Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy

Li, Yanling; Liu, Huiyuan; Chen, Keng; Wu, Xueheng; Wu, Jiawen; Yang, Zhenjun; Yao, Leyi; Wen, Guangwu; Zhang, Change; Chen, Xin; Chen, Xiaohui; Tang, Daolin; Wang, Xuejun; Liu, Jinbao

doi:10.3389/fmed.2021.706407

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…65,66 While the link between biliverdin and HE has not been explicitly elucidated, previous studies have described a strong relationship between HE and free bilirubin. 67–69 Interestingly, free bilirubin is rapidly solubilized by bile acids in vitro , perhaps explaining the potential protective effects of bile acids observed in our study In the context of bilirubin metabolism, our FBMN data suggest that an increase in the chemical reduction of biliverdin is involved in the development of post-TIPS HE ( Fig. 5g) .…”

Section: Discussionmentioning

confidence: 55%

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy

Machado

Ramos

Gauglitz

et al. 2023

Preprint

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Hepatic encephalopathy (HE) is a common complication of advanced liver disease causing brain dysfunction. This is likely due to the accumulation of unfiltered toxins within the bloodstream. A known risk factor for developing or worsening HE is the placement of a transjugular intrahepatic portosystemic shunt (TIPS), which connects the pre-hepatic and post-hepatic circulation allowing some blood to bypass the dysfunctional liver and decreases portal hypertension. To better understand the pathophysiology of post-TIPS HE, we conducted a multi-center prospective cohort study employing metabolomic analyses on hepatic vein and peripheral vein blood samples from participants with cirrhosis undergoing elective TIPS placement, measuring chemical modifications and changes in concentrations of metabolites resulting from TIPS placement. In doing so, we identified numerous alterations in metabolites, including bile acids, glycerophosphocholines, and bilirubins possibly implicated in the development and severity of HE.

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Section: Discussionmentioning

confidence: 55%

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy

Machado

Ramos

Gauglitz

et al. 2023

Preprint

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“…Previous clinical and basic studies have found that free bilirubin in serum is an important cause of kernicterus in neonates and adults (4,5,23,24). Recently, a retrospective case-control study showed that the indirect bilirubin-albumin ratio is an independent factor of hepatic encephalopathy in patients with liver failure (aOR:1.63, 95% CI: 1.32~2.00, p < 0.001) (25). Our finding that DB/TB is negatively correlated to cerebral score for hepatic encephalopathy (aOR: 0.01, 95% CI: 0.00~0.86, p = 0.043) is in accordance with these results.…”

Section: Discussionmentioning

confidence: 99%

“…Our finding that DB/TB is negatively correlated to cerebral score for hepatic encephalopathy (aOR: 0.01, 95% CI: 0.00~0.86, p = 0.043) is in accordance with these results. Notably, the administration of albumin or by pharmacological inhibition of indirect bilirubin production in a genetic model of hyperbilirubinemia could improve neurodevelopment and reduce apoptosis of cerebral cells remarkably (25,26). Similarly, promoting the conversion of indirect bilirubin to direct bilirubin was shown as beneficial in two patients with Crigler-Najjar syndrome type II who developed kernicterus in adulthood (24).…”

Section: Discussionmentioning

confidence: 99%

Association of direct bilirubin to total bilirubin ratio with 90-day mortality in patients with acute-on-chronic liver failure

Ma,

Du,

Zhou

et al. 2023

Front. Med.

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BackgroundHyperbilirubinemia occurs when the liver fails to process bilirubin properly. A disproportionate increase in direct bilirubin indicates a decreased ability of the hepatocytes to uptake and/or convert bilirubin, which may impact the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the association of direct bilirubin to total bilirubin ratio (DB/TB) with outcomes in patients with ACLF remains unclear.MethodsA retrospective study was conducted in West China Hospital of Sichuan University to assess the association between DB/TB and 90-day mortality in patients with ACLF. The diagnosis of ACLF was based on the Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF criteria. Ordinal logistic regression models, linear regression models, and Cox proportional hazards models were applied to evaluate the association between DB/TB and hepatic encephalopathy, disease severity, and outcome, respectively.ResultsA total of 258 patients with ACLF were included. The surviving patients were less likely to have liver cirrhosis and comorbidities, and their disease severities were milder than the dead. DB/TB was negatively correlated to cerebral score for hepatic encephalopathy (adjusted odds ratio: 0.01, p = 0.043), and disease severity (adjusted standardized coefficients: −0.42~−0.31, all p < 0.001), respectively. A significant 90-day mortality risk of DB/TB was observed [all adjusted hazard ratio (aHR) < 0.20 and all p ≤ 0.001]. Compared with patients with DB/TB < 0.80, patients with ACLF and DB/TB ≥ 0.80 had much lower 90-day mortality risk (all aHR < 0.75 and all p < 0.01).ConclusionDB/TB could be an independent risk factor to predict the short-term prognosis in patients with ACLF. More attention should be paid to patients with lower DB/TB due to their poorer prognosis and more urgent need for liver transplantation.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=56960, identifier, ChiCTR2000035013.

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“…Bilirubin neurotoxicity is caused by a high level of unbound unconjugated bilirubin that is unbound to albumin since albumin‐bound bilirubin probably does not cross an intact blood–brain barrier 21,22,24 . Although there is no research on unbound unconjugated bilirubin in ALF to the best of our knowledge, Lin et al 25 reported that the unconjugated bilirubin‐albumin ratio constitutes the most powerful risk factor in the occurrence of HE in adult ALF. In this study, peak serum bilirubin level was significantly higher in patients with NI.…”

Section: Discussionmentioning

confidence: 99%

Perioperative risk factors for neurological impairment in infants with acute liver failure following liver transplantation

Ide

Uchida

Sakamoto

et al. 2023

Pediatric Transplantation

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Background Neurological impairment is not rare in infants with acute liver failure (ALF). This study aimed to investigate the perioperative risk factors for neurological impairment following liver transplantation (LT) in infantile ALF. Methods Retrospective analysis was performed in infants who were younger than 1 year with ALF who subsequently underwent LT at our hospital between January 2005 and December 2016. Patients were considered to have neurological impairment if the Pediatric Cerebral Performance Category score was between 2 and 5 at the age of 6 years. A comparison between the groups of infants with and without neurological impairment was performed, and factors with p < .10 in the comparison were analyzed using univariate logistic regression analysis for neurological impairment. Results Twenty‐six infants survived until 6 years of age, and 31% (8/26) of them had neurological impairment. Patients with neurological impairment were significantly younger in age at ALF onset, had significantly higher pre‐LT bilirubin and prothrombin time/international normalized ratio, and stayed significantly longer in the intensive care unit than those without neurological impairment. Total bilirubin (odds ratio (OR) = 1.12, 95% confidence interval (CI) 1.02–1.22, p = .012), indirect bilirubin (OR = 1.10, 95% CI 1.01–1.20, p = .025), direct bilirubin (OR = 1.22, 95% CI 1.01–1.47, p = .040), and age in month at ALF (OR = 0.76, 95% CI 0.58–0.999, p = .049) showed significant association with neurological impairment. Conclusions High pre‐LT peak bilirubin value and younger age at ALF onset can be perioperative risk factors for neurological impairment after LT in infantile ALF.

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Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy

Cited by 8 publications

References 57 publications

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy

Pre- and Post-Portosystemic Shunt Placement Metabolomics Reveal Molecular Signatures for the Development of Hepatic Encephalopathy

Association of direct bilirubin to total bilirubin ratio with 90-day mortality in patients with acute-on-chronic liver failure

Perioperative risk factors for neurological impairment in infants with acute liver failure following liver transplantation

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