Risk Factors For Advanced Fibrosis Research Articles

Environmental exposures are important risk factors for advanced liver fibrosis in African American adults

The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p=0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

Abstract C077: Understanding the epidemiology of NAFLD in Asian Americans: A literature review and survey development

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the general population in the US. Although epidemiology of NAFLD is well studied in the US, the scientific understanding of how this disease affect Asian Americans is very limited. Given that NAFLD is strongly increases the risks of liver cancer, a condition that disproportionally affect Asian Americans, it is critical that we better understand the burden of NAFLD in this population and identify protective/risk factors. The goals of this study are to (1) review the existing body of literature on the epidemiology of NAFLD in Asian Americans and (2) develop a survey based to better understand the burden of the disease. Methods: In this study we conducted a review of previous studies on NAFLD in Asian Americans and in Asia/Pacific regions. We focused on three aspects: (1) the prevalence and incidence rates of NALFD in the target populations; (2) the risk factors and protective factors of NAFLD; (3) the knowledge of and attitude towards NAFLD and its prevention, diagnosis, and treatment. We also identified limitations in previous studies with regards to study design and methodology. Findings: We have found that so far there has been there is paucity of data for NAFLD burdens in Asian Americans. The few existing studies estimated the prevalence of NAFLD to be between 18% to 43% in Asian Americans, with higher rates in men than women. Comparative studies have inconsistent findings on the prevalence of NAFLD between Asian and non-Asian American populations, likely due to differences in target population and sampling methods. However, one consistent finding so far was that Asian Americans with NAFLD have lower BMI and waist circumference, and aminotransferases and triglycerides, and similar risk factors for advanced fibrosis and atherosclerotic cardiovascular disease, than non-Asian Americans with NAFLD. Though limited, these studies suggested that Asian Americans are potentially at high risks for NAFLD and liver cancer, but the specific mechanisms remained unclear. Survey Development: Recognizing the gaps in previous literature, we designed a survey to better understand the burden of NAFLD in Asian Americans and provide foundation for behavioral and clinical interventions. We developed a survey to examine the knowledge, attitude, and behaviors related to NAFLD prevention, diagnosis, and treatment among Asian Americans. Conclusion: Despite inconsistent findings on how prevalence rates compare between Asian Americans and non-Hispanic white, increased evidence points to an elevated risks for advanced NAFLD and worsen outcomes in Asian Americans. We will discuss the implications for the prevention in Asian Americans, as well as linkage to care for early diagnosis and treatment for Asian Americans with NAFLD. We will also discuss the participant recruitment and data collection process of conducting the survey. Citation Format: Lin Zhu, Dasam Jeong, Yassah N. Lavelah, Yin Tan, Grace X. Ma. Understanding the epidemiology of NAFLD in Asian Americans: A literature review and survey development [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C077.

Nonalcoholic fatty liver disease (NAFLD) among older adults

AbstractNonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease, and its prevalence is expected to increase in the future due to the increasing prevalence of obesity and an increasing aging population. With increases in longevity, NAFLD has emerged as a growing public health concern worldwide. NAFLD is a multisystem disease that has a strong association with metabolic risk factors. The presence of NAFLD increases the risks of liver‐ and cardiovascular‐related mortality. Many studies have found age to be an additional risk factor for advanced fibrosis, which is associated with adverse outcomes. The identification of high‐risk older persons using noninvasive methods is a key step in community management. Limitations in the diagnostic performance of current assessment methods have been encountered. This review provides an update on the new terminology that has changed from NAFLD to metabolic‐associated fatty liver disease (MAFLD), and the epidemiology, clinical characteristics, noninvasive assessment, and prognosis of older persons with NAFLD.

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features.

The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance ≥ 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values ≥ 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.

S1214 Risk Factors for Advanced Fibrosis in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease

S1214 Risk Factors for Advanced Fibrosis in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease

Association of Skeletal Muscle and Adipose Tissue Distribution with Histologic Severity of Non-Alcoholic Fatty Liver.

Adipose tissue and skeletal muscle is associated with non-alcoholic fatty liver disease (NAFLD). This study evaluates the association between body composition and histologic severity in patients with NAFLD. Using the cross-sectional CT images at the level of L3 vertebra and the histologic findings of 178 patients with biopsy-proven NAFLD, we analyzed the correlation of the histologic findings to the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI), which is defined as the body composition area (cm2) by height squared (m2). The clinical and laboratory features with body composition were analyzed to determine the risk factors for advanced fibrosis. The VATI significantly increased in severe non-alcoholic steatohepatitis (NASH) or advanced fibrosis. In addition, the VATI was correlated with the NAFLD activity score (NAS) and the fibrosis stage. In multivariate analyses, age (odds ratio (OR), 1.09; 95% confidence interval (CI), 1.02–1.19; p = 0.025), severe NASH (OR, 8.66; 95% CI, 2.13–46.40; p = 0.005), and visceral adiposity (OR, 6.77; 95% CI, 1.81–29.90; p = 0.007) were independently associated with advanced fibrosis in patients with NAFLD. Visceral adiposity is correlated with the histologic severity of NAFLD, which is independently associated with advanced fibrosis.

Comparative study of clinicopathological features, and risk factors of advanced fibrosis between genders with non-alcoholic fatty liver disease

Objective: To comparatively study the similarities and differences between the clinical, pathological, and risk factors of advanced fibrosis in men and women with non-alcoholic fatty liver disease (NAFLD). Methods: 267 patients with NAFLD diagnosed by liver biopsy were retrospectively included, and were divided into male and female groups. The difference of clinical and pathological indexes were compared between the two groups. The measurement data were in accordance with normal distribution. The comparison between the two groups was performed by independent sample t-test. The non-parametric test was used for non-normal distribution. The classification data were expressed as a percentage, and the chi-square test was used for comparison between groups. Logistic regression analysis was used to analyze the risk factors. Results: The age of onset of NAFLD was significantly lower in male than female patients (P < 0.01). There was no statistically significant difference between the male and female groups in terms of body mass index and the prevalence of type 2 diabetes (P > 0.05). Biochemical index: The levels of alanine aminotransferase, albumin, total bilirubin and uric acid were significantly higher in male than female patients (P < 0.01). Liver pathology: The proportion of ballooning degeneration was significantly lower in male than female patients (P < 0.01). There was not statistically significant difference between the two groups in the proportion of steatohepatitis score, non-alcoholic steatohepatitis (52.0% vs. 61.5%, P = 0.283) and advanced liver fibrosis (14.3% vs. 17.8%, P = 0.162). Thrombocytopenia was a common independent risk factor for advanced stage liver fibrosis (OR = 0.984, 0.978~0.989, P < 0.01). Type 2 diabetes was only an independent risk factor for advanced stage liver fibrosis in men (OR = 6.557, 1.667~25.782), P < 0.01). Elevated AST was only an independent risk factor for advanced stage liver fibrosis in women (OR = 1.016, 1.003~1.028, P = 0.012). Conclusion: In NAFLD patients, there are some clinical and pathological differences between genders. Platelets are a common predictor of advanced liver fibrosis in men and women. Type 2 diabetes in men and elevated aspartate aminotransferase in women can be regarded as independent risk factors for advanced liver fibrosis.

Hepatitis C Testing and Liver Fibrosis Predictors in the Birth Cohort of a Primary Care Practice.

ObjectiveTo determine the prevalence of and risk factors for advanced fibrosis in patients born from 1945 through 1965 (birth cohort) who underwent testing for hepatitis C virus (HCV).Patients and MethodsData were extracted from the electronic health record of all patients receiving primary care at a single academic institution who underwent HCV testing between September 8, 2010, and March 5, 2018. The birth cohort patients were the primary focus of the study. Fibrosis 4 (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) scores were calculated to screen for fibrosis.ResultsDuring the study period, 7097 birth cohort patients had HCV antibody testing, 3462 (48.8%) of whom were men, 6435 (91.0%) were white, 1028 (14.5%) had diabetes mellitus, 2,034 (36.5%) had an alanine aminotransferase (ALT) level greater than 30 U/L, and 2,396 (34.2%) had body mass index of 30 kg/m2 or greater. Hepatitis C virus antibody was present in 124 (1.7%), 33 (26.6%) of whom had HCV viremia. Estimated prevalence of METAVIR [Meta-analysis of Histological Data in Viral Hepatitis] stage 4 fibrosis was 4.1% (180 of 4433) by a FIB-4 score of 3.25 or greater and 4.3% (204 of 4763) by an APRI score greater than 1.0. The odds ratio (OR) for fibrosis, determined by APRI, was significant for HCV RNA positivity (OR, 15.98; 95% CI, 7.23-35.32; P<.001), diabetes mellitus (OR, 1.98; 95% CI, 1.40-2.79; P<.001), and ALT value greater than 30 U/L (OR, 15.07 U/L; 95% CI, 9.27-24.52 U/L; P<.001) but not for body mass index of 30 kg/m2 or greater (OR, 0.77; 95% CI, 0.56-1.06; P=.11).ConclusionHepatitis C virus viremia, diabetes mellitus, and elevated ALT levels were associated with increased odds for development of fibrosis. In addition to HCV testing, diabetes mellitus and elevated ALT level are potential parameters to use for recommending noninvasive testing for fibrosis.

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Evaluation of Hepatic Fibrosis and Steatosis Using Fibroscan.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major guidelines. Transient elastography using FibroScan with CAP (controlled attenuation parameter) can assess both liver steatosis and fibrosis simultaneously. This paper took a new look at the prevalence of NAFLD and the severity of fibrosis among T2DM patients in Vietnam. The study was conducted using a cross-sectional design in T2DM adults who attended Dai Phuoc Ho Chi Minh Polyclinic and Polyclinic of Pham Ngoc Thach University of Medicine. Liver steatosis and fibrosis was assessed by FibroScan. NAFLD was diagnosed if CAP > 233 dB/m (steatosis > 5%). Data were analyzed using STATA 12 software program. We found that a total of 307 type 2 diabetic patients qualified for the study’s criteria. The prevalence of NAFLD in T2DM patients based on FibroScan was 73.3%. Rates of mild, moderate and severe steatosis were 20.5%, 21.8% and 30.9%, respectively. The prevalence of significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) was 13.0%, 5.9% and 3.6%, respectively. On multivariate analysis, aspartate aminotransferase (AST) (OR: 1.067; 95% CI: 1.017–1.119; p = 0.008) and platelet levels (OR: 0.985; 95% CI: 0.972–0.999; p = 0.034) were independent of risk factors of advanced fibrosis. Thus, our study supports screening for NAFLD and for evaluating the severity of liver fibrosis in T2DM patients.

Shorter leucocyte telomere length as a potential biomarker for nonalcoholic fatty liver disease-related advanced fibrosis in T2DM patients.

BackgroundTelomere length has been linked to hepatic fibrosis. Type 2 diabetes mellitus (T2DM) is considered as a particular risk for the development of hepatic fibrosis. This study is to explore the association of leucocyte telomere length (LTL) and nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis in T2DM patients.MethodsA total of 442 patients with T2DM were enrolled from Tongji Hospital, Wuhan, China. Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length. Hepatic advanced fibrosis was determined by both the NAFLD fibrosis score (NFS) and fibrosis-4 score (FIB-4). Explanatory factors for advanced fibrosis in T2DM patients were identified using multiple logistic regressions.ResultsT2DM patients with advanced fibrosis had significant shorter LTL than the no-advanced group. Additionally, LTL, age, male and aminotransferase (ALT) were significantly associated with advanced fibrosis status in T2DM patients. Longer diabetes duration was found to have a strong association with advanced fibrosis in elder T2DM patients.ConclusionsShorter LTL was significantly associated with advanced fibrosis in T2DM patients. Longer diabetes duration was an independent risk factor for advanced fibrosis in old T2DM patients. Shorter LTL may be used as a biomarker for advanced fibrosis in T2DM patients.

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.

1876-P: Impact of Diabetes on Liver Disease Progression in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis (NASH)

Background: Diabetes is a risk factor for advanced fibrosis due to NASH, but the effect of diabetes on disease progression is not well-characterized. Here, we describe clinical outcomes for patients with and without diabetes in two negative, randomized, placebo-controlled trials of simtuzumab. Methods: 217 patients with bridging fibrosis (F3) and 258 subjects with compensated cirrhosis (F4) were enrolled. Liver biopsies were reviewed by a central pathologist at screening and weeks 48 and 96. Patients were stratified based on the presence or absence of diabetes. Adjudicated clinical outcomes included: esophageal varices, variceal bleeding, ascites, hepatic encephalopathy, ≥2 point increase in Child-Pugh-Turcotte score, MELD &amp;gt;15, or death. Results: 145 (67%) of patients with F3 and 179 (69%) of patients with F4 had diabetes at baseline. Median age was 56 years. By week 96, 25% (31/129) of F3 patients with diabetes had progressed to cirrhosis, compared to 18% (11/67) of patients without diabetes [p=0.27]. Cirrhotic (F4) patients with diabetes had a higher rate of clinical events (Figure). Conclusion: Diabetes is common in patients with advanced fibrosis due to NASH and associated with numerically higher rates of progression. Larger studies are needed to confirm these findings. Patients with diabetes have a high unmet need for therapies that target advanced fibrosis due to NASH. Disclosure A.J. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck &amp; Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. M.F. Abdelmalek: Advisory Panel; Self; Allergan, Bristol-Myers Squibb Company, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Prometic Life Sciences Inc. Consultant; Self; TaiwanJ Pharmaceuticals Co., Ltd. Research Support; Self; Akcea Therapeutics, Allergan, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Galectin Therapeutics Inc., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Prometheus, Shire, TaiwanJ Pharmaceuticals Co., Ltd. Speaker's Bureau; Self; Alexion Pharmaceuticals, Inc. S. Caldwell: Research Support; Self; Conatus Pharmaceuticals Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Halyard, Mallinckrodt Pharmaceuticals, TARGET PharmaSolutions, Vital Therapy, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Dova. M.L. Shiffman: Advisory Panel; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. Research Support; Self; Allergan, Conatus, Enanta Pharmaceuticals, Inc., Exhalenz, GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis AG, Shire. Speaker's Bureau; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. R. Ghalib: None. E. Lawitz: Research Support; Self; birdrock bio, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Durect Corporation, Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., madrigal, Novartis AG, octeta, Zydus Cadila. D. Jiang: Employee; Self; Gilead Sciences, Inc. R.E. Aguilar Schall: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. B.J. McColgan: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Myers: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. S. Djedjos: Employee; Self; Gilead Sciences, Inc. A. Muir: Advisory Panel; Self; AbbVie Inc., Gilead Sciences, Inc. Research Support; Self; AbbVie Inc., Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., NGM Biopharmaceuticals. V. Ratziu: Other Relationship; Self; Gilead Sciences, Inc. N. Afdhal: Advisory Panel; Self; Gilead Sciences, Inc., Ligand Pharmaceuticals, Inc. Consultant; Self; Echosens. Employee; Self; Spring bank Pharmaceuticals. Z. Goodman: None. J. Bosch: Advisory Panel; Self; Actelion Pharmaceuticals US, Inc., Conatus Pharmaceuticals Inc., Exhalenz. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc. Funding Gilead Sciences, Inc.

Noninvasive indicators predict advanced liver fibrosis in autoimmune hepatitis patients.

BackgroundLiver biopsy is the criterion standard for diagnosing liver fibrosis, but it is not widely used to monitor liver fibrosis because of the invasiveness, risk of complications, and sample errors. Therefore, it is necessary to involve other techniques to monitor liver fibrosis or cirrhosis during clinical practice. The objective was to explore noninvasive indicators to predict advanced liver fibrosis in autoimmune hepatitis (AIH) patients.MethodsA total of 45 AIH patients and 47 healthy controls were recruited to this retrospective study. Complete blood count and liver function tests were performed for all subjects. AIH patients were divided into “no/minimal fibrosis” group and “advanced fibrosis” group based on liver biopsy.ResultsAIH patients demonstrated significantly higher monocytes, MCV, RDW‐CV, RDW‐SD, NLR, RDW‐CV/PLT, RDW‐SD/PLT, TBIL, DBIL, GLB, ALT, AST, GGT, ALP, and GPR and lower WBC, neutrophils, lymphocytes, RBC, HGB, HCT, LMR, TP, ALB, and AAR compared with healthy controls. Patients with advanced fibrosis showed remarkably higher RDW‐CV, RDW‐SD, RDW‐CV/PLT, RDW‐SD/PLT, AAR, and FIB‐4 and lower RBC, PLT, PCT, and ALB compared with the no/minimal fibrosis group. Logistic regression analysis showed that RDW‐SD/PLT was an independent risk factor for advanced fibrosis with an OR (95% CI) of 2.647 (1.383‐5.170). Receiver operating characteristic (ROC) analysis revealed that RDW‐SD, RDW‐CV/PLT, RDW‐SD/PLT, FIB‐4, and AAR had an area under the ROC curve (AUC) above 0.700 and RDW‐SD/PLT had the largest AUC of 0.785 with a cutoff value of 0.239.ConclusionRDW‐SD, RDW‐CV/PLT, RDW‐SD/PLT, FIB‐4, and AAR were excellent noninvasive biomarkers and RDW‐SD/PLT was an independent risk factor for predicting advanced fibrosis in AIH patients.

Association of low skeletal muscle mass with advanced liver fibrosis in patients with non-alcoholic fatty liver disease.

Although low skeletal muscle mass (LSMM) is known to increase the risk of non-alcoholic fatty liver disease (NAFLD), limited reports have described the relationship between LSMM and advanced fibrosis. Here, we investigated the association between LSMM and advanced liver fibrosis in NAFLD patients. Fatty liver was diagnosed using ultrasound, and appendicular skeletal muscle mass (ASM) was measured using bioelectrical impedance analysis. LSMM was defined in two ways: ASM/body weight percentage (LSMM-BW) and ASM/body mass index. Liver fibrosis stage was assessed by two models, the NAFLD fibrosis score and the Fibrosis-4 index, which determined low and high cutoff values (COVs). Of 10711 NAFLD patients, 615 were diagnosed with LSMM-BW. LSMM patients were older (47.6 vs 52.5years, P=0.001) and had higher body mass index values (23.6 vs 29.1kg/m2 , P<0.001) and waist circumferences (80.1 vs 93.3cm, P<0.001) than non-LSMM patients. LSMM was an independent risk factor for advanced fibrosis assessed by a low COV for the Fibrosis-4 index regardless of its classification (adjusted for metabolic and lipid profiles and sex, odds ratio [OR], 1.27-2.01; all P<0.05). LSMM was an independent risk factor for advanced fibrosis assessed by both COVs of NAFLD fibrosis score (adjusted for obesity, hypertension, lipid profile, and sex; OR, 1.64-2.01, P<0.01 in the low COV group; OR, 2.68-3.12, P=0.002 in the high COV group). Low skeletal muscle mass is associated with advanced fibrosis in NAFLD patients independent of metabolic risk factors.

Prevalence and outcomes of non-alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States.

Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. We utilized NHANES data for 2011-2016. We defined NAFLD using recently derived US-FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non-Hispanic whites. NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non-Hispanic whites.Asian Americans with NAFLD had lower BMI and waist circumference than non-Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR=2.70, 95% CI: 1.00-7.27). Asian Americans have lower prevalence of NAFLD than non-Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non-Hispanic Whites.

Ultrasonographic Nonalcoholic Fatty Pancreas Is Associated with Advanced Fibrosis in NAFLD: A Retrospective Analysis.

Nonalcoholic fatty pancreas disease (NAF-P) is strongly linked with nonalcoholic fatty liver disease (NAFLD), but its relationship with advanced liver disease is unknown. This study investigated the association between NAF-P and both advanced fibrosis and nonalcoholic steatohepatitis (NASH). This retrospective study evaluated adults with biopsy-proven NAFLD with a sonogram within 1year of liver biopsy. NAF-P was diagnosed by comparing the echogenicity of the pancreas to the kidney and was graded by severity. The primary outcome was the effect of NAF-P on the presence of advanced fibrosis and NASH, while secondary outcomes included the association of extensive NAF-P (grade II/III). Propensity score matching for independent risk factors of advanced fibrosis (age, gender, body mass index, and diabetes) was performed. One hundred and four patients were included in the study and 91 (87.5%) had NAF-P. After propensity score matching, NAF-P was significantly associated with advanced fibrosis (OR 10.52, p < 0.001) but not NASH (p = 0.27). Extensive NAF-P was predictive of advanced fibrosis (OR 3.35, p = 0.006) and NASH (OR 5.37, p < 0.001). NAF-P had a negative predictive value (NPV) of 93% for advanced fibrosis. When matching for the NAFLD fibrosis score in addition to the variables above, both NAF-P (OR 5.36, p = 0.001) and extensive NAF-P (OR 5.38, p = 0.002) still significantly predicted advanced fibrosis. NAF-P is predictive of advanced fibrosis, even when controlling for independent predictors of advanced fibrosis and the NAFLD fibrosis score. NAF-P has an excellent NPV and is a safe, inexpensive finding that can rule out advanced fibrosis.

Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n=65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n=76), nonalcoholic steatohepatitis (NASH) without fibrosis (n=68), NAFLD/NASH stage 1-3 fibrosis (n=82), and NAFLD/NASH cirrhosis (n=70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n=38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35kg/m2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P<.001) and BMI (OR 1.4, P<.001) were the most significant predictors of advanced fibrosis. In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity.

Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease.

The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH. (1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE-TOFMS and LC-TOFMS. (1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P=0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(-) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(-) group (P<0.05). Moreover, expression levels of SCD1 and ELOVL6 were significantly reduced. These results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

Stage of liver fibrosis in patients with congenital bleeding disorders and infected with hepatitis C virus.

Hepatitis C virus (HCV) is the major cause of chronic liver disease in patients with hemophilia. However, since liver biopsy should not be routinely used in these patients, the accurate assessment of the stage of fibrosis has been limited so far. The aim of this study was to determine the stage of liver fibrosis in HCV‑infected patients with hemophilia by using noninvasive methods of fibrosis assessment, and to analyze the influence of risk factors on liver fibrosis. The study included 71 HCV‑infected patients with hemophilia and other congenital bleeding disorders. Patients were divided into 3 groups: HCV-RNA negative after successful treatment, HCV-RNA negative after spontaneous elimination of infection, and HCV‑RNA positive. Liver fibrosis was measured with shear wave elastography and FibroTest. The risk factors for liver fibrosis were analyzed, including demographic factors, HCV genotype, coinfections, and comorbidities. Cirrhosis or significant fibrosis (METAVIR score >F2) was observed in 26.8% of the patients. The stage of fibrosis was associated with age and estimated duration of infection (P <0.001). Active and past HBV infection did not affect fibrosis. The stage of liver fibrosis was lower in patients with spontaneous clearance of HCV (P = 0.007). Patients in our study had a similar stage of liver fibrosis to that reported by other studies on hemophilia. The older age and long duration of infection are the main risk factors for advanced fibrosis. Noninvasive methods such as shear wave elastography and FibroTest may allow a proper assessment of the fibrosis stage in hemophilia patients, particularly when used together and in correlation with other clinical parameters. They may also be useful in other groups of HCV‑infected patients.

Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States.

In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988–1994. Our goal was to determine the NAFLD prevalence in the recent 1999–2012 NHANES, risk factors for advanced fibrosis (stage 3–4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93–5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.