Diagnosis of chronic liver disease from liver scintiscans by fuzzy reasoning.

UNLABELLED: We investigated the possibility that fuzzy reasoning might be used to standardize diagnosis of liver disease based on scintigraphic results and compared the results with those obtained when scintiscans were scored conventionally. METHODS: Seventy-five patients with chronic liver disease (11 patients had chronic persistent hepatitis, 26 had chronic aggressive hepatitis and 38 had cirrhosis) and 25 controls were studied. Another 75 patients with hepatitis or cirrhosis were examined to test the effectiveness of the membership functions. Liver scintiscans were taken 20 min after the intravenous injection of 111 MBq of 99mTc-phytate. Fuzzy reasoning was used to evaluate the following five items: the ratio of the sizes of the left and right lobes, splenomegaly, radioactivity in the bone marrow, deformity of the liver and distribution of radioactivity in the liver. The degree of conformity to each of the three liver diseases being investigated was substituted into the membership function for the conclusion. The center of gravity for each patient's results was calculated. Conventional scoring was made with three levels for each of the five items examined by fuzzy reasoning. RESULTS: Distinctions between chronic persistent hepatitis and chronic aggressive hepatitis were difficult to assess with fuzzy reasoning and conventional scoring. The diagnostic accuracy was 95% for patients with cirrhosis and 88% for patients with chronic hepatitis with fuzzy reasoning. With conventional scoring the accuracy was 86% for patients with cirrhosis and 75% for patients with chronic hepatitis. When fuzzy reasoning was used to examine the other 75 patients with chronic liver diseases, the accuracy was 93% for patients with cirrhosis and 86% for patients with chronic hepatitis. CONCLUSION: The method is simple and can be used routinely in clinical settings.

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.

Course before and after treatment of a patient with Budd-Chiari syndrome monitored by iodine-123-iodoamphetamine scintigraphy per os and per rectum.

A 55-yr-old woman with Budd-Chiari syndrome was treated by percutaneous transluminal angioplasty with a balloon catheter. Before and after treatment, portal scintigraphy was performed by the administration of [123I]iodoamphetamine per os and per rectum. An enteric capsule was used for the oral administration. Before treatment, the portal shunt index via the superior mesenteric vein was 40.5%; two weeks after treatment, it was 50.2%; and five months after treatment, it was 41.2%. Before treatment, the portal shunt index via the inferior mesenteric vein was 86.0%; two weeks after treatment, it was 87.6%; and five months after treatment, it was 21.8%. The treatment improved the portal circulation through the inferior mesenteric vein only, with little effect on the portal circulation through the superior mesenteric vein.

Fulminant hepatic failure monitored by technetium-99m-DTPA-galactosyl-human serum albumin scintigraphy.

We describe a 43-yr-old woman with fulminant hepatic failure whose progress was monitored scintigraphically using 99m-Tc-galactosyl-human serum albumin (99mTc-GSA). On admission, the liver was atrophic and the heart was delineated distinctly by scintigraphy with 99m-Tc-GSA. The receptor index, calculated by dividing the radioactivity of the liver region of interest by the radioactivity of the liver plus heart regions of interest at 15 min post-tracer injection, was very low. As the patient's condition improved, the right lobe of the liver enlarged while the left lobe became atrophic; after 4 mo, the left lobe almost completely disappeared. Delineation of the heart gradually became less distinct, and the receptor index slowly increased. Hepatic receptor imaging with 99m-Tc-GSA can define both the hepatic functional reserve and morphological changes of the liver, so it is useful for the diagnosis and follow-up study of fulminant hepatic failure.

Expression of platelet-derived growth factor and its receptor in livers of patients with chronic liver disease.

To find if platelet-derived growth factor contributes to liver fibrosis in chronic liver disease, we studied the expression of the B-chain of this cytokine and its beta-receptor in livers of patients with chronic hepatitis or cirrhosis. Seventeen patients were included in this study. Five specimens of liver tissue obtained during autopsy from subjects without liver disease were used as controls. The location of the peptides was identified by an immunohistochemical technique with monoclonal antibodies. Expression of mRNA for the B-chain was assessed by in situ hybridization. Cells stained for the B-chain and expressing its mRNA were identified as macrophages. In control tissues, only a few cells were stained. In the patients' specimens, most stained cells were in portal areas and their number increased with histologic liver damage. In intralobular areas, the stained cells were seen in regions of focal necrosis. Portal mesenchymal and perisinusoidal cells expressed beta-receptor. These cells were dense in periportal areas, where many myofibroblast-like cells were seen. These findings suggest that the B-chain of platelet-derived growth factor is released mainly by macrophages involved in inflammatory reactions. This cytokine probably acts on myofibroblast-like mesenchymal cells, and may be implicated in liver fibrosis in chronic liver disease.

Measurement of hepatic blood flow by use of per-rectal portal scintigraphy with 133Xe.

A relatively noninvasive method is needed to evaluate the hepatic blood flow of patients with liver disease. We used per-rectal portal scintigraphy with 133Xe, and analysed the time-activity curves of the liver and portal vein. To do this, wash-out curves of the liver were plotted, and the hepatic blood flow and the ratio of the blood flow to the right lobe of the liver to that to the left lobe (R/L ratio) were calculated. The mean hepatic blood flow was 137 +/- 23 ml/100 g/min for four patients with fatty liver, 139 +/- 16 ml/100 g/min for seven patients with chronic persistent hepatitis, 120 +/- 15 ml/100 g/min for ten patients with chronic aggressive hepatitis, and 75 +/- 21 ml/100 g/min for 14 patients with cirrhosis. All seven patients with hepatic blood flow that was less than 100 ml/100 g/min and an R/L ratio less than 1.0 had cirrhosis. Only two of the 22 patients with hepatic blood flow that was greater than 100 ml/100 g/min and an R/L ratio greater than 1.0 had cirrhosis. Per-rectal portal scintigraphy can be used to measure the hepatic blood flow, but it was not useful for the diagnosis of fatty liver.

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.

Hypereosinophilic syndrome appearing as a focal defect on liver scan.

The case reported here is of a 34-year-old man diagnosed as having hypereosinophilic syndrome. Blood tests showed a large increase in the number of eosinophils and a slight increase in aspartate aminotransferase and alkaline phosphatase. In scintigraphy of the liver with Tc-99m-phytate and with Ga-67-citrate, a focal defect was found in the outer part of the right lobe of the liver. Abdominal computed tomography showed a low density lesion in the same area. Histological inspection of the biopsy specimen showed heavy periportal infiltration with eosinophils. The results suggested that the focal defect seen in liver scintigraphy arose from a circulatory disturbance arising from infiltration by eosinophils.

Usefulness of per-rectal portal scintigraphy with Tc-99m pertechnetate for galactosemia in infants.

Galactosemia discovered by newborn screening is rarely caused by enzyme deficiency. It has recently been reported that among patients without enzyme deficiency portosystemic shunting may be a cause of galactosemia in some patients. We did per-rectal portal scintigraphy in patients with such galactosemia detected during screening of newborns to examine the usefulness of this method for the diagnosis of portosystemic shunts via the inferior mesenteric vein. The subjects were eight neonates with galactosemia without enzyme deficiency detected during screening. A solution containing technetium-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was determined by calculating the ratio for counts of the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. A portosystemic shunt was detected in both of the patients with a shunt index of 30% or more, but not in the six patients with a shunt index less than 30%. The blood galactose levels of these six patients later entered the reference range. This method is noninvasive and there is little exposure to the radionuclide. It seemed to be useful for the diagnosis of portosystemic shunt in newborns with galactosemia without enzyme deficiency.

Diagnosis of chronic liver disease from liver scintiscans by artificial neural networks.

Artificial neural networks were used in the diagnosis of chronic liver disease based on liver scintiscanning. One hundred and thirty-seven patients with chronic liver disease (12 with chronic persistent hepatitis, 39 with chronic aggressive hepatitis, and 86 with cirrhosis) and 25 healthy controls were studied. Sixty-five subjects (10 healthy controls, 20 patients with chronic hepatitis, and 35 patients with cirrhosis of the liver) were used in the establishment of a neural network. Liver scintiscans were taken starting 20 min after the intravenous injection of 111 MBq of Tc-99m-phytate. The neural network was used to evaluate five items judged from information on liver scintiscans: the ratio of the sizes of the left and right lobes, splenomegaly, radioactivity in the bone marrow, deformity of the liver and distribution of radioactivity in the liver. The neural network was designed to distinguish between three liver conditions (healthy liver, chronic hepatitis and cirrhosis) on the basis of these five items. The diagnostic accuracy with the neural network was 86% for patients with chronic hepatitis and 93% for patients with cirrhosis. With conventional scoring, the accuracy was 77% for patients with chronic hepatitis and 87% for patients with cirrhosis. Our findings suggest that artificial neural networks may be useful for the diagnosis of chronic liver diseases from liver scintiscans.

[Evaluation of clinical usefulness of 99mTc-GSA, a functional hepatic imaging agent--correlation with per-rectal portal scintigraphy].

Liver scintigraphy using 99mTc-GSA, which binds specifically to the asialoglycoprotein receptors on the surface of the hepatocytes, was performed in 41 patients with chronic liver disease (11 chronic hepatitis cases and 30 liver cirrhosis) to investigate the correlations between the images and the various liver function tests. Two liver functional indexes, HH15 for plasma clearance of 99mTc-GSA and LHL15 for liver accumulation of 99mTc-GSA, showed significant differences between the chronic hepatitis group and the decompensated liver cirrhosis group. These indexes also showed significant correlations with the liver function tests such as serum albumin level and prothrombin time. HH15 and LHL15 correlated with the per-rectal portal shunt index obtained in 10 patients by 99mTcO4- per-rectal portal scintigraphy. These results suggest that HH15 and LHL15 have value as new liver functional indexes.

[Measurement of regional hepatic blood flow with 133Xe per-rectal portal scintigraphy].

The hepatic blood flow (HBF) of patients with liver disease was measured by per-rectal portal scintigraphy with the use of 133Xe. To analyze the time-activity curves of the liver and portal vein, washout curves of the liver were plotted, and from those, the HBF and the ratio of the HBF of the right lobe of the liver to that of the left lobe (R/L ratio) were calculated. The HBF were 143 +/- 17 ml/100 g/min in 5 patients with chronic inactive hepatitis, 119 +/- 20 ml/100 g/min in 4 patients with chronic active hepatitis, and 73.2 +/- 23.4 ml/100 g/min in 7 patients with cirrhosis of the liver. All of four patients whose HBF was under 100 ml/100 g/min and whose R/L ratio was under 1.0 had cirrhosis of the liver. Only one of the 9 patients whose HBF was over 100 ml/100 g/min and whose R/L ratio was over 1.0 had cirrhosis of the liver. The results suggested that per-rectal portal scintigraphy is a useful and noninvasive method to measure the hepatic blood flow.

[Measurement of portal systemic circulation by oral and per-rectal administration of I-123 iodoamphetamine].

In an earlier study, we measured the portal circulation noninvasively by Tc-99m pertechnetate per-rectal portal scintigraphy. This method makes it possible to see the portal circulation and to diagnose portal hypertension from the images of the liver and heart. However, the method mainly reflects circulation from the inferior mesenteric vein, the contribution of which to the portal circulation is less than that of the superior mesenteric vein. Here, we devised capsules of I-123 iodoamphetamine (IMP) that dissolve when the pH changes to evaluate the portal circulation arising from the superior mesenteric vein. I-123 IMP enclosed in an enteric-coated capsule was prepared and given orally, just before I-123 IMP was injected into the rectum. The per-rectal portal shunt index (RSI) and oral portal shunt index (OSI) were calculated from the count of radioactivity of the liver and lungs. The RSI and OSI of patients with cirrhosis were both higher than those of the patients with chronic hepatitis. In individual patients, the RSI was higher than the OSI. This noninvasive method seemed to be useful in evaluation of the portal systemic circulation in chronic liver diseases.

[Evaluation of the formation of esophageal varices by per-rectal portal scintigraphy].

Portal circulation in patients with liver diseases was evaluated by 99mTc-pertechnetate per-rectal portal scintigraphy, and we retrospectively examined the relationship between the extent of abnormality in the portal circulation and the development of esophageal varices. The per-rectal portal shunt index (PRPSI) was calculated for 13 healthy subjects and 79 patients with chronic hepatitis and 214 with cirrhosis of the liver. In the healthy subjects, the mean PRPSI was 4.8%. In the patients with hepatitis, the mean PRPSI was 8.4%, and in the patients with cirrhosis, it was 48.5%. The PRPSI was significantly higher in the cirrhotic patients with esophageal varices than in the without, and also in the cirrhotic patients with encephalopathy than in those without. The cumulative incidence of esophageal varices in the 3 years of the study in patients whose PRPSI was 20% or over was significantly higher than that in patients whose PRPSI was under 20%. The results suggested that this non-invasive method should be useful for predictions of the formation of esophageal varices.

Clinical usefulness of evaluation of portal circulation by per rectal portal scintigraphy with technetium-99m pertechnetate.

OBJECTIVE: Portal circulation, in particular the contribution of the inferior mesenteric vein, can be evaluated in a relatively noninvasive way by per rectal portal scintigraphy (J Nucl Med 1988; 29:460-5). The clinical usefulness of the method was evaluated. METHODS: A solution containing technitium-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. By analyses of the curves, the per rectal portal shunt index (SI) was calculated. RESULTS: The SI was higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis, and the SI was higher in cirrhotic patients than in patients with chronic hepatitis or in healthy subjects. The SI was significantly higher when a complication (varices, ascites, or encephalopathy) was present. Correlation between the SI and classic indicators for functional reserve was significant. The SI was significantly related to survival according to results of regression analysis by Cox's proportional hazards model. On the basis of the SI when patients were first examined, the patients with cirrhosis were divided into three groups of roughly equal size: group A, SI under 30%; group B, SI between 30 and 70%; and group C, SI over 70%. The survival rate was lower in group B than in A, lower in group C than in A, and lower in group C than in B. CONCLUSIONS: This method is clinically useful, especially in establishing the prognosis.

Significance of blood flow in the inferior and superior mesenteric veins for the formation of oesophageal varices.

The degree of involvement of blood flow in the superior mesenteric vein and inferior mesenteric vein in the formation of oesophageal varices is not known. We have developed a method by which the contributions of these veins to portal blood flow can be evaluated simultaneously in a relatively non-invasive way. An enteric-coated capsule containing [123I]iodoamphetamine (IMP) is given by mouth and 3 h later [123I]IMP is instilled into the rectum. The data obtained are treated by computer to calculate the portal shunt index via the inferior and superior mesenteric veins. In chronic hepatitis and cirrhosis, when varices were absent, the difference in these indices was not significant. In the presence of varices, the portal shunt index via the inferior mesenteric vein was significantly higher than that via the superior mesenteric vein. It was suggested that the contribution of blood flow in the inferior mesenteric vein the portal/splenic axis is important in the formation of varices.

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.

Vertical transmission of hepatitis C virus (HCV) detected by HCV-RNA analysis.

The rate of transmission of hepatitis C virus (HCV) from patients with chronic hepatitis C to their children was studied. Of the 64 children with a parent with chronic hepatitis C, two (3%) had abnormal alanine aminotransferase (ALT) activities, six (9%) had anti-HCV detected by c100 ELISA, seven (11%) had anti-HCV detected by ELISA-II, and 21 (33%) had HCV-RNA by polymerase chain reaction (PCR). Anti-HCV detected by ELISA-II disappeared within six months in all six infants. Of the five children whose mothers were given a blood transfusion after the child's first birthday, none had anti-HCV or HCV-RNA. In the five families whose elder or eldest offspring had HCV-RNA, all of the younger offspring had HCV-RNA. The vertical transmission rate of HCV was low if judged by the presence of anti-HCV or abnormal ALT values, but the rate was high (33%) if judged by the presence of HCV-RNA.