Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate serum alpha-1-antitrypsin (A1AT) as a prognostic factor in hepatocellular carcinoma, we studied 75 consecutive patients (60 male, 15 female, mean age +/- SD 63.0 +/- 9.3 years) in whom hepatocellular carcinoma developed with pre-existing cirrhosis. Median survival time was 245 days (range 4-1568+). 30 patients had serum A1AT concentration of < or = 2.20 g/l (Group A) while 45 (Group B) had alpha-1-antitrypsin > 2.20 g/l. Median survival was 518 days in Group A and 81 days in Group B (Mantel-Cox 20.95, P < 0.0001; hazard ratio 0.26, 95% confidence limits 0.15-0.46). By stepwise survival analysis, alpha-1-antitrypsin together with bilirubin, tumour size and blood urea nitrogen were chosen among 17 variables as the only independent predictors of survival. We conclude that measurement of serum A1AT concentration might be useful as an inexpensive, widely available prognostic marker of hepatocellular carcinoma.
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PMID:Prognostic value of serum alpha-1-antitrypsin in hepatocellular carcinoma. 866 31

Liver transplantation (LT) is a therapeutic method in many, otherwise infaust diseases of the liver. During the recent decade the experimental therapeutic procedure has become a routine therapeutical method. The stage of clinical experiment was ultimated by the Washington Conference held on the consensus in LT indications (1983). Large centries (USA, England, Germany) yield 80-100 liver transplantations per year. The recent years have recorded a change in some principal opinions on LT. It is possible to state that liver transplantation is being abstained from cases with more extensive primary neoplamatic affliction of the liver. Conservative therapy in primary biliary cirrhosis of the liver by means of ursodeoxycholic acid has shifted the LT indication into the later stages of the disease. The opinions on the meaning of LT in alcoholic cirrhosis remain still unsettled. LT remains unambiquously indicated in life-endangering fulminant and subfulminant liver failures. Among the viral diseases, attention is paid to liver cirrhosis caused by infection by the hepatitis C virus. Cirrhosis due to hepatitis B has a better prognosis, owing to the complex antiviral therapy. Liver transplantation represents, beside the main indications, the therapy of first selection, e.g. also in Wilson's disease, alpha-1-antitrypsin deficiency, alveolar echinococcosis etc. (Tab. 1, Fig. 2, Ref. 54.)
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PMID:[Indications and contraindications for liver transplantation]. 868 95

Evaluation of liver biopsies in hepatitis C is aimed at confirming the clinical and serologic diagnosis, grading of necroinflammatory activity, staging of consecutive fibrosis, ruling out or confirming liver diseases of different etiology, and assessment of therapeutic effects. Usually, the course of chronic hepatitis C virus (HCV) infection is slow, with mild inflammatory changes. Nevertheless, even in mild asymptomatic chronic hepatitis C episodes of higher inflammatory activity associated with extensive piecemeal necrosis and porto-central bridging, necrosis can accelerate the course of the disease. For this reason, the traditional, morphologically based classification of chronic hepatitis and the term "chronic persistent hepatitis" have lost their predictive usefulness, especially in hepatitis C. Chronic hepatitis should be characterized by etiologic designation as well as grade and stage of the disease. Portal lymphoid aggregates, some inflammatory bile duct damage and mild steatosis are the most characteristic features by which hepatitis C can be differentiated from other progressive inflammatory liver diseases. Antibodies directed against HCV antigens allow identification of viral proteins by immunohistochemistry. Immunostaining for hepatitis B antigens, for alpha-1-antitrypsin and copper staining are helpful in detecting hepatitis B and congenital liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency) as possible causes of chronic progressive inflammatory liver disease. Centrilobular Mallory's hyalin, identified by immunostaining for ubiquitin in combination with perivenular fibrosis, is helpful in diagnosing concomitant alcoholic liver disease. In our own biopsy material (n = 100) and autopsy material (n = 58), HIV/HCV-coinfected patients have a significantly higher rate of fibrosis and cirrhosis than HIV patients without HCV infection. Hepatitis C can apparently aggravate the course of HIV infection. Our morphologic findings support the clinical observation that chronic HCV infection seems to be the main cause of liver failure, especially in the risk group of HCV/HIV-coinfected hemophiliacs.
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PMID:Histopathologic findings in chronic hepatitis C. 883 87

In a previous study in dogs with chronic liver disease it was found that a combination of clinical features and laboratory findings was useful in differentiating liver diseases but could not be used to evaluate a dog's prognosis. When an electrophoretic analysis of the serum proteins was included, marked decreases in the concentrations of albumin and the alpha-globulins alpha-1-antitrypsin and haptoglobin were observed in terminal liver cirrhosis, indicating impaired liver function. However, low albumin concentrations, together with normal or increased concentrations of alpha-1-antitrypsin and haptoglobin, were observed in dogs which, although severely depressed when examined, often recovered and survived for a year or more.
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PMID:Serum protein electrophoresis as a prognostic marker of chronic liver disease in dogs. 896 72

One hundred sixty-four consecutive cases of primary liver carcinoma were evaluated for tumor type, (i.e., hepatocellular carcinoma [HCC], cholangiocarcinoma [CC], and combined hepatocholangiocarcinoma [CHCC]), and for signs of alpha-1-antitrypsin deficiency (AATD) in the surrounding liver tissue. Hepatocellular globular alpha-1-antitrypsin deposits, as detected by a monoclonal antibody to the mutant PiZ alpha-1-antitrypsin (AAT), were seen in 13 cases (7.9%). With regard to tumor type, 4 of 111 HCC cases (3.5%), but 4 of 37 CC cases (10.5%), and even 5 of 16 CHCC cases (30%) were positive for this antitrypsin variant. In all but 1 of 13 cases of alpha-1-antitrypsin deficiency, the carcinoma developed in noncirrhotic liver tissue of elderly people (mean age, 62.9 years). In three patients, a heterozygous state of ATT (PiMZ) could be revealed using isoelectric focusing or direct genetic analysis. We conclude from our findings that CHCC and CC especially might be associated with PiZ alpha-1-antitrypsin deficiency. Primary liver carcinoma might develop even in a heterozygote state of PiZ alpha-1-antitrypsin deficiency without concurrent liver disease. Furthermore, liver cirrhosis is not a precondition for these tumors.
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PMID:Liver carcinoma in PiZ alpha-1-antitrypsin deficiency. 963 Jan 82

Whether heterozygotes with alpha-1-antitrypsin (AAT) deficiency type PiZ bear an increased risk for chronic liver disease is controversial. On the basis of liver tissue from 1,030 autopsies (autopsy series), 1,847 biopsies (biopsy series) and 317 primary liver carcinomas (tumor series), we analysed the effect of heterozygous state PiZ for the development of liver diseases. The PiZ status was screened immunohistochemically and verified in selected cases by SSCP analysis and by sequencing DNA extracted from paraffin embedded tissue. The PiZ frequency in the biopsy series (3.4%) and tumor series (5.99%) was significantly higher than in the autopsy series (1.8%). Hepatic PiZ deposits in heterozygotes sometimes were as extensive as in homozygotes. The amount of PiZ deposits correlated positively with the inflammatory activity and stage of fibrosis, as well as with the age of patients. Patients with concurrent liver disease such as hepatitis and alcoholic liver disease showed significantly higher scores of inflammatory activity, stage of fibrosis and amount of PiZ deposits than those without additional liver disease. Cholangiocarcinomas and combined hepato-cholangiocarcinomas were seen significantly more frequently in patients with PiZ-associated liver carcinoma than in genetic healthy individuals (p = 0.004). Three out of 19 PiZ-associated liver carcinomas had developed in cirrhotic liver tissue. Heterozygotes of type PiZ have an enhanced risk for chronic liver disease including primary liver carcinoma. PiZ-associated liver diseases will become clinically manifest in middle or old aged adults. Rarely this genetic defect causes liver cirrhosis even without concurrent liver disease. PiZ-associated liver carcinomas are frequently characterized by cholangiocellular differentiation and may develop often in non-cirrhotic liver tissue. Immunohistochemistry is a specific method to detect hepatic PiZ deposits.
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PMID:[Liver changes in heterozygote alpha 1-antitrypsin deficiency PiZ]. 1114 23

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include toxins (alcohol, aflatoxin B1), androgens and estrogens, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as well as various inherited metabolic disorders, such as alpha-1-antitrypsin deficiency and hemochromatosis. The molecular pathogenesis of HCC development is very complex and involves alterations in the structure or expression of several tumor suppressor genes, oncogenes and, possibly, mechanisms leading to a genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation. Central to the molecular pathogenesis of HCCs are mutations of various genes and a genetic instability which in most cases result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. The prognosis of HCC patients is generally very poor. Most studies report a five year survival rate of less than 5% in symptomatic HCC patients. Furthermore, these tumors have been shown to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCCs revealed long-term survival of patients only with small asymptomatic HCCs that could be treated surgically or by non-surgical interventions. Apart from exploring and refining new HCC treatment strategies, the implementation of existing and the development of novel measures to prevent HCC development are most important. Primary HCC prevention includes among others universal hepatitis B vaccination, antiviral therapy of patients with chronic hepatitis B or C, reduction of food contamination with aflatoxins, elimination of excessive alcohol etc. Also for some genetic diseases there is the potential for HCC prevention by identifying affected family members at risk, such as patients with precirrhotic hemochromatosis. Reduction of iron overload by phlebotomy has been shown to eliminate the progression hemochromatosis to liver cirrhosis and HCC. Preventive measures, therefore, should have a major impact on the incidence of HCCs in patients with acquired and inherited liver diseases. Further, the prevention of a local recurrence or the development of new HCC lesions in patients after successful surgical or non-surgical HCC treatment (secondary prevention) is of paramount importance and is expected to significantly improve disease-free and overall patient survival. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement and in part replace existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduction of the incidence of HCCs, one of the most devastating malignancies worldwide.
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PMID:Molecular targets for prevention of hepatocellular carcinoma. 1214 24

We previously found that transplantation with bone marrow cells (BMCs) improves liver function and liver fibrosis in cirrhotic mice. In the presence of liver damage induced by carbon tetrachloride (CCl4), transplanted BMC migrated into the peri-portal region and trans-differentiated into hepatocytes that produce albumin. Thus under these conditions, BMC transplantation induces liver regeneration. Detecting serum marker proteins is important to monitor the recovery of liver function of cirrhotic mice after BMC transplantation. We therefore initially resolved proteins extracted from serum samples at 48 h after BMC transplantation by 2-DE and compared spot intensity between control and BMC groups of mice. Six protein spots increased in the BMC group compared with the control group. MS revealed that these spots comprised apolipoprotein A1 (apoA1), apolipoprotein C3 (apoC3), vitamin D-binding protein, alpha-1-antitrypsin and proteasome subunit alpha type 1. We subsequently confirmed the levels of apoA1 in serum and liver samples by immunoblotting. ApoA1 increased at early stage (48 h and 1 wk) after BMC transplantation in this mouse model of liver cirrhosis. The early elevation of apoA1 might be useful to predict liver regeneration in cirrhotic mice after BMC transplantation.
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PMID:Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation. 1654 57

NAFLD likely is the most common liver disease in children and is responsible for significant progression to cirrhosis, portal hypertension, and the need for liver transplantation in adults and even in some adolescents. Early diagnosis and lifestyle interventions appear to be our best hope for controlling progression of disease. The pediatrician is responsible for screening all obese children with measurement of aminotransferases. Those with elevated enzymes (particularly ALT) for longer than 3 months, in the absence of markers of hepatitis B or C, autoimmune chronic active hepatitis, Wilson's disease, hemochromatosis, or alpha-1-antitrypsin deficiency, should follow up with an abdominal ultrasound. In patients with a BMI in the morbidly obese range, an ultrasound to search for a diffusely echogenic liver should be performed even if the liver enzymes are normal. Findings suggestive of NAFLD should prompt the institution of appropriate dietary and exercise regimens. If these are unsuccessful after a 3-month trial, the patient should be referred to a pediatric gastroenterologist and hepatologist for further work-up and treatment, preferably in the context of a controlled therapeutic trial. Only by aggressively engaging this current epidemic will we be able to decrease the mounting human cost of NAFLD.
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PMID:Nonalcoholic fatty liver disease. 1663 58

Based on data reported to the OPTN/UNOS Liver Transplant Registry between 1988-2004: 1. There was a very small difference in 5-year graft survival rates comparing living and deceased donors in adult (4.3%) and pediatric patients (2.4%). 2. Although graft survival rates of split liver transplants were lower than whole liver grafts before 1998, 5-year graft survival results of more recent split grafts (65.8%) have become comparable to those of whole liver grafts (66.5%). Among recipients in good condition, split (67.7%) and whole grafts (70.0%) yielded equivalent survival rates. 3. Lower graft survival rates were noted in ABO incompatible grafts, non-heartbeating donors, regrafted patients, and recipients who were in the ICU before transplantation. 4. There was no recipient gender effect on liver transplant outcome. 5. Primary disease distributions were different for different races. Among adult patients, the largest fraction of white patients had alcoholic cirrhosis. Among Asians, Type B cirrhosis was most frequent. Among pediatric patients, biliary atresia constituted the majority of patients. Most of the patients with alpha-1 antitrypsin deficiency were white. Autoimmune hepatitis was most frequently found among black patients. 6. Although 5-year graft survival of black patients (60.2%) was lower than whites (68.1%), Hispanics (67.6%), and Asians (68.0%), black recipients with PBC (73.3%) and PSC (69.9%) had graft survival rates similar to those of whites (78.1%) (73.6%) and Hispanics (75.3%) (77.1%). 7. Zero HLA-A,-B,-DR mismatched livers had very rapid early failures. HLA matching correlated with graft survival in autoimmune hepatitis patients, but not in cirrhosis patients. 8. Short-term graft survival for liver transplants has improved steadily since 1990. However, long-term graft survival after the first year actually declined over time. 9. In adult transplants, 5-year graft survival of autoimmune-related diseases, PBC (77.3%), PSC (73.3%), AIH (74.2%) yielded higher graft survival rates than those of hepatitis B (71.5%) and C (63.2%). 10. In pediatric patients, 5-year survival of biliary atresia (75.4%), autoimmune cirrhosis (70.8%), and alpha-1-antitrypsin deficiency (85.0%) had high graft survival rates, except for acute liver failure (61.6%). 11. Hepatitis C recurrence is now one of the major causes of graft failure in adults. Thrombosis is a major factor in graft failure for pediatric transplants.
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PMID:An analysis of the OPTN/UNOS Liver Transplant Registry. 1670 60


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