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Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosis.

BACKGROUND: The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. AIM: In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)-alpha treatment and its hepatic metabolism. PATIENTS AND METHODS: Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF-alpha treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. RESULTS: Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF-alpha treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. CONCLUSIONS: Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases.

Adiponectin↗

[Significance of the iron and copper content of the liver for the differential diagnosis of chronic liver diseases].

Liver iron and copper concentrations were estimated in 395 patients undergoing hepatological examination. Relations to clinical, morphological and laboratory data were evaluated. Liver iron concentrations were not significantly different in chronic hepatitis of viral, toxic or immunological origin. Liver iron levels exceeding 100 mg/100 g dry liver tissue (normal range up to 300 mg/100 g) were only found in idiopathic hemochromatosis (n = 8), in a patient with prophyria cutanea tarda and in a multiple transfused patient who suffered from aplastic anemia. Liver copper content was significantly increased in primary biliary cirrhosis compared to chronic hepatitis of other origin. Apart from untreated Wilson's disease (n = 3) copper levels higher than 25 mg/100 g dry liver tissue (normal range up to 6 mg/100 g) were measured in chronic active hepatitis B (n = 2), primary biliary cirrhosis (n = 9) and in chronic hepatitis of uncertain origin (n = 3). Therefore excess accumulation of copper in the liver was typical of Wilson's disease but less diagnostic than severely elevated liver iron stores of idiopathic hemochromatosis.

Adolescent↗

[The behavior of albumin in acute and chronic liver damage. III. Intrahepatic and serum albumin concentrations in human liver diseases].

In 305 patients examined by liver biopsy albumin and the entire soluble protein in the liver puncture as well as albumin in the serum were estimated quantitatively. A significant decrease of the serum albumin level in active cirrhoses and biliary liver damages confirmed the importance of the hypalbuminaemia as facultative symptom of a liver damage. The lacking specifity was emphasized by the low albumin serum concentrations in malignomas and after the intake of contraceptive hormones. The hypalbuminaemia and the increased content of soluble liver protein in the bioptic material might enrich the diagnostics of the activity in cirrhoses. The diagnostic value of the decrease of the relative proportion of albumin is low, since of all liver diseases examined the active cirrhosis alone was accompanied by a significant decrease. The estimation of the albumin content in the bioptically got liver tissue had in contrast to the animal experiment no diagnostic value for liver diseases.

Albumins↗

Comparison of the grade evaluated by "Liver damage" of Liver Cancer Study Group of Japan and Child-Pugh classification in patients with hepatocellular carcinoma.

BACKGROUND: The "Liver damage" classification proposed by the Liver Cancer Study Group of Japan and Child-Pugh classification are both useful classifications for hepatic function. However, the factors responsible for the difference between the two classifications have not been fully investigated. METHODS: The medical records of 594 admissions of 220 patients with hepatocellular carcinoma (HCC) were retrospectively analyzed for encephalopathy, ascites, serum bilirubin and albumin, plasma retention rate (%) at 15min after injection of 0.5mg/kg of indocyanine green (ICG R15), and prothrombin time. RESULTS: Of 594 admissions, ICG R15 was tested in 337 (56.7%). The Child-Pugh classification was evaluated in all 594 admissions, but the "Liver damage" could be evaluated in 510 (85.9%) due to the lack of ICG R15 results. Of the 594 admissions, 372 (62.6%), 162 (27.3%), and 60 (10.1%) were Child-Pugh grade A, B, and C, respectively. Of the 510 admissions, 219 (42.9%), 202 (39.6%), and 89 (17.5%) were "Liver damage" grade A, B, and C, respectively. The grade of "Liver damage" was similar to that of Child-Pugh classification in 369 (72.4%), under-evaluated in 138 (27.1%), and over-evaluated in 3 (0.6%). The Child-Pugh classification was statistically a better classification for predicting outcome than "Liver damage", but the "Liver damage" had better stratification ability than Child-Pugh classification in patients with relatively good liver function. CONCLUSIONS: Although the "Liver damage" could not be evaluated in some cases due to the lack of ICG R15 results, this classification system is useful in the evaluation and prediction of outcome of patients with early-stage liver diseases.

Journal Article↗

Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation.

A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.

Acute Disease↗

Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases.

A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty-two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re-analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion, Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives are mainly attributable to inactive or macronodular cirrhosis.

Adult↗

Intravenous administration of follistatin: delivery to the liver and effect on liver regeneration after partial hepatectomy.

When 1 microgram 125I-follistatin was administered into a rat intravenously, radioactivity levels in serum decreased rapidly. Analysis with a biexponential equation showed that the initial half-life and the terminal half-life were 4.0 and 130.8 minutes, respectively. After 2 hours of infusion, approximately 9% of the follistatin infused remained in the liver, which was much more than that in kidney, spleen, pancreas, intestine, or lung. Autoradiography of the liver obtained at 24 hours of infusion revealed that numerous grains were located in parenchymal cells. Radioactivity of 125I-follistatin in the liver remained elevated until 72 hours and declined markedly thereafter. When a booster shot of 125I-follistatin was administered at 72 hours, radioactivity in the liver at 120 hours was markedly increased compared with that in rats that received a single shot of 125I-follistatin. We then examined the effect of intravenous infusion of follistatin on liver regeneration after hepatectomy of 70%. Immediately after the hepatectomy, either 1 microgram follistatin or saline was infused intravenously. In some rats, a booster shot was infused at 72 hours. After 120 hours of hepatectomy of 70%, remnant liver weight, liver regeneration rate, and DNA content were significantly (P < .05) higher in rats that received a booster shot of follistatin at 72 hours than those in control rats. These results indicate that follistatin administered intravenously accumulates in the liver and promotes liver regeneration after partial hepatectomy.

Animals↗

Infection complicating percutaneous liver biopsy in liver transplant recipients.

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.

Anastomosis, Roux-en-Y↗

Hepatic regeneration in the isolated perfused rat liver followed by liver transplantation.

Controlling the S phase of the hepatocyte cell cycle would be of considerable help for stable retroviral foreign gene transfer. The aim of this article is to study hepatocyte regeneration during S phase in isolated, perfused rat liver followed by liver transplantation. Normal livers (G I: n = 7) were perfused with blood from normal rats for 6.1+/-0.3 hours. Regenerating livers (G II; n = 7) obtained 18 hours after partial hepatectomy were perfused for 6.0+/-0.3 hours with blood from rats partially hepatectomized 18 hours before. Regenerating livers (G III; n = 7) obtained 22 hours after partial hepatectomy were perfused for 2.4+/-0.1 hours with blood from normal rats. In the normothermal perfusion system, a bolus of 25 mg of 5-bromo-2'-deoxyuridine (BrdU) was added to the perfusate. Liver biopsies were taken at the end of each experiment. In group II, a biopsy was also taken 1 hour after BrdU introduction. At the end of each experiment, livers were orthotopically transplanted. The percentage of BrdU positive hepatocyte nuclei was 0.2% in G I; 14.8% and 38.4% after 1 hour and 6.1 hours, respectively, in G II; and 46.5% after 2.4 hours in G III. In G I, five rats died at day 1, 5, 6, 7, and 48 and two rats were still alive after 17 months. In G II, all the rats died before day five. In G III, two rats died at day one, one at day six, and four were still alive after 12 months. This study shows that, after 6 hours of normothermal perfusion, organ viability allows successful liver transplantation and that rat hepatocyte regeneration during cell cycle S phase in isolated normothermal conditions progresses in a similar way-quantity and timing-to liver regeneration found in vivo after partial hepatectomy.

Animals↗

Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage.

Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers that have been sensitized to endotoxin damage by Propionibacterium acnes infection. The latter induces interleukin (IL)-12 and -18, causing a selective reduction of CD4+NK T cells, diminished IL-4 production, deficient production of T-helper type 2 (Th-2) cytokines (e.g., IL-10), and excessive production of Th-1 cytokines (e.g., interferon gamma [IFN-gamma]). Liver and spleen lymphocyte populations and hepatic cytokine production were compared in genetically obese, ob/ob mice (a model for obesity-related fatty liver) and lean mice. Obese mice have a selective reduction of hepatic CD4+NK T cells. Serum IL-18 is also increased basally, and the hepatic mRNA levels of IL-18 and -12 are greater after endotoxin challenge. Thus, up-regulation of IL-18 and IL-12 in fatty livers may reduce hepatic CD4+NK T cells. In addition, mononuclear cells from fatty livers have decreased expression of the adhesion molecule, leukocyte factor antigen-1 (LFA-1), which is necessary for the hepatic accumulation of CD4+NK T cells. Consistent with reduced numbers of hepatic CD4+NK T cells, mononuclear cells from fatty livers produce less IL-4. Furthermore, after endotoxin treatment, hepatic induction of IL-10 is inhibited, while that of IFN-gamma is enhanced. Thus, fatty livers have inherent immunologic alterations that may predispose them to damage from endotoxin and other insults that induce a proinflammatory cytokine response.

Animals↗

Liver transplantation for alcoholic liver disease: current concepts and length of sobriety.

1. The 1-year and 5-year actuarial survival rates following liver transplantation for patients with alcoholic liver disease are 82% and 68%, respectively, in the United States and 85% and 70%, respectively, in Europe. These survival rates are similar to the outcomes of patients who undergo transplantation for other types of chronic liver disease. 2. Posttransplant improvements in health-related quality of life are similar in patients who undergo transplantation for alcoholic liver disease compared to those who undergo transplantation for other causes of end-stage liver disease. 3. Approximately 20% of patients who undergo transplantation for alcoholic liver disease use alcohol posttransplant, with one-third of these individuals exhibiting repetitive or heavy drinking. Surprisingly, little evidence exists to document a significant detrimental effect on graft or patient survival associated with resumption of drinking. 4. There are few reliable predictors of relapse in alcoholic patients after liver transplantation. Although not supported by all studies, abstinence of fewer than 6 months prior to transplantation may be a reasonable predictor of recidivism and is widely employed as a criterion for listing for liver transplantation. There are no good data to determine if some patients with sobriety fewer than 6 months might benefit from liver transplantation.

Alcohol Drinking↗

Nf-kappab activation is associated with free radical generation and endotoxemia and precedes pathological liver injury in experimental alcoholic liver disease.

Endotoxemia and oxidative stress activate nuclear factor kappa B (NF-kappaB) in alcoholic liver injury. In alcohol-fed rats, activation of NF-kappaB is associated with the development of necro-inflammatory changes in the liver. Whether activation of NF-kappaB occurs prior to development of liver injury is unknown. We determined whether activation of NF-kappaB preceded histopathological liver changes. Male Wistar rats were fed a liquid diet containing ethanol by continuous infusion through permanently implanted gastric tubes. Radical intermediates detected by spin trapping were measured in bile prior to killing. After 2 weeks of treatment, samples of liver tissue were obtained for histopathological examination, for evaluation of NF-kappaB, and determination of messenger RNA levels of cytokines, chemokines and cyclo-oxygenase-2. No pathological changes in liver were seen after 2 weeks of intragastric feeding. However, activation of NF-kappaB was seen in the livers from ethanol-fed rats. In addition, elevated mRNA levels of hepatic pro-inflammatory cytokines (TNF-alpha and IL12), chemokines MIPIalpha and MIP-2) and cyclo-oxygenase-2 were seen in association with activation of NF-kappaB and increased levels of free radicals and endotoxin. Thus, activation of NF-kappaB, associated with elevated mRNA levels of pro-inflammatory stimuli, precedes the histopathological liver changes in experimental alcoholic liver disease in rats.

Animals↗

Hyperacute rejection of liver allografts in sensitized rats: role of nonparenchymal liver cells.

Reasons why liver allografts are more resistant to antibody mediated rejection than other organ allografts are not fully understood. In order to define the role of nonparenchymal liver cells, we have compared the fate of liver allografts in two combinations of sensitized inbred rats. In the DA into LEW combination, hyperacute rejection of liver allografts was observed (mean survival time of liver grafted rats was 5.2 +/- 0.6 hr). A sharp decrease of the level of cytotoxic antibodies was observed after transplantation associated with deposits of IgG, IgM, C3, and fibrinogen on sinusoidal cells. Macroscopic and histological aspects of liver allografts were suggestive of an antibody-mediated rejection with congestion and portal hemorrhage. On the contrary, in the LEW into BN combination, survival time was significantly longer (259.2 +/- 25.2 hr), whereas histological studies demonstrated signs of cellular rejection. A decrease in the level of cytotoxic antibodies was present and deposits of IgG, IgM, C3, and fibrinogen were more significant. After blockade of the Kupffer cells of the LEW-transplanted liver, survival time of the BN rats was significantly reduced (38.8 +/- 8.0 hr). Macroscopic and histological aspects of the grafts were suggestive of antibody-mediated rejection and deposits of IgG, IgM, and C3 were reduced. The results suggest the hypothesis that resistance of liver allografts to antibody-mediated rejection is probably due to the ability of nonparenchymal liver cells to absorb preformed cytotoxic antibodies and complement.

Animals↗

Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers.

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2-nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.

Adenosine Triphosphate↗

[Ex situ operation on the liver. A new possibility in liver surgery].

A method for an ex situ operation of the liver is presented with the example of such an operation in a 40-year-old patient. With this operation bilateral liver metastases of a leiomyosarcoma--which were otherwise regarded as irresectable--were resected. Function of the liver after reimplantation was good. Liver protection was performed by perfusion with cardioplegic HTK-solution (Bretschneider). The techniques of liver ex- and implantation are based on the methods of liver transplantation. Extracorporal femoro-porto-axillary bypass for decompression of the inferior caval vein and portal vein was used throughout the anhepatic period of 6 h. It is supposed that the method described here--which according to the authors' knowledge has been performed for the first time in a patient--will open up new perspectives for the surgery of malignant and occasionally of benign tumors, if necessary also for other surgical liver diseases. As an additional possibility, in situ protection of the liver with consecutive operation of the bloodless liver in situ is discussed. This procedure will correspond for the most part to the ex situ technique described here.

Adult↗

Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has been developed in order to benefit from the efficacy of orthotopic liver transplantation (OLT) in the treatment of fulminant hepatic failure (FHF), but to avoid the negative counterpart of OLT which is to eliminate the possibility of native liver (NL) regeneration and which consequently implies a life-long immunosuppression. METHODS: In our institution we performed 16 consecutive APOLTs in 15 patients between October 1992 and December 1999. Patients' mean age was 30 years (range 0.5-65 years). The causes of FHF were viral (HAV = 3; HBV = 3), drugs (n = 4), or others (n = 5). None of the patients had a history of chronic liver disease. The decision to transplant was taken when the patients met well-defined criteria. All but one of the patients were in a coma. RESULTS: Five patients died, 10 patients are alive (66.7%). Regeneration of the NL occurred in 11 of the 15 patients (73.3%) and in 8 of the 10 survivors. Six of these 8 patients have permanently stopped immunosuppressive therapy. These results can be favorably compared with those of OLT for FHF. In the European Transplant Registry, the survival rate is 57% at 5 years (2612 patients receiving OLT for FHF between 1988 and 1998). In our experience the survival rate is 59% at 5 years (42 patients receiving OLT for FHF between 1987 and 1999). CONCLUSIONS: APOLT is feasible in both adults and children; it rapidly restored liver function and reversed encephalopathy. Right APOLT seems more advisable since the right liver provides more functional hepatocytes; however, left APOLT harvested in an adult appears sufficient for a child. APOLT should be proposed only to patients with high chances of liver regeneration: age of recipient, etiology of liver failure, interval between onset of jaundice and occurrence of encephalopathy, and quality of liver graft are early prognostic indicators. Better results have been observed with younger patients (less than 40 years old) presenting with FHF (rather than subfulminant hepatic failure (SHF)) and due to HAV, HBV, or paracetamol.

Adolescent↗

Bloodless liver resection using the monopolar floating ball plus ligasure diathermy: preliminary results of 16 liver resections.

Blood loss during liver transection and ischemia-reperfusion injury associated with hepatic inflow occlusion are significant drawbacks during liver surgery. Sixteen patients underwent liver resection using the Monopolar Floating Ball (FB) plus LigaSure (LS) diathermy without occlusion of the hepatoduodenal ligament (group FB-LS). The liver parenchyma was precoagulated using the FB, and the uncovered tiny vessels were sealed using LS. Surgical outcomes were retrospectively compared with 16 well matched patients who underwent liver resection using the conventional clamp crushing method with Pringle's maneuver (group CC). The amount of blood loss during liver transection was significantly less in group FB-LS than in group CC [200 ml (0-990 ml) vs. 480 ml (120-1800 ml); p = 0.006]. The median time it took to complete the liver transection was significantly longer in group FB-LS than in group CC [144 minutes (43-335 minutes) vs. 58 minutes (18-94 minutes); p < 0.0001]. Hepatic inflow occlusion was temporally used in five patients in group FB-LS to achieve hemostasis in hepatic venous tributaries for 6, 10, 19, 26, and 61 minutes, respectively. Using these two electronic devices allows liver resection to be safely performed, with the advantage of minimal blood loss and a reduced inflow occlusion period compared to the conventional method. The major disadvantage may be a slower transection speed. A prospective randomized trial is needed to clarify the clinical benefits of liver resections performed using this novel technique.

Adult↗

Expression of neural cell adhesion molecule in human liver development and in congenital and acquired liver diseases.

In the liver, neural cell adhesion molecule (NCAM) is a marker of immature cells committed to the biliary lineage and is expressed by reactive bile ductules in human liver diseases. We investigated the possible role of NCAM in the development of intrahepatic bile ducts and aimed at determining whether immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases. Therefore, we performed immunohistochemistry for NCAM and bile duct cell markers cytokeratin 7 and cytokeratin 19 on frozen sections of 85 liver specimens taken from 14 fetuses, 10 donor livers, 18 patients with congenital liver diseases characterized by ductal plate malformations (DPMs), and 43 cirrhotic explant livers. Duplicated ductal plates and incorporating bile ducts during development showed a patchy immunoreactivity for NCAM, while DPMs were continuously positive for NCAM. Bile ducts showing complete or patchy immunoreactivity for NCAM were found in cirrhotic livers, with higher frequency in biliary than in posthepatitic cirrhosis. Our results suggest that NCAM may have a function in the development of the intrahepatic bile ducts and that NCAM-positive immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases.

Biomarkers↗