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)

The ability to produce antibodies against strong (S. typhosa and S. paratyphi) and weak (tetanus toxide) antigens and the consequent changes in serum IgG's, IgA's, and IgM's were compared in patients with cirrhosis of the liver and healthy controls. A significantly higher response, especially to strong antigens, was noted in the cirrhotics, while their bone marrow contained an appreciably greater number of lymphocytes and plasma cells. Increased Ig production in cirrhosis is seen as the expression of general over-production of antibodies and hence devoid of any specific relation to its immune pathogenesis. The conclusion is drawn that the liver may be in some way responsible for the regulation of antibody synthesis and that this capability is "disinhibted" in cirrhosis.
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PMID:[Experimental research on the artificially induced antibody immunity in the healthy man and in the patient with liver cirrhosis]. 84 87

The aim of this study was to examine the immunomodulating effects of rhIL-12 on the immune response induced by hepatitis B virus (HBV) antigens in clinical subgroups of patients with HBV infection. Peripheral blood mononuclear cells (PBMC) of 80 patients were stimulated with HBsAg, HBcAg, pre-S1Ag and tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation by anti-CD3+ anti-CD28 and lipopolysaccharide (LPS) were used as controls. Proliferation and cytokine production were determined by 3H-thymidine uptake and ELISA after 72 h. After stimulation with HBV antigens only, production of tumour necrosis factor-alpha (TNF-alpha) or IL-10 was observed in all patients, while interferon-gamma (IFN-gamma) was detectable in only 27 patients. After costimulation with IL-12 and HBV antigens, however, large amounts of IFN-gamma were found in all patients, while HBV-induced IL-10 production remained mostly unchanged. When clinical subgroups including patients with compensated liver cirrhosis were compared, PBMC from patients with HBeAg+ hepatitis showed the lowest capacity to produce IFN-gamma after HBV antigen-positive IL-12. These data suggest that the ability of IL-12 to enhance IFN-gamma production against HBV antigens is correlated with the presence of HBeAg and is not impaired in patients with advanced liver disease. In addition, IL-12 and IL-10 production by antigen-presenting cells may be a critical factor that determines the efficacy of the immune response against the hepatitis B virus.
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PMID:HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with a dysregulation of pro- and anti-inflammatory cytokines. 1019 26

The study compares the cause of death profile in a rural area of South Africa (Agincourt), with that in a rural area of West Africa (Niakhar), and in a developed country with the same life expectancy (France, 1951) in order to determine causes with high and low mortality and priorities for future health interventions. In the two African sites, causes of death were assessed by verbal autopsies, whereas they were derived from regular cause of death registration in France. Age-standardized death rates were used to compare cause-specific mortality in the three studies. Life expectancy in Agincourt was estimated at 66 years, similar to that of France in 1951, and much higher than that of Niakhar. Causes of death with outstandingly high mortality in Agincourt were violent deaths (homicide and suicide), accidents (road traffic accidents and household accidents), certain infectious diseases (HIV/AIDS, tuberculosis, diarrhea and dysentery), certain chronic diseases (cancer of genital organs, liver cirrhosis, gastrointestinal hemorrhage, maternal mortality, epilepsy, acute rheumatic fever, and pneumoconiosis) and malnutrition of young children (kwashiorkor). Causes of death with lower mortality than expected were primarily respiratory diseases (pneumonia, bronchitis, influenza, lung cancer), other cancers, vaccine preventable diseases (measles, whooping cough, tetanus), and marasmus. Verbal autopsies could be used in a rural area of a developing country without formal cause of death registration to identify the most salient health problems of the population, and could be compared with a formal cause of death registration system of a developed country.
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PMID:Causes of death in a rural area of South Africa: an international perspective. 1089 26

Persons with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-gamma or TNF-alpha in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression.
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PMID:Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV. 1523 95

The majority of hepatitis C virus (HCV)-infected individuals become chronically infected, which can result in liver cirrhosis and hepatocellular carcinoma. Patients with chronic HCV are unable to prime and maintain vigorous T-cell responses, which are required to rid the body of the viral infection. Dendritic cells (DCs) are the professional antigen-presenting cells that probably play a dominant role in priming and maintaining vigorous T-cell responses in HCV infection. Furthermore, inefficient DC function may play an important role in HCV chronicity. In order to determine the effect of HCV NS3 and core proteins on phenotype and function of human DCs, recombinant adenoviral vectors containing NS3 or core genes were used to infect human DCs. HCV NS3- or core-protein expression in DCs was confirmed by Western blotting and immunofluorescence staining. The DCs expressing HCV NS3 or core proteins expressed several inflammatory cytokine mRNAs, had a normal phenotype and effectively stimulated allogeneic T cells, as well as T cells specific for another foreign antigen (tetanus toxoid). These findings are important for rational design of cellular-vaccine approaches for the immunotherapy of chronic HCV.
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PMID:Expression of hepatitis C virus-derived core or NS3 antigens in human dendritic cells leads to induction of pro-inflammatory cytokines and normal T-cell stimulation capabilities. 1636 18

Hepatitis B is a serious public health problem leading to chronic infection, liver cirrhosis, and hepatocellular carcinoma. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) recommend routine universal infant vaccination against hepatitis B as the main strategy for the control hepatitis B and its severe consequences. PAHO additionally recommends routinely vaccinating healthcare workers. As of 2005, all countries in the Americas, except Haiti and Dominica, have hepatitis B vaccine in their childhood immunization schedule; 13 countries/territories include a hepatitis B dose given at birth. Hepatitis B vaccine has been incorporated into national schedules using different modalities; notably, 28 countries use it as a combination vaccine diphtheria tetanus pertussis + Haemophilus influenzae type b + hepatitis B (DTP+Hib+Hep B) for infants. Coverage levels for the third dose of hepatitis B are usually over 80%; however, hepatitis B vaccine coverage overall is lower than for the third dose of DTP. Insufficient information is available at this time to assess the use of hepatitis B vaccine in healthcare workers in the Americas. The most important factor associated with the success in the implementation of hepatitis B vaccination has been the strong commitment of country governments. This experience can be used as a model when implementing new technologies in health as they become available. However, much still needs to be done to improve hepatitis B coverage.
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PMID:Progress in vaccination against hepatitis B in the Americas. 1646 Dec 35

To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.
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PMID:Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C. 2257 2

Since the late 1940s, mass vaccination programs in the USA have contributed to the significantly reduced morbidity and mortality of infectious diseases. To assist the evaluation of the benefits of mass vaccination programs, the number of individuals who would have suffered death or permanent disability in the USA in 2014, had mass vaccination never been implemented, was estimated for measles, mumps, rubella, tetanus, diphtheria, pertussis, polio, Haemophilus influenzae type b (Hib), hepatitis B, varicella, and human papillomavirus (HPV). The estimates accounted for mortality and morbidity trends observed for these infections prior to mass vaccination and the impact of advances in standard of living and health care. The estimates also considered populations with and without known factors leading to an elevated risk of permanent injury from infection. Mass vaccination prevented an estimated 20 million infections and 12,000 deaths and permanent disabilities in 2014, including 10,800 deaths and permanent disabilities in persons at elevated risk. Though 9000 of the estimated prevented deaths were from liver cirrhosis and cancer, mass vaccination programs have not, at this point, shown empirical impacts on the prevalence of those conditions. Future studies can refine these estimates, assess the impact of adjusting estimation assumptions, and consider additional risk factors that lead to heightened risk of permanent harm from infection.
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PMID:Measuring the Benefits of Mass Vaccination Programs in the United States. 3300 80