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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 the hepatitis C virus is widespread in the United States. This disease is associated with a progression of fibrosis of the liver leading to liver cirrhosis in as many as 20% of cases. The current standard of care for the treatment of chronic hepatitis C infection is combination therapy with pegylated interferon alpha plus ribavirin. In more than 50% of patients, this regimen has been shown to induce a sustained viral response, defined as undetectable hepatitis C viral ribonucleic acid (RNA) for 6 months after the end of treatment. Typically, patients are treated for 24 or 48 weeks. A number of possible adverse events are associated with combination therapy, and patient empowerment through supportive nursing care is critical to facilitating patient adherence to treatment. This article provides an update on information concerning the diagnosis and treatment of chronic hepatitis C infection. This information can be tailored to provide patient-focused assessment, education, and treatment.
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PMID:Peginterferon alpha/ribavirin combination therapy for the treatment of hepatitis C infection. 1618 7

Chronic hepatitis C is defined as a long-term disease of the liver that can progress to liver cirrhosis with severe consequences. Use of antiviral therapy prevents these consequences and is advised in relation to whom is considered to be definitely appropriate. Current treatment of adults includes combined regimen of pegylated interferon alpha and ribavirin and has an advantage over monotherapy. Numerous side-effects can occur during treatment. Special population groups without general consensus about the treatment are children, patients with HIV co-infection, persons with renal disease, etc.
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PMID:[Current treatment of chronic hepatitis C]. 1620 13

Advances during the past 20 years have led to a better understanding of the prevention, diagnosis, and treatment of acute and chronic hepatitis B (HBV) and hepatitis C (HCV) infections in the pediatric population. Universal vaccination and prenatal testing for HBV have decreased the incidence rate of acute HBV infections from more than 3/100,000 to 0.34/100,000 in all children. Diagnosis of chronic HBV is confirmed with positive serologic testing on two occasions at least 6 months apart. Current approved therapies with interferon alpha and lamivudine for children with chronic HBV infection have shown some efficacy, but results have been variable. In contrast, the lack of an effective HCV vaccine and the risk of mother-to-child transmission may increase the number of children with vertically acquired HCV that ultimately go on to develop liver fibrosis or cirrhosis. Diagnosis of HCV in the neonate should be postponed until after the child reaches 1 year of age because infants may have transient viremia. Treatment for HCV infected children has not been studied extensively. Peginterferon alpha-2a and Ribavirin are not currently approved for pediatric use; however, recent studies in children have shown potential benefit. More effective and less toxic therapies for young patients with HBV and HCV are needed, as are methods to interrupt perinatal transmission of HBV and HCV.
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PMID:Hepatitis B and C viruses in infants and young children. 1621 Jan 9

Cirrhosis is the result of chronic inflammation and of the progressive increase of fibrosis. In France, hepatitis C infection is the second cause of cirrhosis after alcohol abuse. The other causes of cirrhosis are: hepatitis B infection, genetic haemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, drug-induced cirrhosis, secondary biliary cirrhosis, Wilson's disease and al-antitrypsin deficiency. Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis, the combination of pegylated interferon alpha (PEG IFN) with ribavirin in case of C viral cirrhosis, the PEG IFN and the nucleoside analogs in case of B viral cause; corticosteroids and immunosuppressive drugs in case of autoimmune cirrhosis; venesections in case of genetic haemochromatosis and stopping the drug in case of drug-induced cirrhosis. The complications of cirrhosis such as ascites, oesophageal varices, bleeding, hepatic encephalopathy and hepatocellular carcinoma mainly explain the high rate of morbidity and mortality. Liver transplantation is the established therapy for decompensated liver disease of any etiology significantly changed the outcome of patients with advanced cirrhosis.
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PMID:[Liver cirrhosis in adults: etiology and specific treatments]. 1625 95

We present here a comprehensive review of the current literature plus our own findings about in vivo and in vitro analysis of hepatitis C virus (HCV) infection, viral pathogenesis, mechanisms of interferon action, interferon resistance, and development of new therapeutics. Chronic HCV infection is a major risk factor for the development of human hepatocellular carcinoma. Standard therapy for chronic HCV infection is the combination of interferon alpha and ribavirin. A significant number of chronic HCV patients who cannot get rid of the virus infection by interferon therapy experience long-term inflammation of the liver and scarring of liver tissue. Patients who develop cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. Availability of HCV cell culture model has increased our understanding on the antiviral action of interferon alpha and mechanisms of interferon resistance. Interferons alpha, beta, and gamma each inhibit replication of HCV, and the antiviral action of interferon is targeted to the highly conserved 5'UTR used by the virus to translate protein by internal ribosome entry site mechanism. Studies from different laboratories including ours suggest that HCV replication in selected clones of cells can escape interferon action. Both viral and host factors appear to be involved in the mechanisms of interferon resistance against HCV. Since interferon therapy is not effective in all chronic hepatitis C patients, alternative therapeutic strategies are needed to treat chronic hepatitis C patients not responding to interferon therapy. We also reviewed the recent development of new alternative therapeutic strategies for chronic hepatitis C, which may be available in clinical use within the next decade. There is hope that these new agents along with interferon will prevent the occurrence of hepatocellular carcinoma due to chronic persistent hepatitis C virus infection. This review is not inclusive of all important scientific publications due to space limitation.
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PMID:HCV-hepatocellular carcinoma: new findings and hope for effective treatment. 1627 14

Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenously applied IFN-alpha, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation. These effects of alcohol occurred independently of i) alcohol metabolism via ADH and CYP2E1, and ii) cytotoxic or cytostatic effects of ethanol. In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication. Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink 12.Recombinant interferon alpha (IFN-alpha) therapy produces sustained responses (ie clearance of viremia) in 8-12% of patients with chronic hepatitis C 3. Significant improvements in response rates can be achieved with IFN plus ribavirin combination 456 and pegylated IFN plus ribavirin 78 therapies. However, over 50% of chronically infected patients still do not clear viremia. Moreover, HCV-infected patients who abuse alcohol have extremely low response rates to IFN therapy 9, but the mechanisms involved have not been clarified.MAPKs play essential roles in regulation of differentiation, cell growth, and responses to cytokines, chemokines and stress. The core element in MAPK signaling consists of a module of 3 kinases, named MKKK, MKK, and MAPK, which sequentially phosphorylate each other 10. Currently, four MAPK modules have been characterized in mammalian cells: Extracellular Regulated Kinases (ERK1 and 2), Stress activated/c-Jun N terminal kinase (SAPK/JNK), p38 MAP kinases, and ERK5 11. Interestingly, ethanol modulates MAPKs 12. However, information on how ethanol affects MAPKs in the context of innate antiviral pathways such as the Jak-Stat pathway in human cells is extremely limited. When IFN-alpha binds its receptor, two receptor associated tyrosine kinases, Tyk2 and Jak1 become activated by phosphorylation, and phosphorylate Stat1 and Stat2 on conserved tyrosine residues 13. Stat1 and Stat2 combine with the IRF-9 protein to form the transcription factor interferon stimulated gene factor 3 (ISGF-3), which binds to the interferon stimulated response element (ISRE), and induces transcription of IFN-alpha-induced genes (ISG). The ISGs mediate the antiviral effects of IFN. The transcriptional activities of Stats 1, 3, 4, 5a, and 5b are also regulated by serine phosphorylation 14. Phosphorylation of Stat1 on a conserved serine amino acid at position 727 (S727), results in maximal transcriptional activity of the ISGF-3 transcription factor complex 15. Although cross-talk between p38 MAPK and the Jak-Stat pathway is essential for IFN-induced ISRE transcription, p38 does not participate in IFN induction of Stat1 serine phosphorylation 1416171819. However, cellular stress responses induced by stimuli such as ultraviolet light do induce p38 MAPK mediated Stat1 S727 phosphorylation 18. In the current report, we postulated that alcohol and HCV proteins modulate MAPK and Jak-Stat pathways in human liver cells. To begin to address these issues, we characterized the interaction of acute ethanol on Jak-Stat and MAPK pathways in Huh7 cells, HCV replicon cells lines, and primary human hepatocytes.
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PMID:Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells. 1632 17

Hepatitis B virus currently infects more than 400 million people worldwide. Despite the availability of hepatitis B vaccine, the overall prevalence of hepatitis B virus infection has declined little in recent years. Hepatitis B virus causes liver injury by an immune response against the virus-infected liver cells and is not directly cytopathic, although immunosuppression appears to enhance replication and lead to direct cytotoxicity. The interplay of the host immune response and the virus's ability to replicate is a prime determinant of the likelihood of liver injury, its intensity, and progression to cirrhosis. A series of stages evolve in the life cycle of each patient's infection, with associated decreases in viral load at each successive stage. Viral mutations in the polymerase or the core gene affect replication and may enhance liver injury. Recently, genotypes have been identified that are linked to clinical outcomes, drug responses, and mutations. Four drugs (interferon alpha, lamivudine, adefovir, and entecavir) have been approved by the US Food and Drug Administration for treatment of hepatitis B virus; they effectively decrease replication and reduce inflammation and fibrosis. Treatment of hepatitis B virus in complex situations such as co-infection with human immunodeficiency virus or immunosuppressive therapy remains challenging. The use of hepatitis B vaccine has been shown to reduce the incidence of new infection in many regions. A decline in the prevalence of hepatitis B infection worldwide will require changes in high-risk behavior and the wider use of vaccination.
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PMID:Hepatitis B virus infection: current status. 1637 88

The prevalence and incidence of hepatitis B in hemodialysis patients in Croatia have been estimated to 1.3% and 0.03%, respectively. HBV infection in dialysis patients is usually asymptomatic, has a prolonged course, and progresses to chronic HBsAg hepatitis in 50% of cases. Some 15%-40% of HBsAg carriers on dialysis will develop cirrhosis, liver decompensation or hepatocellular carcinoma. Strict adherence to the standard infection prevention measures, continuous monitoring of HBV markers in patients on hemodialysis, patient and personnel immunization and hepatitis B treatment in hemodialyzed patients are mandatory. Each new patient in a dialysis center must be tested for HBV markers irrespective of prior immunization. All patients in the center should be routinely screened every 3-4 months. HBV immunization is mandatory for all patients on dialysis. In patients with uremia the anti-HBs antibody production is decreased (antibodies will develop in 50%-60% of cases after immunization). It is recommended to immunize all patients with progressive kidney disease, preferably in the preterminal stage. Hepatitis B therapy is recommended in all patients with biopsy proven chronic liver disease. Patients should be treated with standard interferon alpha and/or lamivudine, or peginterferon alpha monotherapy. Hepatitis B treatment is most important in kidney and/or liver transplant candidates. HBV immunization is obligatory for all hospital personnel who are in close contact with infected patients and infective materials.
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PMID:[Prevention and treatment of hepatitis B in patients on hemodialysis and vaccination of hemodialysis health personnel against hepatitis B]. 1638 Dec 47

Nosocomial transmission of blood-borne pathogens, including hepatitis C virus infection, is the most common one in a dialysis center setting. The prevalence of HCV antibodies is by far higher in patients undergoing maintenance hemodialysis therapy than in those on peritoneal dialysis. Standard infection prevention measures in hospital settings and measures of infection prevention in dialysis units should be performed. They include serologic testing for HCV of every new patient in a dialysis unit as well as routine testing of all patients every six months. Hepatitis C therapy is recommended in patients on dialysis who have detectable HCV RNA, positive liver biopsy (portal or bridging fibrosis or moderate stage of necroinflammation), younger patients (less than 65 years), and transplantation candidates. When evaluating ALT, it should be kept in mind that ESRD patients have ALT levels lower than general population, making ALT level not relevant parameter of liver disease activity in these patients. Results of hepatitis C therapy with interferon alpha and peginterferon alpha are similar to those in the general population but with more common side effects, which may require therapy discontinuation. Due to the possibility of anemia, ribavirin is contraindicated in patients with ESRD. Around 30% of patients treated with peginterferon have sustained viral response, 25%-45% of them have end of treatment viral response, and 50%-80% have end of treatment biochemical response (ALT normalization). Numerous clinical trials have established that the decrease in HCV load and prolonged suppression of viral replication during interferon therapy significantly reduce hepatic inflammation and consequently postpone progression of fibrosis to cirrhosis.
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PMID:[Prevention and treatment of hepatitis C in patients on dialysis]. 1638 Dec 48

The authors have reviewed the recent literature on the usage of interferon alpha and beta with patients affected by liver cirrhosis caused by HCV. Broad wide surveys, consisting of ten trials, met the criteria for inclusion in the study. The following points were considered: the degree of complete response (transaminase normalization); complete follow-up response; viremia clearance. Interferon alpha was used in 9 cases out of 10, while interferon beta was used in one case only, with variable dosage and different time of administration, according to the different studies. A total of 539 patients affected by chronic hepatitis or cirrhosis were examined. 245 of them were affected by chronic cirrhosis: the response was complete in 65 patients out of 245 examined (26%), while 17 of 245 (7%) had a limited response. The clearance of viremia, in those studies where this value was reported, was noted in no more than 75% of the responders. The best results were achieved in those cases where it had been possible to use higher dosages of IFN (up to 6 MU x 3) and for a period of more than 12 months, without causing noteworthy side effects. The low percentage of patients with a limited response (7%) should not dissuade from using IFN. In accordance with significant recent reports, in several cases this therapy would lead to a slowing down of the histological progression of the disease and even to a decrease in the percentage of hepato-carcinoma developments, consequently resulting in a longer life for the patient and in less need of hospitalization. These results could justify the use of interferon even though it is a very expensive treatment.
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PMID:Is interferon a useful treatment for virus C cirrhosis? 1649 32


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