Gene/Protein Disease Symptom Drug Enzyme Compound
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Liver transplantation poses enormous and complex medical problems. Of the infective complications, bacterial infections are the commonest overall, but the single commonest is cytomegalovirus and the most deadly are the fungal infections. Therapeutic options and possibilities for prophylaxis are improving. Rejection, both acute and chronic, is the other major cause of mortality, and the balance between immunosuppression and infection is difficult. Cyclosporin treatment contributes to renal impairment, hypertension, and multitudinous potential neurological problems. The risk of long-term neoplasia is unclear. Relatively more minor is the potential for osteoporosis and metabolic complications, such as diabetes and hyperlipidaemia. Hepatitis B disease has a sizable risk of recurrence, but the most recent prophylaxis regimes have improved relapse rates. Having survived the physical problems following transplantation, most of which occur in the first 6 months, there are considerable psychosocial adjustments to be made particularly in the case of children where growth and development may have been delayed. Despite all these difficulties, liver transplantation is an expanding and optimistic area with enormous potential.
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PMID:Medical complications of liver transplantation. 833 63

Hepatocytes are rich in mitochondria, which play an important role in hepatic metabolism. In certain pathologic conditions (most often alcoholic liver disease) mitochondria became enlarged; nevertheless, even in these conditions they are hardly detectable on light microscopy. Recently an antimitochondrial antibody (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of the present study was to study immunoreactivity of this antibody in a series of liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an ultrastructural study was also done, and in 2 cases Western blot analysis was performed. Cases were divided as follows: alcoholic liver disease (ALD, 31); steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)-related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1); sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12). All the patients were investigated for alcohol or drug abuse, pharmacological treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse. Electron microscopic immunogold and Western blot analysis confirmed that in the conditions examined the protein recognized by the mAM showed greater expression. Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic insult even in cases in which the histological picture was blurred by viral infection.
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PMID:Identification of mitochondria in liver biopsies. A study by immunohistochemistry, immunogold and Western blot analysis. 976 31

Transplant recipients are highly motivated to maintain their recovered health status and are generally compliant with pharmacotherapy and medical follow-up. As well as routine blood tests and monitoring of immunosuppressant drug levels, recipients require immunization updates and regular screening for malignancy, diabetes, hypertension, hyperlipidemia, and ophthalmologic complications. Little information is available about the consistent implementation of these health maintenance strategies in this population. A telephone survey of liver transplant recipients was conducted using a 20-item questionnaire. It was designed to assess the frequency and adequacy of health maintenance screening, immunizations, and screening tests for malignancy, which are specific to the liver transplant population. We contacted 60 liver recipients transplanted at our institution between 1992 and 1996. The mean age of the patients (31 men and 29 women) was 48 years (range, 42-56 years). Before transplantation, pneumococcal and hepatitis B vaccination occurred in 13% and 18%, respectively. After transplantation, 27% had received pneumococcal vaccination and none had received primary vaccination for hepatitis B. Forty-eight percent received yearly influenza vaccination. Of 60 questioned recipients, 2 were aware of their varicella exposure status or a possible need for varicella immunoglobulin if a primary exposure to chickenpox were to occur. Two were aware of the need for the recipient's children or grandchildren who were undergoing polio vaccination to receive an inactivated intramuscular polio preparation. Yearly screening for dermatologic or oral malignancies was provided to only 40% of patients. Physician-performed breast examination or screening mammograms was done in 38% of the surveyed women. Eleven percent of the women had received a gynecologic examination with a cervical cytologic examination within the prior 2 years. Of the male recipients, 68% received either digital prostate examination or serum prostate specific antigen determinations or both. Of 60 recipients, 30 had had either flexible sigmoidoscopy or colonoscopy within the previous 2 years. Yearly dental examinations were performed on 75% of patients, and more than 90% had at least yearly blood pressure and weight determinations. Of 60 patients, 41 were aware of cholesterol and lipid profiles having been performed within the past 2 years. Ophthalmologic screening was performed in 83% of surveyed recipients. This survey suggests that routine health maintenance management is less than optimal in this population. Follow-up based on a standard protocol may improve the health care of these patients.
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PMID:Vaccination, screening for malignancy, and health maintenance of the liver transplant recipient. 1120 51

Liver enzyme elevations are common in human immunodeficiency virus (HIV)-infected patients, and their diagnosis or management may be difficult because of the intricacies of the pathogenic mechanisms involved. These include hepatotoxicity related to the highly active antiretroviral therapy (HAART) regimen, idiosyncratic or immunoallergic mechanisms, and direct cytotoxicity enhanced by an underlying liver disease. Liver enzyme abnormalities may also reflect hepatitis B (HBV) or hepatitis C (HCV) infection, which each have their own risks for chronic immune-mediated liver disease (including hepatitis flare after immune reconstitution) and of direct cytotoxicity. Finally, other factors may affect liver deterioration, including alcohol-related liver disease, nonalcoholic steatohepatitis associated with metabolic syndromes (e.g., hyperlipidemia, diabetes, or being overweight) that are potentially HAART related, and use of medication or illicit drugs (e.g., methamphetamine). A better understanding of these complex interactions, including adjustments of dosages of antiretroviral drugs, will probably help in the management of HIV-infected patients with liver enzyme abnormalities.
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PMID:HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. 1498 77

Non-alcoholic steatohepatitis (NASH) is emerging as an important cause of cryptogenic cirrhosis. Obesity, diabetes mellitus and hyperlipidaemia are important risk factors for NASH. The presence of these risk factors in patients with cryptogenic cirrhosis may suggest NASH as an aetiology of cirrhosis in them. Twenty-five patients of cryptogenic cirrhosis were compared with 18 patients of hepatitis B virus and hepatitis C virus related cirrhosis and primary biliary cirrhosis for the presence of obesity, diabetes mellitus and hyperlipidaemia. Patients with cryptogenic cirrhosis were found to have a significantly higher body - mass index increased prevalence of diabetes mellitus and lower high-density lipoprotein compared to the controls. Increased body weight and diabetes mellitus may play a role in the causation of cirrhosis in patients with cryptogenic cirrhosis.
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PMID:Prevalence of obesity, diabetes mellitus and hyperlipidaemia in patients with cryptogenic liver cirrhosis. 1530 64

The study examined health conditions among an aging cohort of male narcotics addicts. This prospective cohort study (1964-1998) included interviews and medical testing for 108 surviving subjects who had been admitted to the California Civil Addict Program during the years 1962 through 1964. Medical testing results were: 51.9% had high blood pressure, 22.4% showed hyperlipidemia, 13.3% had elevated levels of blood glucose, 33.6% had abnormal pulmonary function, half of the sample had abnormal liver function, and 94.2% tested positive for hepatitis C, 85.6% for hepatitis B, 3.8% for syphilis, and 27.3% for TB. The study empirically demonstrated poor health conditions and high morbidity among surviving narcotics addicts.
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PMID:Health conditions among aging narcotics addicts: medical examination results. 1566 46

We report a case of hepatocellular carcinoma (HCC) arising in nonalcoholic steatohepatitis (NASH). The patient, a 64-year-old man, was incidentally found to have multiple tumors in the liver when admitted for pneumonia. He had been obese, had been receiving a standard dose of valproic acid since clipping surgery for subarachnoid hemorrhage 17 years previously, and had not consumed any alcohol since the surgery. Laboratory data revealed moderate hyperlipidemia and no evidence of diabetes mellitus, hepatitis B or C infection. The patient died of hepatic insufficiency, and an autopsy was performed. A tumor, a maximum of 13 cm in diameter, grossly occupied the entire left lobe and one third of the right lobe of the liver. Histologically, moderately differentiated HCC was found with foci of poorly differentiated HCC. The non-tumorous area showed NASH with moderate bridging fibrosis, without interface hepatitis, hemochromatosis, or copper accumulation. In this patient, obesity, hyperlipidemia, and long-term treatment with valproic acid could have all been associated with induction of NASH. The present case suggests that HCC could develop in non-cirrhotic NASH liver, and that chronic inflammation in itself could be an important risk factor in the development of HCC.
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PMID:Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid. 1613 66

Corticosteroids have always played a valuable role in transplantation. Unfortunately, they are subject to a wide range of side effects, such as hyperlipidemia, hypertension, diabetes mellitus, osteoporosis, growth retardation and Cushingoid appearance. Steroids may also exacerbate problems that existed before surgery, including malignancy, hepatitis B and hepatitis C. New, powerful immunosuppressants have allowed steroid use to be reduced or avoided altogether, but use of these regimens is not simple and may be associated with late acute rejection and recurrence of autoimmune disease. The present review examines the rationale for steroid avoidance in liver transplantation and assesses the new regimens that are currently being developed.
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PMID:Steroid avoidance in liver transplantation. 1680 21

Liver transplantation remains an underdeveloped technique in Greece; currently there is no information on outcomes in Greek patients. In this study, data were provided on the outcomes of liver transplantation in 71 patients with a mean follow-up of 6 (0.1 to 16) years in our center. Mean age at transplantation was 46 +/- 13 years, while the main cause for transplantation was hepatitis B (16 patients, 23%) or C (six patients, 8%) virus. In the first posttransplantation year, three patients died, while 18 (25%) required at least one hospitalization with a median stay of 30 days. At the end of follow-up, 56 patients (79%) are alive. The leading cause of death was de novo malignancies (40%), appearing at a mean of 5.2 +/- 3.3 years. Late adverse effects of immunosuppressive therapy included hypertension (42%), hyperlipidemia (24%), chronic renal failure (21%), and diabetes mellitus (24%). With the exception of diabetes, all the above abnormalities were significantly associated with cyclosporine-based but not with tacrolimus-based immunosuppressive regimens. Relapse of primary disease in liver transplants occurred in 21 (29.6%) patients at a mean time of 1.5 +/- 1.4 years, of whom 67% were related to viral hepatitis. The quality of life (Karnofsky scale 1 to 6) was excellent in 64% of surviving patients, affordable in 21%, and poor in 15%. In conclusion, after 6 mean years, the majority of Greek liver transplant recipients conduct a normal life, although metabolic abnormalities are often observed. A national registry is needed to provide more solid evidence of outcomes.
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PMID:Liver transplantation in Greek patients: epidemiological data, morbidity, and mortality of 71 patients from a single center with 6 years of mean follow-up. 1758 Jan 73

Quantitative measurement of anti-HBs is used to evaluate the response to hepatitis B vaccination in health care workers and to optimize postexposure management. The different guidelines for hepatitis B vaccination and booster policy imply that the measurement of anti-HBs levels by different assays is accurate and consistent, yielding comparable quantitative results. We measured anti-HBs levels in 200 serum samples from patients and health care professionals by nine different anti-HBs assays and compared the quantitative results and the performance characteristics of the different test systems. The assay specificity ranged between 96.8 and 100% when sera from individuals without a vaccination history and with negative anti-HBc status were defined as true negatives. Sensitivity ranged between 93.5 and 100%. A high number of sera showed discrepancies between measurements by the different systems. The mean coefficient of variation between the different measurements was 47.1% (range, 15.0 to 201.0%), and the factors of multiplication ranged from 2.8 to 105. Hemolysis or lipemia did not seem to influence the measurement, and there was no difference between anti-HBc-positive and -negative individuals. The classical enzyme immunoassays tend to find lower anti-HBs levels than the automated systems, with higher values by the Abbott AXSYM assay. The serial dilution of the international standard preparation was measured accurately by most of the assays. In conclusion, the quantitative measurement of anti-HBs levels is not reliable, even though an international standard is used for the calibration of the systems. Some systems showed specific problems that should be addressed by the manufacturers.
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PMID:Comparison of nine commercially available assays for quantification of antibody response to hepatitis B virus surface antigen. 1825 21


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