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At least 991 records · Page 55Linked to original sources
PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗
PubMedDate not supplied

The role of progenitor cells in repair of liver injury and in liver transplantation.

There are three levels of cells in the hepatic lineage that respond to injury or carcinogenesis: the mature hepatocyte, the ductular "bipolar" progenitor cell, and a putative periductular stem cell. Hepatocytes are numerous, and respond rapidly to liver cell loss by one or two cell cycles but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for more cycles than hepatocytes, and are generally considered "bipolar," i.e., they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential, and may be multipotent. Extrahepatic (bone marrow) origin of the periductular stem cells is supported by recent data showing that hepatocytes may express genetic markers of donor hematopoietic cells after bone marrow transplantation. These different regenerative cells with variations in potential for proliferation and differentiation may provide different sources of cells for liver transplantation: hepatocytes for treatment of acute liver damage, liver progenitor cell lines for liver-directed gene therapy, and bone marrow-derived cells for chronic long-term liver replacement. A limiting factor in the success of liver cell transplantation is the condition of the hepatic microenvironment in which the cells must proliferate and set up housekeeping.

Animals↗
PubMed1999

Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients.

Alcohol-related liver disease (ALD) is a common indication for orthotopic liver transplantation (OLT) in adults. Although return to 'heavy drinking' post-OLT is believed to be uncommon, the prevalence and severity of alcohol-related liver injury in such patients is not well characterized. We retrospectively reviewed the records of 68 adult patients who underwent OLT for ALD to determine the incidence of return to heavy drinking and to assess their clinical outcome. Follow-up ranged from 8-99 months (mean 42) post-OLT; 54 patients were followed for > or = 12 months. Ten patients (15%) had evidence of coexisting viral hepatitis (hepatitis C in 9 and hepatitis B in 1) before OLT. Six of 68 patients (8%) returned to heavy drinking post-OLT, and three of those died of alcoholic hepatitis at nine months, 2.5 and 3.5 years after OLT. In two of these three patients, premortem liver biopsy showed histologic features of alcoholic hepatitis in addition to bridging fibrosis or cirrhosis. None of the three patients who died of ALD had coexisting viral hepatitis. Of the 57 patients surviving for > or = 3 months post-OLT, 4 of 8 patients (50%) with steatosis and Mallory bodies in their native livers returned to heavy drinking compared to only 2/49 (4%) without these histologic findings (P<0.05). In conclusion, the incidence of heavy drinking post-OLT was uncommon, however, it was associated with fatal alcoholic hepatitis in 50% of patients. Rapidly progressive alcohol-related liver injury was seen even in the absence of coexisting viral hepatitis. The presence of steatosis and Mallory bodies in the native liver, which suggests recent or ongoing alcohol-related liver injury, predicted a return to heavy drinking post-OLT.

Adult↗
PubMed2002

Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation.

BACKGROUND: A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation. METHODS: Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <-2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P<0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for "death-moved to ICU." A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented. CONCLUSION: A model using five objective parameters can accurately predict death or death-moved to ICU in children awaiting liver transplantation.

Child, Preschool↗
PubMed2001

Metabolic heterogeneity of glycogen in hepatocytes of patients with liver cirrhosis: the glycogen of the liver lobule zones in cirrhosis.

The concentrations of total glycogen (TG) and its labile (LF) and stable (SF) fractions were determined in hepatocytes of portal and central zones of the normal human liver and in the liver of patients with cirrhosis of viral and alcohol aetiologies. Using PAS reaction, TG, LF and SF were revealed in histological sections of the material obtained by the liver punch biopsies. The concentrations of TG and its fractions were measured by televisional cytophotometry. In liver cirrhosis, the concentrations of TG, LF and SF in both zones of the hepatic lobule have been found to be much higher than in the normal liver. It has been shown that the ratio of the hepatocyte TG concentrations in the portal zone to the central zone both in the normal liver and in viral cirrhosis exceeds 1.0, amounting to 1.264 +/- 0.021 and 1.030 +/- 0.009, respectively. The glycogen fraction composition in the cells of both the liver lobule zones in viral cirrhosis does not differ significantly from the norm. On the contrary, in the liver of patients with alcoholic cirrhosis, the ratio of the TG concentrations in the portal zone to the central zone is reduced to 0.815 +/- 0.016 and is accompanied by qualitative changes of the glycogen composition.

Biopsy, Needle↗
PubMed2005

Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases.

OBJECTIVES: To evaluate whether chronic therapy with probiotics affects plasma levels of cytokines and oxidative/nitrosative stress parameters, as well as liver damage, in patients with various types of chronic liver disease. PATIENTS AND METHODS: A total of 22 nonalcoholic fatty liver disease (NAFLD) and 20 alcoholic liver cirrhosis (AC) patients were enrolled in the study and compared with 36 HCV-positive patients with chronic hepatitis without (20, CH) or with (16, CC) liver cirrhosis. All patients were treated with the probiotic VSL#3. Routine liver tests, plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and -10, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE), S-nitrosothiols (S-NO), were evaluated on days -30, 0, 90, and 120. RESULTS: Treatment with VSL#3 exerted different effects in the various groups of patients: in NAFLD and AC groups, it significantly improved plasma levels of MDA and 4-HNE, whereas cytokines (TNF-alpha, IL-6, and IL-10) improved only in AC patients. No such effects were observed in HCV patients. Routine liver damage tests and plasma S-NO levels were improved at the end of treatment in all groups. CONCLUSIONS: Results of the study suggest that manipulation of intestinal flora should be taken into consideration as possible adjunctive therapy in some types of chronic liver disease.

Adult↗
PubMedDate not supplied

Remnant liver regeneration and spleen volume changes after living liver donation: influence of the middle hepatic vein.

BACKGROUND AND OBJECTIVES: Graft harvest with or without the middle hepatic vein (MHV) affects venous return and function of the remaining liver. The aims of this study are to compare the remnant liver volume and spleen changes in the donors of different types of graft harvest and to evaluate the influence of resection with or without the MHV on the remnant liver volume regeneration, spleen volume change and serum total bilirubin. PATIENTS AND METHODS: A total of 165 donors were grouped according to the type of graft harvest: 88 donors underwent left lateral segmentectomy (LLS), 10 donors underwent extend LLS or left lobectomy (LL), and 67 donors underwent right lobectomy (RL). Groups LLS and LL were later combined as group LH (left hepatectomy, n = 98). There were 68 men and 97 women. The mean age was 32.9 +/- 8.1 yr. The total liver volume (LV) and spleen volume (S1) before graft harvest, graft weight (GW), regenerated liver volume (LV(6m)) and spleen volume (S2) six months post-donation were calculated. RESULTS: There were no significant differences in the regenerated liver volume six months postoperation (LV(6m)) and recovery ratio (LV(6m)/LV x 100%) among the different groups, albeit significant smaller LV(6m) in both groups compared with the initial liver volume was noted. Postoperative spleen volume (S2), average spleen ratio (S2/S1) and spleen change ratio were significantly larger and higher in group RL than in group LH. A significant increase in spleen volume was noted in both groups six months after graft harvest. A significantly higher TB in group RL (4.1 +/- 1.7 mg/dL, range: 1.4-8.5 mg/dL) was noted compared with that of group LH (1.6 +/- 1.0 mg/dL, range: 0.7-6.2 mg/dL). CONCLUSION: There was a significant increase in the regenerated remnant liver and splenic volumes six months postoperation in all types of hepatectomy following living donor hepatectomy, and there was no difference in the mean TB levels among donors whether the MHV was included or not in the graft.

Adult↗
PubMed2006

Expression of Ki-67, transforming growth factor beta1, and B-cell lymphoma-leukemia-2 in liver tissue of patients with chronic liver diseases.

BACKGROUND: The purpose of the present paper was to assess expression of proliferation, fibrosis and apoptosis markers in different phases of chronic liver diseases. METHODS: Sixty-six adults with chronic liver diseases (chronic hepatitis C, n = 48; chronic hepatitis B, n = 10; alcohol chronic liver disease, n = 8) treated at the Department of Infectious Diseases and Hepatology from 1999 to 2001, composed the study group. Liver biopsy specimens were used for immunohistochemical assessment of expression of Ki-67, transforming growth factor beta1 (TGF-beta1) and B-cell lymphoma-leukemia-2 (Bcl-2). Grade of liver inflammation and stage of fibrosis were evaluated according to the Scheuer scale. RESULTS: Expression of Ki-67 in hepatocytes was most intensive in patients with grade 2 and 3 inflammation. The expression in patients with grade 4 inflammation was low. The expression of Ki-67 in lymphocytes was most intensive in patients with grade 2 inflammation. Expression of TGF-beta1 in hepatocytes reached a maximum in patients with grade 2 or 3 inflammation and dropped in patients with grade 4 inflammation. There was a statistically significant correlation between stage of fibrosis and expression of TGF-beta1 in liver stromal cells. A very strong correlation was found between the expression of Bcl-2 in bile ductules epithelium and the grade of inflammation (P = 0.006). The expression of Bcl-2 in hepatocytes was observed only in patients with very intense liver inflammation (grade 3) and in patients with stage 3 or 4 fibrosis. CONCLUSION: Processes of proliferation, fibrosis and apoptosis are not directly correlated to progression of liver disease. Expression of studied markers can be used for analysis of dynamics of these processes.

Adult↗
PubMed1980

Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease.

A constant relationship was found between the mean CT numbers of the liver and spleen in 100 normal adults. This relationship was characterized by a mean CT number consistently higher for the liver (24.9 +/- 4.6) than for the spleen (21.1 +/- 4.1). The range for liver CT numbers was 16.7-37.2, and for the spleen it was 14.9-34.3. The mean liver-spleen CT number difference for all subjects was 3.8 +/- 2.1 (p < 0.001); in every instance, the livers exhibiting the high mean CT numbers were in subjects with high mean spleen CT numbers, with the same concordance for low mean CT numbers. This relationship between liver and spleen may be useful in the clinical setting in which a normal liver with low CT numbers must be differentiated from one in which the CT number is low because of fatty infiltration; the fatty liver will exhibit a lower mean CT number than the spleen.

Adult↗
PubMed2005

Recent events in alcoholic liver disease V. effects of ethanol on liver regeneration.

Liver regeneration is necessary to recover from alcoholic liver injury. Herein, we review evidence that ethanol interferes with liver regeneration. Briefly, alcoholic fatty livers demonstrate increased rates of hepatocyte death. The latter provides a regenerative stimulus. However, unlike mature hepatocytes in healthy adult livers, most surviving mature hepatocytes in alcoholic fatty livers cannot replicate. Therefore, less mature cells (progenitors) must differentiate to replace dead hepatocytes. Little is known about the general mechanisms that modulate the differentiation of liver progenitors in adults. Delineation of these mechanisms and clarification of how ethanol influences them might suggest new therapies for alcoholic liver disease.

Alcohol Drinking↗
PubMed2002

Analysis of allogeneic versus xenogeneic auxiliary organ perfusion in liver failure reveals superior efficacy of human livers.

PURPOSE: To compare the efficacy of allogeneic and xenogeneic extracorporeal liver perfusion (ECLP). METHODS: An Internet-based keyword search was performed in the established online databases. Univariate and multivariate analysis of variance (general linear method) were performed. RESULTS: Data from 198 patients were included in the statistical analysis, 142 of whom were treated by ECLP using porcine livers. Baboon livers were used in 29 patients, human livers in 14, and other or mixed species in 13 patients. Pig liver perfusions resulted in a 20% long-term-survival whereas the use of human livers was significantly more successful (survival rate (SVR) 43%, p<0.05). Baboon livers also revealed superior success (41%; p<0.05). Twenty-three patients were treated after 1991, 12 surviving long-term (52%). The latter all belonged to a group of 14 patients who received combined treatment consisting of ECLP and LTx (SVR-86% in this subgroup). CONCLUSION: Allogeneic ECLP was accompanied by significantly improved outcome compared with discordant xenogeneic ECLP. The role of hyperacute rejection in acute liver failure with reduced complement levels remains controversial. Physiologic disparity between pig and man may be the even more decisive determinant of outcome.

Animals↗
PubMed2004

Hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV tests but positive liver tissue HCV RNA.

A 70-year-old woman was admitted to our hospital because of a liver tumor. Laboratory data revealed mild liver dysfunction. Neither serum anti-HCV antibody nor HCV-RNA was detected. Computed tomography revealed a tumor lesion measuring 2 cm in diameter within the liver. Histological examination of the tumor revealed moderately differentiated hepatocellular carcinoma while the non-tumorous liver tissue demonstrated liver cirrhosis. By the RT-PCR method, HCV-RNA was detected from the non-tumorous liver tissue. We herein report a very rare case of hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV findings, but positive finding for liver tissue HCV RNA.

Aged↗
PubMed1999

Cirrhotic liver enhancement on dual-phase helical CT: comparison with noncirrhotic livers in 146 patients.

OBJECTIVE: The purpose of this study was to prospectively determine any differences in vascular and liver enhancement between patients with cirrhosis and patients without cirrhosis during both the arterial and portal venous phases on dual-phase helical CT. SUBJECTS AND METHODS: Fifty-eight patients with histologically proven cirrhosis (group 1) and 88 without cirrhosis (group 2 = normal findings on CT, group 3 = metastases, group 4 = other liver diseases) underwent dual-phase helical CT of the liver. Attenuation values of liver and vessels were measured on unenhanced scans and on scans obtained during the arterial and portal venous phases. The mean enhancement values per time interval (5 sec) were determined. Results were analyzed taking into account various intrinsic patient parameters. RESULTS: We found no statistically significant difference in terms of mean vascular enhancement and mean liver enhancement during the arterial imaging phase for each time interval among all the groups. The mean peak enhancement and mean liver enhancement during the portal venous phase were significantly lower in group 1 than in other groups. Time to peak enhancement was significantly delayed in group 1. CONCLUSION: In spite of the hepatic arterial buffer response, mean liver enhancement during the arterial phase was not significantly different in patients with cirrhosis compared with patients without cirrhosis. Although portal vein enhancement did not differ significantly, enhancement of cirrhotic liver was significantly lower during the portal venous phase and delayed, presumably because of decreased peripheral portal perfusion. The contrast injection protocol may be tailored to optimize conspicuity of hypovascular tumor.

Adult↗
PubMed1998

Sinusoidal lymphocytes of liver graft may limit the recurrence of hepatic tumor in liver transplant recipients.

The liver immune function is associated with specific lymphocyte population transiently marginated in the liver sinusoids. These cells are of blood origin, however they are phenotypically and functionally different from peripheral blood lymphocytes. The question arises whether tumor proliferating in the liver can modify cell recruitment and function of marginating sinusoidal lymphocytes. Studies were performed in Wistar rats. Livers of normal and colon cancer (induced by i.v. injection of CC531 cells) metastases bearing rats were perfused for sinusoidal lymphocyte isolation. Our studies showed no difference between the number of lymphocytes retained in sinusoids of tumor bearing and normal rats. T lymphocyte subsets remained in similar proportions in liver with colorectal metastases as in normal rats. Long lasting presence of tumor in the liver was accompanied by decreased cytotoxic activity of liver sinusoidal lymphocytes, whereas it had no influence on cytotoxicity of peripheral blood lymphocytes. Repopulation of tumor liver with peripheral blood cells restored cytotoxic activity of sinusoidal lymphocytes.

Animals↗
PubMed2003

[Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation in a diabetic patient with end-stage liver disease].

OBJECTIVE: To study the effect of combined transplantation of the liver and the pancreas in diabetic patients with end-stage liver disease, and explore the optimal surgical procedure. METHODS: Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations were performed in a patient diagnosed as having chronic hepatitis B, hepatocirrhosis, hepatic cellular cancer, and insulin-dependent diabetes. Immunosuppression therapy utilized prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and simulect. The function of the liver graft, serum amylase and lipase, blood glucose, and C-peptide were monitored after transplantation. RESULTS: Insulin was withdrawn at the 6th day after operation, good liver allograft functional recovery was achieved, without such complications as pancreatitis, thrombosis, and localized infections. CONCLUSION: End-stage liver disease with concomitant insulin-dependent diabetes is the indication for combined liver-pancreas transplantations, for which simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations may constitute the optimal surgical approaches as the primary choice.

Diabetes Mellitus, Type 1↗
PubMed1978

[Comparative laparoscopic, bioptic and clinical enzymological studies in liver cirrhosis and other chronic liver diseases].

The activity of GOT, GPT, APh, liver APh, gamma GTP, AAP and serum cholinesterase were determined in 80 patients with chronic liver diseases, diagnosed clinically, laparoscopically and by liver biopsy. Out of the patients with liver cirrhosis (51), those with portal cirrhosis (40) have a considerably higher activity of gamma GTP, intestinal APh than the patients with postecrotic cirrhosis (11). Cholinesterase activity is markedly lower in patients with cirrhosis and ascites than in the patients without ascites. With the histological data about the activity gamma GTP and GOT are considerably higher without activity. Examinations were carried out also upon patients with chronic aggressive hepatitis (4), chronic persisting hepatitis (9), liver cancer (12) and liver steatosis (4). The data revealed that the majority of the enzymes are with a higher sensitivity (especially gamma GTP, GOT, liver APh, cholinesterase) but with more restricted diagnostic and differential-diagnostic potentialities in view of the great dispersion of the enzyme activities with the separate liver diseases.

Biopsy, Needle↗
PubMed2005

Comparison study of the expressions of myristoylated alanine-rich C kinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells. The aim of this study was not only to evaluate the expression and localization of MARCKS in various pathological liver tissues, including HCC, but also to analyze the difference in MARCKS expression between hepatitis virus-induced HCC and cirrhosis. The level of MARCKS and its phosphorylated proteins, as well as its localization, were determined using Western blot and/or immunohistochemistry in HCC and other pathological liver tissues. We also analyzed the change of MARCKS localization on the influence of MARCKS phosphorylation in the HLF cancer cell line by phosphorylation study. In addition, the relationship between MARCKS expression and proliferative activity was studied in HCC. In the immunohistochemical study, a very small amount of MARCKS protein was found along the contour of the hepatocellular membrane in normal liver and in cases of chronic hepatitis. MARCKS was up-regulated in liver cirrhosis tissue and was localized in the cytoplasm of hepatocytes. The expression of MARCKS was down-regulated in HCC tissues, as compared with non-tumorous liver cirrhosis tissues from the same patients. Furthermore, MARCKS was serine-phosphorylated in liver cirrhosis and HCC, and phosphorylated MARCKS was detected in a cytosolic fraction of these tissues. In a phosphorylation study using the HLF HCC cell line, MARCKS was displaced from the plasma membrane to the cytosol following the activation of protein kinase C (PKC) by phorbol 12-myristrate 13-acetate (PMA). Furthermore, the activity of cyclin D1 and cyclin E kinases was found to be higher in HCCs with low MARCKS expression than in HCCs with high MARCKS expression. These results suggest that up-regulation of MARCKS might be essential in the generation of cirrhotic nodules through chronic hepatitis from normal liver, and that the phosphorylation and/or down-regulation of MARCKS might play an important role in the development and progression of HCC from liver cirrhosis.

Adult↗
PubMed1992

[Hepatic receptor imaging with Tc-99m GSA: estimates of liver function in acute liver disease].

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

Acute Disease↗