No abstract

To dispel the common notion that the practice of hepatology in North America largely consists of the care of middle-aged male patients with alcohol-induced liver disease, and, in the process, provide undergraduate and postgraduate students with a clearer picture of what patient profiles might resemble in an urban, hospital-based hepatology practice, 1,226 charts derived from referrals between July 1, 1987, and January 1, 1994, were retrospectively reviewed for the following information: year of referral, age and sex of the patient, practice of the referring physician, status of ongoing care, and principal diagnosis. The results of the study revealed the following: 1) referrals for assessment and care of patients with liver disease are increasing at a rapid rate, 2) the majority of referred patients are between the ages of 25 and 45 years, 3) there is an equal distribution of men and women, 4) referrals are most often from general practitioners (57%) and internists (27%), 5) turnover is common, with 56% of referred patients no longer being followed, and 6) a variety of liver disorders are seen, including acute and chronic viral hepatitis (47%), nonalcoholic steatohepatitis (11%), drug-induced liver disease (6%), alcoholic liver disease (5%), primary biliary cirrhosis (4%), primary sclerosing cholangitis (3%), autoimmune chronic hepatitis (3%), "cryptogenic" cirrhosis (3%), and miscellaneous or undiagnosed causes (20%). Thus, contrary to popular belief, in this urban, hospital-based practice, the majority of liver disease patients are not middle-aged alcoholics, but rather young adults with a variety of hepatobiliary disorders.

Background: Data on the prevalence and compliance with management of viral hepatitis in the street-involved population are limited. Method: Hepatitis A (HAV), B (HBV) and C (HCV) serology and compliance with HBV vaccination were documented in 533 street-involved individuals. Results: The mean age of the study population was 25.7 years (range: 11-65) and 53% were female. Serologic evidence of HAV infection was present in 53%; HBV, 12% (3% ongoing infection); and HCV, 17%. HAV infections were associated with Aboriginal/Metis ethnicity and age over 25 years; HBV with injection drug use (IDU); and HCV with IDU, sex trade work and age over 25 years. Compliance with three-step HBV vaccination was 98%, 77% and 63%. Conclusions: HAV, HBV and HCV are common infections in urban street-involved persons. Successful HBV (and presumably HAV) vaccination can be achieved in the majority of this population, but concerns exist regarding compliance with more long-term, parenterally-based antiviral therapies.

No abstract

Recently, we documented that immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. The aim of the present study was to determine whether there is any association between serum immunoglobulin levels and hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. Charts from 116 patients with biochemical, serologic, virologic and histologic evidence of chronic hepatitis C infection and serum immunoglobulin levels (IgA, IgG, IgM and total) were reviewed. The mean (+/-SD) age of the study population was 46 +/- 11 years and 67 (58%) were male. There were significant correlations between serum IgA (r = 0.39, P = 0.00001), IgG (r = 0.49, P = 0.000002) and total (r = 0.51, P = 0.000003) immunoglobulin levels and the stage of hepatic fibrosis. When serum immunoglobulin levels were included into logistic regression analysis with variables known to be associated with advanced disease (male gender, age >40 years at onset of infection, duration of infection beyond 20 years and concurrent alcohol abuse) only IgA, IgG and total immunoglobulin levels (P < 0.05, <0.05 and <0.005, respectively) emerged as independent predictors of hepatic fibrosis. Our data indicate a strong association between serum immunoglobulin levels (IgA, IgG and total) and hepatic fibrosis in patients with HCV infection. This finding supports the need to further investigate whether immunoglobulins independently promote disease progression in patients with chronic HCV infection.

No abstract

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.

The gene responsible for transcribing glyceraldehyde-and integrity of RNA present in Northern analyses. 3-phosphate dehydrogenase (GAPDH) is commonly used Whether the GAPDH gene can be used for the same as a reporter gene to estimate the amount of RNA pres-purpose in tumor cell lines or tissues is unclear. Indeed, ent in Northern analyses. However, recent data suggest there are numerous reasons to suspect that GAPDH that GAPDH gene expression may vary with the extent messenger RNA (mRNA) expression may not be useful of cell proliferation and differentiation. 28S-ribosomal in that regard. Specifically, tumor cells are known to RNA (28S-rRNA) has also been employed to normalize exhibit increased rates of glycolysis. 3 Moreover, Northern blots prepared with total RNA. In the present GAPDH mRNA expression is regulated by several study, we compared the expression of GAPDH messengrowth factors, some of which may be operative in liver ger RNA (mRNA) with 28S-rRNA by Northern blot analytumor growth. 4,5 Finally, the expression of GAPDH ses in human hepatocellular carcinoma tissues (HCC) and adjacent non-HCC tissues from eight patients with mRNA is increased in human lung cancer, 6 pancreatic chronic viral hepatitis-induced cirrhosis and normal and colon adenocarcinoma, 7 a human hepatocarcinoma liver tissue from eight healthy control subjects. The re-cell line, 8 and several transformed tumor cell lines. 9 sults of the study revealed that GAPDH mRNA levels inThe human ribosomal RNA (rRNA) constitutes a re-HCC were significantly higher (141-161) than those in petitive family of genes. 10 The 28S-rRNA component of adjacent non-HCC and normal liver tissues. Conversely, the family has been cloned and demonstrated to be 28S-rRNA levels did not vary among HCC, adjacent non-largely conserved in various species of vertebrates. 11 HCC, and normal liver tissues. We also demonstrated As a result, it is used increasingly for normalizing that the 28S-RNA signal was proportional to the amount Northern blots. 12,13 Whether 28S-rRNA gene expresof RNA loaded. These findings indicate that 28S-rRNA, sion is altered in human carcinoma tissue has not been rather than GAPDH mRNA, should be used as RNA loading controls for Northern blot analyses involving HCC reported. Thus, the purpose of this study was to docuand nontumor tissues. The findings also raise the possi-ment and compare GAPDH and 28S-rRNA gene exbility that GAPDH mRNA gene expression might serve pression in human hepatocellular carcinoma (HCC) tis- biopsies. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) PATIENTS AND METHODSis an important enzyme in the glycolytic metabolic Tissue Samples. Human HCC and adjacent non-HCC tispathway. In human nontumor tissue it is encoded by sues were obtained from eight, untreated Chinese patients a single functional gene, the levels of which remain at the time of surgery for tumor resection at the Norman constant during cell growth and the various phases of Bethune University Hospital (Chanchun, China). An addithe cell cycle. 1,2 For that reas...