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At least 19 recordsLinked to original sources

Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis.

Liver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (tcd) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats.

Acute Disease

Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis.

Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.

Adult

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors.

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurements with the volume of the resected liver mass. The correlation coefficient between these methods was 0.899 (P less than 0.01). Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days the liver had regenerated maximally to a volume of 75 +/- 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 +/- 10% for the caffeine clearance and to 100 +/- 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. Our study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy.

Adult

[Serum concentrations of tissue polypeptide antigen and alpha 1-fetoprotein in patients with primary liver cancer, liver metastasis and liver cirrhosis].

Tissue Polypeptide Antigen (TPA) and alpha 1-fetoprotein (AFP) were determined in sera of 21 patients with hepatocellular carcinomas, in 20 patients with extrahepatic carcinomas and metastases of the liver, as well as in 26 patients with cirrhosis of the liver. TPA was increased (greater than 85 U/L) in all patients with malignant hepatomas, in 80% of patients with metastatic liver cancer and in 35% of patients with cirrhosis of the liver. The critical serum TPA level, above which only malignant liver tumours lay, was statistically evaluated and found to be 187 U/L. All patients with benign liver disease and half of the patients with metastatic liver disease showed TPA values lower than 187 U/L. All of the patients with hepatocellular carcinoma and half of the patients with metastatic liver cancer had TPA values greater than 187 U/L; all of our patients with cirrhosis of the liver, as well as half of the patients with metastatic liver cancer had lower TPA values. 86% out of all hepatoma patients showed increased AFP levels (greater than 9 ng/ml), whereby the AFP concentrations were in the range which is highly suggestive of hepatoma (greater than 174 ng/ml) in 67% of all patients with malignant hepatomas. Patients with metastatic liver cancer and cirrhosis of the liver had AFP levels lower than 174 ng/ml AFP. TPA is an unspecific tumour marker, which can be used together with AFP in the diagnosis of unclear defects in liver parenchyma, in supervision of cirrhosis, as well as in control assessment during chemotherapy or after tumour resection.

Antigens, Neoplasm

The mechanism of release of hepatic enzymes in various liver diseases. II. Altered activity ratios of GOT to GPT in serum and liver of patients with liver diseases.

The activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase (GLD) were determined in liver biopsy specimens and sera of patients with various liver diseases. Mitochondrial and cytosol isozymes of GOT were also separated for their assay. The activity ratio of GOT/GPT in serum was found to reflect the ratio in liver cytosol. The increased ratio in advanced or severe liver diseases, such as liver cirrhosis, was due to the greater decrease in liver cytosol GPT activity, this being pronounced in primary hepatoma. The activity of GLD decreased similarly but less markedly. The relatively greater decrease in GPT compared with GOT in advanced liver diseases was not mainly due to leakage of the enzyme from the liver, but to a specific mechanism associated with hepatic injury or its progression. Other pathological conditions of the liver such as those in obstructive jaundice and alcoholic liver injury also appeared to result in reduced liver GPT activity, which was reflected in the serum as an increased GOT/GPT ratio.

Alanine Transaminase

Graft regeneration and host liver atrophy after auxiliary heterotopic liver transplantation for chronic liver failure.

We studied the size of the liver graft and the host liver in six consecutive patients undergoing auxiliary heterotopic liver transplantation for chronic end-stage liver disease. In all cases, a liver reduced in size by left lateral hepatectomy was inserted. The sizes of the graft and host liver were estimated by planimetry of two-dimensional di-isopropyl iminodiacetic acid scintigrams taken 3, 7, 21, 90 and 180 days after surgery. Graft size increased from a mean of 12.2 cm2 (95% confidence interval = 10.2 to 14.1) on day 3 to a maximum of 14.8 cm2 (95% confidence interval = 13.4 to 16.1) on day 21 and remained stable thereafter; in contrast, the host liver decreased in size from 9.6 cm2 (95% confidence interval = 6.8 to 12.3) on day 3 to 3.9 cm2 (95% confidence interval = 3.0 to 4.8) at mo 6. We conclude that in patients with chronic liver failure, an auxiliary allograft reduced in size and placed adjacent to the host liver shows regenerative growth within 3 wk, whereas the host liver atrophies in 3 to 6 mo.

Adult

Depression of liver-specific gene expression in regenerating rat liver: a putative cause for liver dysfunction after hepatectomy.

We carried out studies on the expression of liver-specific genes during regeneration of the liver and searched for changes in the expression of oncogenes and housekeeping genes. Albumin and ornithine transcarbamylase genes were the liver-specific genes examined by Northern blot analysis, using total RNAs isolated from residual livers of Sprague-Dawley rats subjected to a 68% partial hepatectomy. The mRNA levels of both genes began to decrease 8 hr after hepatectomy, both reaching the lowest levels at 24 hr, and then recovered to some extent at 48 hr. In contrast, these levels in the housekeeping and growth-related genes were augmented during this period. This would suggest that there is a selective expression of growth-related and housekeeping genes, in preference to liver-specific genes during liver regeneration. The expression of these genes in the regenerating liver was simulated in primary cultured hepatocytes during the dedifferentiation processes. It would appear that the first step in regeneration of the residual liver is dedifferentiation, in which the depression of liver-specific genes may be linked to liver dysfunction following hepatectomy.

Animals

The use of reduced-size liver transplants in children, including split livers and living related liver transplants.

One of the key problems facing children awaiting liver transplantation is the shortage of donor organs. Surgical procedures that address this problem include: reduced-size liver transplantation (RLT), split liver transplantation (SLT), and living related liver transplantation (LRLT). RLT makes more of the current donor pool accessible to the pediatric recipient. SLT furnishes 2 liver grafts from 1 cadaveric donor, and LRLT provides an innovative supply of donor organs. This report compares the results achieved with RLT, SLT, and LRLT to those seen with full-size orthotopic liver transplantation (OLT). Between November 1984 and February 1991, 457 liver transplants were performed at the University of Chicago. Two hundred fourteen of these transplants were placed into recipients less than 13 years of age. Of these 214 pediatric orthotopic liver transplants (OLT), 103 were full-size livers and 111 were some type of reduced graft (RLT, SLT, or LRLT). There were 57 RLT, 34 SLT, and 20 LRLT. The recipients of the reduced grafts (RLT, SLT, or LRLT) averaged 1.9 +/- 1.8 years of age and 9.6 +/- 6.4 kg compared to the recipients of the full-size livers who averaged 3.5 +/- 3.4 years of age and 14.1 +/- 8.8 kg (p = 0.0001). The most common indication for transplantation was biliary atresia (105 patients). Overall patient survival after primary full-size OLT was 71.8%. Reduced-size OLT (RLT, SLT, and LRLT) resulted in an overall patient survival of 72.6% after primary transplantation. Patient survivals for primary transplants with specific types of reduced-size grafts were: RLT 76.5% (after RLT was used routinely), SLT 66.7%, and LRLT 89.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Liver damage after paracetamol overdose. Comparison of liver-function tests, fasting serum bile acids, and liver histology.

54 patients have been studied after paracetamol (acetaminophen) overdose. Liver-function tests and fasting serum bile-acids were measured daily; liver biopsy was done in all cases, and slides were examined "blind" to assess liver damage. The plasma-paracetamol was measured on one occasion. A histological abnormality was present in the livers of 53 of the 54 patients, and was minor in 23, moderate in 16, and severe in 14. In 6 patients with moderate and 18 with mild histological abnormality liver-function tests were normal. A serum-aspartate-aminotransferase above 400 units/1 was always associated with severe histological liver damage. Fasting serum bile-acids were raised in 51 of the patients with abnormal liver histology; the serum-bile-acid seemed to be a more sensitive indicator of mild liver-cell damage than was the transaminase level. There was, however, little correlation between increase in bile-acid concentration and the degree of histological abnormality. As a result of these investigations empirically determined levels of plasma-paracetamol have been drawn which give a guide to the likelihood of liver damage after paracetamol overdose.

Acetaminophen

[Liver transplantation in acute liver insufficiency: definitive replacement or auxiliary liver?].

Orthotopic liver transplantation (OLT) has greatly improved the chances of survival in patients with acute hepatic failure. However, this mode of treatment requires lifelong immunosuppressive medication and negates the potential recovery of the host liver. In theory, auxiliary heterotopic liver transplantation (HLT) offers the diseased host liver a chance to regenerate, so that immunosuppression can be tapered off and eventually stopped. In the University Hospital Rotterdam Dijkzigt OLT and HLT were performed in two patients, with acute and subacute hepatic failure respectively. The patient undergoing OLT recovered quickly but needed a successful re-OLT after a serious rejection episode. The removed diseased liver showed no signs of regeneration at histology. The patient undergoing HLT also recovered well. HIDA scanning as well as liver biopsies of the host liver and the grafted liver 1 and 6 months after transplantation indicated full recovery of the host liver, so that immunosuppression is being tapered off.

Adult

[Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4].

TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. 1) Effect of TJN-101 on liver fibrosis was investigated in rats which were injected with CCl4 (1 ml/kg) subcutaneously twice a week for 12 weeks. TJN-101 was given orally at the dose of 10 or 30 mg/kg/day for 6 or 3 weeks beginning on the 6th or 9th week after the start of CCl4-intoxication, respectively. The elevations of serum transaminase activities and the increase of liver 4-hydroxyproline content were observed depending on the period of CCl4-intoxication. These changes were marked on the 9th and 12th weeks after. In the histopathological study, the degenerative fatty change on the 6th week after and the formation of pseudolobule caused by fibrosis proliferation on the 9th or 12th week after were mainly observed. When rats were treated with TJN-101, the abnormalities in biochemical parameters and the fibrosis proliferation caused by CCl4-intoxication were improved. 2) Chronic liver injury was induced by the treatment with CCl4 (1 ml/kg) subcutaneously twice a week for 10 weeks to investigate the effect of TJN-101 on liver regeneration after partial hepatectomy. TJN-101, which was given orally at the dose of 10, 30 or 100 mg/kg/day for 6 days from the 1st day after partial hepatectomy, dose-dependently increased the liver regeneration rate and improved the serum BSP retention rate. These results suggest that TJN-101 suppresses the fibrosis proliferation and accelerates both the liver regeneration and the recovery of liver function after partial hepatectomy in chronic liver injury.

Administration, Oral

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged

Dependence of ultrasonic attenuation of liver on pathologic fat and fibrosis: examination with experimental fatty liver and liver fibrosis models.

To clarify the effect of the pathological state of the liver on ultrasonic attenuation, we produced two experimental rabbit models. The influence of fat on ultrasonic attenuation was examined using a fatty liver model without liver fibrosis, and that of fibrosis on attenuation using a liver fibrosis model without fatty infiltration. Ultrasonic data were obtained in vivo directly from the liver, and an acoustic attenuation coefficient slope was obtained by the spectral difference method. Tissue components of the liver, namely the total lipid, hydroxyproline and water contents, were measured precisely by quantitative methods. We revealed that ultrasonic attenuation depends mainly on fatty infiltration of the liver and to a lesser extent on fibrosis, but not on the water content.

Adipose Tissue

Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11.

Anti-liver kidney microsomes (anti-LKM2) autoantibodies, appearing in patients treated with tienilic acid and suffering from hepatitis, react with proteins in rat liver sections. The nature of the rat proteins responsible for this recognition and detection of anti-LKM2 has been investigated. Immunoblot testing of the anti-LKM2 with liver microsomes from diversely treated rats and with purified rat liver cytochromes P450 (IA1, IA2, IIB1, IIB2, IIC6, IIC11 and IVA1) showed that these antibodies cross-reacted with cytochrome P450IIC11 and also with phenobarbital-induced cytochromes P450IIB1 and IIB2. Moreover, metabolic activation of tienilic acid and of a tienilic acid isomer by untreated rat liver microsomes was partially inhibited by anti-LKM2. On the other hand, monospecific polyclonal anti-rat P450IIC11 antibodies cross-reacted with human microsomal cytochromes P450 and recognized the same cytochromes P450 as anti-LKM2. This antibody also gave an immunofluorescence pattern on rat and mouse liver and kidney sections very similar to anti-LKM2. The data presented here show that anti-LKM2 recognize epitopes shared by rat P450 IIC11, and a human P450 of the family IIC. All the results indicate rat P450 IIC11, the major isoenzyme present in normal adult male rat liver, as the main antigen recognized by human anti-LKM2 autoantibodies; this is the basis of the immunofluorescence test for detection of these antibodies.

Animals

The role of liver biopsy in evaluating acute allograft dysfunction following liver transplantation: a clinical histologic correlation of 34 liver transplants.

One hundred six liver biopsy specimens from 34 orthotopic liver transplant (OLT) patients were examined and the histologic findings correlated with the clinical course of the patients to determine if specific morphologic patterns were associated with specific causes of acute allograft dysfunction. The principle causes of allograft injury in these patients appeared to be acute rejection and ischemic injury, with rarer cases of viral infection and biliary obstruction. Graft rejection causing transient liver dysfunction was associated with a mixed inflammatory infiltrate in the portal tracts and involving the interlobular bile ducts. Rejection resulting in severe, persistent dysfunction was associated with destruction and loss of the interlobular bile ducts or portal inflammation, followed by acute centrilobular hepatocyte necrosis. Ischemic liver injury was characterized by hepatocyte ballooning and/or hepatocyte necrosis. Ischemic injury causing transient graft dysfunction demonstrated focal, limited areas of hepatocyte necrosis or transient centrilobular hepatocyte ballooning. Severe ischemic injury resulting in persistent dysfunction caused diffuse hepatocyte necrosis or centrilobular ballooning followed by centrilobular hepatocyte loss and severe cholestasis with evidence of bile duct epithelial injury. The histologic patterns observed were not pathognomonic; radiologic studies, bile cultures, and other laboratory tests were necessary to rule out biliary or vascular obstruction and bacterial cholangitis. However, liver biopsies, especially serial biopsies, were helpful in suggesting the probable cause of liver dysfunction and in predicting subsequent allograft recovery or failure.

Adolescent

The diagnostic significance of liver cell inhomogeneity: serum enzymes in patients with central liver necrosis and the distribution of glutamate dehydrogenase in normal human liver.

16 Patients with acute right-sided cardiac failure associated with a high pressure of the central venous system, exhibited a marked increase in glutamate dehydrogenase activity in serum. This increase was 40-fold higher than in patients with acute viral hepatitis. Histological examination of seven deceased patients revealed central necrosis within the liver lobule. This observation led us to determine glutamate dehydrogenase activity in microdissected peripheral and central portions from the unchanged liver lobule. A 1.7-fold higher glutamate dehydrogenase activity was found in the central part of the liver lobule than in the peripheral portion. The diagnostic significance of the glutamate dehydrogenase activity distribution along the cords of liver cells is discussed in view of liver diseases with central necrosis.

Aged