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 liver is heavily involved in the vast majority of systemic infections. Pathophysiological mechanisms involved in hepatic involvement in generalized sepsis require further study, as does the importance of bacterial infection in the presence of cirrhosis. Although parasitic involvement is theoretically dominated by Plasmodium spp., in clinical practice Entamoeba histolytica, Schistosoma spp. and Echinococcus spp. infections are far more important. Hepatobiliary involvement is also a feature of Ascaris lumbricoides, Fasciola hepatica and 'oriental' cholangiohepatitis. Various bacteria (including Mycobacterium tuberculosis, Treponema pallidum and Salmonella spp.) and viruses (e.g., cytomegalovirus, Herpes simplex and dengue) also cause significant hepatic involvement. A high index of suspicion for infection is required in paediatric hepatology.
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PMID:Liver involvement in systemic infection. 947 Oct 32

We report on a male Egyptian patient who developed myasthenia gravis with typical symptoms, beneficial response to pyridostigmine, and the presence of anti-acetylcholine receptor antibodies and anti-striated muscle antibodies during the course of a chronic hepatitis C infection complicated by liver cirrhosis. As also reported for the herpes simplex and for the HIV virus, hepatitis C may lead to myasthenia gravis via a mechanism of cross-reactivity between viral epitopes and the acetylcholine receptor.
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PMID:Myasthenia gravis: another autoimmune disease associated with hepatitis C virus infection. 995 42

Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.
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PMID:Liver disease in pregnancy. 1006 7

Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene followed by the administration of ganciclovir (GCV) into hepatocellular carcinoma (HCC)-derived cell lines either in vitro or transplanted into nude mice has been shown to provide a potential strategy for HSV-tk-based gene therapy of HCC. We report herein an analysis of the antitumoral efficacy of two recombinant adenoviruses (Ads), Ad.CMVtk and Ad.AFPtk, in a relevant model of multifocal hepatic lesions induced in rats by a potent alkylating chemical carcinogen, diethylnitrosamine. Two routes of administration of the Ad were studied: intratumoral and intrahepatic artery injections. Both recombinant Ads, Ad.CMVtk and Ad.AFPtk, express the HSV-tk gene under the control of the early enhancer/promoter cytomegalovirus and alpha-fetoprotein regulatory gene sequences, respectively. The antitumor response was assessed by magnetic resonance imaging and by autopsy and histological analysis following postmortem. Tumor growth cessation was demonstrated by magnetic resonance imaging in large tumor nodules of size 5-8 mm treated by intratumoral administration of 2x10(9) pfu Ad.CMVtk plus i.p. treatment with GCV. We also show an antitumor efficacy in small tumor nodules of size <3 mm treated with 2x10(9) pfu Ad.CMVtk plus GCV by the intrahepatic artery route, albeit associated with an adverse toxicity. In vivo targeting of the HSV-tk gene to diethylnitrosamine-induced HCC cells with the recombinant Ad.AFPtk suppresses the hepatic toxicity in the nontumoral liver. The lower antitumor response would argue for the use of multiple injections of such adenoviral constructs. These observations may lead to potential approaches for designing gene therapy destined for early treatment of dysplastic nodules or advanced HCC in cirrhosis.
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PMID:Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes. 1070 15

There are a large number of viruses, such as cytomegalovirus, Epstein-Barr, Herpes simplex, mumps, varicella, yellow fever, etc., known to cause inflammatory disease of the liver, but the term viral hepatitis generally refers to the five well described hepatotropic viruses which are divided into enteral and parenteral groups based on their mode of transmission. Hepatitis A and E viruses are enterically transmitted by the faecal-oral route and do not exist in a chronic carrier state. Hepatitis B, C and D viruses are parenterally transmitted, occur both in the acute and chronic forms, and, when they persist in a chronic carrier state, they serve as a reservoir for infection and give rise to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Hepatitis G virus has recently been described but its significance in the causation of human liver disease is yet to be established. Also, the most recently described TT virus in patients with post-transfusion hepatitis awaits further studies. Acute sporadic and epidemic viral hepatitis are common world-wide, mostly in the developing countries, including Ethiopia, and account for high morbidity and mortality, especially among pregnant women. Chronic infection with hepatitis B virus is a significant problem on a global scale, affecting over 300 million people. Hepatitis C virus infection is probably the most common cause of chronic viral hepatitis, end-stage liver disease and hepatocellular carcinoma in the world, especially in sub-Saharan Africa, including Ethiopia. Therefore, this article will review and highlight the relevant epidemiological, preventive and therapeutic aspects of viral hepatitis with emphasis on new developments and recent data obtained from Ethiopian studies.
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PMID:Epidemiology, prevention and treatment of viral hepatitis with emphasis on new developments. 1114 85

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, 35 immortalized rat hepatocyte clones were developed by transduction with the gene encoding the simian virus 40 T antigen (SV40Tag). The SV40Tag sequence and a suicide gene, herpes simplex virus thymidine kinase (HSV-tk), were flanked by loxP sequences so that they could be excised by Cre/lox recombination. When transplanted into the spleens of portacaval-shunted rats, 3 of the 35 immortalized hepatocyte clones prevented the development of hyperammonemia-induced hepatic encephalopathy. The protection was reversed by treatment with ganciclovir, which kills HSV-tk-expressing cells. Transplantation of alginate-encapsulated, immortalized hepatocytes into the spleens of cirrhotic rats resulted in significant improvement in prothrombin time, serum albumin and bilirubin levels, hepatic encephalopathy score, and duration of survival. The metabolic support provided by the immortalized cells equaled that observed after transplantation of primary rat hepatocytes. In conclusion, immortalized hepatocytes can function as well as primary hepatocytes following transplantation and can be engineered to contain safeguards that could make them clinically useful. Further investigation is warranted regarding the mechanisms of loss of mass or function of the transplanted hepatocytes over time and how the relatively few engrafted hepatocytes can ameliorate liver decompensation in cirrhosis.
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PMID:Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes. 1214 47

The outcome of infection with hepatitis C virus (HCV) varies greatly. The virus associates with serum lipoproteins, including those containing apolipoprotein E (apoE) and apolipoprotein B (apoB), and may enter cells via the low-density lipoprotein receptor (LDLR). ApoE genotypes can affect the extent of damage in diseases caused by 2 other viruses--herpes simplex virus type 1 (HSV1; in Alzheimer's disease and herpes labialis) and human immunodeficiency virus (HIV). We therefore investigated whether specific apoE and apoB alleles were associated with different outcomes of HCV infection. A total of 156 anti-HCV-positive patients and 104 non-HCV-infected patients were studied. Liver biopsy specimens from patients with chronic HCV infection (n = 111) were assessed for disease severity by the Knodell system. ApoE and apoB genotypes were determined by standard polymerase chain reaction (PCR) methods. There was no significant difference among the apoE genotypes of HCV-infected subjects compared with previously published population data, or between HCV-RNA positive or negative patients. However, chronically HCV-infected subjects with mild liver disease (n = 65) had a significantly higher apoE-epsilon 4 allele frequency (20.0%) than those (n = 46) with severe disease (6.5%). ApoB alleles alone or in combination with apoE were not associated with mild or severe disease. The overall apoE allele frequencies of patients with liver disease not caused by HCV were similar to those of the total HCV group and in contrast to the HCV patients, the apoE allele frequencies were similar in those patients with no or mild fibrosis as compared with those with bridging fibrosis or cirrhosis. In conclusion, carriage of an apoE-epsilon 4 allele may be protective against liver damage caused by HCV, but not against damage due to various nonviral causes. This is yet another case in which apoE may determine the severity of a viral disease.
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PMID:Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus. 1464 71

Common viral agents known to cause inflammation of the liver (hepatitis) are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Some other viral agents that can cause hepatitis are Epstein Barr virus, herpes simplex virus, and cytomegalovirus. Some patients infected with these viral agents progress to develop chronic viral hepatitis. Approximately 45% of chronic hepatitis cases are associated with hepatitis C and approximately 15% are associated with hepatitis B. In addition to being a leading cause of chronic hepatitis, HCV is most frequently associated with liver cirrhosis and hepatocellular carcinoma. Although much has been published about HAV and HBV, health professionals have learned about HCV only in recent years. For this reason, this article will emphasize the epidemiologic challenges and current treatments for hepatitis C; hepatitis A and B will be discussed in brief.
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PMID:Current treatments for hepatitis. 1246 95

Liver fibrosis is the result from a relative imbalance between synthesis and degradation of matrix proteins. Following liver injury of any etiology, hepatic stellate cells undergo a response known as activation, which is the transition of quiescent cells into proliferative, fibrogenic, and contractile myofibroblasts. Upon this cellular transdifferentiation the effector cell becomes the major source of fibrillar and non-fibrillar matrix proteins resulting in excessive scar formation and cirrhosis, the end stage of fibrosis. Concomitant with progressive liver fibrosis, the tissue inhibitor of metalloproteinases-1 (TIMP-1) is strongly activated in hepatic stellate cells. We have developed a recombinant replication-defective adenovirus in which the TIMP-1 promoter is coupled to the herpes simplex virus thymidine kinase gene rendering activated hepatic stellate cells susceptible to ganciclovir. This novel targeted suicide gene approach was validated in a culture model considered to reflect an accelerated time course of the cellular and molecular events that occur during liver fibrosis. We demonstrate that transfer of the suicide gene to culture-activated hepatic stellate cells results in a strong expression of the respective transgene as assessed by Northern blot and Western blot analyses. The enzyme catalyzed the proper conversion of its prodrug subsequently initiating programmed cell death as estimated by caspase-3 assay and Annexin V-Fluos staining. Altogether, these results indicate that induction of programmed cell death is a promising approach to eliminate fibrogenic HSC.
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PMID:Induction of cell death in activated hepatic stellate cells by targeted gene expression of the thymidine kinase/ganciclovir system. 1504 99

Congenital and neonatal viral infections usually display their acute manifestations in highly recognisable ways, for example, congenital rubella, cytomegalovirus (CMV), varicella, human immunodeficiency (HIV) and herpes simplex virus (HSV) infection. By contrast, congenital hepatitis B virus (HBV) infection may go undetected for years. Some of these are preventable, but what is not immediately apparent is that the long-term consequences are being prevented as well. The long-term consequences of congenital and neonatal infections include endocrine, immunological and cardiovascular disease, deafness, visual problems, intellectual handicap and cerebral palsy. With the survival of HIV-infected infants into adulthood the long-term consequences will soon be described. Maternally and neonatally transmitted HBV infection predisposes to carriage, liver cirrhosis and hepatocellular carcinoma in young adults. Neonatal HBV vaccination prevents adult cancer. Acquired viral infections may predispose to subsequent lung disease, malabsorption, fertility problems or neurological disability. In the prevention of acquired rubella, varicella, HBV, influenza, poliovirus, measles and hepatitis A, one should mention the added bonus of preventing secondary cases by preventing transmission from infants and children to other children and adults. Preventing paediatric HSV, HBV and HIV infection in females may even be preventing subsequent transmission to future generations. Turning to paediatric bacterial infections, vaccinating infants and young children against pertussis could not only prevent transmission to older children and adults but also break the cycle, which then transmits from adults back to infants and young children. There is evidence that disease in older age groups, including adults, has been prevented by virtue of herd immunity from paediatric vaccination, e.g. Neisseria meningitidis Group C and Streptococcus pneumoniae. The add-on benefits for other generations, including for adults, arising from the prevention of paediatric infections are considerable.
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PMID:Paediatric infections: prevention of transmission and disease--implications for adults. 1575 76


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