Project description:With the growing prevalence of obesity and diabetes in the United States and across the world, a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is expected. The risk factors for NAFLD are also associated with the development of chronic kidney disease (CKD). We review the epidemiology, risk factors, genetics, implications of gut dysbiosis, and specific pathogenic mechanisms linking NAFLD to CKD. Mechanisms such as ectopic lipid accumulation, cellular signaling abnormalities, and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population. Transplant evaluation in the setting of both NAFLD and CKD is also reviewed. Potential strategies for surveillance and management include the monitoring of comorbidities, the use of non-invasive fibrosis scoring systems, and the measurement of laboratory markers. Lastly, we discuss the management of patients with NAFLD and CKD, from preventative measures to experimental interventions.
Project description:Background and aimsWhether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident chronic kidney disease (CKD) independent of established cardio-renal risk factors remains controversial. We aimed to provide a quantitative estimate of the association and strength between NAFLD and risk of CKD after adjustment for multiple cardio-renal risk factors.MethodsWe searched electronic databases (PubMed, Embase, and Google Scholar) for studies published from database inception until 30 November 2020. Analysis included cohort studies that reported multivariable-adjusted risk ratios [including odds ratios, relative risks (RRs), or hazard ratios] and 95% confidence intervals (CIs) for CKD of NAFLD compared with individuals without NAFLD.ResultsA total of 11 cohort studies were included comprising 1,198,242 participants (46.3% women) for analysis. The median follow-up duration was 3.7 years, with 31,922 cases of incident CKD. Compared with individuals without NAFLD, unadjusted models showed that NAFLD was associated with a higher risk of CKD (RR 1.54, 95% CI 1.38-1.71). After adjusting for multiple cardio-renal risk factors, the CKD risk was still significantly increased in patients with NAFLD (RR 1.39, 95% CI 1.27-1.52). Compared with individuals without NAFLD, the adjusted absolute risk increase in NAFLD for CKD was 5.1 (95% CI 3.5-6.8) per 1000 person-years.ConclusionNAFLD is associated with an increased risk of incident CKD independent of established cardio-renal risk factors.
Project description:Background/Aims:The number of patients with nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) is on the rise. Epidemiological studies have shown the role of hyperuricemia in the development of NAFLD and CKD through oxidative stress and inflammatory mediators. Therefore, this study was conducted to investigate the prevalence and risk factors of hyperuricemia in patients with CKD and NAFLD in Iran. Patients and Methods:This study was conducted in 450 CKD patients. NAFLD was diagnosed by ultrasonography. According to the serum uric acid level, all CKD+ NAFLD+ patients were divided into non-hyperuricemia and hyperuricemia groups. The patients' demographic and clinical data such as age, sex, abdominal obesity, metabolic syndrome, diabetes, hypertension, CRP, hepatic steatosis, blood pressure, serum uric acid (UA), lipid and creatinine were collected for analysis. Results:A total of 279 cases (62%) were diagnosed with NAFLD. The prevalence rate of NFALD in CKD patients was significantly lower in normal UA level than hyperuricemia (42.7% vs 57.3%) (P=0.039). The prevalence of hyperuricemia was about 57.3% in patients with CKD and NAFLD. Accordingly, 279 CKD patients with NAFLD were enrolled and divided into hyperuricemia (n =160) and non-hyperuricemia groups (n =119). Patients with hyperuricemia showed higher creatinine and lipid levels, and a lower GFR compared to patients with normal uric acid levels (P< 0.05). However, no significant difference was observed in age, sex, abdominal obesity, metabolic syndrome, hypertension, type 2 diabetes, CRP, and steatosis between hyperuricemia and non-hyperuricemia groups (P>0.05). Three factors, including type 2 diabetes, hyperlipidemia, and a low GFR, serve as independent risk factors for hyperuricemia (P<0.05). Conclusion:The results showed a high prevalence of hyperuricemia in patients with CKD and NAFLD. A more comprehensive strategic management is necessary to address the potential harmful effects of hyperuricemia on the health of CKD+ NAFLD+ cases.
Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with incident chronic kidney disease (CKD). We aimed to investigate outcomes and risk factors of CKD progression and regression.MethodsThis is a longitudinal community-based cohort study of patients with NAFLD. Exclusion criteria included alcoholic liver diseases, sero-positive for hepatitis B surface antigen, sero-positive for hepatitis C virus antibodies, fatty liver index <60, individuals with only one year of data, missing data for fibrosis-4 score (FIB-4 score) and NAFLD fibrosis score (NFS), and advanced CKD at baseline. Main outcomes were stratified according to estimated glomerular filtration rate (eGFR) and albuminuria categories as state 1 (low risk), state 2 (moderately increased risk), and state 3 (high-risk/very-high risk of progression). The multi-state Markov model was used for outcome analysis.ResultsThis study included 1628 patients with NAFLD with a median follow-up of 3.4 years. State 2 CKD was found in 9.3% of patients at 5 years (95% CI, 8.1%-10.6%). Most patients with state 2 CKD recovered to state 1 (69%; 95% CI, 63.7%-74%), while 17.6% progressed to state 3 (95% CI, 13.4%-22.7%). Advanced liver fibrosis was found to be associated with the risk of transitioning from state 1 to state 2 ((FIB-4 score) ≥1.3; hazard ratio (HR), 1.42; 95% CI, 1.02-2.00), and reduced recovery from state 2 to state 1 (NFS≥-1.455; HR, 0.56; 95% CI, 0.34-0.91).ConclusionNAFLD severity is associated with CKD, which may be reversible before becoming high-risk. Controlling metabolic risk factors and preventing advanced liver fibrosis are recommended.
Project description:BackgroundChronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and findingsEnglish and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.ConclusionThe presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.
Project description:Objective The correlation between the insulin secretion levels and the risk of hepatocarcinogenesis is clinically important. The aim of the present study was to determine the effects of various clinical parameters on C-peptide (CPR) levels in patients with non-alcoholic fatty liver disease (NAFLD). Methods In this retrospective cohort study, the effects of clinical parameters on insulin resistance (HOMA-IR) and insulin secretion levels (HOMA-β and fasting CPR) were investigated. Patients A total of 244 Japanese patients with histopathologically confirmed NAFLD were evaluated. Of these, 77 underwent the meal tolerance test (MTT) to evaluate the association of various clinical parameters with the CPR levels at 120 minutes. Results A multivariate analysis identified fasting plasma glucose (FPG) (≥110 mg/dL), aspartate aminotransferase (≥1.0×ULN IU/L), and a large waist circumference as independent predictors of insulin resistance (HOMA-IR ≥2.5) or high fasting CPR levels. Significant parameters for a low insulin secretion capacity (HOMA-β <30%) were not detected, except for the parameters mentioned in the diagnostic criteria of diabetes mellitus. Regarding the MTT, the CPR levels at 120 minutes were significantly higher in patients with fibrosis stage 3-4 than in those with stage 0-2. Body composition and genetic variation did not affect the CPR levels at 120 minutes. A multivariate analysis identified fibrosis stage (3-4), hyperuricemia, FPG (≥110 mg/dL), and procollagen III peptide (>1.0 U/mL) as independent predictors of high CPR levels at 120 minutes. Conclusion The present study showed that high plasma glucose levels and severe liver fibrosis stage influence insulin secretion levels in Japanese patients with NAFLD. Conservation of delayed insulin secretion levels was confirmed in patients with severe liver fibrosis.
Project description:Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.
Project description:Non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). The aim of this retrospective study was to determine the risk factors for progression of CKD in patients with biopsy-proven NAFLD including patatin-like phospholipase domain containing 3 (PNPLA3) polymorphism. A total of 344 patients with biopsy-proven NAFLD were enrolled consecutively in this study. Multivariate analysis identified males (odds ratio (OR) 5.46), age (per 1 year, OR 1.07), and FIB-4 index (≥1.30, OR 3.85) as factors associated with CKD. Of the 154 patients with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min, 30 had a deterioration in CKD stage and 15 developed CKD after 3 years. Multivariate analysis identified diabetes mellitus (OR 2.44) as a risk factor for deterioration in CKD stage, while diabetes mellitus (OR 21.54) and baseline eGFR (per 1 mL/min OR 0.88) were risk factors for development of CKD. PNPLA3 did not affect the change in eGFR. In NAFLD patients, a high FIB-4 index was associated with CKD to increases in the index linked to reductions in eGFR. In order to prevent development of CKD, an appropriate therapy focusing on renal function is needed for NAFLD patients, especially those with diabetes.
Project description:BACKGROUND & AIMS:Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography. METHODS:We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ?30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included. RESULTS:Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78). CONCLUSIONS:Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
Project description:MicroRNAs miR-122, miR-34a, miR-16 and miR-21 are commonly deregulated in liver fibrosis and hepatocellular carcinoma. This study examined whether circulating levels of these miRNAs correlate with hepatic histological disease severity in patients with chronic hepatitis C infection (CHC) or non-alcoholic fatty-liver disease (NAFLD) and can potentially serve as circulating markers for disease stage assessment. We first used an in vitro model of hepatitis C virus (HCV) infection to measure the extracellular levels of these four miRNAs. Whereas miR-21 extracellular levels were unchanged, extracellular levels of miR-122, miR-34a and to a lesser extent miR-16, steadily increased during the course of HCV infection, independently of viral replication and production. Similarly, in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher than in control individuals, while miR-21 levels were unchanged. There was no correlation between the serum levels of any of these microRNAs and HCV viral loads. In contrast, miR-122 and miR-34a levels positively correlated with disease severity. Identical results were obtained in an independent cohort of CHC patients. We extended the study to patients with NAFLD. As observed in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher in NAFLD patients than in controls, while miR-21 levels were unchanged. Again, miR-122 and miR-34a levels positively correlated with disease severity from simple steatosis to steatohepatitis. In both CHC and NAFLD patient groups, serum levels of miR-122 and miR-34a correlated with liver enzymes levels, fibrosis stage and inflammation activity. miR-122 levels also correlated with serum lipids in NAFLD patients.Serum levels of miR-34a and miR-122 may represent novel, noninvasive biomarkers of diagnosis and histological disease severity in patients with CHC or NAFLD.