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. (Hepatology Communications 2020;0:1-14).

Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma

“… 23 , 24 , [45] , [46] , [47] , [48] , [49] The most important risk factors for HCC include the presence of diabetes and insulin resistance, obesity, older age, and male sex. 24 , [45] , [46] , [47] , [48] , [49] In the United States, ethnicity has been associated with the development of HCC; Mexican-Americans have been found to be at higher risk. 24 In addition, less physically active individuals, with more metabolic components, are also at increased risk.…”

Predicting Liver‐Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests

“…The rate of development of a decompensation event or HCC was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa) and is consistent with the annual rate of decompensation from baseline compensated cirrhosis (2.4%) in a large community‐based study of NAFLD in the United States (n = 98,312 patients, followed for a median of 4.13 years). ( 23 ) However, due to the high prevalence of NAFLD in people with obesity and T2D, these events are projected to lead to a substantial increase in NAFLD‐related disease burden over the next decade. ( 5 )…”

“…The rate of development of a decompensation event or HCC was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa) and is consistent with the annual rate of decompensation from baseline compensated cirrhosis (2.4%) in a large community-based study of NAFLD in the United States (n = 98,312 patients, followed for a median of 4.13 years). (23) However, due to the high prevalence of NAFLD in people with obesity and T2D, these events are projected to lead to a substantial increase in NAFLDrelated disease burden over the next decade. (5) Although our study lacked a formal protocol to follow patients without advanced fibrosis who were not reviewed in the hepatology clinic, we believe that if liver-related complications, cardiac events, or malignancy occurred, these events were likely to be recorded in the hospital and/or primary care electronic medical record.…”

MAFLD-Epidemiology, Natural History, Outcomes and Prevention

“…Over the past decade, the need of liver transplant due to NAFLD has risen by 170% [52], [53]. According to a recent cohort study, the incidence of diabetic patients requiring liver transplant for decompensated cirrhosis due to NAFLD was 305/100,000 person years [54]. Contrary to the common belief that HCC is not very common in fatty liver disease, recent data reported a surge in the burden of HCC secondary to MAFLD [55].…”