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Decline in serum albumin concentration is a predictor of serious events in nonalcoholic fatty liver disease.

ABSTRACT:

Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events.

SUBMITTER: Kawaguchi K

PROVIDER: S-EPMC8341320 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive biomarkers. The aim of this study was to determine if serum metabolite profiles in patients with NAFLD associate with future liver-related events. We performed a retrospective single-center cohort study of 187 participants with biopsy-proven NAFLD. Metabolomic analysis was performed on serum using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified liver-related events (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary or hepatorenal syndrome) by manual chart review between index biopsy (2007-2013) and April 1, 2018. Generalized linear models and Cox proportional hazards models were used to test the association of metabolites with liver-related events and time to first liver-related event, controlling for covariates and fibrosis stage. Over a mean ± SD follow-up of 6.9 ± 3.2 years, 11 participants experienced 22 liver-related events. Generalized linear models revealed 53 metabolites significantly associated with liver-related events (P < 0.05). In Cox proportional hazards modeling, 69 metabolites were significantly associated with time to future liver-related events (P < 0.05), seven of which met the false discovery rate threshold of 0.10: vitamin E metabolites gamma-carboxyethyl-hydroxychroman (gamma-CEHC) and gamma-CEHC glucuronide; primary bile acid metabolite taurochenodeoxycholate; serotonin metabolite 5-hydroxyindoleacetate; and lipid metabolites (i) 2-hydroxyglutarate, (ii) 3beta,17beta-diol disulfate 1, and (iii) eicosenoyl sphingomyelin. Conclusion: Metabolites of a primary bile acid, vitamin E, and serotonin were associated with future liver-related events. Our results suggest metabolite pathways may be useful for predicting which patients with NAFLD are at higher risk for hepatic decompensation.

Project description:BackgroundThe associations of serum calcium and phosphorus with nonalcoholic fatty liver disease (NAFLD) remain unclear. In addition, there may be an effect of albumin correction on the association between serum calcium and NAFLD. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES).MethodsEligible adult individuals from NHANES 1999-2018 were recruited for the study. We explored the associations of serum calcium, albumin-adjusted serum calcium, and serum phosphorus with NAFLD in multivariable-adjusted regression models. In addition, restricted cubic spline (RCS), stratified analysis, and multiple sensitivity analyses were used for further elaboration.ResultsThe study sample consisted of 20,900 participants, with an observed NAFLD prevalence of 44.65%. Fully adjusted models indicated that serum calcium was inversely associated with NAFLD (odds ratio [OR] and 95% confidence interval [CI] = 0.70 (0.62, 0.78), p<0.0001), whereas albumin-adjusted serum calcium was positively associated with NAFLD (OR and 95% CI=1.59 (1.41, 1.79), p<0.0001). RCS modeling indicated that serum calcium without and with albumin adjustment was linearly(p nonlinear = 0.083) and nonlinearly (p nonlinear < 0.0001) associated with NAFLD, respectively, whereas serum phosphorus showed a U-shaped relationship with NAFLD(p nonlinear < 0.0001). Gender is a significant influence in all associations, and other variables may also have an effect. Sensitivity analyses indicated that these associations were independent of additional significant confounders.ConclusionSerum calcium and phosphorus were significantly associated with the development of NAFLD. These findings suggest the potential clinical significance of serum calcium/phosphorus and albumin levels in individuals at high risk for NAFLD. Our study supports the potential role of serum calcium/phosphorus homeostasis in the pathophysiology of NAFLD and could serve as NAFLD-related biomarkers.

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Decline in serum albumin concentration is a predictor of serious events in nonalcoholic fatty liver disease.

Abstract

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