Dataset Information

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

ABSTRACT:

Background

Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.

Methods

A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m² or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality.

Results

56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]).

Conclusions

In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.

SUBMITTER: Hydes TJ

PROVIDER: S-EPMC10193672 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

Hydes Theresa J TJ Kennedy Oliver J OJ Buchanan Ryan R Cuthbertson Daniel J DJ Parkes Julie J Fraser Simon D S SDS Roderick Paul P

BMC medicine 20230518 1

<h4>Background</h4>Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.<h4>Methods</h4>A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m<sup>2</sup> or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (H ...[more]

PMID: 37198624

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Project description:Background: Although loneliness and social isolation are proposed as important risk factors for metabolic diseases, their associations with the risk of non-alcoholic fatty liver disease (NAFLD) have not been elucidated. The aims of this study were to determine whether loneliness and social isolation are independently associated with the risk of NAFLD and to explore potential mediators for the observed associations. Methods: In this large prospective cohort analysis with 405,073 participants of the UK Biobank, the status of loneliness and social isolation was assessed through self-administrated questionnaires at study recruitment. The primary endpoint of interest was incident NAFLD. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals for the associations between loneliness, social isolation, and risk of NAFLD. Results: During a median follow-up of 13.6 years, there were 5,570 cases of NAFLD identified. In the multivariable-adjusted model, loneliness and social isolation were both statistically significantly associated with an increased risk of NAFLD (HR = 1.22 and 1.13, respectively). No significant multiplicative or additive interaction was found between loneliness and social isolation on the risk of NAFLD. The mediation analysis estimated that 30.4%, 16.2%, 5.3%, 4.1%, 10.5%, and 33.2% of the loneliness-NAFLD association was mediated by unhealthy lifestyle score, obesity, current smoking, irregular physical activity, suboptimal sleep duration, and depression, respectively. On the other hand, 25.6%, 10.1%, 15.5%, 10.1%, 8.1%, 11.6%, 9.6%, 4.8%, and 3.0% of the social isolation-NAFLD association was mediated by unhealthy lifestyle score, obesity, current smoking, irregular physical activity, suboptimal sleep duration, depression, C-reactive protein, count of white blood cells, and count of neutrophils, respectively. Conclusions: Our study demonstrated that loneliness and social isolation were associated with an elevated risk of NAFLD, independent of other important risk factors. These associations were partially mediated by lifestyle, depression, and inflammatory factors. Our findings substantiate the importance of loneliness and social isolation in the development of NAFLD.

Project description:ObjectivesTo investigate if non-alcoholic fatty liver disease (NAFLD) impacts mortality and adverse outcomes for individuals with chronic kidney disease (CKD).DesignSystematic review.Data sourcesPubMed, EMBASE and Web of Science were searched up to 1 February 2020 with no restriction on the earliest date.Eligibility criteria for selecting studiesObservational cohort studies that reported either the risk of all-cause mortality, incidence of non-fatal cardiovascular events (CVE) or progression of kidney disease among adults with established CKD who have NAFLD compared with those without.Data extraction and synthesisTwo reviewers extracted data and assessed bias independently.ResultsOf 2604 records identified, 3 studies were included (UK (n=852), South Korea (n=1525) and USA (n=1413)). All were judged to have a low or moderate risk of bias. Data were insufficient for meta-analysis. Two studies examined the influence of NAFLD on all-cause mortality. One reported a significant positive association for NAFLD with all-cause mortality for individuals with CKD (p<0.05) (cardiovascular-related mortality p=ns), which was lost following adjustment for metabolic risk factors; the second reported no effect in adjusted and unadjusted models. The latter was the only study to report outcomes for non-fatal CVEs and observed NAFLD to be an independent risk factor for this (propensity-matched HR=2.00, p=0.02). Two studies examined CKD progression; in one adjusted rate of percentage decline in estimated glomerular filtration rate per year was found to be increased in those with NAFLD (p=0.002), whereas the other found no significant difference.ConclusionsFew studies have examined the influence of NAFLD on prognosis and major adverse clinical outcomes within the CKD population. The studies identified were diverse in design and results were conflicting. This should be a focus for future research as both conditions continue to rise in prevalence and have end-stage events associated with significant health and economic costs.Prospero registration numberCRD42020166508.

Dataset Information

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

Background

Methods

Results

Conclusions

Publications

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

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