Relationship between the intrahepatic expression of interferon‐α receptor mRNA and the histological progress of hepatitis C virus‐associated chronic liver diseases

Ishimura, Norihisa; Fukuda, Ryo; Fukumoto, Shiro

doi:10.1111/j.1440-1746.1996.tb00319.x

Cited by 24 publications

(22 citation statements)

References 30 publications

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“…The method of mRNA measurement may be applicable in other organ disorders, as has been hypothesized and found for instance in the liver (44), the lungs (45), the heart (46), and in cancer research (47,48). In conclusion, the extent of histologic damage is negatively correlated with the GFR at time of biopsy, but it does not predict the rate of change in GFR after taking of the biopsy.…”

Section: Discussionmentioning

confidence: 81%

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Eikmans¹,

Baelde²,

Hagen

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Molecular biologic techniques are currently considered as new diagnostic and prognostic parameters with a sensitivity and specificity exceeding those of histologic and functional data currently used in clinical practice. The results in various clinical settings have been of limited value up to now. This study is an investigation of the use of tissue levels of RNA determined in routine clinical kidney biopsies as prognostic tools. The focus was on RNA encoding for molecules known to be involved in the pathogenesis of renal disorders. Fresh kidney biopsy tissue was obtained from 52 patients with various renal diseases. The GFR was followed for 12 mo. The extent of glomerulosclerosis and interstitial fibrosis in the biopsies was determined with quantitative digital image analysis. Glomerular and tubulointerstitial compartments from each biopsy specimen were separated, and mRNA levels of TGF-␤, collagen I, collagen IV, and fibronectin were quantitated by real-time PCR. Correlations, along with 95% confidence intervals (CI), between all variables tested at time biopsy were determined. To assess their prognostic value, these variables were correlated with the slope of GFR within several time intervals after biopsy. In addition, to evaluate the predictive value of the variables for outcome in individual patients, differences for each variable were tested between patients showing progressive decline in renal function (slope GFR Ͻ 0) and patients showing stable or improving renal function over time (slope GFR Ն 0). In chronic renal diseases, the extent of histologic damage correlated with the GFR at the time of biopsy (r ϭ Ϫ0.44; CI Ϫ0.68 to Ϫ0.11), but it did not correlate with the slope expressing a change in GFR after the biopsy. Tubulointerstitial TGF-␤ mRNA levels correlated with the rate of change in GFR between time of biopsy and 1 mo later (r ϭ 0.41; CI, 0.07 to 0.67). The GFR at the time of biopsy correlated with the slope of change in GFR between time of biopsy and 12 mo later (r ϭ Ϫ0.50; CI, Ϫ0.73 to Ϫ0.18). In chronic renal diseases, glomerular fibronectin mRNA levels, in comparison with the GFR at time of biopsy, correlated relatively strongly with the slope of change in GFR between 3 and 12 mo (r ϭ 0.50; CI, 0.16 to 0.74). Patients with favorable renal outcome after 12 mo showed significantly higher TGF-␤ mRNA levels and lower proteinuria levels at time of biopsy (P Ͻ 0.05) than patients with a progressive decline in renal function. This study shows that mRNA levels measured in kidney biopsies can function as prognostic tools in human renal diseases. In particular, relatively high levels of tubulointerstitial TGF-␤ mRNA and glomerular fibronectin mRNA are associated with less deterioration in renal function.

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Section: Discussionmentioning

confidence: 81%

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Eikmans¹,

Baelde²,

Hagen

et al. 2003

Journal of the American Society of Nephrology

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“…It is known that the type-I IFN receptor mRNA level in the liver is low in liver cirrhosis [Ishimura et al, 1996;Yatsuhashi et al, 1996;Mizukoshi et al, 1998]. Whether HBV co-infection has an essential role in the development of cirrhosis in chronic hepatitis C, however, is not clear.…”

Section: Discussionmentioning

confidence: 97%

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

et al. 2001

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Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.

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“…Some studies have found no correlation betw een IFNa /b receptor mRNA expression and histology, (20) and others have found lower IFNAR mRNA expression with "histologic progression" of HCV. (19) The HAI, excluding cirrhosis, is not usually considered a predictor of response to IFN therapy. (9,10) Therefore, although responders to IFN therapy had a higher IFNAR mRNA expression than nonresponders, it is not totally surprising that IFNAR mRNA expression did not correlate with the HAI.…”

Section: Discussionmentioning

confidence: 99%

IFN-alpha Receptor mRNA Expression in a United States Sample with Predominantly Genotype 1a/I Chronic Hepatitis C Liver Biopsies Correlates with Response to IFN Therapy

Mathai

Shimoda

Banner

et al. 1999

Journal of Interferon & Cytokine Research

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Our aim was to assess whether, in the United States, with the predominant hepatitis C viral (HCV) genotypes 1a/I and 1b/II, hepatic interferon-alpha receptor (IFNAR) mRNA expression correlated with response to IFN therapy, levels of HCV RNA, or histologic activity index (HAI). Nine of 24 patients (38%) had an initial response to IFN treatment, 5 of whom (21%) had a sustained response. The corrected hepatic IFNAR mRNA expression (measured by RT-PCR) for the sustained responder group (mean +/- SE, 0.16 +/- 0.06, n = 5) was significantly higher than for the nonresponding group (0.059 +/- 0.01, n = 15) (p < 0.02). Patients who relapsed had an intermediate value (0.092 +/- 0.029, n = 4). Higher IFNAR expression was inversely correlated with a lower serum HCV RNA titer (p < 0.01), and responders to IFN treatment tended to have a lower titer of HCV RNA (p = 0.056). We found no significant correlation between the amounts of IFNAR with (1) the total HAI (low HAI < or = 7, IFNAR 0.076 +/- 0.013, n = 10; high HAI > or = 8, IFNAR 0.092 +/- 0.027, n = 14, ns) or (2) individual inflammation, necrosis, or fibrosis components of the HAI. As with Japanese HCV patients with genotypes 1b/II-2b/IV, higher hepatic IFNAR mRNA expression in the United States with predominant genotypes 1a/I and 1b/II appears to correlate with response to IFN therapy and a low HCV RNA titer but not with the total HAI or its components.

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Relationship between the intrahepatic expression of interferon‐α receptor mRNA and the histological progress of hepatitis C virus‐associated chronic liver diseases

Cited by 24 publications

References 30 publications

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

IFN-alpha Receptor mRNA Expression in a United States Sample with Predominantly Genotype 1a/I Chronic Hepatitis C Liver Biopsies Correlates with Response to IFN Therapy

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