Clinically significant portal hypertension (CSPH) represents the major risk factor for developing decompensating events in patients with cirrhosis. While the gold standard technique for its detection is the invasive measurement of the hepatic venous pressure gradient, noninvasive techniques have shown adequate diagnostic potential (1). Several studies have shown that patients with type 2 diabetes (T2D) have a high prevalence of advanced liver fibrosis related to metabolic dysfunction–associated steatotic liver disease or other chronic liver conditions (2). Nonetheless, data are scarce on the prevalence of the most advanced forms of liver disease, including CSPH, in the general population and in patients with T2D. In the current study we aim at filling this gap in evidence.
We performed an analysis of the 2017–2020 cycle of the National Health and Nutrition Examination Survey (NHANES), a complex cross-sectional epidemiologic study aimed at evaluating the health and nutritional conditions of the general, noninstitutionalized population of the U.S. We focused our analysis on adult participants (aged ≥18 years) with available data on vibration-controlled transient elastography, anthropometric parameters, and glycemic status. A controlled attenuation parameter value ≥274 dB/m was considered indicative of liver steatosis (3). With use of the Baveno VII criteria, compensated advanced chronic liver disease (cACLD) was defined according to median liver stiffness measurement (LSM) ≥15.0 kPa (4). Following the same recommendations, we considered an LSM value ≥25 kPa to be indicative of CSPH in patients with viral hepatitis, autoimmune hepatitis, or alcohol-related liver disease and in patients with metabolic dysfunction–associated steatotic liver disease without concomitant obesity. In patients with obesity and an LSM value ≥25 kPa, ANTICIPATE-NASH score (based on BMI, platelet count, and LSM) was calculated (5); patients with a probability of having CSPH ≥90% were considered to be affected by CSPH. Viral hepatitis was diagnosed in the presence of a positive test for hepatitis C virus antibodies or a positive hepatitis B virus surface antigen test. Prevalence rates were weighted to be representative of the U.S. population. Statistical analyses were performed with Stata 17 (StataCorp).
We included a total of 7,463 participants, with 1,280 (12.6%, 95% CI 11.8–13.5) affected by T2D. Prevalence rates of liver steatosis, cACLD, and CSPH among participants with and without diabetes are shown in Fig. 1A–C. For all features, prevalence was significantly higher among patients with T2D compared with their counterparts without diabetes. In particular, cACLD was present in 6.2% and 1.2% of participants with and without T2D (P < 0.001) and CSPH in 0.62% and 0.18%, respectively (P = 0.022).
Prevalence of liver steatosis (A), cACLD (B), and CSPH (C) according to the presence or absence of T2D.
Prevalence of liver steatosis (A), cACLD (B), and CSPH (C) according to the presence or absence of T2D.
Patients with cACLD were significantly older and more commonly male, while no difference was identified in the race-ethnicity distribution. They had a higher BMI and waist circumference and higher levels of liver enzymes, HbA1c, and elastographic parameters; a lower platelet count; and lower albumin. The prevalence of T2D was higher among patients with cACLD (43.0%) than among participants without (12.3%; P < 0.001). Finally, prevalence of chronic hepatitis C was higher among patients with cACLD (8.1% vs. 2.0%; P < 0.001), while no difference was found in the prevalence of hepatitis B or elevated alcohol consumption. In a multivariable logistic regression model with adjustment for age, sex, BMI, race-ethnicity, and viral hepatitis, T2D was a significant and independent predictor of cACLD (odds ratio 2.66, 95% CI 1.69–4.19; P < 0.001).
Taken together, the results of this population-based cross-sectional study show that ∼1 in 20 patients with T2D might have cACLD, a proportion that is significantly higher than that among the general adult population without T2D. Moreover, 1 in 200 patients with T2D might suffer from CSPH, a condition that might lead to severe clinical consequences such as variceal bleeding, ascites, and hepatic encephalopathy. Our study is, to our knowledge, the first to report CSPH prevalence in an unselected population of patients with T2D and might inform future endeavors in the identification of patients at very high risk. Alongside strengths, several limitations of the present analysis should be considered. Data on the gold standard technique to identify CSPH were not available, as the technique is labor intensive and not suitable for large studies in a low-risk setting. For similar reasons, data on liver histology were not retrieved. Finally, the survey did not include consideration of rarer causes of chronic liver disease such as hemochromatosis, Wilson disease, and autoimmune liver diseases.
In conclusion, our study provides estimates of CSPH prevalence in a general population setting and highlights the much higher proportion not only of advanced liver fibrosis but also of more severe liver conditions among patients with T2D.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. S.C. and G.P. designed the study, drafted the manuscript, approved the final version, and made the decision to submit and publish the manuscript. S.C. researched and analyzed data. S.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Handling Editors. The journal editors responsible for overseeing the review of the manuscript were Elizabeth Selvin and Alka M. Kanaya.