Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

Virani, Shohaib; Akers, Austin T.; Stephenson, Kristen; Smith, Steven M.; Kennedy, Lindsey; Alpini, Gianfranco; Francis, Heather

doi:10.4172/2167-0889.1000231

Cited by 8 publications

(4 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the results of this study indicate the superior prognostic value of BAR compared to that of BLR. This discrepancy might stem from cholangiocarcinoma's potential to induce biliary obstruction and cholestatic liver injury, affecting FDG uptake of the liver [32,33]. Furthermore, our study revealed that FDG uptake in the normal liver tissue was influenced by cholangiocarcinoma tumor classification, suggesting that BAR might be a more suitable imaging parameter than BLR for estimating FDG uptake in the BM in patients with cholangiocarcinoma.…”

Section: Discussionmentioning

confidence: 77%

Prognostic Significance of the Bone Marrow-to-Aorta Uptake Ratio on 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in Patients with Cholangiocarcinoma

Lee,

Yoo,

Hong

et al. 2024

Biomedicines

View full text Add to dashboard Cite

2-Deoxy-2-[18F]fluoro-d-glucose (FDG) uptake of the reticuloendothelial system on positron emission tomography/computed tomography (PET/CT) is known to be related to systemic inflammatory response to cancer cells in patients with diverse malignancies. This retrospective study aimed to investigate whether FDG uptake by the reticuloendothelial system had a prognostic value in predicting progression-free survival (PFS) and overall survival (OS) in 138 cholangiocarcinoma patients. Quantifying FDG uptake of the aorta, bone marrow (BM), liver, and spleen from staging FDG PET/CT images, we found significant correlations between the BM-to-aorta uptake ratio (BAR), spleen-to-aorta uptake ratio, and BM-to-liver uptake ratio with tumor stage and serum inflammatory markers. In the multivariate survival analysis, BAR was an independent predictor of PFS (p = 0.016; hazard ratio, 2.308) and OS (p = 0.030; hazard ratio, 2.645). Patients with stages III–IV of the disease and a high BAR exhibited low 1-year PFS (35.8%) and OS (60.2%) rates, while those with stages I–II of the disease and low BAR showed robust rates of 90.0% and 96.7%, respectively. BAR measured on staging FDG PET/CT might be a potential imaging biomarker offering insights into the systemic inflammatory response and predicting prognosis in cholangiocarcinoma. This study highlights BAR as a promising, independent predictor with potential for personalized prognostication and treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 77%

Prognostic Significance of the Bone Marrow-to-Aorta Uptake Ratio on 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in Patients with Cholangiocarcinoma

Lee,

Yoo,

Hong

et al. 2024

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Liver function test is widely used to detect liver condition in terms of ALT and AST, transaminase in hepatocytes and to indicate liver injury (33). Serum γ-GT is an indicator of biliary obstruction and hepatitis activity (34). Bile duct ligation (BDL), is the most common model used to induce cholestatic fibrosis in rodents (35,36).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

et al. 2020

View full text Add to dashboard Cite

Effect of exogenous transforming growth factor-β1 (TGF-β1) on cholestatic mice by inhibiting Kupffer cell immune responses in liver was investigated. To induce cholestasis, BALB/c mice received a sham operation (Mock group), or underwent a bile duct ligation (BDL group) and then were subcutaneously injected with TGF-β1 at multiple sites (TGF group). Liver functions were evaluated according to the levels of alanine aminotransferase (ALT), aspartate aminotransferase AST and γ-glutamyltranspeptidase (γ-GT) in serum samples. Expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) was detected. Expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in Kupffer cells (KCs) of the liver was detected. The isolated KCs were divided into control group, LPS group, TGF group and Galunisertib group and western blot analysis was used to detect the expression of NF-κB, IL-6, IL-1β, TNF-α, iNOS and Arg-1. The percentage of CD40, CD86, CD204 and CD206 as macrophage cell surface antigens were measured by flow cytometry. The indexes of liver function and liver fibrosis of the mice in the TGF group were significantly lower than those in the BDL group (P<0.05). The levels of IL-1β, IL-6 and TNF-α in the liver were lower than those in the BDL group, while the level of IL-10 was significantly increased (P<0.05). M2-type transformation occurred in liver Kupffer cells of mice in the TGF group. In cell experiments, TGF treatment downregulated the expression of IL-1β, IL-6, TNF-α and NF-κB, increased the expression of IL-10, and induced M2-type transformation in macrophages (P<0.05). In conclusion, TGF-ß1 diminished the progression of cholestasis in mice by inhibiting the inflammatory response of KCs and regulating KC polarization.

show abstract

“…(7) The ppatient repeatedly had anemia and received packed red cell transfusion and Ursodeoxycholic acid (UDCA) for cholestasis as a hydrophilic bile acid, and it has been the most extensively studied putative pharmacological treatment for PSC. (8) Immunosuppressive agent and corticosteroid were given to this patient because of the autoimmune etiology of the disease. Biliary stenting was performed in this patient to help the stream of the bile.…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of 18-year-old female with Primary Sclerosing Cholangitis, Mixed Connective Tissue Disease, Short Stature

Siahaan

Purnomo

Seno

et al. 2020

J. Biomed. Transl. Res.

View full text Add to dashboard Cite

Background: Primary sclerosing cholangitis (PSC) is a rare chronic immune-mediated liver disease affecting intra and extrahepatic bile ducts, in which inflammation and fibrosis are the main factors that lead to biliary stricture. The pathogenesis of this disease is still unclear. It happens approximately 0.5 to 1.3 cases per 100,000 person-years in Northern Europe. PSC is difficult to diagnose until complications arise. PSC can also be a manifestation of mixed connective tissue disease (MCTD) in the liver. A chronic immune disease that has occurred since childhood may result in delayed development and short stature. Case Presentation: A 18-year-old female presented with icteric, anemia, short stature, and absence of menstruation. Laboratory and radiological findings suggested obstruction of intra and extrahepatic biliary duct (conjugated bilirubin 11,80 mg/dL), severe anemia, normal sex hormone levels, increased RNP/SM antibodies. Histopathology showed liver cirrhosis suggestive for primary sclerosing cholangitis. The patient then was given biliary stenting, transfusion of packed red cell, immunosuppresive, corticosteroid, ursodeoxycholic acid. Within a year of treatment, there was a significant decrease of direct bilirubin and improvement in symptoms.Conclusion: Patient with PSC, MCTD, and short stature is a very rare case. This is the first case that has been found in dr. Kariadi Hospital, Semarang. It has high mortality rate and difficult to diagnose and treat. According to multiple guidelines, this patient should have liver transplantation , but in this case, biliary stenting and oral treatments have resulted in an excellent outcome.

show abstract

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

Cited by 8 publications

References 115 publications

Prognostic Significance of the Bone Marrow-to-Aorta Uptake Ratio on 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in Patients with Cholangiocarcinoma

Prognostic Significance of the Bone Marrow-to-Aorta Uptake Ratio on 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in Patients with Cholangiocarcinoma

Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

A Rare Case of 18-year-old female with Primary Sclerosing Cholangitis, Mixed Connective Tissue Disease, Short Stature

Contact Info

Product

Resources

About