Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such as the core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed-cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein-protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.
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PMID:Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. 1535 43

At least five hepatitis viruses are known to date. Infection by enterically transmitted viruses (HAV and HEV) is generally benign compared with the disease caused by parenterally transmitted viruses (HBV, HCV, and HDV). Chronic infection by HBV is common and may evolve to cirrhosis and hepatocellular carcinoma (HCC). Eight HBV genotypes (A-H) have been described, with the South American genotype F being the most divergent. Seven clades of HDV have been described; among them, the South American genotype III is associated to a high frequency of fulminant hepatitis. HCV infection leads to a high rate of chronicity and HCC. From the six HCV genotypes, infection with genotype 1 might have the worst prognostic. Chronic infection by HCV and HBV is the major risk factor for HCC, which occurs, in the majority of the cases, as a consequence of cirrhosis. However, there is growing evidence that some HBV and HCV proteins might contribute to the generation of HCC. Some HBV and HCV variants and specific mutations within the viral genomes might be more frequently associated with the evolution to HCC. Although more studies are needed, emerging evidence indicates that it might be important to address the genetic variability of these viruses and their contribution to the development of HCC.
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PMID:Genotypic variability of hepatitis viruses associated with chronic infection and the development of hepatocellular carcinoma. 1600 Sep 30

Chronic infection of hepatitis virus B (HBV) has been proven to be one of the most important risk factors of hepatocellular carcinoma (HCC). HBx has been shown to function in the viral life cycle and the development of HCC. Recently, we have reported that HBx transgenic mice (p21-HBx), generated by gene knockin, develop HCC at the age of 18 months. To further study the function of HBx during the development of HCC in vivo, we performed proteomic analysis of the transgenic and wild-type control mice. The combination of 2-DE and MALDI-TOF MS revealed that proteasome subunits (PSMA6, PSMB4, PSMC2 and PSMD12) were up-regulated in tumor tissues of the p21-HBx transgenic mice. Cathepsin B, ubiquinol-cytochrome C reductase core protein 1 and an ATP-dependent caseinolytic protease, which were involved in the cellular proteolytic process, were also found increased in tumors. The results were confirmed in tumors of transgenic mice and HCCs of human using RT-PCR. All these results suggested that the strengthened ubiquitin-proteasome and lysosomal pathway might contribute to the development of HBx-related HCC.
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PMID:The up-regulation of proteasome subunits and lysosomal proteases in hepatocellular carcinomas of the HBx gene knockin transgenic mice. 1631 74

Chronic infection by hepatitis C virus (HCV) is the leading cause of severe hepatitis that often develops into liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms underlying HCV replication and pathogenesis are poorly understood. Similarly, the role(s) of host factors in the replication of HCV remains largely undefined. Based on our knowledge of other RNA viruses, it is likely that a number of cellular factors may be involved in facilitating HCV replication. It has been demonstrated that elements within the 3'-nontranslated region (3'-NTR) of the (+) strand HCV genome are essential for initiation of (-) strand synthesis. The RNA signals within the highly conserved 3'-NTR may be the site for recruiting cellular factors that mediate virus replication/pathogenesis. However, the identities of putative cellular factors interacting with these RNA signals remain unknown. In this report, we demonstrate that an RNA affinity capture system developed in our laboratory used in conjunction with LC/MS/MS allowed us to positively identify more than 70 cellular proteins that interact with the 3'-NTR (+) of HCV. Binding of these cellular proteins was not competed out by a 10-fold excess of nonspecific competitor RNA. With few exceptions, all of the identified cellular proteins are RNA-binding proteins whose reported cellular functions provide unique insights into host cell-virus interactions and possible mechanisms influencing HCV replication and HCV-associated pathogenesis. Small interfering RNA-mediated silencing of selected 3'-NTR-binding proteins in an HCV replicon cell line reduced replicon RNA to undetectable levels, suggesting important roles for these cellular factors in HCV replication.
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PMID:Identification of cellular factors associated with the 3'-nontranslated region of the hepatitis C virus genome. 1650 Sep 30

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are major causes of liver disease. Chronic infection with these viruses often leads to chronic liver disease, including cirrhosis or primary hepatocellular carcinoma (HCC). Concern is growing among patients and health care workers about possible transmission of bloodborne pathogens during medical procedures. This fear has primarily been focused on nosocomial transmission of human immunodeficiency virus (HIV), but other bloodborne infectious agents may also be transmitted during procedures. Chief among these are the hepatitis viruses, particularly HBVand HCV, both of which are significantly more widespread than HIV Circumstantial evidence suggests that hemodialysis, per se, is an important risk factor for infection with HCV.
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PMID:Hepatitis and transfusions. 1664 31

Chronic infection of hepatitis C (HCV) and B virus (HBV) frequently causes viral hepatitis. Patients with chronic viral hepatitis are at risk for liver cirrhosis and even hepatocellular carcinoma. In patients with chronic hepatitis C, the most effective therapy is elimination of HCV with interferon (IFN). The most effective initial IFN therapy is the combination of pegylated IFN alpha-2b plus ribavirin. Forty-eight weeks of this combination therapy produces sustained viral response rates of approximately 50%. Moreover, several reports showed that long-term IFN therapy also reduced the risk of liver carcinogenesis. In patients with chronic hepatitis B, seroconversion from HBeAg to anti-HBe antibodies suppresses viral replication and attenuates the hepatitis. Twenty-four weeks of IFN therapy produces HBeAg seroconversion rates approximately 30%.
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PMID:[HCV-HBV infection]. 1683 49

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 the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality. The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects. One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV.
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PMID:ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. 2079 5

Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co-infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV-HDV co-infection compared to HBV mono-infection. Chronic infection after acute hepatitis B + D co-infection is infrequent and similar to the rate in mono-infected patients. CDH develops in 70-90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10-15% of patients. However, as with any immune-mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.
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PMID:Natural history and treatment of chronic delta hepatitis. 2072 36

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent manner and contributes to steatosis, progression of fibrosis and resistance to interferon plus ribavirin therapy. Our understanding of HCV-induced IR has improved considerably over the years, but certain aspects concerning its evaluation still remain elusive to clinical researchers. One of the most important issues is elucidating the ideal method for assessment of IR in the setting of hepatitis C. The hyperinsulinaemic euglycaemic clamp is the gold standard method for determining insulin sensitivity, but is impractical as it is labour intensive and time-consuming. To date, all human studies except for four where IR was evaluated in the HCV setting, an estimation of IR has been used rather than direct measurements of insulin-mediated glucose uptake. The most commonly used estimation in the HCV population is the homeostasis model assessment of insulin resistance (HOMA-IR) which is calculated from a single measurement of fasting insulin and glucose. In this article, we review the use and reporting of HOMA in the literature and provide guidance on its appropriate as well as inappropriate use in the hepatitis setting.
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PMID:Use of HOMA-IR in hepatitis C. 2191 84


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