Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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, a noncytopathic hepatotropic RNA virus, affects over 170 million people worldwide. In the majority of cases, neither the early innate immune response nor the later adaptive immune response succeeds in clearing the virus, and the infection becomes chronic. Furthermore, in many patients, the ineffective inflammatory response drives fibrogenesis and the development of cirrhosis. It is critical to understand this immune pathology if preventative and curative therapies are to be developed. Chemokines are a superfamily of small proteins that promote leukocyte migration and orchestrate the immune response to viruses, including hepatitis C virus. Chemokines are crucial for viral elimination, but inappropriate persistence of expression in chronic hepatitis C infection can drive tissue damage and inflammation. Here we review the role of chemokines and their receptors in hepatitis C virus infection.
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PMID:Chemokines in the immunopathogenesis of hepatitis C infection. 1917 77

Currently, >350 million people worldwide are affected by chronic infection with the hepatitis B virus (HBV). Chronic infection may cause cirrhosis and hepatocellular carcinoma; HBV infection is responsible for 328,000 cancer deaths per year. In areas of high HBV endemicity, most infections occur early in life; infected children do not mount an effective immune response and exhibit immune tolerance, so that the risk of chronic infection is high. In areas of low endemicity, infections tend to be in adults within defined risk groups, and the risk of chronicity is much lower. Population migration from areas of high endemicity to areas of low endemicity is creating pockets of HBV infection in areas of low general prevalence, necessitating improved efforts to screen, vaccinate, and treat. Chronic HBV infection is a complicated, nonlinear disease with a variable course of progression; predictors of progression include the duration of time in the immunoactive phase of disease that follows the immune tolerant phase when hepatocytes are attacked. Additionally, the duration of a high viremic state, with ongoing clinical hepatitis and possibly concurrent infections (e.g., hepatitis C, human immunodeficiency virus), influence outcome. Targeted vaccination of high-risk groups has many limitations. Universal childhood vaccination to prevent chronic infection and its sequelae is the only approach that will lead to the global elimination of chronic HBV infection.
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PMID:Demography and presentation of chronic hepatitis B virus infection. 1918 72

Chronic infection with hepatitis C virus (HCV) affects 130 million people worldwide and is a major cause of liver cirrhosis and liver cancer. After translation of the HCV RNA genome into a polyprotein, 2 viral proteases process its non-structural protein (NS) region. While the essential chymotrypsin-like serine protease NS3-4A mediates all cleavages downstream of NS3, the NS2-3 cysteine protease catalyzes a vital cleavage at the NS2/3 site. Protease activity of NS2-3 has been described to require, besides NS2, the N-terminal 181 aa of NS3. The latter domain corresponds to the NS3 serine protease domain and contains a structural Zn(2+)-binding site with functional importance for both viral proteases. The catalytic triad of the NS2-3 protease resides in NS2; the role of the NS3 part in proteolysis remained largely undefined. Here we report a basal proteolytic activity for NS2 followed by only 2 amino acids of NS3. Basal activity could be dramatically enhanced by the NS3 Zn(2+)-binding domain (NS3 amino acids 81-213) not only in cis but also in trans which, however, required a more extended N-terminal part of NS3 downstream of NS2 in cis. Thus, this study defines for the first time (i) NS2 as a bona fide protease, (ii) NS3 as its regulatory cofactor, and (iii) functional subdomains in NS3 that cooperate in NS2 protease activation. These findings give new mechanistic insights into function and regulation of the NS2 protease and have important implications for the development of anti-HCV therapeutics.
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PMID:Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3. 1928 77

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular carcinoma (HCC), mostly in patients with liver cirrhosis. Present study aimed at evaluation of cellular expression of p53 protein, genetic TP53 changes in liver samples and anti-p53 in serum of patients with chronic hepatitis C virus infection. The expression of p53 protein were analysed by immunocytochemistry in liver biopsies from adult patients with chronic, long-lasting hepatitis C. In order to detect TP53 mutations, PCR/SSCP and sequencing were performed. Antibodies against p53 in serum were determined using enzyme immunoassay (ELISA).In two out of 14 examined patients TP53 point mutations were detected in the liver samples. In the first patient, a substitution of C to T was demonstrated in position 1 of the codon 250, resulting in substitution of proline by serine. The other patient carried a substitution of C to G in position 13274 of the intron 6. The patient carrying mutation in the codon 250 demonstrated morphological traits of liver cirrhosis and had high number of p53-immunoreactive cell nuclei in tissue. None of the patients manifested elevated titres of serum anti-p53. In the liver, significant positive correlations were disclosed between expression of p53 on one hand and grading and staging on the other. A negative correlation was disclosed between cellular expression of p53 and duration time of infection. In conclusions, genetic changes in TP53 can be detected also in non-neoplastic lesions linked to chronic HCV infection.
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PMID:p53 immunocytochemistry and TP53 gene mutations in patients with chronic hepatitis C virus (HCV) infection. 1941 35

Infection with the hepatitis C virus is a major public health problem and is the leading cause of liver disease in the United States. Chronic infection with hepatitis C virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferon or peginterferon, and ribavirin. The objective of treatment is to eradicate the infection in an effort to prevent complications of hepatitis C virus infection.
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PMID:Pharmacotherapy of hepatitis C virus infection: a brief review. 1958 4

Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-alpha-2b (PegIFN-alpha-2b) or -alpha-2a (PegIFN-alpha-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon-lambda-3 (IFN-lambda-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06 x 10(-25)) and African-Americans (P = 2.06 x 10(-3)). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.
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PMID:Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. 2043 5

Chronic infection with hepatitis C virus (HCV) is a serious public health problem affecting an estimated 2% of the world's population. The natural history of HCV infection in hemodialysis patients remains incompletely understood and the management is difficult. HCV infection in hemodialysis patients is usually asymptomatic. Given the diminished life expectancy of hemodialysis patients, complications such as decompensated cirrhosis and hepatocellular carcinoma may not have time to develop. The frequency of advanced fibrosis or cirrhosis ranges from 0% to 28 %. We discuss in this presentation several aspects of HCV infection in chronic kidney disease (CKD) patients such as relationship with glomerulopathy, renal allograft outcome, prevalence in hemodialysis patients in the kingdom of Saudi Arabia, treatment of HCV in hemodialysis patients in the kingdom of Saudia Arabia, and finally our experience at Prince Salman Center for kidney disease (PSCKD) in the management of HCV infected hemodialysis patients.
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PMID:Treatment of a common problem in hemodialysis patients: is the juice worth the squeeze? 1973 96

Chronic infection with hepatitis B virus (HBV) is an important cause of cirrhosis and cancer of the liver. HBV is currently classified into eight genotypes, A to H. Accumulated evidence shows that the genotype influences both the clinical course of infection and the response to treatment. We describe a new method for genotyping based on TaqMan real-time PCR, which identifies all HBV genotypes without post-PCR processing. In this assay, each sample is processed in four multiplex real-time PCRs, each targeting two or three genotype-specific segments of HBV. By analyzing 185 samples representing all genotypes and different proportions of genotype mixtures, we could validate high accuracy of the assay. We conclude that this new assay represents a significant advancement for both diagnostics and clinical research because it is accurate, practical, and based on a technique that is well established in many virological laboratories.
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PMID:Novel method for genotyping hepatitis B virus on the basis of TaqMan real-time PCR. 2010 90

Chronic infection with hepatitis B virus (HBV) is strongly associated with hepatocellular carcinoma (HCC), and the viral HBx protein plays a crucial role in the pathogenesis of liver tumors. Because the protooncogene pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in HCC, we investigated the regulation of this protein by HBx. We analyzed PTTG1 expression levels in liver biopsies from patients chronically infected with HBV, presenting different disease stages, and from HBx transgenic mice. PTTG1 was undetectable in biopsies from chronic hepatitis B patients or from normal mouse livers. In contrast, hyperplastic livers from transgenic mice and biopsies from patients with cirrhosis, presented PTTG1 expression which was found mainly in HBx-expressing hepatocytes. PTTG1 staining was further increased in HCC specimens. Experiments in vitro revealed that HBx induced a marked accumulation of PTTG1 protein without affecting its messenger RNA levels. HBx expression promoted the inhibition of PTTG1 ubiquitination, which in turn impaired its degradation by the proteasome. Glutathione S-transferase pull-down and co-immunoprecipitation experiments demonstrated that the interaction between PTTG1 and the Skp1-Cul1-F-box ubiquitin ligase complex (SCF) was partially disrupted, possibly through a mechanism involving protein-protein interactions of HBx with PTTG1 and/or SCF. Furthermore, confocal analysis revealed that HBx colocalized with PTTG1 and Cul1. We propose that HBx promotes an abnormal accumulation of PTTG1, which may provide new insights into the molecular mechanisms of HBV-related pathogenesis of progressive liver disease leading to HCC development.
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PMID:Expression of pituitary tumor-transforming gene 1 (PTTG1)/securin in hepatitis B virus (HBV)-associated liver diseases: evidence for an HBV X protein-mediated inhibition of PTTG1 ubiquitination and degradation. 2019 33

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-alpha and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support.
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PMID:Role of Sleep Disturbance in Chronic Hepatitis C Infection. 2020 85


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