Higher Fibrosis-4 Scores Research Articles

Advanced fibrosis leads to overestimation of steatosis with quantitative ultrasound in individuals without hepatic steatosis.

The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease

ObjectivesThe prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association. MethodsThe study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death. ResultsDuring a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84–0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216). ConclusionsLower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.

Liver fibrosis in pars cohort study: A large-scale study on the prevalence and correlated factors

Backgrounds and study aimsThe fibrosis-4 (FIB-4) is a non-invasive scoring system for estimating liver fibrosis severity as a biomarker of chronic liver disease. We aimed to estimate the prevalence and severity of chronic liver disease at the community level using FIB-4. Patients and methodsThis cross-sectional study was conducted using the Pars Cohort database collected in Valashar, Fars province, Iran. Participants were divided into three groups based on their FIB-4 scores: low risk of liver fibrosis (FIB < 1.45), intermediate cases (1.45 ≤ FIB-4 ≤ 3.25), and high risk of liver fibrosis (FIB-4 > 3.25). ResultsIn total, 9269 individuals with a mean age of 52.65 years were enrolled in the study, of which 4278 (46.2 %) were male. Among all participants, 7853 (84.7 %) were in the low-risk, and 65 (0.7 %) were in the high-risk groups. In the final ordinal regression model, male gender, being a farmer or rancher, living in rural areas, history of opioid use, history of jaundice, no history of diabetes, history of depression, and positive HBs Ag were independently associated with higher FIB-4 scores. ConclusionOur study revealed that males, individuals residing in rural areas, and those engaged in farming and ranching occupations face a heightened risk of liver fibrosis. These findings emphasize the need for future programs for early detection and effective management of liver fibrosis in these at-risk populations.

Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis.

Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis. Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure. ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively). Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke

Background and aimStroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. Methods and resultsYoung adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7–4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359–10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. ConclusionsYoung stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

Liver Fibrosis Scores and Coronary Artery Disease: Novel Findings in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed term as a more appropriate definition for nonalcoholic fatty liver disease (NAFLD). Previous studies have shown an association between liver fibrosis scores and cardiovascular disease (CVD) in patients with NAFLD. In this study, we aimed to investigate the relationship between liver fibrosis scores and coronary artery disease (CAD) severity in patients with MAFLD. This study was conducted on 1346 patients with MAFLD at the Second Hospital of Dalian Medical University between January 2018 and December 2021. We calculated the liver fibrosis scores, including the fibrosis 4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). We divided the participants into three groups based on the degree of coronary artery stenosis assessed using coronary computed tomography angiography (CCTA): CAD (≥50%), non-obstructive (1-49%), and normal (no stenosis). An increased FIB-4 score and NFS were significantly associated with CAD severity in patients with MAFLD. The percentage of patients with a high FIB-4 score was higher in the CAD group than in the other two groups (5.80%, 4.31%, and 2.24%, respectively; p<0.001), as was the percentage of patients with NFS (11.12%, 5.19%, and 0.93%, respectively; p<0.001). Carotid atherosclerosis, creatinine levels, and CAC scores were significant predictors of CAD. The FIB-4 score and NFS were independently associated with CAD even after adjusting for sex and well-known cardiovascular risk factors. The APRI was not a significant factor for CAD in any model. In the bivariate correlation analysis, the FIB-4 score and NFS were directly correlated with CAC scores. Non-invasive liver fibrosis scores (FIB-4 and NFS) were significantly associated with the CAD severity and CAC scores in patients with MAFLD. Screening for CAD may be beneficial for subjects with high liver fibrosis risk MAFLD.

Various ambient air pollutants, residential green spaces, fibrosis 4 scores, genetic susceptibility, and risk of severe liver disease

BackgroundThe relationship of air pollutants and residential exposure to greenspace with severe liver disease remains inconclusive. ObjectiveOur objective was to assess the relationship of joint exposure to air pollutants, residential exposure to greenspaces with new-onset severe liver disease. MethodsWe included 427,697 participants without prior liver diseases from UK Biobank. A weighted air pollution score was calculated based on PM2.5, PM10, PM2.5–10, NO2, and NOX. The percentage of land coverage by residential greenspaces was estimated using land use data. The primary outcome was new-onset severe liver disease, defined as a composite outcome including hospitalization or death due to compensated or decompensated liver cirrhosis, liver failure, and hepatocellular carcinoma. ResultsDuring a median follow-up of 12.0 years, 4572 participants developed severe liver disease. A higher air pollution score was significantly associated with an increased risk of new-onset severe liver disease (per SD increment; adjusted hazard ratio [HR],1.07; 95% confidence interval [CI],1.04–1.10). Moreover, residential greenspace coverage was inversely associated with new-onset severe liver disease (per SD increment; adjusted HR, 0.95; 95% CI,0.92–0.98). Genetic risks of liver cirrhosis did not significantly modify the associations (both P-interactions >0.05). However, we observed a stronger positive association between air pollution scores and new-onset severe liver disease in individuals with higher fibrosis-4 (FIB-4) scores, lower residential greenspaces, hypertension, and smokers (all P-interactions <0.05). Similarly, a more pronounced inverse association between residential exposure to greenspaces and new-onset severe liver disease was found in smokers and individuals with higher FIB-4 scores (both P-interactions<0.05). ConclusionsOur findings suggest a positive association between air pollution scores and the risk of new-onset severe liver disease, while residential greenspaces show an inverse association. These results underscore the importance of maintaining high exposure to green space and reducing air pollution to prevent serious liver disease.

Low vitamin A levels are associated with liver-related mortality: a nationally representative cohort study.

Vitamin A, a fat-soluble vitamin that includes retinol and carotenoids, is implicated in liver fibrosis, whereas its deficiency has been associated with various liver diseases and higher overall mortality. This study aims to determine the relationship between levels of vitamin A species and liver fibrosis, as well as liver-related mortality in the population of the US. A total of 12,299 participants from the National Health and Nutrition Examination Survey III (NHANES III) were analyzed to provide nationally representative estimates of the relationship between the levels of vitamin A species and liver fibrosis measured by Fibrosis-4 (FIB-4) index and liver-related mortality. A low blood level of retinol, but not other retinoid derivatives, was associated with significant liver fibrosis after adjustment for demographics, anthropometric measurements, medical history, retinol, and carotene intakes. Compared with vitamin D and E, retinol deficiency demonstrated much stronger associations with a high FIB-4 score. Individuals with known risks of chronic liver disease (CLD) and the lowest pentile of retinol levels had ORs of 3.12 (95% CI, 1.64-5.91) for possible fibrosis and 19.7 (95% CI, 5.71-67.7) for likely fibrosis, and an HR of 7.76 (95% CI, 1.19-50.5) for liver-related mortality compared with those in the highest retinol-level pentile. These relationships were more pronounced among individuals with known risks of chronic liver disease than without. A low circulating retinol level is associated with liver fibrosis and liver-related mortality in chronic liver disease. This relationship is potentially driven by a mechanistic link rather than the malabsorption of fat-soluble vitamins and may be leveraged for disease prognostication and have therapeutic implications.

Subclinical Liver Fibrosis is Associated with More Rapid Cognitive Decline in Parkinson’s Disease (P7-11.013)

<h3>Objective:</h3> To determine the impact of liver fibrosis on motor scores and cognition in Parkinson’s disease. <h3>Background:</h3> It is increasingly apparent that even subclinical liver fibrosis is associated with cognitive impairment and frailty. However, it’s impact on motor and cognitive performance in Parkinson’s Disease (PD) is not well understood. <h3>Design/Methods:</h3> We conducted a retrospective cohort study using the Parkinson’s Progression Marker Initiative (PPMI), a longitudinal study collecting data on PD patients. Our exposure was liver fibrosis at baseline, based on the validated Fibrosis-4 (FIB4) score calculated using age, platelet count, aspartate and alanine aminotransferase values. We dichotomized participants as high (≥1.3) versus low (&lt;1.3) FIB4. Our outcomes were the Montreal Cognitive Assessment (MoCA) and Unified Parkinson’s Disease Rating Scale part III (UPDRSIII) on-and off-treatment scores. We used linear mixed models to assess the relationships between FIB4 at baseline and MoCA and UPDRSIII scores, both at baseline and over time during the eight years of available follow-up data. Models were adjusted for demographics, comorbidities, and alcohol use. <h3>Results:</h3> In adjusted models, UPDRSIII on-treatment and off-treatment scores were not significantly different at baseline or over time when comparing participants with high versus low FIB4. High FIB4 score was not associated with low MoCA scores at baseline. However, MoCA scores in the high FIB4 group declined more over time, with an average difference in rate of change of 0.13 (95% CI, 0.06–0.20). This relationship was maintained after adjusting for potential confounders, with a difference in rate of change of 0.12 (95% CI, 0.05–0.20). <h3>Conclusions:</h3> In PD, a high liver fibrosis score was not associated with motor progression but was associated with faster cognitive decline. Liver health may therefore be an under-appreciated determinant of cognitive outcomes in PD. <b>Disclosure:</b> Dr. Zolin has nothing to disclose. Miss Zhang has nothing to disclose. Dr. Ooi has nothing to disclose. Dr. Sarva has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. Sarva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Sarva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluerock Therapeutics. The institution of Dr. Sarva has received research support from Insightec. The institution of Dr. Sarva has received research support from NeuroNext. The institution of Dr. Sarva has received research support from Neuroderm. The institution of Dr. Sarva has received research support from Covance. The institution of Dr. Sarva has received research support from Prevail. The institution of Dr. Sarva has received research support from Bluerock Therapeutics. The institution of Dr. Sarva has received research support from Biogen. The institution of Dr. Sarva has received research support from Roche. Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim. Dr. Parikh has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for cases of neurological illness. The institution of Dr. Parikh has received research support from Leon Levy Foundation. The institution of Dr. Parikh has received research support from Florence Gould Foundation. The institution of Dr. Parikh has received research support from NY State Empire Clinical Research Investigator Program. The institution of Dr. Parikh has received research support from NIA. The institution of Dr. Parikh has received research support from Medtronic.

Administrative coding for non-alcoholic fatty liver disease is accurate in Swedish patients

Background and Aims: Epidemiological studies of non-alcoholic fatty liver disease (NAFLD) frequently use the International Classification of Disease (ICD) codes to identify patients. The validity of such ICD codes in a Swedish setting is unknown. Here, we aimed to validate the administrative code for NAFLD in Sweden. Methods: In total, 150 patients with an ICD-10 code for NAFLD (K76.0) from the Karolinska University Hospital between 1 January 2015 and 3 November 2021 were randomly selected. Patients were classified as true or false positives for NAFLD by medical chart review and the positive predictive value (PPV) for the ICD-10 code corresponding to NAFLD was calculated. Results: The PPV of the ICD-10 code for NAFLD was 0.82 (95% confidence interval [CI] = 0.76–0.89). After exclusion of patients with diagnostic coding for other liver diseases or alcohol abuse disorder (n = 14), the PPV was improved to 0.91 (95% CI 0.87–0.96). The PPV was higher in patients with coding for NAFLD in combination with obesity (0.95, 95%CI = 0.87–1.00) or type 2 diabetes (0.96, 95%CI = 0.89–1.00). However, in false-positive cases, a high alcohol consumption was common and such patients had somewhat higher Fibrosis-4 scores than true-positive patients (1.9 vs 1.3, p = 0.16) Conclusions: The ICD-10 code for NAFLD had a high PPV, that was further improved after exclusion of patients with coding for other liver diseases than NAFLD. This approach should be preferred when performing register-based studies to identify patients with NAFLD in Sweden. Still, residual alcohol-related liver disease might risk confound some findings seen in epidemiological studies which needs to be considered.

Sex-specific changes in triglyceride profiles in liver cirrhosis and hepatitis C virus infection

BackgroundHepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV. MethodsThe study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons.ResultsHCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females.ConclusionsThe decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.

Potential link between high FIB-4 score and chronic kidney disease in metabolically healthy men

Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or proteinuria) and a habit of alcohol consumption were excluded. The cut-off FIB-4 score was 1.30, indicating increased risk of liver fibrosis. Overall, 5353 participants (men only) were analyzed without exclusion criteria. After propensity score matching, high FIB-4 score (≥ 1.30) was not an independent risk factor for incident CKD (odds ratio [OR] 1.57; 95% confidence interval [CI] 0.97–2.56). However, high FIB-4 score was a significant risk factor for CKD in non-obese (OR 1.92; 95% CI 1.09–3.40), non-hypertensive (OR 2.15; 95% CI 1.16–3.95), or non-smoking (OR 1.88; 95% CI 1.09–3.23) participants. In these participants, FIB-4 score was strongly associated with eGFR decline in the multiple linear regression analysis (β = − 2.8950, P = 0.011). Therefore, a high FIB-4 score may be significantly associated with CKD incidence after 5 years in metabolically healthy participants.

The Relationship between Hepatic High FIB-4 Score and COVID-19 Pneumonia.

We aimed to compare the level of hepatic FIB-4 scores between COVID-19 patients who had pneumonia and COVID-19 patients who had no pneumonia in an attempt to develop a risk assessment after the treatment and recovery of active COVID-19 infection. The study included 80 patients who were consecutively selected and admitted to an internal medicine outpatient clinic for a control examination after COVID-19 infection. Chest tomography was performed on all patients during the COVID-19 infection. Patients were divided into two groups as those with and without lung involvement on CT. COVID-19 infection was diagnosed using real-time reverse transcription-polymerase chain reaction (RT-PCR). The hepatic fibrosis 4 (FIB-4) index score was calculated for each patient. The statistical analyses were performed using Student's t-test and chi-squared tests. We found that the increased hepatic FIB-4 index score in patients with pneumonia group was statistically significant compared to the control group (p < 0.001). The regression analysis showed that the hepatic FIB-4 index has significant prognostic efficiencies in both uni- and multivariate models (p < 0.05). The hepatic FIB-4 index appears to be a simple parameter with a good prognostic value in patients with COVID-19 infection.

Abstract 9610: High Levels of Myeloperoxidase Are Similar Across ASCVD Risk Groups and Are Associated with Markers of Liver Fibrosis and Kidney Function in a Workforce Population

Background: High blood levels of free myeloperoxidase (MPO) identify patients at risk for cardiovascular disease. We investigated levels of MPO according to 10-year ASCVD risk and the association between high MPO and markers of liver fibrosis and kidney disease. Methods: The study included participants in employer-sponsored annual health assessment (August 2020 to March 2021, n=33,984, 63% women, median age 47, IQR 36 to 56). Age and sex adjusted logistic models assessed the association between high MPO and non-alcoholic fatty liver disease (NAFLD) fibrosis score, liver Fibrosis-4 (FIB4) score, and estimated glomerular filtration rate (eGFR), stratified by 10-year ASCVD risk groups. Results: High MPO (&gt;540 pmol/L) was found in 3% (n =925), 4% (n=184), and 5% (n =63) of the low (&lt;7.5%), intermediate (7.5% to 20%), and high (&gt;20% or prevalent disease) ASCVD risk groups, respectively. High MPO (&gt;540 vs. ≤540 pmol/L) was associated with high NAFLD fibrosis score (&gt;0.676 vs. &lt;-1.455): OR = 4.7, 95%CI 3.5 to 6.2, high FIB4 score (&gt;3.25 vs. ≤3.25): OR =3.4, 95%CI 1.8 to 6.4 and low eGFR (&lt;60 vs. ≥60 mL/min/1.73m 2 ): OR =1.8, 95%CI 1.4 to 2.4. The associations varied according to ASCVD risk (Figure). In the high ASCVD risk group, MPO was not associated with either NAFLD fibrosis score, FIB4 score, or eGFR (P ≥0.2 for all) and the risk differed according to ASCVD risk group (&gt;20% vs. ≤20%) for NAFLD fibrosis score (P int =0.03) and eGFR (P int =0.01). Conclusion: The fraction of those with high MPO did not appreciably differ across ASCVD risk groups and most participants with high MPO levels in this workforce population were in the low ASCVD risk group. This observation is consistent with the hypothesis that subjects in the high ASCVD risk group are more likely to be receiving preventive therapies, whereas guidelines dictate that those in moderate and low risk groups may not. Investigating the association of MPO levels in ASCVD risk groups according to preventive therapy intensity is warranted.

Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients.

Background/AimsAlthough hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, some patients do not experience recurrence for more than 5 years after resection or radiofrequency ablation for early-stage HCC. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.MethodsA total of 1,451 consecutive patients (median, 55 years old; males, 79.0%; hepatitis B virus-related, 79.3%) with good liver function (Child-Pugh class A) diagnosed with early-stage HCC by Barcelona Clinic Liver Cancer Staging and received radiofrequency ablation or resection as an initial treatment between 2005 and 2010 were analyzed.ResultsDuring a median follow-up period of 8.1 years, 961 patients (66.2%) experienced HCC recurrence. The cumulative recurrence rates increased to 39.7%, 60.3%, and 71.0% at 2, 5, and 10 years, respectively, and did not reach a plateau. Five years after HCC diagnosis, 487 patients were alive without experiencing a recurrence. Among them, during a median of 3.9 additional years of follow-up (range, 0.1–9.0 years), 127 patients (26.1%) experienced recurrence. The next 5-year cumulative recurrence rate (5–10 years from initial diagnosis) was 27.0%. Male sex, higher fibrosis-4 scores, and alpha-fetoprotein levels at 5 years were associated with later HCC recurrence among patients who did not experience recurrence for more than 5 years.ConclusionsThe HCC recurrence rate following 5 recurrence-free years after HCC treatment was high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years.

Evaluation of Fibrosis in Intestinal Failure-Associated Liver Disease in the Sustain Registry.

Intestinal failure-associated liver disease (IFALD) is one of the leading complications in type III intestinal failure (IF). Early recognition of liver-fibrosis development in IFALD is crucial to the development of strategies aimed at reducing the risk of complications secondary to IFALD. Our aim was to identify patients with advanced fibrosis using a noninvasive index and to study the risk factors for fibrosis development in the Sustain registry. Using the Sustain registry, patients requiring >3 months of parenteral nutrition (PN) support were identified. The presence or absence of advanced fibrosis was identified using the Fibrosis-4 (FIB-4) index. Risk factors for the presence of a high FIB-4 score were identified using univariable logistic regression. Two hundred seventy-one adult patients were included. Sixty-three patients (23.2%) were at risk for advanced fibrosis based on the FIB4-index. Risk factors for advanced fibrosis included short-bowel syndrome (odds ratios [ORs]: 1.84; 95% confidence interval [CI], 1.03-3.28), receipt of PN for >1 year (OR: 2.6; 95% CI, 1.46-4.64), receipt of PN for >5 years (OR: 3.05; 95% CI, 1.67-5.59), and days of lipid emulsion use (OR: 1.11; 95% CI, 1-1.24). Small-intestine-remnant length was inversely associated with advanced fibrosis (OR: 0.97, 95% CI, 0.95-0.99). Advanced fibrosis, as guided by FIB-4 index, is associated with known risk factors for IFALD. Therefore, the FIB-4 index is potentially a useful noninvasive tool for identification of individuals at risk for fibrosis in IFALD. Further studies utilizing a gold-standard fibrosis assessment will be required to validate these results.

Additional role of liver stiffness measurement in stratifying residual hepatocellular carcinoma risk predicted by serum biomarkers in chronic hepatitis B patients under antiviral therapy.

The risk of hepatocellular carcinoma (HCC) remains among patients who are treated with antiviral therapy (AVT). The degree of liver fibrosis has been suggested as an important biomarker to stratify the risk of developing HCC. We tested whether liver stiffness (LS) measured using transient elastography is useful over two noninvasive serum biomarkers of fibrosis [the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4)]. A retrospective cohort of 1014 CHB patients who were under AVT with nucleos(t)ide analogs for at least a year was analyzed. The risk of HCC development according to serum biomarkers (APRI and FIB-4) and LS was compared. The HCC risk was higher for those with a higher degree of liver fibrosis, as estimated by the LS, APRI, and FIB-4. When the two serum biomarkers were used to group the patients, the 3-year HCC incidence rates were 7.3, 3.0, and 1.3% for both high APRI (≥0.5) and FIB-4 (≥1.45) scores, either a high APRI or FIB-4 score, and both low APRI and FIB-4 scores, respectively (P<0.001). Among the 758 patients with discordant or both low APRI and FIB-4 scores, the LS value was high (>6) for a significant proportion of the patients (39.9%). The HCC risk was significantly different according to the LS value (3-year HCC incidence rate of 1.1, 2.0, and 6.8% for LS <6, 6-9, and >9, respectively, P<0.001). Among CHB patients under AVT, LS could stratify risk for HCC, including patients with discordant or both low APRI and FIB-4 score. This finding indicates that LS measurement plays an additional role over the serum biomarkers in stratifying the residual risk of HCC.

Hepatocellular Carcinoma Occurrence and Recurrence in Hepatitis C-infected Patients Treated with Direct-acting Antivirals

IntroductionMultiple studies have shown the efficacy of the new direct-acting antivirals (DAAs) with a cure rate of over 90% in hepatitis C virus (HCV)-infected patients. Some recently published studies have suggested an increased incidence of de novo and recurrent hepatocellular carcinoma (HCC) in cirrhotic patients in sustained virological response (SVR) after completing therapy. A possible mechanism is the breakdown of immune surveillance after starting DAAs. We report a retrospective analysis on a population of chronic HCV infected patients, with and without a prior history of HCC, who developed HCC after receiving DAAs in the hope of adding to existing literature and in pursuit of greater clarity into this emerging concern with DAAs. MethodsWe analyzed 497 HCV-infected patients who were treated with DAAs, or a combination of DAA with interferon, from January 2014 to April 2017 at the Veterans Medical Center, Oklahoma City. Descriptive analysis, including the mean and standard deviation for different variables, was used. The cohort was divided into two groups: cirrhotic and non-cirrhotic. The analysis was run in the cirrhotic group between the subgroups who developed HCC and who did not. ResultsData from a total of 233 cirrhotic patients were analyzed. We further subdivided these patients into those who eventually were diagnosed with HCC (group 1) and those who were not (group 2). These subgroups were comparable in regards to race, gender, baseline serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, sodium, HCV genotypes, and pretreatment viral load. All patients completed therapy. The rate of SVR was much lower in group 1 compared to group 2 (62.5% vs 88.94%, p = 0.002), respectively. Model End-stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, and Fibrosis-4 (FIB-4) score were higher in the group that developed HCC. The average time period (weeks) from DAA therapy to HCC diagnosis was 48.2 weeks. The remaining 264 non-cirrhotic patients had no reported cases of HCC. ConclusionFrom a total of 497 treated HCV-infected patients, 233 (46.88 %) had cirrhosis, out of which 16 (6.86%) were reported to develop HCC during or after DAA therapy was initiated. The remaining 217 (93.1%) cirrhotic patients did not develop HCC. As per our comparison, achieving SVR in cirrhotic patients should not preclude HCC screening, and more studies are needed to assess the risk of HCC in patients who achieve SVR but have a high FIB-4 score. In fact, patients who do not achieve SVR may be at a higher risk of eventually developing HCC and may be candidates for closer surveillance.

Association between non-alcoholic fatty liver disease and cancer incidence rate

Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and cancer development. This study investigated the cancer incidence rates in NAFLD and analysed the association between NAFLD and cancer development. This historical cohort study included subjects who were followed up for >1 year after having a heath checkup at a tertiary hospital in Korea from September 1, 2004 to December 31, 2005. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other known liver disease, including alcoholic or viral hepatitis. Cox proportional hazards regression model was conducted to assess the association between NAFLD and cancer development. Of 25,947 subjects, 8,721 (33.6%) had NAFLD. During the total follow-up of 164,671 person-years (median 7.5 years), the cancer incidence rate of the NAFLD group was higher than that of the non-NAFLD group (782.9 vs. 592.8 per 100,000 person-years; hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.17-1.49; p <0.001). When demographic and metabolic factors were adjusted for, NAFLD showed a strong association with three cancers: hepatocellular carcinoma ([HCC]; HR 16.73; 95% CI 2.09-133.85; p = 0.008), colorectal cancer in males (HR 2.01; 95% CI 1.10-3.68; p = 0.02), and breast cancer in females (HR 1.92; 95% CI 1.15-3.20; p = 0.01). A high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score were associated with the development of all cancers and HCC. NAFLD was associated with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NFS and a high FIB-4 score showed a strong association with the development of all cancers and HCC. Non-alcoholic fatty liver disease (NAFLD) is associated with developing hepatocellular carcinoma (HCC). There have been limited data on the association between NAFLD and extrahepatic cancers. This study demonstrated that patients with NAFLD showed a higher association with the development of HCC, colorectal cancer in males, and breast cancer in females. A high NAFLD fibrosis score and a high fibrosis-4 score showed a strong association with the development of all cancers and HCC.

Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low-level viremia.

We tested whether non-invasive tests for liver disease severity can stratify hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV)-infected patients showing low-level viremia (LLV, HBV DNA <2000 IU/mL). A retrospective cohort of 1006 chronic hepatitis B patients showing persistently LLV, defined by at least two consecutive assessments in the year before enrolment, was assessed for HCC development. Two non-invasive serum biomarkers, the aspartate aminotransferase to platelet ratio index (APRI) and the Fibrosis-4 (FIB-4), were tested. Cirrhosis was defined with ultrasonography. During a median 5.1years of follow-up, HCC developed in 36 patients. HCC incidence rate at 5years was significantly higher for cirrhotic patients (19/139, 13.7%), but was not null for non-cirrhotic patients (17/867, 2.0%, P<.001). APRI at a cut-off of 0.5 was more specific but less sensitive for HCC development, and FIB-4 at a cut-off of 1.45 was more sensitive but less specific. When both APRI and FIB-4 were used to group patients, the 5-year cumulative HCC incidence rate was 13.9%, 1.4% and 1.2% for both high, any high, and both low APRI and FIB-4 score among all patients (n=1006, P<.001), respectively, and was 11.4%, 1.5% and 0.4% in the same respective order among non-cirrhotic patients (n=867, P<.001). The combined use of two non-invasive serum biomarkers (APRI and FIB-4) could stratify HCC risk for chronic HBV-infected patients with LLV.