<scp>YKL</scp>‐40‐gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis <scp>C</scp> virus‐induced liver disease

Eurich, Dennis; Neumann, Ulf; Boas-Knoop, Sabine; Neuhaus, R.; Kießling, Anja; Yahyazadeh, Ali; Wasmuth, Hermann E.; Puhl, Gero; Bahra, Marcus

doi:10.1111/j.1440-1746.2012.07270.x

Cited by 10 publications

(3 citation statements)

References 44 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of abstracts focused on polymorphisms, immunosuppressive therapy, and donor factors associated with HCV recurrence and antiviral responses. YKL‐40 gene polymorphisms (G allele) were highly associated with both rejection and HCV fibrosis and portended a poor outcome 3. Data on IL‐28B polymorphisms showed a high correlation with the TT genotype and the risk of post‐LT diabetes4 and supported the known association with this genotype and the lack of an antiviral response 1.…”

Section: Viral Hepatitismentioning

confidence: 71%

Meeting report of the 2011 joint international congress of the international liver transplantation society, the European liver and intestine transplant association, and the liver intensive care group of Europe

Levitsky

Guckelberger

2012

Liver Transpl

View full text Add to dashboard Cite

The International Liver Transplantation Society held its yearly meeting as a joint conference with the European Liver and Intestine Transplant Association and the Liver Intensive Care Group of Europe at the Valencia Congress Center (Valencia, Spain) from June 22 to 25, 2011. Nearly 1500 registrants attended the meeting, which opened with a premeeting conference entitled “Global Challenges and Controversies in Liver Transplantation.” This was followed by numerous oral and poster abstract sessions and topic sessions focused on medical, surgical, and intensive care aspects of liver transplantation (LT). This report summarizes key symposia and oral abstracts delivered at the meeting and is conveniently divided into subsections relevant to LT. It is not meant to be a critical or comprehensive evaluation of all the meeting presentations and is merely intended to highlight presentations and associated published literature dealing with key topics. Liver Transpl 18:282–289, 2012. © 2011 AASLD.

show abstract

Section: Viral Hepatitismentioning

confidence: 71%

Meeting report of the 2011 joint international congress of the international liver transplantation society, the European liver and intestine transplant association, and the liver intensive care group of Europe

Levitsky

Guckelberger

2012

Liver Transpl

View full text Add to dashboard Cite

show abstract

“…Additionally, YKL-40-gene polymorphism involves in acute cellular rejection and fibrosis progression after liver transplantation with HCV infection. A nucleotide substitution in YKL-40-gene (rs4950928; chromosome 1; G->C) induced higher YKL-40-levels in serum and more severe fibrosis in the presence of C-allele in HCV infection (23,24). A previous study reported that HCV modulates YKL-40 through the NOTCH signaling pathway (25).…”

Section: Introductionmentioning

confidence: 97%

Reciprocal induction of hepatitis C virus replication and stimulation of hepatic profibrogenic cytokine release and cellular viability by YKL-40

Cheng¹,

Zhu²,

Liao³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Previous studies have suggested the YKL-40/chitinase 3-like protein 1 protein is upregulated in chronic hepatitis C virus (HCV) infection with fibrosis. We sought to determine whether HCV regulates YKL-40 expression and to elucidate the mechanisms by which YKL-40 mediates the liver fibrosis caused by HCV infection. Methods: We used purified protein, small molecule inhibitors and short-interfering RNAs to over-express or knock down certain kinases to explore the mechanisms underlying the regulation by HCV of YKL-40 expression in the Japanese fulminant hepatitis 1 (JFH1) model. Results: HCV induced YKL-40 production in hepatic parenchymal cells. Further, HCV-mediated upregulation of YKL-40 through cooperative induction of tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS)-mitogen-activated protein kinase MAPKs, which are nuclear factor-κB (NF-κB)-dependent pathways. YKL-40 protein also mildly increased HCV replication, triggering hepatic profibrogenic cytokine release and cellular viability as feedback. Additionally, hepatic parenchymal cells were the sole source of YKL-40 production in the infectious JFH1 model, whereas YKL-40 was under-detected in hepatic stellate cells (HSCs) in the presence or absence of the JFH1 supernatant, which was not investigated so far. Conclusions: HCV induced and maintained secretion of YKL-40 through sustained activation of NF-κB via cooperative induction of the TNF-α and ROS-MAPKs pathways. HCV interacted with YKL-40 to enhance the progression of hepatic fibrosis. These findings support a potential role for blockade of YKL-40 as an antifibrotic strategy.

show abstract

“…These clinical risk factors can only in part explain why some patients develop very fast RC, within a few years after LT, while others show no significant fibrosis at the 5-year protocol biopsy [12]. Beside factors related to the ORIGINAL PAPER transplant procedure or the immunosuppressive management, genetic factors of the donor or recipient appear to influence FP after LT [13].…”

Section: Introductionmentioning

confidence: 99%

Cirrhosis Risk Score of the Donor Organ Predicts Early Fibrosis Progression after Liver Transplantation

Zimmermann¹,

Darstein²,

Hoppe‐Lotichius³

et al. 2019

JGLD

View full text Add to dashboard Cite

Background & Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient’s seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients.Method: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at 1 and 5 years after LT.Results: Fibrosis ≥F2 was documented in 26.5% of the recipients’ CRS group (R-CRS) (defined by recipient’s genotype) and in 23.4% of the donors’ CRS- group (D-CRS) (defined by donor’s genotype). Cumulative incidence for fibrosis ≥F2 was higher in patients with D-CRS >0.7 (p=0.03). While the R-CRS showed no prognostic relevance, D-CRS >0.7 was associated with higher hazard ratios (HRs) for fibrosis ≥F2 (HR=2.04; p=0.01), especially in HCV-negative patients (HR=2.59, p=0.03). Donors’ CRS >0.7 was associated with higher risk for ≥F2 in 1-year protocol biopsies (p<0.001). Among the patients in whom both the recipient’s and donor’s CRS were available, fibrosis ≥F2 was encountered more frequently in patients with a D-CRS >0.7, in combination with any R-CRS, compared to patients with D-CRS scores ≤0.7 (p=0.034). Donors’ AZIN1, STXBP5L, TRPM5 genotypes carried a higher risk for fibrosis ≥F2 in subgroups.Conclusion: High D-CRS >0.7 predicted early FP after LT, especially in HCV negative patients.

show abstract

YKL‐40‐gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis C virus‐induced liver disease

Abstract: Fibrosis progression and ACR-incidence after transplantation for HCV-induced liver disease seem to be under genetic control. The negative impact of G-allele on post-transplant events observed in our study, deserves attention and should be verified in larger liver transplantation-cohorts.

Cited by 10 publications

References 44 publications

Meeting report of the 2011 joint international congress of the international liver transplantation society, the European liver and intestine transplant association, and the liver intensive care group of Europe

Meeting report of the 2011 joint international congress of the international liver transplantation society, the European liver and intestine transplant association, and the liver intensive care group of Europe

Reciprocal induction of hepatitis C virus replication and stimulation of hepatic profibrogenic cytokine release and cellular viability by YKL-40

Cirrhosis Risk Score of the Donor Organ Predicts Early Fibrosis Progression after Liver Transplantation

Contact Info

Product

Resources

About