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Hepatic protein synthesis rate of liver specimens as a predictor of viability in rat cold ischemia liver transplantation model.

BACKGROUND/AIMS: We have previously reported that the hepatic protein synthesis rate, calculated as the uptake rate of L-[4.5 3H] leucine by the protein fraction during a 10-min incubation of a 16-G needle biopsy specimen of liver tissue, represents a high level of liver function and is therefore useful for evaluating liver function. We investigated the hepatic protein synthesis rate level in a pre-transplant liver to learn if it might predict the outcome in a rat orthotopic liver transplantation model. METHODS: Grafts were stored, liver specimens were obtained using a 21-G Chiba type II skinny needle, and the hepatic protein synthesis rate was calculated. Subsequently, liver transplantation was performed, and the hepatic protein synthesis rate level of revascularized liver, tissue blood flow rate, serum alanine aminotransferase, lactate dehydrogenase, hyaluronic acid, ketone body rate, and 2-week survival were examined. RESULTS: The hepatic protein synthesis rate of pretransplant liver was correlated with parameters of post-transplant liver function: hepatic protein synthesis rate of the revascularized liver (r=0.92, p<0.0001), tissue blood flow rate (r=0.77, p<0.004), serum alanine aminotransferase (r=-0.69, p<0.003), lactate dehydrogenase (r=-0.54, p<0.03), hyaluronic acid (r=-0.86, p<0.0002), and ketone body rate (r=0.57, p<0.02). Pretransplant hepatic protein synthesis rate in survivors was 263.6+/-54.2 nmol/mg protein/10 min, while that in nonsurvivors was significantly lower at 162.0+/-39.0 (p<0.0001). When evaluation was made using a logistic regression model, the accuracy predicted using the value of hepatic protein synthesis rate was 95% (19/20). CONCLUSIONS: These results suggest that measuring the hepatic protein synthesis rate of the grafts with a 21-G Chiba type II skinny needle may be a predictive criterion in the assessment of graft viability.

Alanine Transaminase↗

Extracorporeal liver support: cell-based therapy for the failing liver.

It is perhaps self-evident to state that a liver support device is possible as long as the artificial organ provides liver function. This basic concept has received woefully little attention, mainly because "liver function" escapes precise definition. We have seen a variety of liver-assist devices that have little to do with liver function over the past 30 years. Recent work has focused on the liver as a biochemical reactor, rather than an excretory organ, and the paradigm has shifted away from blood purification and toward metabolic support. This new generation of devices includes viable liver cells, which provide the necessary biochemical function without needing to identify the numerous metabolic pathways necessary to support the patient with a failing liver. This approach is the most effective and least invasive method available with current technology, and it has yielded exciting data. Questions about the mass of cells required to provide adequate support, the timing and length of treatment, and the source of cellular material continue to be debated. Here we address theoretical and practical problems in developing an extracorporeal liver-assist device (ELAD) and suggest the future role of extracorporeal liver support in the management of liver failure.

Animals↗

Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population.

Our aim was to evaluate incidence and risk factors of liver involvement in obese Italian children as assessed by both ultrasonographic and biochemical parameters. In seventy-five consecutive obese children (age 9.5 +/- 2.9 years, males/females 41/34), serum levels of enzymes and ultrasonography of the liver were evaluated. Tests were repeated one, three, and six months after starting a moderate hypocaloric diet and an exercise program. Three obese children who were found to have chronic viral hepatitis were excluded from the study. Thirty-eight of 72 (53%) obese children had an ultrasonographic image of bright liver consistent with liver steatosis. The latter was severe in nine children, moderate in 16, and mild in 13. Eighteen obese children (25%) had elevated transaminase levels. Bright liver and hypertransaminasemia were not due to any of the most common causes of liver disease. Both were rapidly responsive to loss of weight, confirming that liver involvement was secondary to obesity and that steatosis or steatohepatitis rather than fibrosis were involved. Obesity duration not more than three years (odds ratio = 4.77), a higher degree of obesity (odds ratio = 2.09), and hypertransaminasemia (odds ratio = 2.15) appeared as important predictive factors of liver involvement at ultrasonography. Incidence of liver involvement assessed by means of ultrasonography is significantly higher than that revealed by measurement of serum liver enzymes. A short duration of obesity emerged as a potentially new risk factor of liver involvement in the pediatric obese population and needs to be confirmed in future studies.

Child↗

Changes in portal vein flow after adult living-donor liver transplantation: does it influence postoperative liver function?

In adult living donor liver transplantation, using small grafts in cirrhotic patients with severe portal hypertension may have unpredictable consequences. The so-called small-for-size syndrome is present in most series worldwide. The goal of this study was to prospectively evaluate the influence of hemodynamic changes on postoperative liver function and on the percentage of liver volume increase, in the setting of living donor liver transplantation. Twenty-two consecutive adult living donor liver transplantations were performed at our institution in a 2-year period. We measured right portal flow and right hepatic arterial flow with an ultrasonic flow meter in the donor, and then in the recipient 1 hour after reperfusion. Postoperative liver function was measured by daily laboratory work. We also performed duplex ultrasounds on postoperative days 1, 2, and 7. Liver volume increase was estimated by magnetic resonance imaging graft volumetry at 2 months posttransplantation. We compared the blood flow results with the immediate liver function and its liver volume increase rate at 2 months. There was a significant increase in portal flow in the recipients compared with the donors (up to fourfold in some cases). Higher portal flow increase rates significantly correlated with faster prothrombin time normalization and faster liver volume increases. Median graft volume increase at 2 months was 44.9%. The increase in blood flow to the graft is well tolerated by the liver mass not affecting hepatocellular function as long as the graft-to body weight ratio is maintained (>0.8) and adequate outflow is provided.

Body Weight↗

Correlation of ultrasound attenuation and histopathological parameters of the liver in chronic diffuse liver diseases.

OBJECTIVE: In patients with chronic diffuse liver diseases two characteristic ultrasound patterns of bright liver, the low (DI) and the high (DII) attenuation types, are seen. Correlation was studied between liver attenuation and histopathological analysis of biopsy specimens of the same patients. METHODS: Ultrasound attenuation of the liver was measured quantitatively using a homogeneous tissue-equivalent reference phantom. Semiquantitative scores were used for histopathological analysis of biopsy specimens. RESULTS: One hundred and twenty-two patients were investigated; 40 of them showed a normal liver echopattern. The average attenuation was 0.68+/-0.03 dB/cm per MHz. Histopathological parameters were normal in most of the patients, except for four cases where a minimal amount of collagen and 14 cases where a subtle amount of lipid content could be detected, in three cases accompanied by some cells indicating inflammation. From 82 patients with bright liver, 47 showed the DI type. The average attenuation was 0.80+/-0.03 dB/cm per MHz. In all of these patients, significant increases of collagen content and inflammatory reaction were found. In 23 cases a negligible amount of lipid deposition could also be revealed. Thirty-five patients exhibited a DII-type bright liver. The average attenuation was 1.21+/-0.06 dB/cm per MHz. A significant amount of lipid deposition was detected in all cases. In 13 patients a minimal amount of collagen and in 14 patients some inflammatory cells were detected. CONCLUSIONS: In livers with a normal echopattern, none or minimal pathological changes were seen. In DI-type bright liver, connective tissue dominance exists, in DII-type bright liver lipid deposition dominance. On this basis it is proved that the diagnosis of a fatty liver can be established without biopsy, if no other indication for biopsy exists.

Adult↗

Fetal and adult liver stem cells for liver regeneration and tissue engineering.

For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

Animals↗

Evaluation of liver volume and liver function following hepatic resection in man.

In a longitudinal study liver volume and liver function were measured in a series of 12 patients undergoing partial liver resection for focal hepatic lesions. Ultrasonography revealed that liver volume, reduced by about 50% by the resection, progressively increased, and 6 months after surgery it returned to nearly normal values. A variable reduction in routine liver function tests was observed, possibly reflecting the influence of the different reserve synthetic capacity of the liver and, in the early postoperative phase, plasma half-life of liver products and blood loss or changes in plasma volume. The galactose elimination capacity was only marginally reduced in the early period (from a pre-surgery value of 2.49 +/- SE 0.21 mmol/min to 2.31 +/- 0.14 after 7 days; p = ns) and reached a nadir at 14 days (1.97 +/- 0.16; p less than 0.001). When expressed per unit of liver volume, the galactose elimination (22 +/- 2 mumol/min per unit before resection) progressively decreased during the regeneration phase from 36 +/- 4 at 14 days to 26 +/- 3 at 6 months (P vs 14-day: less than 0.01). At 6 months both galactose elimination and galactose elimination per unit of liver volume were no longer different from baseline values. Our data show that, following hepatic resection, both liver volume and liver function increase and progressively return to nearly normal values. In agreement with data obtained in animal studies, it appears that the metabolic activity of the remaining parenchyma is increased in the early postoperative phase, and it slows down in the course of regeneration.

Adult↗

Long term prognosis of fatty liver: risk of chronic liver disease and death.

BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival estimates were significantly (p<0.01) different between the two groups, for men as well as for women, with a higher death rate in the alcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study revealed that patients with type 1 non-alcoholic fatty liver disease have a benign clinical course without excess mortality.

Adult↗

Transforming growth factor-beta1 in plasma and liver of children with liver disease.

Although several liver diseases of childhood, particularly biliary atresia (BA) and cystic fibrosis (CF) liver disease (CFLD) are characterized by hepatic fibrosis, the pathogenesis of this process is incompletely understood. The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in hepatic fibrosis in experimental animals, in which both the hepatic expression and plasma concentration of this cytokine are increased. The objective of our study was to determine whether there are similar alterations of TGF-beta1 in patients with hepatic fibrosis secondary to either BA and/or CFLD. The study design was as follows. In study 1, plasma TGF-beta1 was assessed by ELISA in 9 children with BA undergoing liver transplantation, 11 patients with CFLD, and appropriate control subjects. In study 2, hepatic expression of TGF-beta1 protein (assessed immunohistochemically) and hepatic fibrosis were scored semiquantitatively, on a 1-3 scale, by blinded investigators, in archival liver biopsy specimens from 10 children with BA, 10 with CFLD, and from 10 older children with normal hepatic histology, as well as in 4 patients with liver diseases of various etiologies. Simultaneous plasma and liver TGF-beta1 studies were performed in 8 patients with liver disease. Results were as follows. Plasma TGF-beta1 values were inversely correlated with age in healthy subjects (r=-0.54, p < 0.0001). The plasma TGF-beta1 protein of children with BA was decreased (13+/-2 ng/mL) compared with values for healthy children (42+/-6 ng/mL, n=10, p < 0.005). Similarly, the plasma TGF-beta1 concentration in patients with CFLD was also decreased compared with values for children with CF and normal serum liver profiles (n=14) (2+/-1 ng/mL versus 12+/-1, p < 0.05). However, the plasma TGF-beta1 concentration was increased in two patients with other types of liver disease. The hepatic expression of TGF-beta1 was increased in the presence of hepatic fibrosis in all types of liver diseases studied. Forty-six percent of patients had both marked hepatic fibrosis and marked TGF-beta1 labeling; 86% of samples without fibrosis showed no TGF-beta1 labeling, p=0.007. In conclusion, these studies have established the association of hepatic TGF-beta1 protein and hepatic fibrosis in several common liver diseases of childhood. Our data also suggest that, in children, plasma TGF-beta1 does not appear to be a useful marker of hepatic expression of this cytokine.

Adult↗

Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

Alanine Transaminase↗

The development of a new bioartificial liver and its application in 12 acute liver failure patients.

AIM: Bioartificial liver is a hope of supporting liver functions in acute liver failure patients. Using polysulfon fibers, a new bioartificial liver was developed. The aim of this study was to show whether this bioartificial liver could support liver functions or not. METHODS: Hepatocytes were procured from swine using Seglen's methods. The bioartificial liver was constructed by polysulfon bioreactor and more than 10(10) hepatocytes. It was applied 14 times in 12 patients, who were divided into 7 cases of simultaneous HBAL and 5 cases of non-simultaneous HBAL. Each BAL treatment lasted 6 hours. The general condition of the patients and the biochemical indexes were studied. RESULTS: After treatment with bioartificial liver, blood ammonia, prothrombin time and total bilirubin showed significant decrease. 2 days later, blood ammonia still showed improvment. within one month period, 1 case (1/7) in simultaneous group died while in non-simultaneous group 2 cases (2/5) died. The difference was significant. Mortality rate was 25 %. CONCLUSION: The constructed bioartificial liver can support liver functions in acute liver failure. The simultaneous HBAL is better than non-simultaneous HBAL.

Adolescent↗

Heart and liver disease in 32 patients undergoing biopsy of both organs, with implications for heart or liver transplantation.

OBJECTIVE: To determine underlying conditions in patients undergoing both heart and liver biopsies. PATIENTS AND METHODS: Our study group consisted of 32 patients at the Mayo Clinic in Rochester, Minn, who underwent both endomyocardial and nonsurgical liver biopsies and who underwent at least one of these procedures between January 1,1981, and December 31,2000. Patients were categorized as having (1) heart disease affecting the liver, (2) liver disease affecting the heart, (3) the same disease affecting both organs, or (4) different diseases affecting each organ independently. RESULTS: Among 32 patients, cardiac dysfunction was present in 28 (19 systolic, 9 diastolic), and hepatic dysfunction was present in 31. In group 1, 3 of 4 patients had cardiac amyloidosis with secondary hepatic congestion. In group 2, all 3 patients had cirrhosis with cirrhotic cardiomyopathy. Group 3 included 5 patients with hemochromatosis, 3 with alcoholism, and 1 with amyloidosis. In group 4, 8 of 16 patients had idiopathic cardiomyopathy, and 8 had hepatitis. Overall, of 8 patients with hemochromatosis, 3 without cardiac iron had improved cardiac function after phlebotomy, and 1 with cardiac iron had no cardiac dysfunction. Among 7 patients with alcoholism, 3 had alcoholic liver and heart disease. Of 5 patients with cardiac amyloidosis, 1 had hepatic amyloid. Ten patients underwent transplantation (6 liver, 3 heart, and 1 heart and liver). CONCLUSIONS: In one half of the patients in the study group, heart and liver diseases had independent causes. In patients with hemochromatosis, there was little correlation between cardiac iron and systolic dysfunction. In patients with chronic alcoholism, liver and heart disorders often had nonalcoholic causes. With cardiac amyloidosis, hepatic dysfunction was generally due to congestion. Specific disease in one organ did not necessarily imply similar involvement in the other. Thus, heart or liver biopsy may be useful in patients being evaluated for liver or heart transplantation, respectively.

Adolescent↗

[Relationship between the expression of IL-10 and liver regeneration following reduced-size orthotopic liver transplantation in rats].

OBJECTIVES: To explore the relationship between the expression of IL-10 and liver regeneration following reduced-size orthotopic liver transplantation in rats. METHODS: Rats models with reduced-size orthotopic liver transplantation were established. The rats were divided in three groups: partial liver resection (I), orthotopic liver transplantations (II), and reduced-size orthotopic liver transplantation (III). The expression of IL-10 and regenerative response of liver in rats were evaluated by immunohistochemistry and flow cytometry on the 1st, 2nd, 4th and 7th days after the operations, respectively. RESULTS: The liver grafts were capable of regeneration, the proliferation activity peaked on the fourth day with 26.3+/-0.9, 35.8+/-2.2, and 32.4+/-1.8 in I, II, and III groups, respectively. The expression of IL-10 was negative correlation to liver regeneration (r=-0.58, P<0.01). CONCLUSIONS: Whole and reduced-size transplanted livers show the same regenerative activity. The maximal regenerative response delayes slightly, compared with that after partial hepatectomy. IL-10 plays an important immunomodulatory role in liver regeneration,and the effect is affected by general immune system and other cytokines.

Animals↗

Characterization of liver enzymes on living related liver transplantation patients with acute rejection.

BACKGROUND/AIMS: To determine the biochemical data that reliably predict allograft injury from acute rejection (AR) in patients with living related liver transplantation (LRLT), liver function test and histopathological characteristics of AR were compared and analyzed retrospectively. METHODOLOGY: From Aug. 1994 to Nov. 2000, 101 cases received orthotopic liver transplantation (OLT), which included 53 patients with LRLT in our series. Completed liver functions including aspartate transferase (AST), alanine transferase (ALT), bilirubin total/direct (Bil.T/D), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) were collected with peak level when AR was diagnosed by liver biopsy. The best data of the same patients when disease free, were compared and analyzed with non-parametric Wilcoxon signed ranks test and Mann-Whitney test. All of the ARs were reversed with steroid pulse therapy, and two cases converted to FK506. No steroid-resistant rejection or chronic rejection was found in our series. RESULTS: In the patients with LRLT, 17 episodes in 13 patients with AR were found. The incidence of histological analysis proved AR was 12.9% (13/101) in OLT and 24.5% (13/53) in LRLT respectively. Among the liver function tests, AST (p<0.0001), ALT (p<0.0001), Bil.T (p=0.001), Bil.D (p=0.001), GGT (p<0.0001), and INR (p=0.034) were the significant predictors respectively in the patients with AR episode. Once liver enzymes had elevated, the AST/ALT ratio <1.0 showed a more significant difference in AR than in those of the no rejection group (p<0.0001). ALP showed significant difference in our series. The severity of histological change was not correlated to the degree of liver enzymes elevation. CONCLUSIONS: Complete liver function tests especially AST, ALT, Bil.T/D, GGT and the ratio of AST/ALT are very sensitive tests in a group of patients receiving LRLT with AR. The severity of AR is based on the histopathologic change but is not related to the degree of liver enzymes elevation itself. Meanwhile, the outcome of acute rejection in living related liver transplantation is quite good.

Acute Disease↗

[Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases].

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-Galactosyl-Human-Serum-Albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver diseases. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images was not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku and PT values were more significantly decreased or prolonged in the patients with liver cirrhosis than those in the patients with chronic hepatitis. Kd, Ku and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degrees of hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chronic liver disease: value of volumetry of liver and spleen with computed tomography.

Volumetric comparisons of portions of liver and spleen were performed in patients with chronic liver diseases to determine their diagnostic value. Volumetric ratios of liver and spleen were determined by CT examination in 34 normal subjects and 125 consecutive patients with histologically proved liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis, acute hepatitis, or fatty liver. Ratios of caudate lobe, spleen, and lateral segment of the left lobe of the liver to the remainder of the liver, right lobe and medial segment of the left lobe (RL+LM), were calculated. The product of caudate lobe/RL+LM and spleen/RL+LM was of value in differentiating liver cirrhosis from other liver disease, with a sensitivity of 60%, specificity of 98%, and accuracy of 86%. The same ratios differentiated liver cirrhosis and chronic active hepatitis from other liver diseases with a sensitivity of 79%, specificity of 100%, and accuracy of 90%. Volumetric ratio measurements are useful in the diagnosis of cirrhosis and chronic active hepatitis.

Acute Disease↗

Cell lineages in liver carcinogenesis: possible clues from studies of the distribution of alpha-fetoprotein RNA sequences in cell populations isolated from normal, regenerating, and preneoplastic rat livers.

We analyzed in isolated rat liver cell populations and in fetal and neoplastic livers the distribution of RNA sequences which hybridize with alpha-fetoprotein (AFP) complementary DNA clones. Parenchymal and nonparenchymal cell populations were isolated from normal, regenerating, preneoplastic, and bile duct-ligated rat livers. We found that oval cells, fetal liver, and a primary hepatocellular carcinoma contain the full length 2.3-kilobase AFP messenger RNA (mRNA); in normal adult rat liver, 2.3-kilobase AFP mRNA is found at low levels in an unidentified subpopulation of nonparenchymal cells but is not detected in hepatocytes; both parenchymal and nonparenchymal cells from normal or preneoplastic livers contain in variable proportion a smaller AFP RNA which hybridizes only with complementary DNA clones containing sequences located near the 5' end of the rat AFP gene; during liver regeneration induced by CCl4, elevation of the full length AFP mRNA occurs in nonparenchymal cells but seemingly not in hepatocytes. The results suggest that some cells in the nonparenchymal cell fraction of normal adult rat liver might retain the capacity to produce the 2.3-kilobase AFP mRNA found in large amounts in fetal livers, oval cells, and hepatic tumors. Although the nature of these cells remains to be determined, we suggest that such cells might be the source of the small amounts of AFP synthesized in normal rat liver and may constitute the proposed but as yet uncharacterized "facultative stem cell" compartment in rat liver.

Animals↗

Liver blood flow after liver hilus dearterialization.

Changes in liver blood flow immediately after and during one week after a standardized liver hilus dearterialization were studied in a series of 16 dogs. An additional six dogs were sham-operated and used as controls. The liver blood flow was measured using Xe133 injections administered by two methods in every animal: into the liver parenchyma, and into the portal vein. The measurements were taken immediately before, and 15, 30, 60 minutes, and one and seven days after the operation. Xe133 wash out from the liver was found to be reduced 15 minutes after the dearterialization, measured both by liver parenchymal and portal venous injection routes (p less than 0.05). Return to normal took place rapidly thereafter. On the next day some increase in the liver blood flow was observed in both dearterialized and sham-operated dogs. The aleration was significant in the dearterialized animals as measured by portal vein injections, and in the sham-operated dogs as measured by liver parenchymal injections (p less than 0.05). On the seventh day normal Xe133 liver wash out was recorded in all animals. It can be concluded that after liver hilus dearterialization in the dog liver blood flow was decreased for a very short period of time only. Increased flow was noted as early as the next day, not only in the dearterialized, but also in the sham-operated animals. The use of adequate controls is important.

Animals↗