Intriguing findings of liver fibrosis following COVID-19

Background Studies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4. Methods The study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3–6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups. Results Sixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT. Conclusion More than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.

Effect of 12 weeks of continuous burdock sprout extract intake on oxidized LDL: A placebo-controlled, randomized, double-blind, parallel-groups study

Background: Arctigenin, a lignan polyphenol found in burdock sprout, is a potent activator of AMP-activated protein kinase (AMPK) and has beneficial effects on metabolic disorders in mice. This highlights the potential value of arctigenin for the reduction of oxidized LDL (oxLDL) by activation of AMPK in human, but not well elucidated.Methods: We conducted a placebo-controlled, randomized, double-blind, parallel-groups study in healthy adults to investigate the effects of 12 weeks of a continuous intake of burdock sprout extract enriched with arctigenin on lipid metabolism. The subjects were 100 Japanese individuals with low-density lipoprotein cholesterol (LDL-C) < 140 mg/dl and a body mass index (BMI) of 23–30 kg/m2 who were randomly assigned to receive either burdock sprout extract (test food) or a placebo. The test food was encapsulated burdock sprout extract containing approximately 40 mg of arctigenin equivalent per day, and the placebo capsules contained no burdock sprout extract. The subjects consumed the assigned foods daily for 12 weeks.Results: The test food significantly suppressed oxLDL after 12 weeks in subjects with a body mass index (BMI) of 25 kg/m2 or higher. The test food inhibited an increase in the FIB-4 index (liver fibrosis index), an indicator of hepatic fibrosis. Pearson’s correlation coefficient analysis revealed a significant correlation between oxLDL and FIB-4 index changes, suggesting that the test food suppressed the rise in the FIB-4 index by controlling oxLDL while maintaining the platelet count.Conclusions: We conclude that the consumption of a burdock sprout supplement containing arctigenin is effective in suppressing oxLDL, which may prevent liver fibrosis.Clinical trial registration: UMIN000036664Keywords: arctigenin, burdock sprout, oxidized LDL, FIB-4 index, randomized controlled study

Elevation of Liver Fibrosis Index FIB-4 Is Associated With Poor Clinical Outcomes in Patients With COVID-19

Background COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19. Methods In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35–65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. Results Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30–8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90–13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36–15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01–1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor. Conclusions In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.

The Enhanced Liver Fibrosis Index Predicts Hepatic Fibrosis Superior to FIB4 and APRI in HIV/HCV Infected Patients

Background Accurate noninvasive biomarkers of fibrotic progression are important for hepatitis C virus (HCV) management, but commonly used modalities may have decreased efficacy in human immunodeficiency virus (HIV)/HCV-coinfected persons. The enhanced liver fibrosis (ELF) index is a highly sensitive noninvasive marker of hepatic fibrosis that has had limited assessment in the HIV/HCV population. We compared ELF index performance to FIB4 and aspartate to platelet ratio index (APRI) at different stages of liver fibrosis as determined by liver histology, and validated the efficacy of the three noninvasive biomarkers in HIV/HCV-coinfected versus HCV-monoinfected. Methods The ELF index was determined in 147 HIV/HCV-coinfected and 98 HCV-monoinfected persons using commercial ELISA assays for the component elements of the index. Area under the receiver-operator curve was used to validate ELF and to compare its performance to liver histology as well as to other noninvasive biomarkers of liver fibrosis, FIB4, and APRI. Results The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with Metavir score in all subjects. ELF performance was comparable between HIV/HCV and HCV with advanced liver fibrosis/cirrhosis. In the HIV/HCV cohort ELF cutoffs of 8.45 and 9.23 predicted mild and moderate fibrosis with 85% sensitivity, whereas the ELF cutoff of 9.8 had the highest specificity for advanced fibrosis and the cutoff of 10.4 was 99% specific for cirrhosis. ELF performance was superior to FIB4 and APRI in all subjects regardless of HIV status. Conclusions ELF index demonstrated excellent characteristics toward accurate prediction of liver fibrosis and cirrhosis with superior performance to APRI and FIB4 in HIV/HCV coinfection. Applying this noninvasive biomarker index for diagnosis of liver fibrosis and progression in HIV/HCV is warranted.

The liver fibrosis index is superior to the APRI and FIB-4 for predicting liver fibrosis in chronic hepatitis B patients in China

Background The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters. Methods Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF. Results The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity. Conclusions The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.