NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

Non-Invasive Assessment Of Liver Fibrosis In Patients With Non-Alcoholic Fatty Liver Disease In A Tertiary Care Hospital

Aims :To compare the NAFLD fibrosis score and FIBROSIS 4 score to fibroscan, and affirm whether the scores shall be used as a screening tool for liver fibrosis, in place of fibroscan. Methodology: It was a cross-sectional study. Patients with fatty liver on ultrasonological examination with 200 sample size. After obtaining the informed consent the following details were collected socio-demographic details, history, co-morbidities, anthropometric measurements, Laboratory investigations. Results: the ROC curve analysis of fibroscan reveals the area under curve of 0.499 and based on the cut off value of 4.50Kpas the sensitivity and specificity was found to be 85.7% and 83.5% respectively. The ROC curve analysis of fibrosis-4 reveals the area under curve of 0.495 and based on the cut off value of 0.80 the sensitivity and specificity was found to be 91.9% and 92.1% respectively. Analysis of NAFLD fibrosis score reveals the area under curve of 0.476 and based on the cut off value of -1.53 the sensitivity and specificity was found to be 93.1% and 93.9% respectively. Conclusion: Henceforth the study suggests that NAFLD fibrosis score shall be used as a non -invasive bedside assessment of liver fibrosis in high risk population and hence guiding their follow up for prevention of morbidity in resource limited settings.

Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD

ObjectiveIn non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction.MethodsWe included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds.Results129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient’s profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions.ConclusionIn patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis—A Pilot Study

Takayasu arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Detection of pancreatic fibrosis using magnetic resonance imaging: correlation with histopathology

Background and Hypothesis: Diagnosis of chronic pancreatitis (CP) is challenging and controversial. Magnetic Resonance Imaging (MRI) offers a noninvasive modality to diagnose CP, but its findings have been rarely correlated with histopathology. We aimed to assess the correlation of T1 signal intensity ratio of pancreas to spleen (T1 SIRp/s) and arterio-venous ratio (AVR) of the parenchyma on MRI and Cambridge score on MRCP with surgical histopathology in patients who underwent pancreatic resection. Methods: We identified 160 pancreatic resections performed in adults between 2017 and 2019 by searching our institution’s surgery database. Seventy-one of them had surgical pathology specimens available and 59 of them had MRI/MRCP within 3 months prior to the surgery. Histologic grading was performed by a gastrointestinal pathologist using Ammann’s fibrosis score. Two image analysts blinded to the clinical information and fibrosis score measured T1 SIRp/s from unenhanced T1-weighted fat-saturated gradient-echo images and arterio-venous ratio (AVR) from post-contrast dynamic phase. Cambridge score was also recorded from MRCP. Statistical analysis included Pearson’s correlation coefficient of the T1 SIRp/s, AVR, and Cambridge score with the fibrosis score and weighted kappa for interobserver agreement. Results: Correlations between T1 SIRp/s and AVR with the fibrosis score were (r= -0.30, p=0.02, 95%CI: -0.51 to -0.04 and r= -0.36, p=0.01, 95%CI: -0.58 to -0.09, respectively). In comparison, there is less correlation between the Cambridge grade and the fibrosis (r= 0.17, p=0.15, 95% CI for r= -0.07 to 0.39). Interobserver agreement was good (kappa=0.80). Conclusion: There is moderate correlation between the T1 signal intensity and enhancement ratio of the pancreas with pancreatic fibrosis. This is higher than the correlation between the Cambridge grade and fibrosis. Multi-institutional, prospective studies are needed to verify T1 SIR and AVR as potential imaging biomarkers of pancreatic fibrosis.

Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin

<b><i>Purpose:</i></b> This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. <b><i>Methods:</i></b> The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. <b><i>Results:</i></b> The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. <b><i>Conclusion:</i></b> The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.

Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes

The association between nonalcoholic fatty liver (NAFL) or liver fibrosis and diabetic peripheral neuropathy (DPN) has not been well studied. We aimed to investigate the association of NAFL or liver fibrosis indices and DPN in individuals with type 2 diabetes. In this observational study, we included 264 individuals with type 2 diabetes, and calculated non-alcoholic fatty liver disease (NAFLD) liver fat score, NAFLD fibrosis score, and Fibrosis-4 (FIB-4) index to evaluate the status of NAFLD or liver fibrosis. DPN was diagnosed when the Michigan Neuropathy Screening Instrument—Physical Examination score was ≥ 2.5. The NAFLD fibrosis score and FIB-4 index were significantly higher in individuals with DPN than in those without DPN. Logistic analyses showed that the NAFLD fibrosis score and FIB-4 index were associated with DPN after adjustment for covariates (adjusted odds ratio 1.474 and 1.961, respectively). In the subgroup analysis, this association was only significant in the group with a high NAFLD liver fat score (> − 0.640). Serum levels of fetuin-A, a hepatokine, were decreased in individuals with abnormal vibration perception or 10-g monofilament tests compared with their counterparts. The present study suggests that liver fibrosis might be associated with DPN in individuals with type 2 diabetes.

The Interplay between Myocardial Fibrosis, Strain Imaging and Collagen Biomarkers in Adults with Repaired Tetralogy of Fallot

Background: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 (Gal-3), procollagen type III (PCIII), and NTproBNP. Methods: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured. Results: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score (p = 0.007). A LV GLS value of −15.9% predicted LGE RV score > 8 (AUC 0.754 (p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points (AUC 0.729, (p = 0.03)). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% [AUC 0.704, (p = 0.05)]. Conclusions: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.

Does the FT3-to-FT4 ratio easily predict the progression of NAFLD and NASH cirrhosis?

Background Factors causing progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH) and liver cirrhosis remain relatively unknown. We aimed to evaluate the power and effectiveness of the free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio to predict non-alcoholic fatty liver disease (NAFLD)/liver fibrosis and NASH cirrhosis severity. Methods Patients (n = 436) with NASH-associated liver cirrhosis (n = 68), patients with liver biopsy-proven NAFLD (n = 226), or healthy participants (n = 142) were enrolled between January 2010 and January 2020. The aspartate aminotransferase-to-thrombocyte ratio (APRI), NAFLD fibrosis score, albumin–bilirubin score (ALBI), aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio, FT3-to-FT4 ratio, and Fibrosis-4 (FIB-4) were calculated and evaluated. Results All parameters were significantly higher in NASH cirrhosis than in the healthy group. Body mass index, ALT, fasting insulin, homeostatic model assessment for insulin resistance, and triglyceride levels were significantly higher in liver biopsy-proven NAFLD than in the healthy group. The APRI, NAFLD fibrosis score, ALBI, AST-to-ALT ratio, FT3-to-FT4 ratio, and FIB-4 were significantly higher in the NASH cirrhosis group than in the healthy group. In patients with biopsy-proven NAFLD, the FT3-to-FT4 ratio was significantly lower than in the healthy group. Conclusion The FT3-to-FT4 ratio is an effective and useful indicator to predict NAFLD/liver fibrosis and NASH cirrhosis severity.