Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis.

BACKGROUND AND AIMS: A simple noninvasive score, the Agile 3+ score, combining liver stiffness measurement, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for the identification of advanced fibrosis in patients with suspected NAFLD. We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease, so currently, the two terms are interchangeable. APPROACH AND RESULTS: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the April 24, 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤ 0.451) and rule-in (≥ 0.679) cutoffs. We included 6 observational studies (total of 6955 participants) with biopsy-proven NAFLD [mean age 53 (SE 4) years, mean body mass index 30.9 (SE 2.3) kg/m 2 , 54.0% men, prevalence of diabetes 59.6%]. The pooled prevalence of advanced fibrosis (≥ F3) was 42.1%. By the rule-out cutoff, the overall sensitivity and specificity were 88% (95% CI: 81-93%; I2 = 89.2%) and 65% (95% CI: 54-75%; I2 = 97.6%), respectively. By the rule-in cutoff, the overall sensitivity and specificity were 68% (95% CI: 57-78%; I2 =91.1%) and 87% (95% CI: 80%-92%; I2 =96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age ( p < 0.01), body mass index ( p < 0.01), and, although not statistically significant, sex ( p = 0.06). CONCLUSIONS: Our systematic review and meta-analysis suggests that Agile 3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Can Frequent Toothbrushing Reduce the Risk of Cirrhosis among Patients with Nonalcoholic Fatty Liver Disease? Hints from a Registry-Based Study.

INTRODUCTION: While poor oral hygiene has been previously associated with an increased risk of nonalcoholic fatty liver disease (NAFLD), its association with hepatic fibrosis remains unclear. Here, we sought to analyze if toothbrushing frequency, an easy-to-assess indicator of oral health habits, would be associated with liver stiffness measurement (LSM) by transient elastography (TE) in patients with an established diagnosis of NAFLD. METHODS: In this registry-based study, LSM was measured in 1,156 patients with NAFLD and analyzed in relation to the self-reported daily frequency of toothbrushing. LSM values ≥12 kPa were considered indicative of cirrhosis. RESULTS: A trend toward a stepwise decrease (cross-sectional p = 0.13) in LSM was found in patients who reported having their teeth brushed more frequently: less than once a day (10.6 ± 8.6 kPa; 13% of the study sample), once a day (9.95 ± 8.40 kPa; 40%), twice a day (9.21 ± 7.63 kPa; 43%), and after every meal (8.91 ± 5.30 kPa; 4%). Patients who brushed their teeth less than once a day had a significantly higher prevalence of LSM values ≥12 kPa (p < 0.05). In multivariable logistic regression analysis, the association of LSM values ≥12 kPa with toothbrushing habits remained statistically significant for less than once a day (odds ratio = 1.69, 95% confidence interval = 1.07-2.66, p = 0.02) with reference to twice a day or after every meal. CONCLUSION: Among patients with NAFLD, there is an independent association between brushing teeth less than once a day and TE-established cirrhosis.

The risk of development of primary biliary cholangitis among incidental antimitochondrial M2 antibody-positive patients.

Background and Aim: This study investigated the risk of the development of primary biliary cholangitis (PBC) in individuals who were incidentally identified as having positive antimitochondrial antibodies (AMA)-M2. Materials and Methods: We retrospectively reviewed extractable nuclear antibody (ENA) panel test results to identify the incidental AMA-M2-positive patients. Patients who filled the diagnostic criteria for PBC were excluded. AMA-M2-positive patients were further evaluated by physical examination, liver biochemistry, liver ultrasonography, and transient elastography (TE) and were also closely followed. Results: We included 48 (n=45, 93% female) individuals with a median age of 49 (range: 20-69) years. The median follow-up duration was 27 months (range: 9-42) after the detection of AMA-M2. Thirty-three (69%) patients had concomitant autoimmune/inflammatory disorders. Twenty-eight (58%) individuals showed seropositivity for ANA, and 21 had (43%) positive AMA. Fifteen (31%) patients developed typical PBC according to the international PBC diagnostic criteria during the follow-up, and five of them (18%) had significant fibrosis (≥8.2 kPA) by TE at the time of PBC diagnosis. Conclusion: Two-thirds of the incidental AMA-M2-positive patients developed typical features of PBC after a median 27-month follow-up. Our results suggest that AMA-M2 patients should be closely followed up to detect the late development of PBC.

Impairment of patient-reported outcomes among patients with non-alcoholic fatty liver disease: a registry-based study.

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) and more advanced fibrosis tend to have more impairment in their health-related quality of life and other patient-reported outcomes (PROs). AIM: To assess the association of PROs with select non-invasive tests (NITs) for fibrosis including FAST, Agile 3+ and Agile 4 scores METHODS: We enrolled patients with an established diagnosis of NAFLD who were seen in a tertiary care clinic into the NAFLD/NASH Registry. The FAST, Agile 3+ and Agile 4 scores were calculated using liver stiffness measurements by transient elastography and laboratory parameters. PROs were assessed using FACIT-F, CLDQ-NASH and WPAI instruments (total of 17 domain and summary scores). RESULTS: There were 1509 patients with NAFLD (mean age: 49 ± 11 years, 50% men, 41% employed, 30% advanced fibrosis and 20% cirrhosis). The mean FAST, Agile 3+ and Agile 4 scores were 0.39 ± 0.26, 0.35 ± 0.31 and 0.12 ± 0.23, respectively. Subjects with lower FAST, Agile 3+ and Agile 4 scores had the highest scores in select domains of FACIT-F, CLDQ-NASH and WPAI (p < 0.05 in comparison to subjects with elevated or high-risk NIT scores). Correlations with continuous NITs were significantly negative for Emotional and Functional well-being (FACIT-F), Activity/energy, Systemic symptoms, Worry and total scores (CLDQ-NASH), and Activity of WPAI (p < 0.05); the strongest was for Worry (CLDQ-NASH) with FAST (R = -0.17, p < 0.0001). The PRO scores of patients with NAFLD were lower than those of matched patients with chronic hepatitis B (p < 0.05 for 9/17 domain and summary scores). CONCLUSION: Patients with NAFLD and high FAST, Agile 3+ or Agile 4 scores experience impairment of health-related quality of life.

Characteristics of patients with hepatocellular carcinoma: A multicenter study.

Background and Aim: The aim of the present study was to examine the etiology of hepatocellular carcinoma (HCC) by underlying cause and determine the characteristics and clinical features of patients with HCC. Materials and Methods: The study comprised 1802 HCC patients diagnosed and followed up by Liver Diseases Outpatient Clinics in 14 tertiary centers in Turkey between 2001 and 2020. Results: The mean age was 62.3±10.7 years, and 78% of them were males. Of the patients, 82% had cirrhosis. Hepatitis B virus (HBV) infection was the most common etiology (54%), followed by hepatitis C virus (HCV) infection (19%) and nonalcoholic fatty liver disease (NAFLD) (10%). Of the patients, 56% had a single lesion. Macrovascular invasion and extrahepatic spread were present in 15% and 12% of the patients, respectively. The median serum alpha-fetoprotein level was 25.4 ng/mL. In total, 39% of the patients fulfilled the Milan Criteria. When we compared the characteristics of patients diagnosed before and after January 2016, the proportion of NAFLD-related HCC cases increased after 2016, from 6.6% to 13.4%. Conclusion: Chronic HBV and HCV infections remain the main causes of HCC in Turkey. The importance of NAFLD as a cause of HCC is increasing.

Mutation Spectrum of Familial Adenomatous Polyposis Patients in Turkish Population: Identification of 3 Novel APC Mutations.

BACKGROUND: Familial adenomatous polyposis (OMIM #175100) and MUTYH-associated polyposis (OMIM #608456) are rare cancerprone disorders characterized by hundreds of adenomatous polyps in the colon and rectum, which have a high probability of malignant transformation. Attenuated familial adenomatous polyposis is a variant of familial adenomatous polyposis, which is a term used for the condition in which patients have less than 100 colorectal polyps. Germline heterozygous Adenomatous polyposis coli (APC) and biallelic MUTYH (mutY DNA glycosylase) pathogenic variations are responsible for familial adenomatous polyposis and MUTYH-associated polyposis respectively. The aim of this study is to discuss the clinical manifestations of patients having pathogenic APC and MUTYH variations. METHODS: We included 27 probands who have more than 10 colonic polyps in this study. After evaluation of their clinical and family histories, the probands were screened for APC and MUTYH variations via next generation sequencing. The family members of the probands carrying pathogenic variations were screened via Sanger sequencing. RESULTS: Among 27 probands, pathogenic APC and MUTYH variations were detected in 3 and 6 probands respectively. In the APC gene, 3 novel truncating variations (p.Leu360*, p.Leu1489Phefs*23, and p.Leu912*) were detected in 3 unrelated probands. In the MUTYH gene, only 2 distinct pathogenic variations were detected (p.Pro295Leu and p.Glu480del) in the homozygous or compound heterozygous state. CONCLUSION: In this study, molecular etiology was clarified in 9 familial polyposis patients. The p.Pro295Leu and p.Glu480del variations seem to be common in the Turkish population and may be considered as a first-step genetic test in Turkish familial polyposis patients showing autosomal recessive inheritance. However more studies are needed to reveal the exact frequency of these variations.

Hepatocellular Carcinoma in Non-cirrhotic Liver Arises with a More Advanced Tumoral Appearance: A Single-Center Cohort Study.

BACKGROUND: A small proportion of all hepatocellular carcinomas (HCCs) arise in a non-cirrhotic liver (NCL). However, our knowledge about the HCCs developing in a NCL is scarce. This study was undertaken to investigate the characteristics and survival course of this patient group. METHODS: We retrospectively analyzed the database of patients with HCC at a tertiary center during a 10-year period (2009-2019). All demographic, clinical, laboratory, and tumoral features with survival outcomes were compared between the HCC-CL and HCC-NCL groups. RESULTS: Out of 384 HCC cases, 11.2% (n = 43) had no cirrhosis. The dominant etiology in the HCC-NCL group was hepatitis B virus (n = 26, 60.5%), followed by non-alcoholic fatty liver disease (n = 10, 23.2%), and hepatitis C virus (n = 7, 16.3%). The maximum tumor diameter was approximately 2 times larger in the HCC-NCL group (HCC-NCL: 90 mm vs. HCC-CL: 46.5 mm, P < .001). The proportion of patients with vascular (HCC-NCL: 27.9% vs. HCC-CL: 8.6%, P < .001) and extrahepatic invasion (HCC-NCL: 14% vs. HCC-CL: 3%, P = .001) were prominently higher in the HCC-NCL group. Patients with HCC-NCL were less often detected in early-curable stages (BCLC 0-A) than those in the HCC-CL group (HCC-NCL: 16.3% vs. HCC-CL: 34.9%, P = .004). The overall survival was not different between the 2 groups (HCC-NCL: 19.4 ± 9.8 months vs. HCC-CL: 17.5 ± 2.3 months, P = .581). CONCLUSION: HCC in NCL is diagnosed at more advanced tumoral stages with larger tumor size and more often with vascular and extrahepatic spread. Despite the preserved liver functions, the overall survival is not prolonged in HCCs without cirrhosis, due to the late recognition.

Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND: Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD. METHODS: We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced. RESULTS: In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosis. CONCLUSION: Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.

Recommendations for Reopening Endoscopy Units in Turkey: A Set-up Plan from a Tertiary Center in Istanbul.

In the midst of Coronavirus-19 (COVID-19) pandemic, endoscopic procedures have been separated for only urgent and semi-urgent cases for the last few months to prevent transmission in endoscopy units. This approach will perhaps resolve the burden of elective procedures in the months ahead of us. As we observe a downtrend in new cases of COVID-19 in Turkey, a strategy for reopening endoscopy units is required. We are stepping into a time period where we should not only re-provide the essential services to our patients but also maintain the safety of healthcare workers and preserve the valuable personal protective equipment as well. Herein, we aim to share the available knowledge in performing endoscopy during the pandemic and the set-up plan of a tertiary center in Istanbul for reopening the endoscopy unit in the era of the COVID-19 pandemic.

Liver stiffness is associated with disease severity and worse clinical scenarios in coronavirus disease 2019: A prospective transient elastography study.

BACKGROUND: Pre-existing chronic liver disease is currently considered a poor prognostic factor for coronavirus disease 2019 (COVID-19). The present study aimed to investigate the association of liver stiffness measurement (LSM) with disease severity and clinical course of COVID-19. METHODS: We prospectively recruited consecutive hospitalised adult patients with COVID-19 in a 3-month period. Demographic, laboratory, clinical and vibration-controlled transient elastography (VCTE) features were recorded at entry, and all patients were prospectively followed-up. Severe liver fibrosis was defined as an LSM value higher than 9.6 kPA. Multivariate logistic regression analysis was performed to reveal factors associated with disease severity and outcomes. RESULTS: Out of 98 eligible patients with COVID-19, 12 (12.2%) had severe liver fibrosis. Patients with severe liver fibrosis had higher baseline disease severity (P = .022), more commonly required oxygen treatment at entry (P = .010), and had intensive-care unit (ICU) requirements during the 6 (1-39)-day median follow-up time (P = .017). The presence of severe liver fibrosis was independently associated with disease severity (odds ratio (OR): 7.685, 95% confidence interval (CI): 1.435-41.162, P = .017) and ICU requirement (OR: 46.656, 95% CI: 2.144-1015.090, P = .014). LSM was correlated with alanine aminotransferase levels (P = .005, r: 0.283), but not with other markers of acute hepatic injury or inflammation. CONCLUSION: Initial VCTE application might help physicians identify patients who are more likely to have severe illness or worse clinical outcomes, in addition to other well-established clinical and laboratory factors. Further multicentre prospective studies are warranted to validate our results.

Causes of erectile dysfunction in non-alcoholic fatty liver disease.

Background and Aim: Erectile dysfunction (ED) is an important and commonly seen disorder in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study was to assess the rate of ED and its causes in a group of NAFLD patients. Materials and Methods: The International Index of Erectile Function questionnaire (IIEF-5) was used to evaluate the presence, causes, and severity of ED. Participants with an IIEF-5 score of <22 who agreed to undergo a urological evaluation were referred to a urologist for further assessment. Results: A total of 136 NAFLD patients were enrolled in the study. According to the IIEF-5, 68 (50.0%) patients had ED. Multivariate analysis indicated that older age, obesity, and hypertension were associated with ED. Seventeen patients had multiple etiological factors for ED. Psychogenic ED was identified in 19 patients (39.6%), vasculogenic ED in 35 patients (72.9%), drug-related ED in 3 patients (6.3%), and neurogenic ED in 6 patients (12.5%). Conclusion: ED is frequently seen in NAFLD patients, which may, at least in part, be due to common risk factors. Vasculogenic dysfunction is the most common single source of ED in NAFLD patients. Nonetheless, all potential etiologies should be carefully investigated, with special attention given to psychogenic factors, since they may be more frequent and relevant than expected.

Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study.

BACKGROUND AND AIMS: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. METHODS: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. RESULTS: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). CONCLUSION: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

External validation of the Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients.

OBJECTIVES: Toronto hepatocellular carcinoma risk index is developed to stratify cirrhotic patients according to 10-year hepatocellular carcinoma risk. We aimed to validate the performance of Toronto hepatocellular carcinoma risk index in a large Turkish cohort. MATERIALS AND METHODS: We retrospectively reviewed the database of 1287 cirrhotic patients followed-up in a 10-year period (February 2008 to January 2018). All patients were stratified into three groups based on the Toronto hepatocellular carcinoma risk index score as follows: low-risk, < 120; intermediate risk, 120 to 240; and high risk, > 240. Area under the curve and optimal cutoff value of Toronto hepatocellular carcinoma risk index were obtained from receiver operator curve. To reveal the parameters related with hepatocellular carcinoma development, logistic regression analysis was conducted. The cumulative incidences of hepatocellular carcinoma were calculated using the Kaplan-Meier method, and the curves were compared using the log-rank test. RESULTS: Out of 403 enrolled patients, 57 developed hepatocellular carcinoma. The median Toronto hepatocellular carcinoma risk index value was higher in hepatocellular carcinoma (+) group comparing to hepatocellular carcinoma (-) group [267 (70-366) vs. 224 (36-366), P < 0.001]. Out of 57 detected hepatocellular carcinomas, 45 (78.9%) were high risk, 11 (19.3%) were intermediate risk, and only one (1.8%) was low risk at the entry. The area under the curve of the Toronto hepatocellular carcinoma risk index to predict hepatocellular carcinoma was 0.750 (95% confidence interval, 0.683-0.817, P < 0.001). The optimal cutoff value of Toronto hepatocellular carcinoma risk index was 239.5, giving a sensitivity of 78.9% and specificity of 62.7%. As a result, Toronto hepatocellular carcinoma risk index remained to be the only significant parameter that has an affect on hepatocellular carcinoma development [adjusted-odds ratio: 1.016 (95% confidence interval, 1.007-1.024), P<0.001]. CONCLUSION: The present study validated the performance of Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients to predict hepatocellular carcinoma risk, which can be considered as a tool for personalized surveillance.

Simple Noninvasive Scores Are Clinically Useful to Exclude, Not Predict, Advanced Fibrosis: A Study in Turkish Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease.

Background/Aims: Advanced fibrosis (F≥3) indicates poor outcomes in nonalcoholic fatty liver disease (NAFLD). Here, we examined the diagnostic performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) for detecting (or excluding) advanced fibrosis in patients with biopsy-proven NAFLD. Methods: The diagnostic performance of each noninvasive test according to previously identified cutoff points indicating low and high risk for advanced fibrosis was determined in 463 patients with NAFLD. Patients who scored <1.3 and >2.67 on the FIB-4 were considered at low and high risk for advanced fibrosis, respectively. Patients who scored <-1.455 and >0.676 on the NFS were considered at low and high risk for advanced fibrosis, respectively. Results: Eighty-one patients (17.5%) had biopsy-proven advanced fibrosis (F≥3). The published FIB-4 cutoff values for low and high risk were able to exclude advanced fibrosis with negative predictive values (NPVs) of 0.907 and 0.843 and specificities of 74% and 97%, respectively. The published NFS cutoff values for low and high risk were able to exclude advanced fibrosis with NPVs of 0.913 and 0.842 and specificities of 63% and 96%, respectively. If biopsies were performed in only patients with a FIB-4 above the low cutoff point (≥1.3), 67.1% could be avoided. Conversely, if biopsies were performed in only patients with an NFS above the low cutoff point (≥-1.455), 57.0% could be avoided. Conclusions: The main clinical utility of the FIB-4 and NFS in patients with NAFLD lies in the ability to exclude, not identify, advanced fibrosis.

Arterial stiffness is associated independently with liver stiffness in biopsy-proven nonalcoholic fatty liver disease: a transient elastography study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased arterial stiffness. However, the question as to whether an association exists between the extent of vascular and liver stiffness in patients with biopsy-proven NAFLD remains open. In this study, we sought to investigate whether pulse wave velocity (PWV) and augmentation index (AIx) - two common indices of arterial stiffness - are associated with (a) liver stiffness measurement (LSM) on transient elastography (TE) and (b) histological liver fibrosis. PATIENTS AND METHODS: We examined 125 patients with biopsy-proven NAFLD and 55 age-matched and sex-matched controls. Arterial stiffness of the brachial artery was measured using a Mobil-O-Graph arteriography system. LSM was assessed using TE, whereas the presence of advanced fibrosis (F ≥ 3) was determined on histology. RESULTS: Patients with NAFLD had higher PWV [median: 7.2 (6.3-8.2) and 6.2 (5.5-6.7) m/s, respectively, P < 0.001] and AIx (mean: 21.3 ± 13.5 and 17.2 ± 11.9%, respectively, P=0.01) compared with the controls. LSM showed positive correlations with both PWV (ρ = 0.300; P<0.01) and AIx (ρ = 0.223, P = 0.02). Both indices of arterial stiffness were higher in patients with advanced fibrosis than in those with nonadvanced fibrosis (F ≤ 2). CONCLUSION: The severity of arterial and liver stiffness increases in parallel in patients with biopsy-proven NAFLD. Systematic risk assessment for reducing arterial stiffness is recommended in the presence of TE-determined advanced fibrosis.