20 patients with cirrhosis (six with a spontaneous splenorenal shunt and 14 without it). Portal venous flow 1 month after combined therapy (measured by pulsed Doppler flowmeter) was significantly increased compared with that before therapy (n = 20, 843 +/- 339 vs. 669 +/- 253 ml/min, p less than 0.001). Portal vein catheterization and portal venous flow measurement were repeated 18 months after therapy in eight patients without a splenorenal shunt before therapy and in two patients with a splenorenal shunt before therapy. Two of the former developed a splenorenal shunt. In these 10 patients, portal venous flow before, one month, and 18 months after therapy was 617 +/- 219, 784 +/- 227, and 720 +/- 224 ml/min, respectively, and in 8 of 10 patients the portal venous flow at 18 months remained similar to the values at one month. Portal vein pressures were not significantly elevated 18 months after therapy (35.4 +/- 6.4 vs. 33.6 +/- 5.1 cm H2O) and the mean portal vein pressure change was 2.75 cm H2O (range -6 to +7.5 cm H2O). To summarize, portal venous flow was significantly increased one month after combined sclerotherapy in cirrhotics, the portal venous flow at 18 months remained similar to the values at 1 month in most patients, and the change in portal vein pressure after therapy was small.

The acute effects of histamine H2 receptor antagonist, famotidine, on hepatic hemodynamics were studied in six normal volunteers and eight patients with chronic liver disease, and its chronic effects on peptic ulcer, portal hemodynamics, and hepatic function were studied in 20 patients with chronic liver disease and peptic ulcer (16 with gastric ulcer, four with duodenal ulcer). Infusion of 20 mg famotidine did not reduce hepatic blood flow and portal blood flow in normal subjects, nor did it reduce cardiac output, the gradient between wedged hepatic vein pressure and free hepatic vein pressure, hepatic blood flow, and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg famotidine twice daily for 2 months healed peptic ulcer in 19 of 20 patients (95%) with chronic liver disease and peptic ulcer, without any change in portal blood flow and hepatic function. Thus famotidine does not appear to alter hepatic hemodynamics and hepatic function in normal subjects and patients with chronic liver disease.

Intrahepatic pressure was measured in 148 patients with liver disease (32 outpatients, 116 inpatients) and 13 controls with almost normal liver histology (inpatients), with a 23-gauge needle (inner diameter 0.38 mm). Intrahepatic pressure was significantly elevated in the group order of chronic active hepatitis without bridging necrosis (n = 17, 9.2 +/- 3.0 mm Hg), chronic active hepatitis with bridging necrosis (n = 24, 12.3 +/- 5.7), and posthepatitic liver cirrhosis (n = 65, 18.8 +/- 4.2), compared with controls (n = 13, 6.8 +/- 2.7), whereas it was not elevated in the group of idiopathic portal hypertension (n = 9, 7.8 +/- 2.5 mm Hg), acute hepatitis (n = 10, 8.4 +/- 2.6 mm Hg), and chronic persistent hepatitis (n = 23, 7.9 +/- 2.7 mm Hg), compared with controls. As complications, four patients had abdominal discomfort continuing for more than a day; however, patients were allowed to walk after they had rested on their beds for 30 min. In 37 patients (27 with cirrhosis, seven idiopathic portal hypertension, and three others), portal vein and/or hepatic vein catheterization was performed during the same procedure of intrahepatic pressure measurement. Intrahepatic pressure showed significant correlations with corrected wedged hepatic vein pressure (r = 0.91), portohepatic gradient (r = 0.69), wedged hepatic vein pressure (r = 0.79), and portal vein pressure (r = 0.68). Slopes were 0.97, 0.83, 0.66, and 0.65, respectively. In conclusion, intrahepatic pressure reflects hepatic sinusoidal pressure (corrected wedged hepatic vein pressure), and intrahepatic pressure starts to elevate at the stage of chronic active hepatitis.

A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension.

Clinical and portal hemodynamic features in 28 cirrhotic subjects with a large spontaneous spleno- and/or gastrorenal shunt were studied in comparison with 30 control cirrhotic cases without such collaterals. Forty-six percent of the former had chronic hepatic encephalopathy, but none of the latter was encephalopathic. These patients with large renal shunts were divided into those with and those without encephalopathy. Large esophageal varices were significantly less common in patients with a large shunt and encephalopathy compared with those who had a large shunt but no encephalopathy, and the control. But there was no significant difference of past variceal bleeding among these three groups. In all those with encephalopathy, part of superior mesenteric venous blood was shunting through these collaterals into the left renal vein or inferior vena cava, but the same was not demonstrable in patients with a large shunt and no encephalopathy and control cirrhotics. In the chronic encephalopathic, portal venous flow was estimated to be less than one-half of that in control cirrhotics, and the portion of superior mesenteric venous blood that was flowing hepatofugally through a large shunt into the left renal vein seemed about the same or greater than the portal venous flow. Thus, a large spontaneous spleno- and/or gastrorenal shunt might prevent development of large esophageal varices but not variceal hemorrhage and it increased a risk of chronic hepatic encephalopathy.