Search

Background: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD., Methods: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking., Results: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend  = .02)., Conclusion: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD., (© 2023 American Cancer Society.)

Background: HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis., Methods: We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis., Results: Of 47,165 patients with NAFLD aged 40-89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3-43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex., Conclusions: Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B-related hepatocellular carcinoma (HCC). However, studies in non-alcoholic fatty liver disease (NAFLD) patients are lacking., Methods: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow-up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count., Results: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01-2.03, p trend  = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis-4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43-0.94, p trend  = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk., Conclusions: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Nonalcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the United States and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiologic data on iron overload without hemochromatosis in relation to HCC are sparse. This study aimed to examine the associations between serum biomarkers of iron and the risk of HCC in patients with NAFLD., Methods: We identified 18,569 patients with NAFLD using the University of Pittsburgh Medical Center electronic health records from 2004 through 2018. After an average 4.34 years of follow-up, 244 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of HCC incidence associated with elevated levels of iron biomarkers with adjustment for age, sex, race, body mass index, history of diabetes, and tobacco smoking., Results: The HRs (95% CIs) of HCC for clinically defined elevation of serum iron and transferrin saturation were 2.91 (1.34-6.30) and 2.02 (1.22-3.32), respectively, compared with their respective normal range. No statistically significant association was observed for total iron-binding capacity or serum ferritin with HCC risk., Conclusions: Elevated levels of serum iron and transferrin saturation were significantly associated with increased risk of HCC among patients with NAFLD without hemochromatosis or other major underlying causes of chronic liver diseases., Impact: Clinical surveillance of serum iron level may be a potential strategy to identify patients with NAFLD who are at high risk for HCC., (©2021 American Association for Cancer Research.)