Previous studies indicated that the Fibrosis-4 Index (FIB-4), an evaluation metric for liver fibrosis, is associated with adverse outcomes in coronary artery disease. However, the correlation between FIB-4 and myocardial infarction (MI) in Chinese patients with Type 2 Diabetes Mellitus (T2DM) has not been well-defined. Thus, this study aims to elucidate the association between FIB-4 and MI in Chinese T2DM patients.

Cross-sectional data were collected from T2DM patients at two hospitals in China, designated as the discovery and validation centers. The exposure variable, FIB-4 index, was derived from patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. This index was stratified into four distinct clusters via k-means clustering analysis. The primary outcome was defined as the incidence of co-occurring MI. Logistic and restricted cubic spline regression was conducted to assess the association between the FIB-4 index and MI in Chinese T2DM patients.

In the discovery phase, data were analyzed from 2,980 T2DM patients, including 1,114 females (37.38%), with 58 years average age (SD: 10.4). Among them, 190 were also MI patients. Based on the fully adjusted logistic regression analysis, the odds ratio (OR) for the second cluster was 1.00 (95% CI, 0.60-1.40); for the third cluster, it was 1.94 (95% CI, 1.32-2.57), and for the poorest controlled cluster it was 16.18 (95% CI, 14.97-17.39) in comparison to the best-controlled cluster of FIB-4. Restricted cubic spline regression revealed a linear relationship between the FIB-4 index and MI risk. Subgroup analysis demonstrated that this association was significant in elderly adults, females with high BMI, and those with comorbidities such as hypertension, coronary artery disease, and chronic heart failure. These findings yield consistent results in the validation set (n = 224).

Among Chinese patients with T2DM, elevated FIB-4 levels have been independently associated with MI, particularly among females and individuals with concomitant hypertension. Consequently, the FIB-4 index is anticipated to serve as a promising tool for early detection and risk stratification in this population.

Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.

To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.

One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.

HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively.

Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.