Alterations in bile formation and the expression of hepatobiliary transportes in human orthotopic liver transplantation

Geuken, E; Visser, Dorien S.; Blokzijl, Hans; Leuvenink, Henri; Knegt, R de; Kuipers, Folkert; Slooff, Maarten J. H.; Jansen, Petér L. M.; Porte, Robert J.

doi:10.1016/s0016-5085(03)83348-6

Cited by 4 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MDR3 variants could be more relevant in specific subphenotypes of PSC (e.g., pediatric PSC, female patients with gallstones) [60]. Moreover, MDR3 defects have been linked to nonanastomotic intrahepatic bile duct strictures (NAS) after liver transplantation.Bile cytotoxicity, in particular a low biliary phospholipids/bile salt ratio may be involved in the pathogenesis of NAS [61], since biliary bile acid excretion recovers more rapidly than phospholipid excretion after liver transplantation, leading to a more hydrophobic biliary bile acid composition [62]. These data suggest that the impact of cold ischemia/reperfusion injury on MDR3 expression and function -in particular in genetically susceptible individuals with an MDR3 genetic variation could contribute to NAS.…”

Section: Mdr3 (Abcb4)mentioning

confidence: 90%

New molecular insights into the mechanisms of cholestasis

Wagner

Zollner

Trauner

2009

Journal of Hepatology

236

185

View full text Add to dashboard Cite

Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in bile formation. Ligand-activated nuclear receptors for bile acids and other biliary compounds play a key role in the regulation of genes required for bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications.

show abstract

Section: Mdr3 (Abcb4)mentioning

confidence: 90%

New molecular insights into the mechanisms of cholestasis

Wagner

Zollner

Trauner

2009

Journal of Hepatology

236

185

View full text Add to dashboard Cite

show abstract

“…Schmuck et al (27) CD44, CXCL19 ELISA -/45 ACR miR-122, miR-133a, miR-148a, and miR-194 qPCR Kim et al (28) APN Proteomics -/9 ACR Adams et al (29) ICAM1 ELISA -/61 ACR Adams et al (30) IL2R Unknown -/18 ACR Tono et al (31) IL6 ELISA 11/-ACR Umeshita et al (32) IL6 ELISA -/51 ACR Morimoto et al (33) CXCL10 ELISA -/41 ACR Ericzon et al (34) Bile acids ELISA -/10 Graft function CA/CDCA ratio HPLC Buis et al (35) Bile phospholipid/bile salt ratio ELISA, spectrophotometry -/111 NAS Chen et al (36) Bile salt/phospholipid ratio ELISA 90/-Bile duct injury/NAS Geuken et al (37) Bile salt/phospholipid ratio ELISA -/28 NAS ALP Spectrophotometry…”

Section: Rt-qpcrmentioning

confidence: 99%

“…At the time of donor procurement ↑ PC Identify steatotic grafts (41) ↓ Choleretic activity Identify suboptimal grafts (10) ↓ CA/CDCA ratio Identify suboptimal grafts (34) During NMP HCO − 3 >18 mmol/L, pH >7.48, glucose <16 mmol/L, bile/perfusate glucose ratio <0.67, and LDH concentration <3689 U/L Predict low histological degree of bile duct injury (2) Bile production >10 mL and pH >7.45 Predict bile duct viability (14) pH <7.85 Predict NAS (16) pH <7.4 Predict NAS (53) After transplantation ↓ Na + and ↑ bile glucose-blood glucose Predict NAS (12) ↓↓↓ Lipids Identify PNF (24) ↑ CDmiR Predict ACR (26) ↑ miR-133a, miR-148a, and miR-194 Predict ACR (27,31,46,49,50) ↑ IL2, IL6, and IL8 Predict ACR (30)(31)(32) ↑ CXCL9/10 Predict ACR (27,33) ↓ Bile salt, phospholipids, and cholesterol during the first week after LT Predict NAS (35) ↑ Bile salt/phospholipid ratio during the first week after LT Predict histologically severe bile duct injury (37) ↑ miR-517a, miR-106a, and miR-892a…”

Section: Bile Composition Goalmentioning

confidence: 99%

“…(35) In line with this, another study observed higher biliary bile salt/phospholipid ratios during the first week after LT in bile from livers with histological evidence of severe bile duct injury. (37) Also, both extended cold ischemia time as well as prolonged warm ischemia time were associated with a more toxic bile composition, due to a high biliary bile salt/phospholipid ratio. (38,62) These studies suggest that the development of NAS after LT is preceded by early changes in bile composition several weeks before the clinical symptoms of bile duct injury appear.…”

Section: Bile Composition After Lt: Predicting Biliary Complicationsmentioning

confidence: 99%

See 1 more Smart Citation

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

2020

View full text Add to dashboard Cite

Bile secretion and composition reflects the functional status of hepatocytes and cholangiocytes. Bile composition can have a role in the assessment of donor grafts before implantation in the recipient. In addition, changes in bile composition after liver transplantation can serve as a diagnostic and prognostic tool to predict posttransplant complications, such as primary nonfunction, acute cellular rejection, or nonanastomotic biliary strictures. With the popularization of liver machine perfusion preservation in the clinical setting, there is a revisited interest in biliary biomarkers to assess graft viability before implantation. This review discusses current literature on biliary biomarkers that could predict or assess liver graft and bile duct viability. Bile composition offers an exciting and novel perspective in the search for reliable hepatocyte and cholangiocyte viability biomarkers.

show abstract

“…It has been observed that, early after LT, bile has a relatively high bile acid/phospholipid ratio that may transiently increase its toxicity. (20) Although it has been hypothesized that the use of UDCA may ameliorate this toxicity and reduce the frequency of biliary strictures, this was not seen in our analysis. Although bile toxicity may contribute to biliary strictures, other factors, namely, technical and vascular issues, may ultimately be more important in their pathogenesis.…”

Section: Discussionmentioning

confidence: 68%

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation: A Meta‐Analysis

et al. 2021

View full text Add to dashboard Cite

After liver transplantation (LT), the role of ursodeoxycholic acid (UDCA) is not well characterized. We examine the effect of UDCA after LT in the prophylaxis of biliary complications (BCs) in all‐comers for LT and the prevention of recurrent primary biliary cholangitis (rPBC) in patients transplanted for PBC. Two authors searched PubMed/MEDLINE and Embase from January 1990 through December 2018 to identify all studies that evaluate the effectiveness of UDCA prophylaxis after LT for BCs in all LT recipients and rPBC after LT in patients transplanted for PBC. Odds ratios (ORs) were calculated for endpoints of the BC study. Pooled recurrence rates were calculated for rPBC. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. A total of 15 studies were included, comprising 530 patients in the analysis for BCs and 1727 patients in the analysis for rPBC. UDCA was associated with decreased odds of BCs (OR, 0.70; 95% confidence interval [CI], 0.52‐0.93; P = 0.01) and biliary stones and sludge (OR, 0.49; 95% CI, 0.24‐0.77; P = 0.004). Prophylactic use of UDCA did not affect the odds of biliary stricture. For patients transplanted for PBC, the rate of rPBC was lower with the prophylactic use of UDCA (IR 16.7%; 95% CI, 0.114%‐22.0%; I2 = 36.1%) compared with not using prophylactic UDCA (IR 23.1%; 95% CI, 16.9%‐29.3%; I2 = 86.7%). UDCA after LT reduces the odds of BC and bile stones and sludge in all‐comer LT recipients and reduces or delays the incidence of rPBC in patients transplanted for PBC. UDCA use after LT could be considered in all LT recipients to reduce the odds of BC and may be particularly beneficial for patients transplanted for PBC by reducing the incidence of rPBC.

show abstract

Alterations in bile formation and the expression of hepatobiliary transportes in human orthotopic liver transplantation

Cited by 4 publications

References 0 publications

New molecular insights into the mechanisms of cholestasis

New molecular insights into the mechanisms of cholestasis

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation: A Meta‐Analysis

Contact Info

Product

Resources

About