Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis B and hepatitis C virus infections are the major causes of liver disease, hepatocellular carcinoma (HCC) and liver-related mortality worldwide. Among factors known to influence the natural history of viral hepatitis are age at the time of infection, duration of infection, serum alanine aminotransferase (ALT) levels, male sex, alcohol consumption, and coinfections. In hepatitis B, serum HBV DNA concentration emerges as the key factor for predicting the development of liver disease. Even patients with low viraemia seem at increased risk for liver cirrhosis and HCC. Coinfections with hepatitis C, hepatitis D and/or HIV are common and are associated with a more severe liver disease. The course of chronic hepatitis C is variable, but usually fibrosis advances slowly. In addition to the better-known factors- including coinfections with HBV and HIV- progression of liver disease is adversely affected by smoking, hepatic steatosis and insulin resistance.
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PMID:Natural history: the importance of viral load, liver damage and HCC. 1918 67

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease throughout the world, leading to cirrhosis and hepatocellular carcinoma in many individuals. Children are more likely to develop chronic HBV infection as they demonstrate greater immunotolerance to the virus, and response to therapy in children remains disappointing. Three therapeutic agents for chronic HBV infection in children have been approved in the USA, including standard IFN-alpha, lamivudine and adefovir. IFN-alpha has been the most effective ( approximately 30% hepatitis B e antigen [HBeAg] seroconversion; 10% hepatitis B surface antigen [HBsAg] seroconversion), although benefits are primarily observed in children with alanine aminotransferase levels over two-times the upper limit of normal and must be weighed against significant side effects. Studies comparing the long-term outcome of chronic hepatitis B in children treated with IFN-alpha and in untreated controls show that the rate of anti-HBeAb seroconversion tends to overlap in treated and untreated patients within a few years of follow-up, suggesting that IFN-alpha simply accelerates a spontaneous event. Lamivudine's virologic response rates mirror those of IFN-alpha (23-31% HBeAg seroconversion) with easier administration and a better safety profile but lower HBsAg seroconversion (2-3%) and high rates of drug resistance. Adefovir data show low rates of resistance and a good safety profile, but virologic response was limited to adolescent patients and was lower than that of lamivudine (16% HBeAg seroconversion; <1% HBsAg seroconversion). Entecavir and tenofovir, both approved therapies for adults with chronic HBV infection, are in trials for use in children. Future therapies will probably include these agents as well as combined therapies. Finally, watchful waiting of children is an option since current therapies are only 30% effective at best, although the long-term impact of therapy in childhood on rates of cirrhosis and hepatocellular carcinoma remains unknown.
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PMID:Hepatitis B therapy in children. 1921 Jan 12

Chronic hepatitis B virus (HBV) is estimated to be present in 350 million people worldwide. One of its major complications is reactivation of dormant HBV, which is associated with significant morbidity and mortality. Although reactivation can occur spontaneously, the most common risk factor is initiation of immunosuppression. As the use of immunosuppressive therapy increases, the incidence of HBV reactivation is expected to rise. Screening with serologic markers for hepatitis B is recommended before initiating immunosuppressive therapy. In patients with no evidence of HBV infection, immunization is recommended. In chronic carriers, prophylactic antiviral treatment has been shown to decrease overall morbidity and mortality. Patients with inactive HBV should be monitored closely during immunosuppressive treatment with alanine transaminase and serum HBV-DNA levels and treated promptly if they develop HBV reactivation. Although HBV reactivation is a serious complication, it can be prevented with screening and prophylactic treatment.
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PMID:Reactivation of hepatitis B: pathogenesis and clinical implications. 1923 1

Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major pattern recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-alpha production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly ( approximately 50%) reduced, supported by approximately 70% reduction of TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-alpha production in vitro. Furthermore, pDCs frequency in these patients was substantially reduced ( approximately 30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection.
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PMID:Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9. 1928 78

Chronic hepatitis B virus (HBV) infection has a complicated course. Three phases are identified: an immune tolerant phase with high HBV DNA and normal alanine aminotransferase (ALT) levels associated with minimal liver disease; an immune active phase with high HBV DNA and elevated ALT levels with active liver inflammation; and an inactive phase with HBV DNA levels < 2000 IU/mL and normal ALT levels with minimal inflammation and fibrosis on liver biopsy. Affected persons can move progressively from one phase to the next and may revert backward. The primary adverse outcomes of chronic HBV infection are hepatocellular carcinoma (HCC) and cirrhosis. Published natural history studies were reviewed and ranked by the strength of evidence regarding the study design. Factors with the highest evidence of risk for development of HCC or cirrhosis from population-based prospective cohort studies include male sex, family history of HCC, HBV DNA level above 2000 IU/mL in persons above age 40, HBV genotypes C and F, and basal core promoter mutation. Those with the next highest level of evidence include aflatoxin exposure, and heavy alcohol and tobacco use. Improved methods to identify persons at highest risk of developing HCC or cirrhosis are needed to allow intervention earlier with antiviral therapy in appropriate patients. Future studies should include prospective follow-up of established population-based cohorts as well as new cohorts recruited from multiple centers stratified by HBV genotypes/subgenotypes and clinical phase to determine the incidence of the various HBV phases, HCC, and cirrhosis. Also, nested case-control studies assessing immunological and host genetic factors among persons with active and inactive disease phases, HCC, and cirrhosis could be conducted using these types of cohorts.
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PMID:The natural history of chronic hepatitis B virus infection. 1939 92

Chronic hepatitis B virus (HBV) infection is estimated to be the cause of 55-60% of hepatocellular carcinoma (HCC) in the world. It has been estimated that up to 40% of HBV-related HCC occur in persons who do not have cirrhosis while almost all cases of hepatitis C virus (HCV)-related HCC occur in the setting of cirrhosis. Data on the performance of non-invasive tests for liver fibrosis in patients with hepatitis B are limited. FibroTest may be superior to the Forns index, APRI, Goteborg University Cirrhosis Index (GUCI) and Hui model in detecting significant fibrosis (Metavir>F2) or cirrhosis (Metavir F4) but an algorithm that uses APRI for screening, FibroTest for confirmation, and biopsy for indeterminate cases has the greatest accuracy. Liver stiffness correlates with fibrosis stages but may be influenced by necroinflammatory activity with falsely high values in patients with alanine aminotransferase (ALT) flares and falsely low values in patients with viral suppression and ALT normalization during antiviral therapy. Therefore, additional studies are needed to determine the clinical settings in which liver stiffness measurement can accurately predict liver fibrosis and to establish cutoff values for differentiating different stages of fibrosis or cirrhosis. These studies should also compare the performance of liver stiffness measurement with serum markers of fibrosis in patients with varying degrees of necroinflammation and in untreated patients as well as patients receiving antiviral therapy. Until recently, older age, male gender and cirrhosis were the major risk factors associated with HCC development. Recent studies showed that HBV replication status, HBV genotype and mutations in the basal core promoter region play an important role in HCC development. These data indicate that algorithms incorporating demographics, viral factors, degree of necroinflammation and extent of fibrosis may be more accurate in predicting the risk of HBV-related HCC than fibrosis staging alone.
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PMID:Hepatitis B: liver fibrosis and hepatocellular carcinoma. 1957 71

Chronic hepatitis B is considered a major public health problem, and its treatment entails increasing health budget expenses with high-cost drugs covered by Unified National Health System. The objective of this study was to compare the efficacy of interferon (conventional; pegylated - PEG2a) and lamivudine (LAM) for the treatment of chronic hepatitis B through a systematic review, selecting randomized, controlled clinical trials identified in PubMed and LILACS. Target outcomes were virological, biochemical, and histological response, seroconversion, and adverse effects. The review selected 35 articles. Presence or absence of HBeAg and pre-treatment alanine aminotransferase (ALT) levels were considered important factors in the initial therapeutic indication. Treatment with conventional interferon enables lasting disease inactivation and can result in HBsAg seroconversion. PEG2a showed better efficacy than interferon and LAM and similar side effects to interferon. LAM presents advantages such as its sensitivity in the HbeAg-negative phenotype, while its main disadvantage is the development of resistance.
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PMID:[Efficacy of interferon (conventional, pegylated) and lamivudine for treatment of chronic hepatitis B: a systematic review]. 1964 8

Chronic hepatitis B affects 5-10% of HIV patients in Western countries. Lamivudine should no longer be used as a single anti-HBV agent in HIV-HBV co-infected patients, given its limited antiviral potency and high risk of selection of resistance, which further results in wide cross-resistance to all other nucleoside analogues. Recent reports of transmission of lamivudine-resistant HBV in HIV patients are of especial concern, and large surveillance studies suggest that it may occur in up to 10% of new HBV infections in Western countries. Another worrisome aspect of the selection of lamivudine-resistant HBV is the potential for selection of vaccine escape mutants. Currently, tenofovir must be viewed as the drug of choice in HIV-HBV co-infected patients in whom antiretroviral therapy is advised. Its co-formulation with emtricitabine (Truvada) is particularly convenient for treating both HIV and HBV in co-infected individuals. While pegIFN-alpha monotherapy for 1 year may be considered for HIV-HBV coinfected individuals with good spontaneous HIV control (elevated CD4 cell count, low plasma HIV-RNA), and certain HBV features (genotype A, HBeAg+, low serum HBV-DNA and elevated ALT), it is clear that very few coinfected patients fulfill these criteria. In HBeAg-negative HIV patients, adefovir may be an option but the relatively low antiviral potency of this drug discourages its wide use. Given its potential anti-HIV activity, both entecavir and telbivudine must only be prescribed with antiretroviral agents. Lack of information about potential pharmacodynamic interactions between entecavir and abacavir (both are guanosine analogues) or between telbivudine and zidovudine or stavudine (all are thymidine analogues) further discourages their concomitant use. At this time, most experts agree that early introduction of anti-HBV active HAART is the best strategy for the treatment of chronic hepatitis B in HIV patients, and Truvada must be part of the triple regimen.
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PMID:Hepatitis B in HIV patients: what is the current treatment and what are the challenges? 1973 60

Chronic hepatitis B was characterized by fluctuant immune response to infected hepatocytes resulting in hepatic inflammation and virus persistence. Recently, Programmed Death-1 (PD-1) and its ligand PD-L1 have been demonstrated to play an essential role in balancing antiviral immunity and inflammation in the livers of acute hepatitis B patients, significantly influencing disease outcome. PD-1 up-regulation in peripheral T cells is associated with immune dysfunction in chronic hepatitis B patients. However, the effect of PD-1/PD-L1 on hepatic damage and chronic infective status is still unknown in patients with chronic HBV infection. Here, we report up-regulation of PD-1 and PD-L1 in liver biopsies from 32 chronic HBV patients compared to 4 healthy donors. PD-1/PD-L1 up-regulation was significantly associated with hepatic inflammation and ALT elevation. Moreover, appropriate up-regulation but not overexpression of PD-L1 in the active phase of chronic hepatitis B as well as lower expression of PD-L1 in the inactive phase in liver residential antigen presenting cells (including Kupffer cells and sinusoidal endothelial cells) may contribute to viral inhibition. Our data suggest that the intrahepatic interaction of PD-1 and PD-L1 might play an important role in balancing the immune response to HBV and immune-mediated liver damage in chronic HBV infection.
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PMID:Intrahepatic PD-1/PD-L1 up-regulation closely correlates with inflammation and virus replication in patients with chronic HBV infection. 1981 26

Chronic hepatitis B virus (HBV) infection in children presents a therapeutic challenge for the practitioner. Decisions regarding selection of patients who may benefit from treatment, appropriate timing of treatment, and the choice of antiviral therapy are complex and are compounded by the limited number of drugs that have been studied in children. An expert panel of nationally recognized pediatric liver specialists was convened by the Hepatitis B Foundation on August 11, 2009, to consider clinical practice relative to the therapeutic options available for children. A detailed account of these discussions is provided, and the opinions expressed are based on consensus of the experts, as well as on published evidence when available. The panel concludes that, at this time, there is no established benefit of treatment of children in the immune tolerant phase, and there is a very high risk of development of drug resistance. In addition, there is no indication for treatment of children in the inactive carrier state. For children in the immune active or reactivation phases, liver histology can help guide treatment decisions, and family history of liver disease, especially hepatocellular carcinoma, may argue for early treatment in some cases. Outside of clinical trials, interferon is the agent of choice in most cases. Nucleos(t)ide analogues are secondary therapies, and children who receive these agents require careful monitoring for development of resistance. There are a few situations when treatment is indicated regardless of HBV DNA or alanine aminotransferase levels. There is still much to be elucidated about the appropriate use of HBV therapy in children. Until more clinical data and therapeutic options are available, a conservative approach is warranted.
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PMID:Treatment of children with chronic hepatitis B virus infection in the United States: patient selection and therapeutic options. 2089 Sep 47


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