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)

Chronic infection with hepatitis C virus (HCV) is a growing problem worldwide, with up to 300 million individuals infected, and those with chronic infection are at risk for cirrhosis and hepatocellular carcinoma. HCV infection is the most common indication for liver transplantation in the United States and Europe. Unfortunately, although transplantation is effective for treating decompensated cirrhosis and limited hepatocellular carcinoma associated with hepatitis C, HCV reinfection is virtually the rule among transplant recipients. Reinfection of the graft is associated with more rapidly progressive disease, with a median time to cirrhosis of 8 to 10 yr. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments begun for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially from cytopenias, and drug discontinuations in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virological response rates. Future therapies may include ribavirin alternatives with lower rates of anemia, alternative interferons with lower rates of cytopenias, and new antiviral drugs that can be used alone or in combination with either interferon or ribavirin to enhance sustained virological response rates and improve tolerability. Liver Transpl 12:1192-1204, 2006. (c) 2006 AASLD.
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PMID:Treating hepatitis C infection in liver transplant recipients. 1686 44

Chronic infection with hepatitis C virus (HCV) is causally associated with the development of hepatocellular carcinoma (HCC). HCV is not cytolytic and replicates entirely in the cytoplasm. Viral interaction with the host leads to subversion of immune response and other defense mechanisms. The recent development of robust cell culture systems for HCV infection provides new opportunities for the study of virus-cell interaction and viral pathogenesis. HCV infection causes active inflammation and fibrosis, which ultimately progresses to cirrhosis. The onset of cirrhosis usually precedes the multistage process of tumor development, in which common themes of viral carcinogenesis can be identified. While chronic inflammation and cirrhosis are thought to play an important role in tumor initiation, the underlying mechanisms are incompletely understood. Recent studies have revealed that infection with HCV induces genome instability, leading to further genetic and epigenetic alterations which contribute to the full development of HCC tumor. The expression of viral oncoproteins such as C and NS5A is critically involved both in the induction of genome instability and in dysregulating cellular control of growth and signal transduction. A better understanding of the molecular pathogenesis of HCV will reveal novel strategies for the prevention and treatment of related diseases including HCC.
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PMID:Molecular pathogenesis of hepatitis C virus-associated hepatocellular carcinoma. 1712 95

Despite effective prophylactic vaccines against hepatitis B virus existing for over 20 years, more than 2.5 billion people worldwide have been exposed to the disease and approximately 370 million people are chronically infected with it. Chronic infection in more than two thirds of infected patients results in chronic liver disease, which may lead to cirrhosis, exposure to noncarcinomatous complications and hepatocellular carcinoma. Currently available therapies fail to allow complete control of viral replication in most patients. Viral persistence has been associated with a defect in the development of hepatitis B virus-specific cellular immunity. Immunomodulatory strategies to boost or to broaden the weak virus-specific T-cell response have been proposed to bypass the chronic hepatitis B infection, including hepatitis B virus envelope- and nucleocapsid-based vaccines, and new formulations for recombinant and DNA-based vaccines, which are currently being evaluated in clinical trials.
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PMID:Therapeutic vaccination in chronic hepatitis B virus carriers. 1718 43

Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA virus that replicates through an RNA intermediate produced from a stable covalently closed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one-third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long-term remissions in disease in one-third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long-term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long-term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B.
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PMID:Management of hepatitis B: summary of a clinical research workshop. 1739 13

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway.
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PMID:Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways. 1739 59

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause persistent viral infection in humans. Chronic infection is associated with a risk of cirrhosis and hepatocellular carcinoma. The cause of chronic infection is unknown. A large body of evidence suggests that a failure of the adaptive immune response is critical in the establishment of chronic infection. Recently a new group of T cells (T-regulatory cells), that express CD4(+)CD25(+) and Foxp3, which can inhibit the cellular (CD4(+)/CD8(+)) immune response have been described. In this review the authors explore the thoughts regarding immune responses to HBV and HCV infections and the role of these T-regulatory cells in relation to the pathogenesis of chronic HBV and HCV infection and the potential for therapeutic intervention.
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PMID:T-regulatory lymphocytes and chronic viral hepatitis. 1796 Oct 92

Hepatitis B virus (HBV) is a small DNA virus that targets the liver almost exclusively. Chronic infection with HBV might lead to severe liver-related pathologies including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Based on its enhancer composition, which links nutritional signals that control hepatic glucose and fat metabolism in the liver to HBV gene expression and replication, it appears that the virus has adopted a regulatory system that is unique to the major hepatic metabolic genes. This unique virus-host interaction, mediated by metabolic events in the liver, is designated by us the "metabolovirus model". We hypothesize that by mimicking the expression of key genes implicated in glucose homeostasis, HBV sophisticatedly exploits the host resources to ensure its persistence. Specifically, by recruiting transcription factors and coactivators common to essential hepatic metabolic genes the virus avoids a possible resistance by its host, on the one hand, and ensures a timely and proper response to changes in its environment in terms of metabolic milieu, on the other hand. Furthermore, by coupling its gene expression to the expression of hepatic metabolic genes that fluctuate during the day, we predict a fluctuating nature of HBV gene expression. This can serve the virus in its attempts to escape the host immune system in addition to other immune evading strategies adopted by the virus, such as the secretion of the e antigen. Based on our "metabolovirus model", we suggest new mechanisms to previously unexplained clinical phenomena, such as the observed diversity in disease severity between different geographical areas that differ in nutritional habits. Furthermore, given the up-regulatory effect of food deprivation on HBV gene expression and replication, we suggest that conditions of short-term starvation should be completely avoided by HBV-infected individuals, and dietary recommendations such as the ingestion of complex carbohydrates before sleep should be adopted. Thus, our hypothesis sets the stage for viral manipulation by controlling food intake, and opens additional avenues towards food or nutritional therapy as an effective anti-HBV weapon.
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PMID:The "metabolovirus" model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon. 1833 85

Hepatitis C viral is a problem of population health. The World Health Organization considers Hepatitis C an epidemic, a "silent" epidemic because a patient living with Hepatitis C can be infected for decades before being discovered. Recent data show an estimated number of 170 million patients infected with hepatitis C virus in the world. Number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. The incidence of HCV infected patients is estimated to 500-600 new cases in a year in Italy. Chronic infection is present in 55%-85% of infected persons. Approximately one third of the patients develop cirrhosis over a number of years, which can lead to liver failure and other serious complications. There is no vaccine and no completely effective treatment. Recent data show PEG-IFN-RBV combination therapy is most effective. We describe one HCV infected individual case report with HCV genotype 1b who received combination therapy for 4 weeks. Levels of HCV RNA became undetectable after an mouth of treatment.
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PMID:[Virus C hepatitis: successful therapy in a health care worker]. 1840 47

Chronic infection with hepatitis B affects nearly 350 million individuals worldwide and is the leading cause of hepatocellular carcinoma and liver cirrhosis. Universal infant immunization has decreased rates of HBV infection, although transmission continues to occur via vertical (mother-to-child) and horizontal (sexual, parenteral and household) routes. Treatments are now available for children with chronic HBV infection, but appropriate selection of those most likely to respond to treatment is important. Interferon alpha and lamivudine are currently approved in the US for the treatment of children older than 2 years of age who have chronic HBV infection. Hepatitis C infection affects almost 170 million individuals worldwide. Of individuals exposed to HCV, 60-80% develop chronic hepatitis, and 10-15% of those chronically infected develop cirrhosis within several decades. No vaccine exists for HCV; therefore, prevention of parenteral transmission is important. A high index of suspicion is essential for the diagnosis of HCV infection given its silent clinical presentation. Appropriate evaluation of infected individuals is warranted when considering their suitability for therapy. Interferon alpha and ribavirin, used in combination, are currently approved in the US for the treatment of children older than 3 years of age with chronic HCV infection.
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PMID:Hepatitis B and C in children. 1841 57

Chronic infection with hepatitis B virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferons and antiviral drugs. The interferons have immunomodulatory, antiproliferative, and antiviral effects. Nucleoside analogs, such as entecavir, lamivudine and telbivudine, and neucleotide analogs, such as adefovir and tenofovir, exhibit antiviral effects by inhibiting viral replication. Treatment is directed at suppressing viral replication and halting the progression of disease.
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PMID:Pharmacotherapy of hepatitis B infection: a brief review. 1885 82


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