Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease
Abstract
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD. APPROACH AND RESULTS: We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow-up through December 31, 2015. We performed competing risk-adjusted cause-specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow-up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio [HR] = 1.8, 95% confidence interval [CI] = 1.59-2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3-2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort. CONCLUSIONS: Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.
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Individuals with both hypertension and dyslipidaemia had a 1.8-fold higher risk of progression to cirrhosis or HCC compared to individuals with no cardiometabolic risk factor.
“those with both hypertension and dyslipidaemia had a 1.8-fold higher risk of progression to cirrhosis or HCC compared to individuals with no cardiometabolic risk factor.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [57]
The HR for HCC significantly increased from 1.07 in the absence of T2D to 8.36 in the presence of T2D.
“Furthermore, the HR for HCC signi fi cantly increased from 1.07 in the absence of T2D to 8.36 in the presence of T2D.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [57]
In a large US cohort, individuals with only one cardiometabolic risk factor had a low risk of progression to cirrhosis or HCC, but each additional metabolic trait led to a stepwise increase in this risk, with T2D having the strongest association.
“In a large US cohort, individuals with only one cardiometabolic risk factor ( e.g. hypertension, dyslipidaemia, or obesity) had a low risk of progression to cirrhosis or HCC, but each additional metabolic trait led to a stepwise increase in this risk, with T2D having the strongest association.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [57]
Factors associated with a higher risk of HCC occurrence in MASLD include presence and duration of T2D, obesity or both, older age, concurrent alcohol intake and/or smoking, FIB-4 > 3.25, and LSM > 10 kPa and increasing change in LSM.
“Table 8. Factors associated with a higher risk of HCC occurrence in MASLD.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [57]
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- Authors
- Kanwal, F., Kramer, J. R., Li, L., Dai, J., Natarajan, Y., Yu, X., Asch, S. M., & El‐Serag, H. B.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Kanwal, Fasiha
- ORCID
- Venue
- Hepatology
- Published
- 2020-02-26
- Volume
- 71
- Issue
- 3
- Pages
- 808-819
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2988945504
- Cited by
- 319
- References
- 29
- Citations by year
- 2026: 35 · 2025: 48 · 2024: 61 · 2023: 57 · 2022: 52 · 2021: 50 · 2020: 15 · 2019: 1
- FWCI
- 23.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, liver cirrhosis, hepatocellular carcinoma, metabolic phenotypes, diabetes mellitus, hypertension, dyslipidemia, obesity, disease progression, veterans, secondary prevention
- MeSH terms
- Adult, Aged, Female, Carcinoma, Hepatocellular, Humans, Hypertension, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Obesity, Retrospective Studies, Risk, Diabetes Complications, Dyslipidemias, Non-alcoholic Fatty Liver Disease
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