Elevated cholesterol levels have a poor prognosis in a cholestasis scenario

Nuño‐Lámbarri, Natalia; Barbero-Becerra, Varenka J.; Uribe, Misael; Chávez-Tapia, Norberto C.

doi:10.1002/jbt.21831

Cited by 10 publications

(8 citation statements)

References 49 publications

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“…Several studies have shown that lipid metabolic disorders are a common complication of cholestasis. 14 , 18 Basaranoglu et al reported that patients with intrahepatic cholestasis had a significantly higher TC level than healthy controls ( P <0.01), 19 similar to our results. The TC and sdLDL-C levels were significantly increased in patients with ECCA, who usually show more obvious biliary obstruction and cholestasis.…”

Section: Discussionsupporting

confidence: 90%

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Transiently Elevated TC and sdLDL-C Levels and Falsely Low LDL-C Levels in Patients with Extrahepatic Cholangiocarcinoma

Guo¹,

Zhang²,

Li³

et al. 2021

OTT

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Purpose Most patients diagnosed with extrahepatic cholangiocarcinoma (ECCA) exhibit cholestasis caused by obstruction of the bile duct. Cholestasis is associated with lipid disorders, but studies focused on the changing lipid parameters in patients with ECCA are lacking. Here, we observed lipid profiles in patients with ECCA and investigated whether the removal of biliary obstruction could correct dyslipidemia. Patients and Methods We consecutively included patients admitted to the hepatobiliary surgery department at the Affiliated Hospital of Xuzhou Medical University. The patients were divided into an ECCA group or a non-ECCA group based on the disease assessment. Patients with histological confirmation of ECCA were included in the ECCA group. Blood samples were collected on admission as well as five days after treatment. An automatic biochemistry analyzer was used to test liver function and serum lipid levels. Serum lipoprotein electrophoresis was performed using barbitone sodium buffer and Sudan black B. Results A total of 180 patients met inclusion criteria and were enrolled for this study. Of these, 76 patients were diagnosed with ECCA; all other patients were enrolled in the non-ECCA group. Total cholesterol (TC) and small and dense low-density lipoprotein cholesterol (sdLDL-C) levels were significantly elevated in the ECCA group. LDL-C levels were found to be slightly lower in the ECCA group. In the ECCA group, serum samples were detained in sample wells and lipoproteins failed to be separated. TC and sdLDL-C levels significantly decreased after cholestasis relief in the ECCA group. Lipoprotein electrophoresis revealed that patients with ECCA showed normal lipoprotein patterns after treatment. Conclusion Patients with ECCA exhibited transiently elevated TC and sdLDL-C levels and falsely low LDL-C results. TC, sdLDL-C, and LDL-C levels could be restored to normal levels after biliary obstruction removal and cholestasis relief.

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Section: Discussionsupporting

confidence: 90%

“… 21 This lipoprotein could increase the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and enhance hepatic cholesterol synthesis. 18 …”

Section: Discussionmentioning

confidence: 99%

Transiently Elevated TC and sdLDL-C Levels and Falsely Low LDL-C Levels in Patients with Extrahepatic Cholangiocarcinoma

Guo¹,

Zhang²,

Li³

et al. 2021

OTT

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“…BAs play an essential role in the deterioration of liver cirrhosis. Hydrophobic BAs, such as CDCA and GCDCA, are considered to be highly toxic (31). Accumulation of high levels of hydrophobic BAs in hepatocytes may induce cell injury through promotion of inflammation and mitochondrial oxidative stress-mediated death pathways (7,32).…”

Section: Discussionmentioning

confidence: 99%

Role of bile acids in the diagnosis and progression of liver cirrhosis: A prospective observational study

Liu

Jiao

et al. 2019

Exp Ther Med

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The accumulation of toxic bile acids (BAs) is closely related to liver injury, inflammation and tumorigenesis. The aim of the present study was to determine the role of the serum BA spectrum in the diagnosis and progression of liver cirrhosis. This was a prospective observational study involving patients with chronic hepatitis (n=23), liver cirrhosis (n=101), and cirrhosis complicated with hepatocellular carcinoma (CC-HCC; n=56). The 6-month survival of cirrhotic patients was recorded after blood collection. Comparisons of serum total BAs and individual BAs between different groups were performed using the Mann-Whitney U or Kruskal-Wallis tests. Correlation analysis was conducted by Spearman's correlation. Diagnosis and prediction analyses were performed using receiver operating characteristic curves. Survival was analyzed using the Kaplan-Meier method and multivariable Cox regression analysis. The concentrations of total BAs, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA), taurochenoxycholic acid and tauroursodeoxycholic acid (TUDCA) were increased significantly in patients with early cirrhosis compared to patients with chronic hepatitis (P<0.05) and were associated with the diagnosis of cirrhosis (P=0.049, 0.004, 0.002, 0.003, 0.010 and 0.009, respectively). The levels of total BAs, primary conjugated BAs, and TUDCA increased as liver cirrhosis progressed (P<0.05). Serum total BAs, GCA, GCDCA, and TCA predicted the 6-month survival of patients with liver cirrhosis (P=0.0003, 0.005, 0.002, and 0.010 respectively). Based on multivariate Cox regression analysis, the level of total BAs was an independent predictor of mortality in cirrhotic patients (hazard ratios, 4.046; 95% CI, 1.620–10.108; P=0.003). In the early-stage cirrhosis group, the concentrations of total BAs and primary conjugated BAs were significantly elevated in patients with CC-HCC compared with patients with cirrhosis alone. In conclusion, total and individual BAs, especially primary conjugated BAs, are effective non-invasive markers in the diagnosis and prognosis of liver cirrhosis, and may be potential indicators in the occurrence of hepatocellular carcinoma in patients with early cirrhosis.

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“…Secondary BAs cannot be generated in the intestine via bacterial biotransformation after BDL, so we examined the concentration of two primary BAs: CA and CDCA. CDCA is a hydrophobic BA which causes liver damage, whereas CA is a hydrophilic BA which reduces anti-inflammatory and anti-oxidative stress on hepatocytes during cholestasis [ 44 ]. Surprisingly, we found that the levels of the hydrophobic CDCA were lower while those of the hydrophilic CA were higher in the liver of Tg BDL mice than in WT BDL mice.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

Zhang

Guo

Hamada

et al. 2018

IJMS

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Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

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Elevated cholesterol levels have a poor prognosis in a cholestasis scenario

Cited by 10 publications

References 49 publications

Transiently Elevated TC and sdLDL-C Levels and Falsely Low LDL-C Levels in Patients with Extrahepatic Cholangiocarcinoma

Transiently Elevated TC and sdLDL-C Levels and Falsely Low LDL-C Levels in Patients with Extrahepatic Cholangiocarcinoma

Role of bile acids in the diagnosis and progression of liver cirrhosis: A prospective observational study

Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

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