Presence Of Advanced Fibrosis Research Articles

Interleukin-23 inhibitors decrease Fibrosis-4 index in psoriasis patients with elevated Fibrosis-4 index but not inteleukin-17 inhibitors.

Recent studies indicate that hepatic diseases are associated with psoriasis. Non-invasive tests, including the Fibrosis-4 (FIB-4) index, which can confidently rule out the presence of advanced fibrosis, are currently receiving attention. However, data on the FIB-4 index in psoriasis patients and the effects of biologics on the FIB-4 index are limited. We investigated the relationships between the FIB-4 index and demographic or clinical characteristics as well as the effects of biologics on the FIB-4 index in psoriasis patients. Psoriasis patients aged 36-64 years, whose treatment was initiated with interleukin (IL)-17 inhibitors or IL-23 inhibitors for psoriasis from May 2015 to December 2022, were consecutively included. Data were collected retrospectively from the patients' charts. A total of 171 psoriasis patients were included in this study. Thirty-four, 43, 21, 32, and 41 psoriasis patients were treated with secukinumab, ixekizumab, brodalumab, guselkumab, or risankizumab, respectively. In biologics-naïve patients, a significant but weak positive correlation was observed between the FIB-4 index and age (r = 0.3246, p = 0.0018). There was no significant correlation between the FIB-4 index and other demographic or clinical characteristics. Regarding the effects of biologics on the FIB-4 index, no significant change was observed in psoriasis patients treated with any biologics. However, in psoriasis patients with a baseline FIB-4 index of >1.3, patients treated with guselkumab and those treated with either IL-23 inhibitor showed significantly decreased FIB-4 index scores 6 months after initiating the biologics (p = 0.0323, p = 0.0212). In contrast, no change was observed in FIB-4 index scores in patients treated with IL-17 inhibitors. In conclusion, our study revealed that the FIB-4 index was correlated with age in psoriasis patients. Furthermore, IL-23 inhibitors (but not IL-17 inhibitors) decreased the FIB-4 index score at 6 months in psoriasis patients with elevated FIB-4 index scores at baseline. Further studies are needed to clarify whether IL-23 inhibitors improve liver fibrosis physiologically and functionally.

Velacur ACE outperforms FibroScan CAP for diagnosis of MASLD.

As the prevalence of metabolic dysfunction-associated steatotic liver disease increases, it is imperative to have noninvasive alternatives to liver biopsy. Velacur offers a non-invasive, point-of-care ultrasound-based method for the assessment of liver stiffness and attenuation. The aim of this study was to perform a head-to-head comparison of liver stiffness and liver fat determined by Velacur and FibroScan using MRI-based measurements as the reference standard. This prospective cross-sectional study included 164 adult participants with well-characterized metabolic dysfunction-associated steatotic liver disease. Patients underwent a research exam including Velacur, FibroScan and contemporaneous magnetic resonance elastography, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) scans. The primary outcome was the presence of advanced fibrosis (>F2) as measured by magnetic resonance elastography and the presence of liver fat (>5%) as measured by MRI-PDFF. The mean age and body mass index were 57±12 years and 30.6±4.8kg/m2, respectively. The mean liver stiffness on magnetic resonance elastography was 3.22±1.39kPa and the mean liver fat on MRI-PDFF was 14.2±8%. The liver stiffness assessments by Velacur and FibroScan were similar for the detection of advanced fibrosis (AUC 0.95 vs. 0.97) and were not statistically different (p=0.43). Velacur was significantly better than FibroScan (AUC 0.94 vs. 0.79, p=0.01), for the detection of MRI-PDFF >5% (diagnosis of metabolic dysfunction-associated liver disease). Velacur was superior to FibroScan for liver fat detection with MRI-PDFF as the reference. Velacur and FibroScan were not statistically different for liver stiffness assessment as defined by magnetic resonance elastography.

Factors Associated with Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Introduction. Nonalcoholic fatty liver disease includes conditions such as nonalcoholic steatosis and nonalcoholic steatohepatitis, with varying degrees of fibrosis that can progress to cirrhosis and hepatocellular carcinoma. Although the gold standard for its diagnosis remains liver biopsy, many non-invasive methods have been proposed to aid in both the diagnosis of the disease and the evaluation of the presence of liver fibrosis, which is a strong and independent factor for liver related mortality. Objectives. The objectives of this study were: 1) to identify the clinical and laboratory features associated with the presence of advanced fibrosis in individuals with biopsy-confirmed nonalcoholic fatty liver disease; 2) to evaluate the performance of non-invasive markers in identifying patients with advanced fibrosis. Methods. A cross-sectional-analytic study that evaluated patients with nonalcoholic fatty liver disease treated in the outpatient clinic of a university hospital of reference in hepatology, between January 2013 and December 2016. Results. 81 patients aged 53.3 ± 9.8 years were included in this study; 39.5% were men and 70.1% were obese. When comparing patients with advanced fibrosis to those without advanced fibrosis, patients with advanced fibrosis had a lower proportion of males than females (17.6 vs. 45.4%, p = 0.038), a higher proportion of hypothyroidism (29.4 vs. 6.3%, p = 0.017) and a higher median AST (52 vs. 31 U/L, p = 0.005). In logistic regression analysis, only hypothyroidism was independently associated with advanced fibrosis (OR = 4.975; CI 95% 1.050 - 23.574; p = 0.043). Spearman correlation analysis showed that higher levels of fibrosis on liver biopsy, were associated with higher levels of TSH (r = 0.304; p = 0.036), AST (r = 0.277; p = 0.019), GGT (r = 0.284; p = 0.017) and LDL (r = 0.258; p = 0.037). Regarding the performance of the non-invasive markers, the area under the ROC curve of Fibrosis 4 score was 0.723 (p = 0.008), that of Nonalcoholic fatty liver disease fibrosis score was 0.713 (p = 0.022), that of gamma-glutamyl transferase platelet ratio was 0.697 (p = 0.019) and that of aspartate-to-alanine aminotransferase ratio was 0.689 (p = 0.031). Conclusions. Hypothyroidism is a factor independently associated with advanced fibrosis. In the outpatient setting, non-invasive markers may be useful in identifying patients with advanced fibrosis.

Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study

The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54-0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75-0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86-0·94]), ADAPT (0·85 [0·81-0·89]), and FibroScan liver stiffness measurement (0·83 [0·80-0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4-5]), then ADAPT (six [5-7]), MACK-3 (seven [6-8]), and PRO-C3 (nine [7-11]). None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. The Innovative Medicines Initiative 2 Joint Undertaking.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Prevalence and clinical determinants of non-alcoholic fatty liver disease by liver scores in adults with type 1 diabetes

AimsTo investigate the prevalence and clinical risk factors for non-alcoholic fatty liver disease (NAFLD) in type 1 diabetes (T1DM) by liver scores. MethodsA retrospective, unicenter, cross-sectional analysis was performed of adults with T1DM from 2015 to 2018. Steatosis scores (hepatic steatosis index-HSI, Framingham steatosis index-FSI) and fibrosis scores (FIB-4 index, AST-to-platelet ratio index-APRI) were associated with clinical parameters. ResultsWe identified 447 patients, 38 ± 14.5 yrs, 54 % female, BMI 28 ± 5.9 kg/m2. Liver steatosis was prevalent at 61 % by HSI ≥ 36 and 52 % by FSI ≥ 23. A majority of these individuals had normal liver transaminase levels. The presence of advanced fibrosis was 4 % by APRI > 0.7 and 4 % by FIB-4 > 2.67. BMI ≥ 25 kg/m2 correlated with steatosis scores (P < 0.001) but not fibrosis scores. Older age (≥40 yrs), hypertension, dyslipidemia, and history of cardiovascular disease were associated with steatosis markers. Only 21 % had any abdominal imaging, 2 % had hepatology referral and 1 % had a liver biopsy. Glucagon-like peptide-1 agonist was prescribed in 5 % and thiazolidinedione in 4 %. ConclusionLiver scores indicating steatosis but not fibrosis is common in adults with T1DM with obesity and/or metabolic syndrome, and is associated with older age, hypertension, and dyslipidemia. NAFLD is under-diagnosed and under-investigated; a minority of patients have had any liver evaluation or treatment.

Chronotype preference, sleep quality, and night-eating behaviors in patients with metabolic dysfunction-associated steatotic liver disease: Assessing the relationship with disease severity and fibrosis.

Our primary objective is to examine the variance in chronotype, night-eating patterns, and sleep quality in patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease. In addition, we aim to establish a correlation between these variables and the severity of the disease and fibrosis. Patients who were following up with biopsy-proven metabolic dysfunction associated steatotic liver disease (MASLD) were included in the study. Histologically severe disease is characterized by a Steatosis, Activity, and Fibrosis activity score of ≥3 or the presence of advanced fibrosis (≥F3). Participants who met the inclusion criteria were given the Morningness and Evening Questionnaire (MEQ), the Pittsburgh Sleep Quality Index, and the Night Eating Questionnaire to complete. A total of 93 patients were included in this study. According to the MEQ, 48 patients were morning type (51.6%), and 42 (45.2%) were neither type. Sleep quality was determined to be inferior in the non-morningness group (p=0.002). A significantly higher proportion of patients with nocturnal eating syndrome had a non-morningness chronotype preference (n=22, 23.7%), compared to those with a morningness chronotype (n=9, 9.7%) (p=0.001). In the multivariate analysis, both age and poor sleep quality had significant impacts on advanced fibrosis, with odds ratios of 1.11 and 3.81, respectively. Despite the non-morningness chronotype demonstrating poorer sleep quality and a higher prevalence of night-eating behavior, our findings revealed no statistically significant differences in terms of sleep quality, nocturnal eating habits, or chronotype preferences among patients with varying degrees of MASLD severity. On the other hand, advanced fibrosis was significantly impacted by poor sleep quality.

The role of elastography for liver fibrosis screening in alcoholic liver disease.

A prospective study was performed on 172 subjects, without previously known liver disease, with a positive AUDIT-C score, serum markers, and vibration-controlled transient elastography (VCTE) with Controlled Attenuation Parameter (CAP). From 172 subjects with positive AUDIT-C test, VCTE diagnosed advanced fibrosis (F3) in 13.9% (24/172) of the subjects and liver cirrhosis (F4) in 17.5% (30/172). Moderate and severe steatosis was found in 18.6% (32/172), respectively 52.3% (90/172). Significant correlations were found between liver stiffness and APRI (r=0.33, p=0.001), FIB-4(r=0.31, p=0.0012) and the age-platelet index (r=0.25, p=0.008). FIB-4 (p=0.01) and age-platelet index (p=0.03) were independently associated with the presence of advanced fibrosis. Age-platelet index (AUC- 0.82) performed significantly better than AST/ALT (AUC- 0.55) and APRI (AUC- 0.58) (p= 0.0001 and p= 0.0014, respectively), but no differences were found when compared to FIB-4 (AUC- 0.77) (p=0.35) for predicting advanced fibrosis. In conclusion, in a cohort of patients with AUD, 70.9% presented moderate and severe liver steatosis and 17.5% were newly diagnosed with liver cirrhosis.

Urinary neutrophil gelatinase‐associated lipocalin: A novel biomarker for predicting chronic kidney disease in patients with nonalcoholic fatty liver disease

AbstractAimsNonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are common diseases worldwide. Reports of a high prevalence of CKD in NAFLD patients have been documented. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) is a reliable biomarker for renal dysfunction, and it is recommended for early detection of acute kidney injury (AKI) in cirrhotic patients. Currently, there is no evidence for using urine NGAL to predict CKD in NAFLD patients. We aim to determine the proportion of CKD and identify the predictive value of NGAL and other factors associated with CKD in these patients.MethodsA single‐center, cross‐sectional study was conducted between July 2018 and December 2019 in consecutive NAFLD patients diagnosed by transient elastography (TE) or liver biopsy at a tertiary care university hospital in Bangkok, Thailand. Advanced liver fibrosis is defined as fibrosis stages 3–4. The definition of CKD is estimated glomerular filtration rate (eGFR) &lt;60 ml⋅min−1⋅1.73 m−2 based on the Kidney Disease Improving Global Outcomes (KDIGO) guideline 2012. Urine NGAL level was measured by enzyme linked immunosorbent assay technique.ResultsA total of 101 NAFLD patients were included with a mean age of 54 ± 16 years. Among these patients, 14 (13.9%), 13 (12.9%), and 32 (31.7%) had fibrosis stages 2, 3, and 4, respectively. Nine percent (9 of 101) of patients with NAFLD with a mean eGFR of 42.66 ± 17.42 ml⋅min−1⋅1.73 m−2. The statistically significant factors associated with CKD were a higher level of urine NGAL (55.1 [25.15–150.60] vs. 15.1 [9.67–25.15] ng/ml; p = 0.006), a higher level of TE (17.3 [6.85–46.20] vs. 7.7 [5.6–11.7] kPa; p = 0.038), and a presence of advanced fibrosis (77.8% vs. 40.7%; p = 0.041), compared to those without CKD. Urine NGAL was the only significant factor associated with CKD in NAFLD patients. The cutoff level of urine NGAL at 36.75 ng/ml showed odds ratio of 21.27 (95% CI: 3.97–113.82; p &lt; 0.001) and 1.02 (95% CI: 1.00–1.04; p = 0.024) by univariate and multivariate analyses, respectively. The selected urine NGAL cutoff demonstrated a sensitivity and specificity of 77.8% and 85.9% for predicting CKD, respectively.ConclusionsThe proportion of CKD in NAFLD patients was 9% and the presence of advanced fibrosis was a significant risk factor associated with CKD. Additionally, urine NGAL was significantly associated with CKD in NAFLD patients using a cutoff level of 36.75 ng/ml for predicting CKD with acceptable sensitivity and specificity. A larger prospective cohort study is needed to validate our findings.

1104-P: Prevalence and Clinical Determinants of Nonalcoholic Fatty Liver Disease by Liver Scores in Adults with T1DM

NAFLD is common in diabetes, however the prevalence and clinical features of NAFLD in T1DM are not well defined. A retrospective, unicenter, cross-sectional analysis was performed of adults with T1DM at our institution from 2015-2018. The hepatic steatosis index (HSI) , Framingham steatosis index (FSI) , FIB-4 index, and AST-to-platelet ratio index (APRI) were calculated and associated with clinical parameters. We identified 447 patients, 38.6 ± 14.5 yrs, 54% (N=241) female, HgA1c 8.4 ± 1.8 %, BMI 28 ± 5.9 kg/m2. The prevalence of NAFLD by HSI ≥36 was 61% (N=271) and by FSI ≥23 was 52% (N=230) . The presence of advanced fibrosis by APRI &amp;gt;0.7 was 4% (N=18) and FIB-4 &amp;gt;2.67 was 4% (N=8 of 221 included) . Patients with metabolic syndrome (N=103, 23%) were significantly more likely to have NAFLD by HSI (86% vs. 53%, p&amp;lt;0.001) and FSI (93% vs. 39%, p&amp;lt;0.001) . Compared to BMI &amp;lt;30, nearly all patients with BMI ≥30 (N=125, 28%) had NAFLD by HSI (100% vs. 45%, p&amp;lt;0.001) and FSI (98% vs. 34%, p&amp;lt;0.001) . Older age (44 vs. 33 yrs) , HTN, HLD, cardiovascular disease, and higher TG/HDL ratio (median 1.8 vs. 1.1) were associated with FSI ≥23. Older age (41 vs. 30 years) , HTN, HLD, and lower HDL (58 vs. 66 mg/dL) were associated with HSI ≥36. On multivariable analysis, older age, metabolic syndrome features, and BMI were associated with higher HSI and FSI. HgA1c was inversely related to HSI. Twenty of 94 patients (21%) with abdominal imaging reported hepatic steatosis; 8 (2%) had hepatology referral and 6 (1%) had a liver biopsy. Of 447 patients, GLP-1 agonist was prescribed in 5% (N=24) and thiazolidinedione in 4% (N=16) . Liver scores indicating liver steatosis but not fibrosis is common in adults with T1DM with obesity and/or metabolic syndrome, and is associated with older age, HTN, HLD, and high TG/HDL. NAFLD is overlooked; only 21% of patients had any liver imaging and only 1% had a liver biopsy. Thiazolidinedione and GLP-1 agents are effective at preventing and reversing NAFLD damage but appear underutilized in the T1DM population. Disclosure M.D.Lundholm: None. J.F.Bena: None. K.Zhou: None. Y.Tsushima: None. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc.

AGILE 3+ Score for Assessing Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) – Validation in an Indian Cohort

Background: Non-invasive tests have emerged as important tools for ruling out the presence of advanced fibrosis in NAFLD. However, many patients still require liver biopsy due to the comparatively poor positive predictive value (PPV) and substantial grey-zone associated with non-invasive tests. AGILE-3+ score is a novel, non-invasive score which includes liver stiffness measurement (LSM) on transient elastography and commonly measured clinical parameters (age, gender, AST, ALT, platelet count and presence or absence of diabetes mellitus).

Prediction of liver stiffness by serum indexes in HCV-infected patients with or without HIV coinfection.

Identification of advanced fibrosis/cirrhosis in hepatitis C virus (HCV)-infected patients should be a mainstay before starting treatment; however, the limited access of many centres to transient elastography (TE) is often a barrier for early assessments. We aimed to investigate the diagnostic accuracy of serum indexes for predicting liver stiffness.Retrospective analysis of HCV patients (with or without HIV coinfection) routinely assessed in 7 centres in Spain. The diagnostic accuracy of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), and their combinations was evaluated using a recent TE examination as a reference test (liver stiffness ≥ 9.5 kPa and ≥12.5 kPa for advanced fibrosis and cirrhosis, respectively). In addition to area under the receiving operating characteristic curves, sensitivity, specificity, and negative predictive value (NPV) and positive predictive value were estimated.The analysis included 1391 patients: 346 (25%) HIV-positive, 732 (53%) people who inject drugs, and 178 (13%) incarcerated. Advanced fibrosis and cirrhosis were found in 557 (40%) and 351 (25%) patients, respectively. APRI < 0.5 (n = 595; 43%) had an NPV of 95% for excluding cirrhosis. Combined FIB-4 < 1.45 with APRI < 0.5 (n = 467; 34%) had an NPV of 87% for excluding advanced fibrosis. Combined APRI > 2 and FIB-4 > 3.25 (n = 134; 10%) had a positive predictive value of 89% for advanced fibrosis. Globally, this approach would avoid the need for TE in 53% of patients. HIV coinfection did not influence diagnostic accuracy.Inexpensive and simple serum indexes confidently allowed identifying the absence of cirrhosis and the presence of advanced fibrosis in 53% of a heterogeneous series of real-world HCV patients with or without HIV infection.

P-107 EPIDEMIOLOGICAL AND CLINICAL PROFILE OF AUTOIMMUNE HEPATITIS IN A BRAZILIAN TERTIARY HOSPITAL

Autoimmune hepatitis (IAH) is a rare inflammatory liver disease with an autoimmune nature that is characterized by predominantly affecting female patients. Variable patterns of presentation of this disease should be observed at time of diagnosis and there are few epidemiological data in Brazil in relation to this disease. Our objective was to evaluate the epidemiological profile of patients with IAH of the Gastroenterology Service of Hospital do Servidor Público Estadual “Francisco Morato de Oliveira”, HSPE-FMO, São Paulo, SP, Brazil. Descriptive, retrospective and observational study, with analysis of data from the medical records of patients, from July 2002 to July 2020. 35 patients were selected, with a female predominance (91.4%) and the average age at the diagnosis was 54.7 ± 14.2 years. The presence of extrahepatic autoimmune disease was observed in 45.7% of the cases with a predominance of thyroiditis (31.4%). Regarding the initial presentation, 59.4% of the patients presented with an acute jaundice, 31.3% with isolated elevated serum transaminases and 6.3% with decompensated liver cirrhosis. At the time of diagnosis, 50% presented with elevated gamma globulins, 79.4% with a positive standard ANA and 37.4% with positive anti-smooth muscle antibody. In relation to the initial histological evaluation, the presence of advanced fibrosis (F3 / F4) was observed in 39.2% and the most common histological finding observed was interface hepatitis in 58,3%. The present study showed a high prevalence of females among IAH patients with an average age higher than that observed in other studies already published in our country. In relation to the main form of initial clinical presentation, the acute jaundice form was predominantly similar to the other national studies and the presence of advanced fibrosis in the initial histological evaluation was seen in a considerable proportion of patients.

Macro- and micronutrients in metabolic (dysfunction) associated fatty liver disease: association between advanced fibrosis and high dietary intake of cholesterol/saturated fatty acids.

There is still no approved pharmacotherapy for metabolic (dysfunction) associated fatty liver disease (MAFLD). Although dietary and lifestyle modifications for weight loss remain the mainstay for disease management, the association between macro- and micronutrients and fibrosis stage in patients with MAFLD remains unclear. This study was undertaken to address this issue. This is a retrospective analysis of prospectively collected data from patients in whom MAFLD was diagnosed with vibration controlled transient elastography. Steatosis was defined by a controlled attenuation parameter ≥238 dB/m, whereas a liver stiffness measurement ≥11 kPa was considered to indicate advanced fibrosis. The study sample consisted of 106 patients with MAFLD (mean age 49 ± 10 years, 52 men and 54 women). Among the different micro- and macronutrients tested, only the dietary intake of cholesterol and saturated fatty acid (SFA) was independently associated with the presence of advanced fibrosis. Our findings suggest that cholesterol/SFA-restricted dietary regimens - as exemplified by the traditional Mediterranean diet - may reduce the risk of advanced fibrosis in patients with MAFLD.

Hepamet Fibrosis Score in Nonalcoholic Fatty Liver Disease Patients in Mexico: Lower than Expected Positive Predictive Value.

Nonalcoholic fatty liver disease (NAFLD) has been associated with different negative outcomes in the presence of advanced fibrosis. The Hepamet Fibrosis Score (HFS), a recently described noninvasive score, has shown excellent performance for the detection of advanced fibrosis. The aim of this study was to assess its performance in a Mexican population with NAFLD. This was a retrospective cross-sectional study performed in 222 patients with biopsy-proven NAFLD, of whom 33(14%) had advanced fibrosis. We retrieved clinical data from each patient's medical record to compute the HFS, the NAFLD Fibrosis Score (NFS), and the Fibrosis-4 (FIB-4), and assess their performance. When considering the models as continuous variables, the area under the receiving operating characteristics curve of the HFS(0.758) was not different from that of the NFS(0.669, p = 0.09) or FIB-4(0.796, p = 0.1). The HFS had a sensitivity, specificity, positive and negative predictive values of 76.7% (95% CI 57.7-90.1), 90.1% (95% CI 85-93.9), 36.7% (95% CI 19.9-56.1), and 94.3% (95% CI 88.5-97.7), respectively. Indeterminate results (i.e., gray area) were more common with FIB-4 and HFS when compared with NFS [139(63%) and 122(55%) vs 80(36%), p < 0.001]. The variables that were associated with misclassification using the HFS were diabetes [OR 3.40 (95% CI 1.42-8.10), p = 0.006] and age [OR 1.06 (95% CI 1.01-1.11), p = 0.01]. The HFS showed sensitivity and specificity similar to that reported in the original publication; however, the positive predictive value was 36.7% at a pretest probability of 14%. The role of the HFS in prospective studies and in combination with other methods should be further explored.

42 Advanced Fibrosis Is Unlikely in the Majority of Patients from an Appalachian Emergency Department’s Non-Targeted Hepatitis C Virus Screening

We have previously demonstrated a high prevalence of Hepatitis C Virus (HCV), particularly among young, publicly insured patients, reflecting the escalating syndemic of opioid injection and HCV transmission. We aim to describe the degree of hepatic fibrosis among patients with evidence of HCV infection identified from an adult academic emergency department (ED) non-targeted HCV screening program. The study was a retrospective cohort analysis of ED systematic, non-targeted, opt-out HCV testing outcomes from July 2018 through January 2019. To assess the degree of liver disease as evidenced by fibrosis, Fibrosis-4 (FIB4) and aspartate transaminase to platelet ratio (APRI) scores were calculated from available AST, ALT and Platelet lab values pulled from the electronic medical record, collected on the same day as the initial ED visit. The absence or presence of advanced fibrosis or cirrhosis was determined using validated cut-offs: FIB4 < 1.45, APRI < 1; FIB4 > 3.25, APRI > 2 respectively. As previously reported there were 21,359 unique adult visitors during the time period studied. Of these, 16,700 individuals were verbally engaged and did not opt out of testing. A total of 11,635 individuals received HCV Ab testing with 1,459 patients (12.5%) having reactive results. Newly identified information shows that 1,241 (85%) of these patients had concomitant labs as part of routine ED care sufficient to calculate a FIB4 and APRI score. Data indicate that advanced fibrosis or cirrhosis was not likely in the majority of patients (FIB4 56%, 707/1241 patients; APRI 72.6%, 901/1241 patients). Those with available FIB4 and APRI were more likely to be born after 1965 (857/1241 patients, 69.1%), of whom 90.9% (779) had government insurance or were uninsured (Medicaid 85.6%, 667 patients; Medicare 8.5%, 66 patients; Uninsured 5.9%, 46 patients). Of these, advanced fibrosis or cirrhosis was not likely in the majority of patients : medicaid (FIB4 64.9%, 433/667 patients; APRI 67.2%, 462/667 patients), medicare ( FIB4 57.6%, 38/66 patents; APRI 71% 47/66 patients), uninsured (FIB4 69.6%, 32/46 patients; APRI 71.7%, 33/46 patients). ED non-targeted, opt-out testing identified a high prevalence of HCV infection among adult visitors in whom the majority do not have evidence of advanced fibrosis or cirrhosis. The majority of those patients were young and insured. For a curable disease that carries severe morbidity and mortality, along with known financial costs of inaction, our program has demonstrated that the ED may be a prime location to identify and treat viremic HCV patients.

Rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

Background & AimsA common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis.MethodsWe performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models.ResultsData from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02–0.05], pz = 4.8×10–5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05–1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03–1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5×10–4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.ConclusionsOur study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.Lay summaryFatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including ‘cirrhosis’). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change (‘variant’) in one gene (‘MBOAT7’) was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.

Association between muscle strength and advanced fibrosis in non-alcoholic fatty liver disease: a Korean nationwide survey.

BackgroundWe investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with non‐alcoholic fatty liver disease (NAFLD) using a nationwide cross‐sectional survey.MethodsIndividuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (N = 14 861), with sample weights applied. Muscle strength was quantified as the handgrip strength divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q1) of the handgrip strength/BMI for our sample population. NAFLD was defined as hepatic steatosis index >36. Advanced fibrosis was defined as a fibrosis‐4 index score ≥1.30 (FibrosisFIB4).ResultsThe mean age of the study population was 45.6 ± 0.2 years, and 42.4% were male. As muscle strength increased, the mean BMI and age decreased accordingly, and the proportions of diabetes, dyslipidaemia, hypertension, and obesity decreased significantly (P < 0.001 for all). In a crude analysis, the LMS was associated with an increased prevalence of NAFLD (odds ratio [OR] 3.62, 95% confidence interval [CI] 3.25–4.03, P < 0.001), which remained significant even after adjustment for age, sex, obesity, insulin resistance, diabetes, hypertension, dyslipidaemia, and high‐sensitivity C‐reactive protein (OR 1.66, 95% CI 1.28–2.16, P < 0.001). In this logistic regression model, the prevalence of NAFLD decreased by 24% with each quartile increment in muscle strength (OR 0.76, 95% CI 0.68–0.85, P < 0.001). Among individuals with NAFLD (n = 2092), LMS was significantly associated with the presence of advanced fibrosis (FibrosisFIB4) independently of age, sex, obesity, diabetes, hypertension, dyslipidaemia, and high‐sensitivity C‐reactive protein (OR 1.66, 95% CI 1.01–2.49, P = 0.015), which lost its statistical significance after additional adjustment for insulin resistance.ConclusionsLow muscle strength is independently associated with NAFLD. The significant association between LMS and advanced fibrosis in NAFLD may be mediated through insulin resistance.

221-LB: Association between Muscle Strength and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: Korean Nationwide Survey

Background: We investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with nonalcoholic fatty liver disease (NAFLD) using a nationwide cross-sectional survey. Methods: Individuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (n = 14,861), with sample weights applied. Muscle strength was quantified as the hand grip strength (HGS) divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q1) of the HGS/BMI scores for our sample population. NAFLD was defined by hepatic steatosis index (HSI) &amp;gt;36 (NAFLDHSI). The highest quartile of NAFLD fibrosis score (NFS) (FibrosisNFS) was used to define advanced fibrosis. Results: In a crude analysis, LMS was associated with the increased prevalence of NAFLDHSI (OR 3.62, 95% CI 3.25-4.03), which remained significant even after adjustment for age, sex, obesity, and insulin resistance (OR 1.69, 95% CI 1.30-2.18). Even in those without obesity, individuals with LMS had a higher prevalence of NAFLDHSI compared to those without LMS (OR 1.93, 95% CI, 1.42-2.63). Among individuals with NAFLDHSI (n = 3,320), LMS was also associated with the presence of advanced fibrosis (FibrosisNFS) even after adjustment for age, sex, obesity, and insulin resistance (OR 1.68, 95% CI 1.09-2.58). Conclusion: Muscle strength is independently associated with NAFLD and advanced fibrosis. Disclosure S. Kang: None. M. Moon: None. B. Koo: None.

A Microbial Signature Identifies Advanced Fibrosis in Patients with Chronic Liver Disease Mainly Due to NAFLD

The presence of advanced fibrosis is an important measure of the severity of chronic liver disease. Prior works that have examined the gut microbiome as a novel biomarker for advanced fibrosis have only examined patients with nonalcoholic fatty liver disease. Therefore, our goal was to examine the gut microbiome across varying etiologies of liver disease to create a predictive model for liver fibrosis based upon a microbial signature. Stool samples were obtained from patients with chronic liver disease (n = 50) undergoing FibroScan (ultrasound elastography) at the VA Greater Los Angeles Healthcare System. Healthy control patients (n = 25) were also recruited as a reference population. Fecal samples underwent 16S ribosomal RNA sequencing. Using differentially abundant microbes, a random forest classifier model was created to distinguish advanced fibrosis from mild/moderate fibrosis. The findings were then validated in a separate cohort of chronic liver disease patients (n = 37). Etiologies for liver disease included non-alcoholic liver disease (58.0%), hepatitis C (26.0%), hepatitis B (10.0%), and alcohol (6.0%). Microbiome composition was distinct in liver patients with advanced fibrosis compared to those with minimal fibrosis and healthy controls (p = 0.003). In multivariate negative binomial modeling, 26 bacterial taxa were differentially abundant in patients with advanced fibrosis as compared to those with minimal/moderate fibrosis (q-value < 0.05). A random forests classifier based on these taxa had an AUROC of 0.90 to predict advanced fibrosis. Prevotella copri, which was enriched in patients with advanced fibrosis, was the most strongly predictive microbe in the classifier. The classifier had an AUROC of 0.82 for advanced fibrosis in the validation cohort and Prevotella copri remained the strongest predictive microbe for advanced fibrosis. There is a distinct microbial signature for patients with advanced fibrosis independent of liver disease etiology and other comorbidities. These results suggest that microbial profiles can be used as a non-invasive marker for advanced fibrosis and support the hypothesis that microbes and their metabolites contribute to hepatic fibrosis.