Injurious effects of ethanol on rat Kupffer cells.

The effects of ethanol on rat Kupffer cells were studied functionally and morphologically. Eight g ethanol per kg body weight per day was intragastrically administered to rats for 7 days. An isocaloric glucose solution was administered to control rats. The phagocytic activity of the reticuloendothelial system was measured by the carbon clearance method (57 mg carbon particles per kg body weight) on the 7th day. Kupffer cells having phagocytized carbon particles were counted under the light microscope. Kupffer cells were also observed by scanning electron microscopy. Both the carbon clearance and Kupffer cell number were lower in ethanol-administered rats (32 +/- 8 X 10(-4) mg/ml; 0.6 +/- 0.3/0.01 mm2 liver lobule) as compared to control rats (63 +/- 15; 3.1 +/- 1.0). Microvilli and filopodia of Kupffer cells were fewer in ethanol-administered rats than in control rats. Carbon clearance correlated with Kupffer cell number per 0.01 mm2 liver lobule and liver weight. These results suggest that the decrease in carbon clearance induced by ethanol is due mainly to the decrease in Kupffer cell number and partly to the decrease in Kupffer cell activity as demonstrated by the disappearance of microvilli and filopodia.</p

Evaluation of Talbot's Safety Zone of Infusion Volume and Osmolality in Infusion Therapy for Decompensated Liver Cirrhosis

Problems with infusion therapy for correcting fluid and sodium imbalance in decompensated liver cirrhosis (DLC) were investigated by establishing the safety zone of Talbot et al. for parenteral fluid therapy in 4 DLC patients infused with over 900 ml of fluid each day for at least 9 days. The safety zone was different in each case. The safe infusion volume decreased and the safe electrolyte concentration shifted to a lower osmolality when there was ascites with renal failure than ascites without renal failure. Infusion therapy was performed without deterioration of the water and sodium balance in those patients whose infusion volume and fluid osmolality were in the safety zone. In contrast, ascites retention increased and peripheral edema appeared in patients whose infusion volume and osmolality were out of the safety zone. Therefore, the safety zone should be determined repeatedly during infusion therapy.</p

Clinical studies of hepatocellular carcinoma with liver cirrhosis and ascites.

A comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC) accompanied with hepatocellular carcinoma (HCC) (of which 35 had ascites and 24 did not at the time of admission) and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not). HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96%) died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.</p

Clinical studies of resistant ascites in liver cirrhosis.

Resistant ascites was studied in 34 patients with liver cirrhosis and ascites. The patients were initially divided into 3 groups on the basis of the weekly cumulative ascites retention curve: patients relieved of ascites within 3 weeks of admission, patients relieved between 4 and 12 weeks and patients with ascites persisting beyond 13 weeks. &#34;Resistant ascites&#34; was defined as &#34;ascites persisting for more than 13 weeks after admission to the hospital&#34;. The patients were then reclassified into 3 groups : Group A being those patients relieved of ascites within 12 weeks, Group B being those with resistant ascites and group C being those who died within 12 weeks of admission. There were no differences in age and sex distribution, etiology of liver cirrhosis, past medical history or physical findings among the 3 groups. However, Group B had higher levels of serum creatinine and blood urea nitrogen than Group A on admission. Serum bilirubin was higher and serum albumin was lower in Group C than in Group B, which indicates that Group C had greater liver cell failure.</p

Phalloidin-induced alterations of bile canaliculi.

Phalloidin, a toxin from the plant Amanita phalloides, irreversibly polymerizes actin filaments and causes cholestasis. Three-dimensional structural changes induced by phalloidin in the bile canaliculi and the intra-acinar localization of these changes were studied in the rat liver by scanning and transmission electron microscopy. After 3 days of treatment, canalicular changes appeared mainly in zones 2 and 3 of Rappaport's acinus, but after 7 days of treatment changes occurred in bile canaliculi of the whole acinus. The changes in the bile canaliculi included tortuosity, saccular dilatation, loss of microvilli, bleb formation and elongation of canalicular side branches. Some side branches extended near to Disse's space, leaving only a thin cytoplasmic rim between the canalicular lumen and Disse's space. Kupffer cells were occasionally situated near such extended bile canaliculi and protruded their processes into the hepatic cord. These results suggest that bile canaliculi in zone 3 are more susceptible to phalloidin toxicity than those in zone 1 and that biliary constituents may leak from such altered bile canaliculi.</p

Two cases of constitutional unconjugated hyperbilirubinemia with marked retention of indocyanine green.

Two cases of chronic unconjugated hyperbilirubinemia and marked retention of indocyanine green (ICG) are described. Since bilirubin uridine diphosphate (UDP)-glucuronyl transferase activities were depressed in their liver, the patients seemed to have bilirubin metabolism similar to that in Gilbert's syndrome. However, the ICG fractional disappearance rates of the cases were rather low (0.018 and 0.019) compared to the rates reported for Gilbert's syndrome. These results suggest that the patients had a new metabolic disorder which results in constitutional unconjugated hyperbilirubinemia and ICG intolerance.</p

Enhanced visualization of the portal vein system in superior mesenteric arterial portography using prostaglandin E1.

The portal vein system was clearly visualized in superior mesenteric arterial portography using prostaglandin E1. Angiographic examination was performed in 68 patients with various liver diseases during the 2 year period from 1980 to 1981. Twenty microgram of prostaglandin E1 was injected into the superior mesenteric artery 30 seconds before injection of 60 ml of contrast medium. The main portal vein was visualized in all of 68 cases. A high rate of success for visualization of the intrahepatic portal vein system by prostaglandin E1 was achieved. The first branches of the intrahepatic portal vein were visualized in 100% of the cases, the second branches in 82%, the third branches in 44%, and the fourth branches in 4% in the right portal vein system. In the left portal vein system, the first branches were visualized in 87%, the second branches in 41%, and the third branches in 3% of the cases. The intrahepatic portal vein system was more clearly visualized in females than in males (P less than 0.05). This procedure is simple, safe and useful for clear visualization of the portal vein system.</p

Hepatitis B virus markers in patients with schistosomiasis, liver cirrhosis and hepatocellular carcinoma in Khartoum, Sudan.

Markers of hepatitis A and B virus were tested in 88 adult Sudanese subjects in Khartoum, Sudan. The subjects consisted of 25 control hospitalized patients, 21 volunteer blood donors, 23 patients with hepatosplenic schistosomiasis, 13 patients with liver cirrhosis and 6 patients with hepatocellular carcinoma (HCC). Antibody to hepatitis A virus was detected in 96% of the total. Hepatitis B surface antigen (HBsAg) was positive in 4, 24, 22, 31, and 67% of the subject groups, respectively. Antibody against hepatitis B core antigen (HBcAb) of undiluted serum was positive in 60, 57, 65, 77 and 83%, and there was no difference in incidence among the groups. It was positive in 200X diluted serum in 4, 24, 17, 23 and 60%. HBsAg and HBcAb (200X) were detected more often in HCC patients than in the control subjects (p less than 0.01). Hepatitis B virus is an important factor in the etiology of HCC in the Sudan.</p

Comparison of estimation methods of liver maximum removal rate of indocyanine green.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).</p

Hyperbilirubinemia and enhanced mitosis of hepatocytes in phalloidin-treated female rats.

Cholestasis with htperbilirubinemia was induced in female, but not male, Sprague-Dawley rats by daily treatment with phalloidin for 7 days. Increases in serum direct bilirubin level and alkaline phosphatase (Al-Pase) activity were observed concomitantpy with diminished bile flow and a decreased output of bile acid and cholesterol. Kidht microscope findings of the liver revealed proliferated bile ductules and enhanced mitosis of hepatocytes.</p