bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rejection in Liver Transplantation
Authors: Klintmalm Goran B.G. , Nery Joseph R. , Husberg Bo S. , Gonwa Thomas A. , Tillery Glenn W. 
Published: March 2007

One hundred four liver transplant recipients were retrospectively reviewed for the incidence of liver allograft rejection, the response to antirejection therapy and the impact of rejection on graft and patient survival. Liver biopsies were performed weekly during episodes of graft dysfunction and to follow response to treatment. Baseline immunosuppression consisted of cyclosporine and low–dose prednisolone. Rejection was treated with steroids and with OKT3 as rescue. Azathioprine was given to patients with preoperative or perioperative renal insufficiency and was added to patients' treatment after the first sign of rejection.
Seven complications were observed in approximately 1,100 liver biopsies, only one necessitating surgery. We found that 39.4% of the patients never experienced acute rejection, and 60.6% had at least one episode of acute rejection. Overall, 42.3% of the patients had only one episode of acute rejection, 13.5% had two, 3.8% had three and 1% had five episodes of acute rejection. Sixty of 63 first acute rejection episodes occurred within 21 days of transplant. Primary disease, sex or patient age had no significant influence on the incidence of rejection. There was a lower incidence of rejection (p < 0.005) in patients transplanted after October, 1986, despite lower mean cyclosporine levels. Mean cyclosporine level during the first postoperative month was 679 ng per ml vs. a mean level of 910 ng per ml prior to October, 1986, when the immunosuppressive protocol was altered. Antirejection therapy was very effective in that only two of the 63 patients had graft failure due to acute rejection. Both of these patients were subsequently retransplanted. One patient died directly as a result of the acute rejection. In six patients (4.8%), chronic rejection was diagnosed, 29 to 545 days after transplantation. Two of these patients never had previous acute rejection but had suffered severe viral infections. Four of the six chronic rejection patients had primary sclerosing cholangitis as their primary disease. One patient underwent a suspected hyperacute rejection and was successfully retransplanted. We conclude that rejection is a major cause for morbidity after liver transplantation but is presently only a minor cause for mortality. The importance of the primary disease and viral infections in the development of chronic rejection needs further study.
Insulin and Steatonecrosis: Are They Related?
Authors: Amatruda John M. , Salhanick Arthur I. 
Published: March 2007

Hepatic steatosis and steatonecrosis occur in non–alcoholic individuals, usually in a setting of obesity, type II diabetes mellitus, and after jejunoileal bypass. We propose an hypothesis for the pathogenesis of these hepaic lesions based on an observation in peritoneal dialysis patients.
Hepatic histology was examined at autopsy in eleven patients with type I diabetes mellitus and renal failure who had received intraperitoneal insulin in conjunction with continuous ambulatory perritoneal dialysis (CAPD). Steatosis in a unique subcapsular distribution occurred in 10 of 11 patients treated with intraperitoneal insulin and in none of 9 controls receiving CAPD without insulin. Three of the 11 had steatonecrosis, 2 of whom had Mallory bodies.
We suggest that isulin has an important role in the pathogenesis of steatosis and steatoncrosis. In CAPD patients the lesions occurred only under the capsule where concentrations of insulin are high secondary to its intraperitoneal administration. In obese patients the lesions occur throughhout the liver where insulin concentrations are high because of elevated levels in the portal vein. Free fatty acids (FFA) are oxidized in the liver by a pathway that is blocked by insulin. In the presence of insulin, FFA are preferentially esterified into triglycerides which accumulate in large quantities leading to steatosis; small amounts of FFA escaping local control may lead to membrane injury and steatonecrosis. Steatosis and/or steatonecrosis will occur when there is insulin secretion sufficient to block FFA oxidation but not sufficient to block FFA mobilization from adipose tissue. This situation occurs in obesity associated with type II diabetes where adipose tissues are resistant to insulin, and in obesity after jejunoileal–bypass where continued eating and insulin secretion occurs in the face of marked weight loss.
Extrahepatic Replication of Duck Hepatitis B Virus: More Than Expected
Authors: Hosoda Kazuhiko , Omata Masao , Uchiumi Katsuo , Imazeki Fumio , Yokosuka Osamu , Ito Yoshimi , Okuda Kunio , Ohto Masao 
Published: March 2007

Replication of duck hepatitis B virus in extrahepatic tissue such as pancreas, kidney and spleen has been well documented. To assess whether there is more widespread extraheptic virus replication, we assayed brain, heart, lung, thymus, pancreas, kidney, spleen and intestine of 1– to–wk–old ducklings for the presence of duck hepatitis B virus DNA and mRNA by blotting in in situ methods. Replicative intermediates and single–stranded duck hepatitis B virus DNA and RNA transcripts were detected in the brain, lung, heart, intestine, kidney, pancreas and spleen. In situ hybridization showed evidence of viral replication in the lung epithelium, germinal center of spleen, acinar cell of pancreas and tubular epithelium of kidney.
These data suggest that extrahepatic duck hepatitis B virus replication is more widespread than previously thought. It is yet to be determined whether widespread extrahepatic replication is unique to duck hepatitis B virus infection or is a common feature of other mammalian hepatitis B–like viruses. (HEPATOLOGY 1990; 11: 44-48.)
Plasma Gaba–Like Activity in Rats With Hepatic Encephalopathy Is Due to Gaba and Taurine
Authors: Maddison Jill E. , Leong Dorothy K. , Dodd Peter R. , Johnston Graham A.R. 
Published: March 2007

Significant discrepancy exists between radioreceptor and high–performance liquid chromatographic estimates of plasma GABA concentrations in animal models of hepatic encephalopathy. A possible explanation for this discrepancy is the presence in plasma of a substance that can inhibit [3H]–GABA binding but is not GABA itself. The aim of this study was to determine whether any of the amino acids that are increased in the plasma of animal models of acute and chronic hepatic encephalopathy (glutamine, glutamate, phenylalanine, tyrosine, citrulline and taurine) can significantly inhibit [3H]–GABA binding and contribute to the GABA–like activity of plasma aliquots.
At final assay concentrations equivalent to plasma concentrations found in hepatic encephalopathy, only taurine was found to significantly inhibit [3H]–GABA binding to whole rat brain synaptosomal membranes (36% inhibition at 30 μmol/L final assay concentration). The concentration of taurine that resulted in 50% inhibition (final assay concentration) was 158 μmol/L, corresponding to a plasma concentration of 1.58 mmol/L. Taurine inhibition of [3H]–GABA binding was competitive because the receptor density was unaltered, but the receptor affinity decreased with increasing concentration of taurine.
Plasma GABA–like activity (determined by radioreceptor assay) and plasma GABA and taurine concentrations (determined by high–performance liquid chromatography) were measured in 18 rats with acute or chronic hepatic encephalopathy and 9 control rats. Plasma GABA–like activity and plasma GABA and taurine concentrations were significantly increased in rats with hepatic encephalopathy compared with control rats.
A comparison of the percent inhibition of [3H]–GABA binding expected by known concentrations (determined by high–performance liquid chromatography) of taurine and GABA in each plasma sample indicated that the inhibition of [3H]–GABA binding by plasma aliquots could be entirely attributed to the presence of GABA and taurine in plasma. Therefore the plasma “GABA–like factor” in animal models of hepatic encephalopathy is taurine. The implications of this finding to the pathogenesis of hepatic encephalopathy are unknown at present.
The Effect of Liver Dysfunction on Colchicine Pharmacokinetics in the Rat
Authors: Leighton Jonathan A. , Bay Michael K. , Maldonado Alma L. , Johnson Raymond F. , Schenker Steven , Speeg K. V. 
Published: March 2007

Recent work has shown that colchicine may benefit patients with primary biliary or alcoholic cirrhosis. However, very little is known about its pharmacokinetics in the presence of impaired liver function. To study this we examined the effects of three models of experimental liver dysfunction and one of cytochrome P–450 inhibition on colchicine elimination in the rat. The models of experimental liver dysfunction included bile duct ligation (with sham–operated controls), α–naphthylisothiocyanate–induced intrahepatic cholestasis and galactosamine–induced diffuse hepatocelluar necrosis.
The control group had a colchicine clearance of 77.33 ml/min. kg ± 8.27 ml/min kg, a half–life of 16.68 min ± 0.97 min and a volume of distribution of 1.84 L/kg ± 0.15 L/kg.
Cimetidine administration, 120 mg/kg intraperitoneally 15 min before colchicine administration, caused clearance to decrease by 32% (p < 0.05) and half–life to increase by 38% (p < 0.05). Volume of distribution did not change.
At 48 hr after bile duct ligation, colchicine clearance decreased by 84% (p < 0.05), terminal half–life increased to 513.7 min ± 106.6 min (p < 0.05) and volume of distribution increased by 175% (p < 0.05). Colchicine pharmacokinetics in sham–operated rats were not statistically different from the above mentioned controls.
After α–naphthylisothiocyanate administration, colchicine clearance decreased by 55% (p < 0.05), the halflife increased by 56% (p < 0.05) and the volume of distribution decreased by 30% (p < 0.05).
After administration of galactosamine, 1,000 mg/kg, colchicine clearance decreased by 62% (p < 0.05), half–life increased to 144.72 min ± 35.30 min (p < 0.05) and volume of distribution increased by 124% (p < 0.05).
These data show that experimental hepatic injury in the rat significantly impairs colchicine pharmacokinetics. They also support the hypothesis that the liver is a major route of colchicine elimination.
Collagen Type I and Iii Occur Together in Hybrid Fibrils in the Space of Disse of Normal Rat Liver
Authors: Geerts Albert , Schuppan Detlef , Lazeroms Sylvia , De Zanger Ronald , Wisse Eddie 
Published: March 2007

Collagen type I and procollagen type III were localized at the ultrastructural level on ultrathin frozen sections of rat liver by the protein A-gold technique using affinity–purified primary antibodies. Both collagen type I and procollagen type III were localized on nearly all solitary and bundled fibrils in the space of Disse. Simultaneous localization of collagen type I and procollagen type III by a double–labeling procedure using protein A-gold probes of different sizes unequivocally demonstrated the presence of both collagens in the same fibrils.
Measurement of the diameter of large numbers of collagen fibrils in the space of Disse of the rat liver showed a unimodal distribution of the fibril diameters around an average value of 62.4 nm (S.D. = 12.8 nm), and 91% of the collagen bundles contained less than 30 fibrils. Additional measurements on epoxy resin-embedded material of five biopsy specimens of normal human liver showed a comparable unimodal distribution of the fibril diameters around an average value of 57.2 nm (S.D. = 9.6 nm), and 74% of the bundles contained less than 60 fibrils. The latter observation demonstrates that human liver contains broader interstitial collagen bundles than rat liver.
From these results, we conclude that the space of Disse of normal rat and human liver contains a uniform population of striated interstitial collagen fibrils. In the rat liver, these fibrils contain both collagen type I and procollagen type III. Therefore the concept that procollagen type III is predominantly localized in small diameter fibrils or bundles, whereas collagen type I is preferentially localized in thick ones, does not hold. (Hepatology 1990;12:233-241).
HBV-DNA sequences in tumor and nontumor tissue in a patient with the fibrolamellar variant of hepatocellular carcinoma
Authors: Davison Fergus D. , Fagan Elizabeth A. , Portmann Bernard , Williams Roger 
Published: March 2007

One patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti-HBe. DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences. Undigested DNA from the tumor gave a high-molecular-weight smear, and restriction-enzyme analysis indicated a single instance of integration. Nontumor liver tissue was analyzed from three separate areas. Hepatitis B virus DNA was detected in two of these; restriction-enzyme digestion suggested they contained different sites of viral integration.
As with the typical hepatitis B virus—related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high-molecular-weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor. The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus—related hepatocellular carcinoma. (HEPATOLOGY 1990;12:676-679).
Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors
Authors: Wanless Ian R. , Lentz John S. 
Published: March 2007

Steatohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass. A similar lesion occurs rarely in obese patients without bypass surgery, but the risk factors are poorly understood. Hepatic steatosis, steatohepatitis and fibrosis were sought in 351 apparently nonalcoholic patients at autopsy and various risk factors were evaluated. Incidence of steatosis and steatohepatitis correlated with the degree of obesity. Steatohepatitis was found in 18.5% of markedly obese patients and 2.7% of lean patients. Additional risk factors for steatohepatitis were type II diabetes, weight loss in the preterminal period shortly before death and intravenous glucose therapy in the last week of life. Severe fibrosis was found in 13.8% of markedly obese patients and in 6.6% of lean patients; this difference was largely explained by the higher prevalence of diabetes in obese groups.
The risk factors defined in this study are known to be associated with abnormalities of free fatty acid metabolism. Obesity, type II diabetes and intravenous glucose therapy are associated with hyperinsulinemia, which may inhibit fatty acid oxidation. Obesity and weight loss increase the presentation of fatty acids to the liver. Similar metabolic changes may occur in obese patients after jejunoileal bypass surgery. Thus this study supports the hypothesis that fatty acids have a role in the hepatocellular necrosis found in some obese individuals. (HEPATOLOGY 1990;12:1106-1110).
Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: A clinicopathological study of 145 patients examined at autopsy†
Authors: Wanless Ian R. , Peterson Powers , Das Asha , Boitnott John K. , Moore William G. , Bernier Vincent 
Published: March 2007

The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had > 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension.
We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. (HEPATOLOGY 1990;12:1166-1174).
Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity
Authors: Kwekkeboom Jaap , Princen Hans M. G. , van Voorthuizen Eline M. , Kempen Herman Jan M. 
Published: March 2007

Feedback regulation of bile acid synthesis by its end products was studied in cultured hepatocytes of young weaned pigs. We previously showed that conversion of exogenous [14C] cholesterol into bile acids was suppressed by addition of bile acids to the culture medium. In the present study, the effects of bile acids on bile acid mass production and cholesterol 7α-hydroxylase activity were examined. Mass production of bile acids was strongly inhibited by addition of taurocholic acid (50 and 100 μmol/L) to the culture medium. The inhibitory action was exerted specifically on activity of cholesterol 7α-hydroxylase because conversion of [14C] 7α-hydroxycholesterol to bile acids by pig hepatocytes was not affected. Suppression of cholesterol 7α-hydroxylase activity after incubation of the hepatocytes with taurocholic acid was concentration- and time-dependent. Maximum suppression (−80%) was achieved after a 20 to 30 hr incubation of hepatocytes with 100 μmol/L of this bile acid. Decline of enzyme activity caused by 100 μmol/L taurocholic acid followed first-order kinetics with a half-life of 10 hr. Taurocholic acid had no direct effect on cholesterol 7α-hydroxylase activity in homogenates of hepatocytes as assessed by addition of the bile acid to the assay mixture.
The effects of several other bile acids in a concentration of 100 μmol/L on cholesterol 7α-hydroxylase activity were examined in 48 hr incubations. Glycochenodeoxycholic and glycohyodeoxycholic acids, which are the major bile acids in pig bile, their unconjugated forms and also deoxycholic and cholic acid pronouncedly inhibited activity of the enzyme. In contrast, hyocholic acid almost failed to inhibit, whereas ursodeoxycholic acid was a weak inhibitor.
It is concluded that bile acids, in physiological concentrations (i.e., as observed in portal blood), inhibit bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity through a direct effect on the hepatocoyte. (HEPATOLOGY 1990;12:1209-1215).
Alcohol content of various beverages: All booze is created equal
Authors: Conn Harold O. 
Published: March 2007

After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant “first pass metabolism” of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics.
The first pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (r8 = 0.659) between first pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished.
We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism.
Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection
Authors: Vitvitski-Trépo Ludmila , Kay Alan , Pichoud Christian , Chevallier Philippe , de Dinechin Stéphane , Shamoon Blanche-Marie , Mandart Elisabeth , Trépo Christian , Galibert Francis 
Published: March 2007

To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme-linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays.
Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p < 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p < 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%).
The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se.
HBxAg was also frequently detected by immunoperoxidase staining in paraffin liver sections of 60 chronic HBsAg carriers with liver disease. Its localization overlapped that of HBcAg. A discrepancy between the detection of HBxAg in liver and that of anti-HBx in serum was observed in chronic hepatitis cases, which was not found in patients with more advanced forms of liver disease. (HEPATOLOGY 1990;12:1278-1283).