Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis

Czaja, Albert J.; Cookson, Sharon; Constantini, Patrizia K.; Clare, Michael; Underhill, James A.; Donaldson, Peter

doi:10.1016/s0016-5085(99)70458-0

Cited by 155 publications

(88 citation statements)

References 44 publications

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“…When compared with the frequencies determined by Perrey et al 21 and Tanaka et al, 24 there appears to be an under-representation and overrepresentation respectively of the ''AA'' genotype in our HCV patients. However, there was no significant difference when the frequency of this polymorphism in our HCV patients was compared with the control populations in studies by Huang et al 25 and Czaja et al 26 The age of the patients (70% men) ranged from 23 to 66 years, with a mean age of 37.9 (SD 6.6) years. The possible source of hepatitis was previous intravenous drug use in 88 (68.8%), posttransfusion in 20 (15.6%), and other risk factors or unknown in 20 (15.6%).…”

Section: Polymorphisms Of the Cytokine And Ras Genes In Patients Withmentioning

confidence: 57%

Host genetic factors influence disease progression in chronic hepatitis C

et al. 2000

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Progressive hepatic fibrosis and cirrhosis develops in 20% to 30% of patients with chronic hepatitis C virus (HCV). We propose that host genetic factors influencing fibrogenesis may account for some of the variability in progression of this disease. In progressive fibrosis of other organs, particularly heart and kidney, production of the profibrogenic cytokine, transforming growth factor β1 (TGF‐β1), may be enhanced by angiotensin II, the principal effector molecule of the renin‐angiotensin system. The inheritance of polymorphisms in TGF‐β1, interleukin 10 (IL‐10), tumor necrosis factor α (TNF‐α), and genes of the renin‐angiotensin system was examined in 128 patients with chronic HCV. The influence of genotypes on the stage of hepatic fibrosis was tested after adjustment for potential confounders (age, gender, alcohol consumption, portal inflammation, and steatosis), which may have independent effects on histological severity. The stage of fibrosis was 0 in 30 (23.4%), 1 in 44 (34.4%), 2 in 27 (21.1%), and 3 or 4 in 27 (21.1%). A statistically significant relationship was seen between inheritance of high TGF‐β1– and angiotensinogen (AT)‐producing genotypes and the development of progressive hepatic fibrosis. This association persisted after correcting for potential confounders. Patients who inherited neither of the profibrogenic genotypes had no or only minimal fibrosis. Knowledge of these polymorphisms may have prognostic significance in patients with chronic HCV and may direct more aggressive therapy towards those patients with an increased risk of disease progression. The documentation of a significant relationship between AT genotype and fibrosis raises the novel suggestion that angiotensin II may be another mediator of extracellular matrix production in the liver.

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Section: Polymorphisms Of the Cytokine And Ras Genes In Patients Withmentioning

confidence: 57%

Host genetic factors influence disease progression in chronic hepatitis C

et al. 2000

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“…Moreover, they did not describe the distribution of TNF-␣ genotypes among the different indications for liver transplantation despite numerous reports showing a higher prevalence of the TNFA-308 A allele in patients with autoimmune hepatitis and PSC than in normal controls. [24][25][26][27][28][29] One of the major problems with genetic association studies is that they are often inappropriately controlled and analyzed by inadequate statistical methodologies. To our knowledge, this is the first case-control (1 case: 4 controls) study designed to specifically address the association of TNF-␣ genetic polymorphisms and the development of ACR.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α promoter polymorphisms and the risk of rejection after liver transplantation: A case control analysis of 210 donor-recipient pairs

Jazrawi¹,

Zaman²,

Muhammad³

et al. 2003

Liver Transplantation

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“…Last, treatment failure may reflect intrinsic pathogenic mechanisms promoted by host-dependent genetic predispositions that cannot be suppressed by conventional corticosteroid regimens. [28][29][30][31] HLA DRB1*03 has been the principal risk factor associated with treatment failure in white North American and northern European patients, but its sensitivity, specificity, and predictability for treatment failure are unknown. 28 The model of end-stage liver disease (MELD) is an established method for predicting early mortality associated with severe liver disease.…”

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confidence: 99%

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

2007

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Autoimmune hepatitis may fail to respond to corticosteroid therapy, but the frequency and bases for this outcome are uncertain. We aimed to determine the frequency and nature of treatment failure in patients with type 1 autoimmune hepatitis, define features associated with its occurrence, and assess if the model for end-stage liver disease can predict this outcome. Patients failing conventional corticosteroid regimens were compared to patients who responded to similar regimens. Fourteen of 214 patients (7%) failed corticosteroid treatment. Patients who failed therapy were younger (33 ؎ 3 years versus 48 ؎ 1 years, P ‫؍‬ 0.0008), had higher serum levels of bilirubin at accession (4.1 ؎ 0.9 mg/dL versus 2.3 ؎ 0.2 mg/dL, P ‫؍‬ 0.02), presented acutely more frequently (43% versus 14%, P ‫؍‬ 0.01), and had a higher frequency of HLA (human leukocyte antigen) DRB1*03 (93% versus 53%, P ‫؍‬ 0.004) than did patients who achieved remission. An alternative disease (fatty liver disease) emerged in only 1 patient who failed therapy (7%). Scores determined by the model of end-stage liver disease at presentation of patients who failed treatment were higher than those of who achieved remission (16 ؎ 1 versus 10 ؎ 0.3 points, P < 0.0001), and score greater than 12 points had greater sensitivity (97%) and specificity (68%) for treatment failure than did HLA DRB1*03 or other features. Conclusion: Onset at an early age, acute presentation, hyperbilirubinemia, and presence of HLA DRB1*03 characterize patients who fail corticosteroid treatment. The model for end-stage liver disease may be a useful instrument for identifying patients prone to this outcome. (HEPATOLOGY 2007;46:1138-1145

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Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis

Cited by 155 publications

References 44 publications

Host genetic factors influence disease progression in chronic hepatitis C

Host genetic factors influence disease progression in chronic hepatitis C

Tumor necrosis factor-α promoter polymorphisms and the risk of rejection after liver transplantation: A case control analysis of 210 donor-recipient pairs

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

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