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)

Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.
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PMID:The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase. 1057 81

NATURAL HISTORY OF HEPATITIS C-INFECTION AND VIRAL CHARACTERISTICS: Hepatitis C-virus (HCV) infection is a major cause of non-A, non-B-hepatitis and, additionally, is associated with liver cirrhosis and hepato-cellular carcinoma. The high degree of chronificity of HCV-infection is reasonable due to antigenic variability of neutralizing epitopes leading to incomplete immunoresponse with subsequent virus persistence. Besides genetic variants of HCV within a virus population (quasispecies nature of HCV), different genotypes are classified being genetically and phenotypically distinct, and geographically restricted in part. Genotyping of HCV is not only important for phylogenetic and epidemiological studies, but also a predictive marker for pathogenesis and therapy. VIRAL PREDICTORS OF HCV THERAPY: In a meta-analysis of 18 therapeutical studies of chronical HCV infections, genotype 1 and high levels of viremia determined markedly the response to interferon therapy. In this context, clinical trials have proven the effect of a combined therapy with interferon and ribavirin. Especially patients with HCV genotype 1 or high levels of viremia had a real benefit from combined antiviral therapy in comparison to monotherapy with interferon. CONCLUSION AND FUTURE CONCEPTS: Besides recent concepts improving the therapeutical response to HCV infection, further effort is necessary to develop more successful strategies for eradication of hepatitis C virus. In this context, variations of interferon therapy should be evaluated (e.g. higher and daily doses, longer duration of interferon therapy, "retarded" interferon (PEG-IFN). In addition, new therapeutical concepts should be performed including a combination of interferon with other known antiviral agents (amantadine), a combination with immunomodulators (GM-CSF, thymosin alpha 1), the development of new antiviral agents (inhibitors of viral proteases, helicases and polymerases) and the exploration of anti-viral, molecular strategies (specific ribozymes, antisense oligonucleotides and DNA-vaccination). Nevertheless, the development of an effective vaccination should be the most important challenge for the future.
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PMID:[Characteristics of the hepatitis C virus and viral predictors of therapeutic response]. 1060 34

PROTEASE SPARING REGIMEN: Due to the problems of tolerance an acceptability of tritherapy regimens, generally composed of 2 nucleosidic reverse transcription inhibitors (NRTI) and a protease inhibitor (PI), it might be beneficial to use a protease sparing regimen replacing the PI by a third antiretroviral agent. HIV/HCV CO-INFECTION: Co-infection with the hepatitis C virus may seriously compromise long-term survival due to the rapid progression of HCV infection to chronic hepatitis and/or cirrhosis.
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PMID:[Managing HIV infection. 2 new aspects]. 1060 61

The tropical features of hepatitis C have not yet been fully elucidated due to the scarcity of data. However it has been estimated that two-thirds of the infected population lives in tropics. The most heavily affected regions are Africa, China, and southeast Asia with prevalence rates of 5.3, 3.0, and 2.4 p. 100 respectively. In several countries mostly in Africa, prevalence rates range from 5 to 10 p. 100 or higher. Age is a major risk factor for infection. The classic transmission modes, i.e., blood transfusion and intravenous drug use, do not account for these high prevalence rates. Another mechanism could be parenteral injection under unsafe conditions. The most widespread genotypes in tropical areas are genotypes 1, 2, and 3. Other genotypes can be encountered locally including genotype 4 in black Africa and Egypt, genotype 6 in southeast Asia, and genotypes 1 and 3 in India. The association of hepatitis C with chronic liver disease has been the focus of several studies, mainly in Africa. The seroprevalence of virus C ranges from 2 to 55 p. 100 in cases of chronic hepatitis or cirrhosis and from 0 to 47 p. 100 in cases of hepatocellular cancer. Hepatitis C could be the underlying cause of 33 to 50 p. 100 of chronic liver diseases not linked to virus B. It is observed more often in patients with chronic hepatitis or cirrhosis than cancer in which virus B is dominant. Infection by both virus is rare without liver disease but is more frequent in patients with cancer than chronic non-tumoral liver disease.
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PMID:[Hepatitis C in tropical areas]. 1090 56

Infection with the hepatitis C virus leads to chronic hepatitis in the majority of patients. Diagnosis is based on the presence of anti-HCV antibodies and confirmed by positive HCV RNA. The natural course of the disease is slow. Cirrhosis is found in a minority of patients two decades post infection. Nevertheless, cirrhosis is much more frequently observed than in patients with hepatitis B infection. Treatment of choice is interferon-alpha. Today combination with ribavirin is recommended for most patients. In combination therapy the sustained response rate six months after stop of treatment is about 40% in naive patients with respect to virus elimination. In patients treated with high doses of interferon-a for one year the sustained response rate is comparable. The response rate is higher in patients with HCV infections of non-1 genotype and in patients with lower virus titers, e.g. less than 2 Mill. genome equivalents per ml. Interferon-a treatment also leads to an improvement of liver histology. Necro-inflammatory scores are reduced. It has also an antifibrogenic effect. Progression of fibrosis is reduced. The antiproliferative effect of interferon-a leads a lower rate of hepatocellular carcinomas, which has been demonstrated in several retrospective studies. In patients with Child A cirrhosis the time till decompensation is delayed. Because of the slow progression, the relatively low response rate and the adverse events of interferon-a and ribavirin treatment should be instituted on an individual base depending on host factors such as age, co-morbidity and stage of liver disease.
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PMID:[Hepatitis C--standard therapy]. 1090 61

This report summarizes a state-of-the-art workshop held in September 1998 on the "Natural History and Outcome of Hepatitis C Infection". Sixteen Canadian and two internationally renowned hepatologists were invited. A practical classification of HCV infection served as a framework for the meeting. The concepts of modelling of chronic disease, the epidemiology of HCV infection before the introduction of anti-HCV testing, and the outcome of various forms of chronic hepatitis C in adults and children were presented. Lectures on the outcome of HCV cirrhosis, hepatocellular carcinoma, the role of liver transplantation, the influence of host factors on outcome, iron overload in chronic hepatitis C and possible modification of the natural history by antiviral therapy were followed by discussion and consensus statements pertaining to each presentation. "The European Experience in Assessing Chronic Hepatitis C" was presented by Prof G Dusheiko from the United Kingdom, and Prof Leonard Seeff from the National Institutes of Health (United States) presented "The Epidemiology and Outcome of Hepatitis C Infection in the United States and the World".
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PMID:Hepatitis C infection: its sequelae and outcomes--State-of-the-Art Workshop, September 24 to 25, 1998. Canadian Association for the Study of the Liver. 1093 6

Infection with influenza virus poses specific problems in pediatric and adult liver transplant recipients, both before and after liver transplantation. These include a higher rate of pulmonary and extrapulmonary complications, development of rejection with graft dysfunction, prolonged shedding of influenza virus, and increased drug-resistance. Hepatic decompensation may occur during influenza infection in patients with cirrhosis. Current prophylaxis includes yearly vaccination with trivalent inactivated vaccine. Appropriate diagnosis and prompt treatment of any upper respiratory infections are indicated in these patients. In this review, we describe a case of influenza viral pneumonia in an adult liver transplant recipient, review basic and clinical aspects of influenza infection in this patient population, and discuss current modes of prevention and treatment in detail.
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PMID:Influenza infection in patients before and after liver transplantation. 1098 51

Infection by Hepatitis C Virus (HCV) leads to a slowly progressing disease that over two decades can lead to liver cirrhosis or liver cancer. Currently, one of the most promising approaches to anti-HCV therapy is the development of inhibitors of the NS3/4A protease, which is essential for maturation of the viral polyprotein. Several substrate-derived inhibitors of NS3/4A have been described, all taking advantage of binding to the S subsite of the enzyme. Inspection of the S' subsite of NS3/4A shows binding pockets which might be exploited for inhibitor binding, but due to the fact that ground-state binding to the S' subsite is not used by the substrate, this does not represent a suitable starting point. We have now optimized S'-binding in the context of noncleavable decapeptides spanning P6-P4'. Binding was sequentially increased by introduction of the previously optimized P-region [Ingallinella et al. (1998) Biochemistry 37, 8906-8914], change of the P4' residue, and combinatorial optimization of positions P2'-P3'. The overall process led to an increase in binding of more than 3 orders of magnitude, with the best decapeptide showing IC(50) < 200 pM. The binding mode of the decapeptides described in the present work shares features with the binding mode of the natural substrates, together with novel interactions within the S' subsite. Therefore, these peptides may represent an entry point for a novel class of NS3 inhibitors.
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PMID:Optimization of the P'-region of peptide inhibitors of hepatitis C virus NS3/4A protease. 1104 54

Infections with Bartonella henselae or Bartonella quintana present with vasoproliferative lesions in skin and parenchymatous organs in immunocompromised patients. A case report of a 38-year-old patient with HIV infection and hepatitis B surface antigen status is described. The dominant clinical symptoms in our patient were fever and icterus. Ultrasonography of the abdomen showed a picture similar to that of liver cirrhosis. Irregular (echorich) nodes with hyper-vascularization were suspected to be hepatocellular carcinoma. Ultrasound guided puncture of one of these lesions and histological examination revealed the diagnosis of bartonella infection. Under antibiotic treatment with clarithromycin and doxycycline the fever and the hyperbilirubinemia decreased. The sonographically detectable lesions reduced in size. Vasoproliferative lesions in immunodeficient patients caused by bartonella infection show a characteristic slightly hyperechogenic irregular pattern at ultrasound. Typically, circumscribed hypervascularization might be shown by color Doppler imaging. Liver cirrhosis and diffuse tumor infiltration should be excluded.
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PMID:[Bacillary angiomatosis of the liver, a suspected ultrasound diagnosis?]. 1107 74

Hepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection.
Infection
PMID:Hepatitis B virus vaccine for patients with hepatitis C virus infection. 1113 51


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