Review article: management of patients with chronic hepatitis C virus infection and ‘normal’ alanine aminotransferase activity

Zeuzem, Stefan; Alberti, Alfredo; Rosenberg, William; Marcellin, Patrick; Diago, M.; Negro, Francesco; Prati, Daniele; Puoti, Claudio; Roberts, S.; Shiffman, M.L.

doi:10.1111/j.1365-2036.2006.03073.x

Cited by 44 publications

(32 citation statements)

References 136 publications

(215 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…pyridoxal phosphate), ionic strength of buffers, sample handing and storage conditions [11]. These factors introduce variability in serum ALT activity measurement among laboratories and make it difficult to compare data obtained from different sources [16].…”

Section: Discussionmentioning

confidence: 99%

“…These factors introduce variability in serum ALT activity measurement among laboratories and make it difficult to compare data obtained from different sources [16]. Thus, a standardization of ALT assay is being recommended [11]. The discovery of ALT isoenzymes provides a new opportunity to improve the sensitivity and specificity of ALT in that these two isoenzymes are encoded by two separated genes, and differentially distributed in tissues, liver lobule and subcellular compartment (Yang et al, unpublished data).…”

mentioning

confidence: 99%

“…Thus, measurement of ALT isoforms may have more diagnostic value than the currently-being-used ALT activity assay, which presumably measure total ALT1 and ALT2 activity. Currently, ALT catalytic activity is measured in clinical chemistry by a spectrophotometric assay, whose accuracy is vulnerable to the influence of a numbers of factors including temperature, substrate concentration and sample handling and storage conditions [11]. The variations of ALT activity assays among and within the laboratories and the lack of a protein-based reference have made it difficult to define a "normal" range of serum ALT levels in healthy people and hence, a standardization of ALT assays is recommended [11,12].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Expression, purification, and initial characterization of human alanine aminotransferase (ALT) isoenzyme 1 and 2 in High-five insect cells

Liu

Zhong

Yang

et al. 2008

Protein Expression and Purification

View full text Add to dashboard Cite

Alanine aminotransferase (ALT) is a key enzyme for gluconeogenesis as well as a widely-used serum marker for liver injury. We have identified two ALT isoenzymes, ALT1 and ALT2, which are encoded by separate genes. In this study, we described the expression, purification and initial characterization of human ALT1 and ALT2 proteins in High-five insect cells. Human ALT1 and ALT2 were expressed as His-tagged fusion proteins by recombinant baculovirus in insect cells and purified into homogeneity in one step by using immobilized Ni 2+ -affinity chromatography. Tag-free ALT1 and ALT2 were obtained by cleavage of enterokinase digestion and used for initial characterization of the enzymes. The specific ALT activity of purified fusion or His-tag-removed ALT1 is about 15-fold higher than that of ALT2 and their enzymatic activities decrease quickly at 37°C and −20°C, but are well preserved at −80°C. Nevertheless, the ALT1 and ALT2 activities remained stable in a buffer containing 25% glycerol. The pH profile was similar between hALT1 and hALT2 in that both enzymes remained fully active between pH 6.5 and 8.0. The purified ALT recombinant proteins can not only be used as a reference protein standard for the ALT assay in clinical chemistry, but also will be useful for understanding biochemical and biological significance of the isoenzymes and for developing the ALT isoform-specific assays for clinical or preclinical diagnostic use.Alanine aminotransferase (ALT) [EC 2.6.1.2., formerly glutamate-pyruvate transaminase], is a pyridoxal enzyme catalyzing reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Through producing those four important intermediary metabolites, ALT plays an important role in gluconeogenesis and amino acid metabolism, 6Corresponding author: Da-Wei Gong, M.D., Ph.D., Associate Professor, University of Maryland School of Medicine, 660 W. Redwood St., HH#426, Baltimore, MD 20210. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recently, two isoforms of ALT, ALT1 and ALT2, each encoded by a different gene, have been identified in human and mouse with distinct tissue expression at the mRNA level; ALT1 is mainly expressed in intestine, liver, kidney, and heart, whereas ALT2 is mainly expressed in muscle, brain, fat, kidney and liver [2,3], suggesting a functional difference in biology between the isoenzymes. On the other hand, the measurement of serum ALT activity is one of the most widely-used assays in clinical chemistry. An elevated serum ALT activity is regarded as evidence of liver damage, including hepatitis, nonalcoh...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Expression, purification, and initial characterization of human alanine aminotransferase (ALT) isoenzyme 1 and 2 in High-five insect cells

Liu

Zhong

Yang

et al. 2008

Protein Expression and Purification

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

“…Patients could develop anaemia or, for those with anaemia, worsening anaemia was defined as a haemoglobin level 8 mg/dL. For the liver function tests, 40 IU/L was taken as the ULN (for both ALT and AST) [18].Patients were followed until they experienced an event or to the date of their last measurement for each clinical or laboratory marker in EuroSIDA. It should be noted that not all patients in all groups had information on these markers available for all analyses; therefore, the number of patients included in each analysis differed according to the availability of data.…”

mentioning

confidence: 99%

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

et al. 2010

View full text Add to dashboard Cite

ObjectivesThe durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures. MethodsPatients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started 3 months after initiation of treatment if viral load was o500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. ResultsA total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P 5 0.43) or lopinavir (P 5 0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P 5 0.0002) and those on lopinavir a 63% (Po0.0001) lower risk of discontinuation because of treatment failure and a 31% (P 5 0.01) and 66% (Po.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P 5 0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P 5 0.39). ConclusionsThe long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen. [5][6][7]. Such long-term adverse events can influence the durability of a regimen. Combination antiretroviral therapy (cART) regimens most often include a nonnucleoside reverse transcriptase inhibitor, such as efavirenz or nevirapine, or a ritonavirboosted protease inhibitor, such as lopinavir [8,9]. cART regimens with durability as well as virological efficacy are required in order to achieve long-term virological suppression and to maintain CD4 cell counts at a level that significantly reduces the risk of morbidity and mortality. Many cohort studies have compared the short-term and long-term efficacies of different cART regimens [10][11][12][13][14], but less is known about the durability of different regimens, particularly in patients who have started a cART regimen more recently. If a regimen is virologically effective, durability can then be measured as the time to discontinuat...

show abstract

Diagnosis of Nonalcoholic Fatty Liver Disease

Lee¹

2003

JAMA

View full text Add to dashboard Cite

Review article: management of patients with chronic hepatitis C virus infection and ‘normal’ alanine aminotransferase activity

Cited by 44 publications

References 136 publications

Expression, purification, and initial characterization of human alanine aminotransferase (ALT) isoenzyme 1 and 2 in High-five insect cells

Expression, purification, and initial characterization of human alanine aminotransferase (ALT) isoenzyme 1 and 2 in High-five insect cells

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

Diagnosis of Nonalcoholic Fatty Liver Disease

Contact Info

Product

Resources

About