Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIVER DISEASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1995

Role of hepatitis C virus in chronic liver disease occurring after orthotopic liver transplantation.

Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were positive for both serology and serum hepatitis C virus RNA. Serum hepatitis C virus RNA detection occurred five to 33 months before hepatitis C virus antibodies. Liver tissue hepatitis C virus RNA and hepatitis C virus core antigen were detected in five. In one patient, tissue hepatitis C virus core antigen was detected when other tests for hepatitis C were negative. Two patients had positive human cytomegalovirus serum antibodies and RNA before transplantation. Although serum hepatitis C virus RNA was not detected after transplantation, serum enzyme immunosorbent assay and tissue core antigen were still detectable in both patients. In another child, serum hepatitis C virus RNA was positive and hepatitis C virus core antigen was found on a liver biopsy specimen but antihepatitis C virus antibodies were negative as well as liver hepatitis C virus RNA. No patient developed severe liver disease or cirrhosis during a follow up of up to 72 months. It is concluded that hepatitis C virus is a significant cause of morbidity after paediatric orthotopic liver transplantation. Diagnosis cannot rely on serological testing only. The patients remained stable on follow up, but longer prospective histological studies remain necessary to establish prognosis.

Antigens, Viral↗
PubMed1983

Hepatitis B virus DNA in children's liver diseases: detection by blot hybridisation in liver and serum.

Molecular hybridisation using cloned hepatitis B virus DNA (HBV DNA) was applied to liver and serum samples from 46 children (39 with liver diseases and seven controls) for detection of HBV DNA sequences, free and integrated into the liver cell genome. HBV DNA integration was observed in 10 children. The young age of some of these cases indicates that such integration can occur early in liver disease and is not related to the duration of viral infection. Thirteen children exhibited serological evidence of active viral multiplication. All but one had free HBV DNA in liver tissue and integrated HBV DNA sequences were found in four cases. Integrated HBV DNA sequences alone were also detected in three children with neither HBV-antigens nor HBV DNA in serum. One had inactive cirrhosis, and the two others, chronic active hepatitis. Consequently DNA hybridisation may be useful for diagnosis, in the absence of serological signs of HBV infection; its specificity was enhanced in the present investigation by negative results in six children with autoimmune chronic active hepatitis. Taken together, the above results imply that HBV-DNA integration can occur in both active and inactive liver disease. Integrated HBV DNA was also observed in the liver of three children with fatal hepatic failure who presented with antibodies to HBsAg and/or to hepatitis B core antigen in the serum. This finding raises the question of the relationship between the host immune factors and the state of HBV DNA.

Adolescent↗
PubMedDate not supplied

Protein binding and kinetics of drugs in liver diseases.

Although the liver is the major site for drug biotransformation, the effect of hepatic dysfunction on drug disposition has not been consistent or predictable. Most early studies of drug kinetics in liver disease measured only half-life. Only in the past few years has it been realised that liver diseases can affect drug absorption, hepatic metabolism, tissue distribution, and protein binding, which complicate interpretation of any change, or lack of change in drug half-life. Furthermore, it is now apparent that the efficiency with which a drug is metabolised by the liver, the extent of binding to blood constituents, and the aetiology and stage of the hepatic disorder are each important in determining whether significant alterations in drug disposition will occur. A pharmacokinetic perfusion model which takes into account many of the above factors has been proposed, and appears to be useful for predicting changes in the disposition of rapidly metabolised compounds. Nevertheless, the state of knowledge about those factors which limit the rate of metabolism of individual drugs or classes of drugs in inadequate, and no general model or guidelines which are useful clinically have been developed. Patients with hepatic disorders may show increases or decreases in sensitivity independent of alterations in drug disposition. The clinician caring for such patients must be cautious about the use of any drugs, and rely heavily on careful patient observation to determine efficacy or toxicity.

Absorption↗
PubMed2005

Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease has been defined by the presence of hepatic steatosis in the absence of other chronic liver diseases. We sought to determine whether obesity, insulin resistance, and the metabolic syndrome, which are the main risk factors for nonalcoholic fatty liver disease, are associated with similar elevations in serum alanine aminotransferase activity in persons with and those without other causes of chronic liver disease. METHODS: Adult participants of the third National Health and Nutrition Examination Survey were divided into those with causes of chronic liver disease (n = 1037), defined as viral hepatitis, excessive alcohol consumption, or increased transferrin-iron saturation, and those without (n = 8004). RESULTS: Among persons with other causes of chronic liver disease, obesity (adjusted odds ratio, 4.9; 95% confidence interval, 2.5-9.4), insulin resistance (adjusted odds ratio, 6.8; 95% confidence interval, 3.0-15.5, comparing the highest and the lowest quartile), and the metabolic syndrome (adjusted odds ratio, 3.3; 95% confidence interval, 1.4-8.0) were all strongly associated with increased alanine aminotransferase activity (>43 IU/L). Among persons without other causes of chronic liver disease, statistically similar associations were identified. CONCLUSIONS: Obesity, insulin resistance, and the metabolic syndrome are strong predictors of increased alanine aminotransferase activity in the US population, both in persons with and in persons without other causes of chronic livers disease. We hypothesize that metabolic fatty liver disease related to these conditions is the cause of the increased alanine aminotransferase activity and may be underrecognized in persons with other causes of chronic liver disease.

Adult↗
PubMed2006

Model for end-stage liver disease and organ allocation in liver transplantation: where are we and where should we go?

The Child-Turcotte-Pugh (CTP) score has been used for decades to measure the severity of chronic liver disease. Recent studies have shown that the model for end-stage liver disease (MELD) more accurately predicts the short- and mid-term survival for patients with cirrhosis compared to the CTP system. MELD, which has 3 parameters (serum bilirubin, creatinine, and prothrombin time) that need logarithmic transformation, has the advantage of a wide-range continuous scale and is more objective and less variable. The liver allocation system has changed from a status-based algorithm using the CTP score, to one using a continuous MELD severity score as a reference system to prioritize adult patients on the waiting list since 2002 in the USA. However, there are potential limitations of MELD. An intrinsic defect is that some important parameters, such as hepatic encephalopathy and ascites, which are common adverse complications in cirrhosis, are not included in MELD. It has been suggested to incorporate a low serum sodium level into the prognostic model to enhance the predictive ability. Moreover, the change of MELD over time may provide updated information for patients on the transplant waiting list. In summary, although there was encouraging evidence supporting the prognostic advantage of MELD, the optimal role of MELD in the setting of outcome assessment for cirrhotic patients needs more study. Appropriate modifications and fine tuning of MELD are necessary for determining the ranking status of patients on the waiting list, to avoid a futile transplantation and improve overall patient survival.

Humans↗
PubMed2005

Mechanisms of Disease: pathogenesis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome. The metabolic syndrome is characterized by insulin resistance, which is produced by a complex interaction between genetic factors, macronutrient intake and lifestyle that alters the cytokine profile, cell biology and biochemical milieu of the liver, adipose tissue and striated muscle. The resultant disequilibrium in lipid homeostasis causes triglycerides to accumulate in the liver. An increase in oxidative stress, due to the generation of reactive oxygen species as a result of mitochondrial abnormalities and induction of the cytochrome P-450 system could be one mechanism by which the nonalcoholic fatty liver develops into nonalcoholic steatohepatitis. The pathogenesis of cytologic ballooning and Mallory body formation and their role in NAFLD remain to be defined. In addition, inflammation and fibrosis are likely to be secondary to hepatocyte injury and death.

Cytochrome P-450 Enzyme System↗
PubMed2004

The immunology of fibrogenesis in alcoholic liver disease.

CONTEXT: Alcoholic liver disease in humans frequently leads to cirrhosis. Experimental models of hepatic fibrogenesis are available, but extrapolation of those findings to human ethanol-induced liver injury is difficult. Hepatic ethanol-induced fibrosis in humans has often been studied in relatively small patient populations. During the past decade, several animal models and human studies have attributed fibrogenesis in the liver to the role played by hepatocytes, Kupffer cells, endothelial cells, and especially stellate cells. OBJECTIVE: To determine the contribution of the main liver cell types to ethanol-induced fibrogenesis. For that purpose, we studied the expression of the following immunologic parameters: smooth muscle-specific alpha actin (SMSA), CD68, CD34, transforming growth factor beta1, intercellular adhesion molecule 1, and collagen types 1 and 3. The Dako LSAB+ kit (peroxidase method) was used. DESIGN: We recently studied a large cohort of patients with alcoholic liver disease in France. In this cohort, we found 87 cases in which liver biopsies revealed only pericentral injury with nonpathologic portal areas. We compared cases in which the portal areas were nonpathologic with 324 patients in whom staging ranged from F0 to F3. Patients with cirrhosis (F4) were excluded from evaluation. To stage fibrosis, we used the METAVIR system. Furthermore, we selected 40 cases in which the biopsies measured at least 25 mm in length for further histochemical evaluation. Ten additional normal cases from our archives were used as controls. We divided this patient population into the following 5 groups of 10 patients each: group 1A, F0 with steatosis; group 1B, F0 without steatosis; group 2, F0 to F1, central injury; group 3, F3, fibrosis with multiple septa; and group 4, nonpathologic livers (controls). RESULTS: Smooth muscle-specific alpha actin was expressed by stellate cells, pericentrally, with increasing severity and intensity in the advanced stage of fibrosis of group 3, less intense expression was noted in group 2, and expression was practically absent in group 1 and in nonpathologic controls. CD68 was the best marker for Kupffer cells and was expressed diffusely within the lobules in all groups. Its expression correlated directly with the degree of disease severity, progressing from stage I through stage III, but was absent in nonpathologic livers. CD34 was consistently expressed by endothelial cells in the periportal areas in all groups. The expression of collagen type 1 was intense in the bands of fibrosis or bridging, while type 3 expression was poor. Transforming growth factor beta1 and intercellular adhesion molecule 1 were not expressed in any group. CONCLUSIONS: In this study, stellate cell activation (SMSA) was most intense pericentrally in the early stages and diffusely with progression to fibrosis and maximum intensity in stage III. Kupffer cell activation, as determined by CD68 expression, was intense and diffuse, while endothelial cells expressed CD34 periportally in a similar manner in all stages. Fibrogenesis in human ethanol injury is due to the activity of stellate cells, Kupffer cells, and to a lesser extent, to endothelial cells.

Adult↗
PubMed1985

Heparin response and clearance in acute and chronic liver disease.

Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.

Acute Disease↗
PubMed2005

Severity of liver disease does not predict osteopenia or low bone mineral density in primary sclerosing cholangitis.

BACKGROUND: The association between metabolic bone disease and cholestatic liver disease has been poorly characterized. To date a single institution has published data suggesting that in primary sclerosing cholangitis (PSC), advanced liver disease predicts advanced bone disease. AIM: To determine the association between the severity of liver disease and bone mineral density (BMD) in PSC patients. METHODS: We identified 30 PSC patients who had undergone dual energy X-ray absorptiometry (DXA) scan. We compared lumbar spine DXA scores between patients with more and less advanced liver disease. RESULTS: Nine patients were osteopenic (30%), and one patient was osteoporotic. Five patients were female (17%), and none was postmenopausal. BMD was not different between patients listed and not listed for liver transplantation (P = 0.49) or between patients with and without hepatic decompensation (P = 0.63). Model for end-stage liver disease (MELD) score (P = 0.99) and the modified Mayo risk score (P = 0.25) did not predict BMD. CONCLUSIONS: Our study is the first to suggest that low bone density cannot be predicted by the severity of liver disease in PSC. Perhaps other known risk factors for osteoporosis will be important predictors of abnormal bone density in this patient population.

Absorptiometry, Photon↗
PubMed2005

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection.

AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection. METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined. RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.

Adult↗
PubMedDate not supplied

[Liver diseases complicating pregnancy].

Liver disease in pregnancy represents a broad spectrum of disorders. Most of the common forms of acute and chronic liver disease occur during pregnancy and often present special difficulties in diagnosis and management. In addition, there is a group of hepatic disorders unique to pregnancy, which also must be identified appropriately. Rapid institution of therapy is important in preventing the unfavorable perinatal outcome and maternal mortality. The changes in liver function related to gestation will be reviewed initially. The major forms of hepatic disease specifically associated to pregnancy will be then described and the obstetrical management as well as the therapeutic modalities proposed.

Adult↗
PubMed2005

Keratins as susceptibility genes for end-stage liver disease.

BACKGROUND & AIMS: Keratins 8 and 18 protect the liver from stress. Keratin 8 and 18 variants in 17 of 467 liver disease explants and 2 of 349 blood bank controls were previously reported in 5 analyzed exonic regions. We asked whether mutations were present in the remaining 10 exons of keratins 8 and 18. METHODS: Exonic regions were polymerase chain reaction-amplified from genomic DNA, isolated from the above-mentioned 2 cohorts, and analyzed for the presence of mutations. Mutant keratins were also studied biochemically. RESULTS: We identified 10 novel keratin 8 and 18 heterozygous variants in 44 of 467 explants and 11 of 349 controls: keratin 18 deletion (delta64-71), a keratin 8 frameshift that truncates the last 14 amino acids; 8 missense keratin 8 and 18 alterations; and several new polymorphisms. The most common variant, keratin 8 R340H, at the highly conserved R340 was found in 30 of 467 explants and 10 of 349 controls (P = .02) and was confirmed in the diseased livers by generation of an R340H-specific antibody. Germline transmission and variant protein expression were verified. The mutations involved a variety of liver diseases, and some variants had an ethnic background preponderance. Mutations that introduced disulfide bonds (keratin 8 G61C or R453C) decreased keratin solubility, particularly after oxidative stress, whereas others decreased keratin 8 phosphorylation (keratin 8 G433S). CONCLUSIONS: The overall frequency of keratin 8 and 18 variants was 12.4% in 467 liver disease explants and 3.7% in 349 blood bank controls (P < .0001). Variants can alter keratin solubility or phosphorylation and may render individuals susceptible to end-stage liver disease, depending on their genetic background and exposure to other insults, such as alcohol or viral infection.

Female↗
PubMed2000

Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer.

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.

Amino Acids, Branched-Chain↗
PubMed2005

Evaluation of oxidant stress in Wilson's disease and non-Wilsonian chronic liver disease in childhood.

BACKGROUND/AIMS: Oxygen free radicals have an important role in the pathogenesis of acute and chronic liver disease. Free radical formation and oxidative damage, probably mediated with copper accumulation, are important in Wilson's disease pathogenesis. This study was performed to determine if accumulating copper in Wilson's disease is a cause of further oxidant stress compared to non-Wilsonian liver disease. METHODS: In this study, we investigated plasma malondialdehyde and nitric oxide levels to estimate the oxidant stress and total antioxidant capacity and vitamin E/cholesterol, vitamin C and beta-carotene levels to estimate the antioxidant status of patients. The groups investigated included 24 patients with Wilson's disease (group I), 25 patients with non-Wilsonian chronic liver disease (group II) and 23 healthy controls (group III). Wilson's disease and non-Wilson's disease patients were divided into subgroups according to disease stage (i.e. chronic hepatitis and cirrhosis) and all parameters were compared between subgroups and controls. RESULTS: Malondialdehyde and nitric oxide levels were higher than controls in groups I and II (p=0.013, p=0.01), but these levels did not differ between the Wilson's disease and non-Wilson's disease groups. The parameters were also evaluated with respect to the disease stage (i.e. chronic hepatitis and cirrhosis), and there was no difference between groups I and II. Although malondialdehyde and nitric oxide levels were significantly different between both disease stage groups and the controls, we observed decreased vitamin C and beta-carotene levels only in cirrhosis stage (p=0.01, p=0.01). CONCLUSIONS: We observed the presence of oxidant stress unrelated to the etiology of the liver disorder in our study. Deficiency of the major antioxidants, vitamin C and beta-carotene, develops as the disease stage advances from chronic hepatitis to cirrhosis.

Antioxidants↗
PubMed2005

Preoperative assessment of the patient with liver disease.

Patients with liver disease are at appreciable risk when undergoing anesthesia and surgery. Attempts to quantify this risk have been thwarted by the diversity of disease states and illness severity that such patients bring to the operating theater and the myriad of procedures they may undergo. This review discusses the indications and contraindications for surgery in patients with liver disease and attempts to give specific recommendations for optimizing the clinical status of a patient with hepatic dysfunction prior to operative intervention.

Anesthesia↗
PubMed2005

Surgical therapy options in polycystic liver disease.

INTRODUCTION: Polycystic liver disease (PLD) is a rare affliction frequently observed in association with polycystic kidney disease. Only symptomatic patients require treatment, which can be conservative or surgical, i.e. laparoscopic or conventional. We report the results of our experience in the surgical management of polycystic liver disease. METHODS: Between 1994 and 2003, 19 patients (16 female, 3 male) were referred to our center for the management of PLD. Their median age was 50 years (range 33-72). All were symptomatic and their cysts had a median diameter of 11 cm (range 5-22). RESULTS: Laparoscopic management was undertaken in eight patients, with one conversion to open technique because of bleeding from a superficial hepatic vein. An open procedure was performed in 11 patients: one left hemihepatectomy, deroofing in two patients, segment resection 2/3 plus deroofing in six patients, and segment resection 5/6 plus deroofing in two patients. Four patients had complications: one case of biliary leakage was managed conservatively; two patients had pneumothorax caused by the cava catheter inserted for anesthesia, and one patient's abdominal drain tore off and had to be removed by relaparotomy on the fourth postoperative day. Median follow-up of all patients was 49 months (range 7-98). In one patient there was symptomatic recurrence with hepatomegaly and compression of the inferior vena cava 84 months after the first operation. CONCLUSIONS: Careful selection of patients and meticulous surgical technique are recommended in the management of PLD. The treatment of choice for symptomatic Gigot or Morino type 1 PLD is laparoscopic surgery, and for advanced stage PLD combined hepatic resection and cyst fenestration.

Adult↗
PubMed2005

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse-transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention.

Adult↗