The Natural History of NAFLD, a Community-Based Study at a Large Health Care Delivery System in the United States

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. However, the natural history of NAFLD is incomplete. This is a retrospective cohort study of patients identified with NAFLD by diagnosis codes in a large, community-based health care delivery system. The objectives were (1) to follow patients from initial NAFLD presentation through progression to cirrhosis and/or decompensated cirrhosis to liver cancer, liver transplant, and death for up to 10 years; and (2) to conduct disease progression analysis restricted to patients with NAFLD identified as having diabetes at baseline. A total of 98,164 patients with full NAFLD and 26,488 with diabetes were divided into three baseline prevalent states: (1) no cirrhosis, (2) compensated cirrhosis, and (3) decompensated cirrhosis. In baseline patients without cirrhosis, annual rates of compensated cirrhosis, decompensated cirrhosis, and death were 0.28%, 0.31%, and 0.63% per year, respectively. With baseline compensated cirrhosis, the annual rates of decompensation and death were 2.4% and 6.7% per year. Finally, in those with decompensated cirrhosis at baseline, the death rate was 8.0% per year. In those without cirrhosis and with cirrhosis at baseline, the rates of liver cancer and death were increased approximately 2-fold in the diabetic subpopulation compared with the full NAFLD cohort. Age and comorbidities increased with increasing disease severity. Cox proportional hazards regression analysis showed that cirrhosis was strongly associated with death and liver cancer, and that diabetes was associated with a significant increase in the hazard of both liver cancer and death (2.56 [2.04-3.20] and 1.43 [1.35-1.52]), respectively. Conclusion: The findings of this community-based study further our understanding of the natural history of NAFLD and demonstrate that diabetes is a major factor in the progression of this disease.

FIG. 1

Selection of patients from 3,534,604 total KPSC members. After inclusion and exclusion criteria were applied, the full NAFLD study cohort of 98,164 was further divided into the three prevalent states at study baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis.

FIG. 2

(A) Progression of disease for the full NAFLD cohort from the three prevalent states at baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis. Time (in years) and conditional probabilities of progressing from one state to the next are shown. (B) Progression of disease for the full NAFLD cohort from the three prevalent states at baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis. The proportions of the subpopulations that reached one of the outcomes of liver cancer, liver transplant, or death during the study period are shown. Time (in years) and conditional probabilities of progressing from one state to the next are shown. Note: Outcome events are related to the latest disease state (no cirrhosis, compensated cirrhosis, and decompensated cirrhosis). Thus, an outcome event before compensated or decompensated cirrhosis is associated with no cirrhosis. An outcome event after compensated cirrhosis but before decompensated cirrhosis is associated with compensated cirrhosis. Finally, an outcome event after decompensated cirrhosis is associated with decompensated cirrhosis.

FIG. 3

(A) Progression of disease for the subpopulation with diabetes from the three prevalent states at baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis. Time (in years) and conditional probabilities of progressing from one state to the next are shown. (B) Progression of disease for the subpopulation with diabetes from the three prevalent states at baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis. The proportions of the subpopulations that reached one of the outcomes of liver cancer, liver transplant, or death during the study period are shown. Time (in years) and conditional probabilities of progressing from one state to the next are shown. Note: Outcome events are related to the latest disease state (no cirrhosis, compensated cirrhosis, and decompensated cirrhosis). Thus, an outcome event before compensated or decompensated cirrhosis is associated with no cirrhosis. An outcome event after compensated cirrhosis but before decompensated cirrhosis is associated with compensated cirrhosis. Finally, an outcome event after decompensated cirrhosis is associated with decompensated cirrhosis.

FIG. 4

Final disposition for the full NAFLD cohort from the three prevalent states at baseline: (1) no cirrhosis; (2) compensated cirrhosis; and (3) decompensated cirrhosis. Annualized rates of progression are shown.