Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease

Abstract

Background & Aims Nonalcoholic fatty liver disease and chronic kidney disease share similar pathophysiologic features. Our aim was to assess the association between different stages of chronic kidney disease and mortality in patients with nonalcoholic fatty liver disease. Methods Third National Health and Nutrition Examination Survey‐linked mortality files were utilized. Nonalcoholic fatty liver disease was diagnosed by hepatic ultrasound and chronic kidney disease was defined according to the Kidney Disease Improving Global outcomes guideline. Multivariable Cox proportional hazard model was used to assess the effect of chronic kidney disease on overall and cardiovascular mortality. Results Total cohort included 11 695 adult participants; mean age 43.3 years, 48.4% male, 76.4% white, 18.6% had nonalcoholic fatty liver disease and 9.3% had chronic kidney disease. 5.6% had diabetes, 21.3% had hypertension, 4.3% had cardiovascular disease. Compared to subjects without chronic kidney disease or nonalcoholic fatty liver disease, nonalcoholic fatty liver disease patients with chronic kidney disease were more likely to be older, had less income, and higher prevalence of comorbidities (all P < 0.001). Prevalence of chronic kidney disease among nonalcoholic fatty liver disease cohort was 11.31%. Compared to non‐nonalcoholic fatty liver disease group, patients with nonalcoholic fatty liver disease had higher rates of stage 1, 2 and 3a chronic kidney disease, but similar rates for stage 3b, 4 and 5. Mortality rate was 18.5% in 17 years. Among nonalcoholic fatty liver disease cohort, the presence of chronic kidney disease stages 2‐3a (HR = 2.31, 95% CI: 1.70‐3.15) and stages 3b‐5 (HR = 4.83, 95% CI: 2.40‐9.71) were independently associated with increased overall mortality. Conclusions Among patients with nonalcoholic fatty liver disease, moderate to advanced stages of chronic kidney disease are associated with overall mortality. Identification of chronic kidney disease in nonalcoholic fatty liver disease has important prognostic implications.

The impact of modifiable risk factors on the long‐term outcomes of non‐alcoholic fatty liver disease

“…Hazard ratios of each ideal CV health metric as well as the number of ideal health metrics as a categorical variable on all‐cause or CV mortality by NAFLD status were estimated by Cox proportional hazards model while adjusting for demographic characteristics, income level, college degree, the 7 CV health metrics and family history of CVD, according to the published literature . The proportional hazards assumption of the Cox models was examined by testing time‐dependent covariates, which showed no significant departure from proportionality over time. The proportion of all‐cause and CV mortality that would have been prevented by reaching ideal CV health metrics among both NAFLD subjects and non‐NAFLD controls was estimated by population‐attributable fraction (PAF) using hazard ratios .…”

“…23 For the current analysis, NAFLD was diagnosed by having the presence of mild, moderate or severe hepatic steatosis by ultrasound in the absence of other causes of chronic liver disease (hepatitis B surface antigen negative, anti-hepatitis C virus antibody negative, transferrin saturation <50%) and excessive alcohol consumption (EAC) (<20 g/d for males and, 10 g/d for females). 25,26 Participants without any degree of hepatic steatosis and other causes of chronic liver disease were presumed to have no chronic liver disease and were used as the control cohort (non-NAFLD).…”

Prevalence and outcomes of non‐alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States

“…NAFLD is bidirectionally associated with metabolic syndrome and its components such as obesity, diabetes (DM), hypertension, insulin resistance, and dyslipidemia . It is increasingly recognized that NAFLD not only causes liver disease, but is also associated with a number of extrahepatic manifestations, including sleep apnoea, cardiovascular disease (CVD), chronic kidney disease (CKD) and extrahepatic malignancies . In this context, CKD is an important predictor of mortality in NAFLD and CVD is the leading cause of death among patients with NAFLD …”

“…It is important to recognize that NAFLD covers a spectrum that encompasses both non‐alcoholic steatohepatitis (NASH) and non‐NASH NAFLD . Although all patients with NAFLD are at risk for increased CVD‐related mortality, it is the subgroup of NAFLD patients with histologic evidence for NASH (hepatocyte balloon degeneration and hepatic lobular inflammation in the presence of hepatic steatosis) who are at increased risk for cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality . There is also increasing evidence that the rate of progression for NASH is not linear and a number of factors can impact this progression.…”

“…[1][2][3][4][5] Although all patients with NAFLD are at risk for increased CVD-related mortality, it is the subgroup of NAFLD patients with histologic evidence for NASH (hepatocyte balloon degeneration and hepatic lobular inflammation in the presence of hepatic steatosis) who are at increased risk for cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. [1][2][3][4][5][7][8][9] There is also increasing evidence that the rate of progression for NASH is not linear and a number of factors can impact this progression. In this context, environmental, genetic and host factors have been implicated as the potential risk factors influencing the progression of NASH.…”