Unusual Pattern of Dyslipidemia in Children Receiving Steroid Minimization Immunosuppression after Renal Transplantation

Lau, Keith K.; Tancredi, Daniel J.; Perez, Richard V; Butani, Lavjay

doi:10.2215/cjn.08431109

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…Predictors of posttransplant hypertriglyceridemia include cirrhosis resulting from HCV, HBV, alcohol, cryptogenic cirrhosis and posttransplant renal insufficiency [35]. Although, long-term therapy with corticosteroids can result in dyslipidemia, it is unclear how corticosteroids impact long-term dyslipidemia in posttransplant population [40]. Corticosteroids can lead to dyslipidemia by increasing the hepatic production of lipids, increased production of very low-density lipoprotein (VLDL) cholesterol, and decreased hepatic LDL reuptake.…”

Section: Posttransplant Dyslipidemiamentioning

confidence: 99%

Posttransplant Metabolic Syndrome

Siddiqui

Sterling

2012

International Journal of Hepatology

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Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients.

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Section: Posttransplant Dyslipidemiamentioning

confidence: 99%

Posttransplant Metabolic Syndrome

Siddiqui

Sterling

2012

International Journal of Hepatology

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“…The effect on posttransplant diabetes is potentially reversible because the prevalence of diabetes once steroids are discontinued is decreased and is no different from that in patients on steroid‐free regimens 13. Corticosteroids are also associated with hyperlipidemia in patients on long‐term therapy, but this association may not be as strong with short‐term use 14. Corticosteroids generally affect low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) levels (both increase), but they have less effect on triglycerides with prolonged use.…”

Section: Immunosuppression and Msmentioning

confidence: 99%

Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance

Preiss

Littlejohn

Angus³

et al. 2008

Hepatology

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Defective hepatitis B virus DNA (dDNA) is reverse-transcribed from spliced hepatitis B virus (HBV) pregenomic messenger RNA (pgRNA) and has been identified in patients with chronic HBV (CH-B). The major 2.2-kb spliced pgRNA encodes a novel HBV gene product, the hepatitis B splice protein (HBSP) via a deletion and frame shift within the polymerase. Although spliced RNA and HBSP expression have been associated with increased HBV DNA levels and liver fibrosis, the role of dDNA in HBV-associated disease is largely undefined. Our aims were to (1) compare the relative proportions of dDNA (% dDNA) in a range of HBV-infected serum samples, including patients with human immunodeficiency virus (HIV)/HBV coinfection and HBV-monoinfected persons with differing severities of liver disease, and (2) determine the effect of mutations associated with drug resistance on defective DNA production. Defective DNA was detected in 90% of persons with CH-B. There was no significant difference in the relative abundance of dDNA between the monoinfected and HIV/HBVcoinfected groups. We also found no association between the % dDNA and alanine aminotransferase, hepatitis B e antigen status, HBV DNA levels, fibrosis levels, compensated or decompensated liver cirrhosis, genotype, or drug treatment. However, the % dDNA was significantly lower in individuals infected with lamivudine-resistant (LMV-R) HBV compared with wild-type HBV (P < 0.0001), indicating that antiviral drug resistance alters the balance between defective and genomic length DNA in circulation. Experiments in vitro using HBV encoding LMV-R mutations confirmed these results. Conclusion: Our results identified no association between dDNA and parameters associated with disease status and suggested that the relative abundance of dDNA is largely dependent on the integrity of the HBV polymerase and is unrelated to the severity of liver disease. (HEPATOLOGY 2008;48:741-749.) H epatitis B (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. HBV infection is normally not cytopathic, with liver disease resulting from immune-mediated lysis of HBV-infected cells. 1 A more aggressive form of hepatitis is associated with human immunodeficiency virus (HIV)/HBV coinfection, with liver mortality rates 14-fold higher than HBV-monoinfected individuals, 2 despite these individuals having immune dysfunctions. The reasons for this are unclear, although HBV DNA levels are higher in HIV/ Abbreviations: % dDNA, relative proportions of defective hepatitis B

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“…Since humoral rejection can have very significant long term implications on graft survival, this is an area that needs to be studied more meticulously. Another potential concern is the long term impact of the low HDL levels that are seen in patients who are not receiving corticosteroids, on cardiovascular health [29].…”

Section: Advantages Seen In Childrenmentioning

confidence: 99%