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12 pages, 12339 KiB

Open AccessArticle

Determination of Non-Invasive Biomarkers for the Assessment of Fibrosis, Steatosis and Hepatic Iron Overload by MR Image Analysis. A Pilot Study

by Alba Meneses, José Manuel Santabárbara, Juan Antonio Romero, Roberto Aliaga, Alicia María Maceira and David Moratal

Diagnostics 2021, 11(7), 1178; https://doi.org/10.3390/diagnostics11071178 - 29 Jun 2021

Cited by 3 | Viewed by 2143

Abstract

The reference diagnostic test of fibrosis, steatosis, and hepatic iron overload is liver biopsy, a clear invasive procedure. The main objective of this work was to propose HSA, or human serum albumin, as a biomarker for the assessment of fibrosis and to study [...] Read more.

The reference diagnostic test of fibrosis, steatosis, and hepatic iron overload is liver biopsy, a clear invasive procedure. The main objective of this work was to propose HSA, or human serum albumin, as a biomarker for the assessment of fibrosis and to study non-invasive biomarkers for the assessment of steatosis and hepatic iron overload by means of an MR image acquisition protocol. It was performed on a set of eight subjects to determine fibrosis, steatosis, and hepatic iron overload with four different MRI sequences. We calibrated longitudinal relaxation times (T1 [ms]) with seven human serum albumin (HSA [%]) phantoms, and we studied the relationship between them as this protein is synthesized by the liver, and its concentration decreases in advanced fibrosis. Steatosis was calculated by means of the fat fraction (FF [%]) between fat and water liver signals in “fat-only images” (the subtraction of in-phase [IP] images and out-of-phase [OOP] images) and in “water-only images” (the addition of IP and OOP images). Liver iron concentration (LIC [µmol/g]) was obtained by the transverse relaxation time (T2* [ms]) using Gandon’s method with multiple echo times (TE) in T2-weighted IP and OOP images. The preliminary results showed that there is an inverse relationship (r = −0.9662) between the T1 relaxation times (ms) and HSA concentrations (%). Steatosis was determined with FF > 6.4% and when the liver signal was greater than the paravertebral muscles signal, and thus, the liver appeared hyperintense in fat-only images. Hepatic iron overload was detected with LIC > 36 µmol/g, and in these cases, the liver signal was smaller than the paravertebral muscles signal, and thus, the liver behaved as hypointense in IP images. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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12 pages, 750 KiB

Open AccessArticle

Associations between Pre-Bariatric High-Sensitivity C-Reactive Protein and Post-Surgery Outcomes

by Tannaz Jamialahmadi, Mohsen Nematy, Simona Bo, Valentina Ponzo, Ali Jangjoo, Ladan Goshayeshi, Aida Tasbandi, Nikita G. Nikiforov and Amirhossein Sahebkar

Diagnostics 2021, 11(4), 721; https://doi.org/10.3390/diagnostics11040721 - 18 Apr 2021

Cited by 1 | Viewed by 2115

Abstract

Background: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) [...] Read more.

Background: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) values and post-surgery weight loss and liver steatosis and fibrosis in patients with severe obesity undergoing Roux-en-Y gastric bypass. Methods: We conducted an observational prospective study on 90 individuals with morbid obesity, who underwent gastric bypass. Anthropometric indices, laboratory assessment (lipid panel, glycemic status, liver enzymes, and hs-CRP), liver stiffness and steatosis were evaluated at baseline and 6-months after surgery. Results: There was a significant post-surgery reduction in all the anthropometric variables, with an average weight loss of 33.93 ± 11.79 kg; the mean percentage of total weight loss (TWL) was 27.96 ± 6.43%. Liver elasticity was significantly reduced (from 6.1 ± 1.25 to 5.42 ± 1.52 kPa; p = 0.002), as well as liver aminotransferases, nonalcoholic fatty liver disease fibrosis score (NFS) and the grade of steatosis. Serum hs-CRP levels significantly reduced (from 9.26 ± 8.45 to 3.29 ± 4.41 mg/L; p < 0.001). The correlations between hs-CRP levels and liver fibrosis (elastography), steatosis (ultrasonography), fibrosis-4 index, NFS, and surgery success rate were not significant. Regression analyses showed that serum hs-CRP levels were not predictive of liver status and success rate after surgery in both unadjusted and adjusted models. Conclusions: In patients with morbid obesity, bariatric surgery caused a significant decrease in hs-CRP levels, liver stiffness and steatosis. Baseline hs-CRP values did not predict the weight-loss success rate and post-surgery liver status. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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12 pages, 7256 KiB

Open AccessArticle

Shear Wave Elastography and Shear Wave Dispersion Imaging in the Assessment of Liver Disease in Alpha1-Antitrypsin Deficiency

by Marten Schulz, Moritz Kleinjans, Pavel Strnad, Münevver Demir, Theresa M. Holtmann, Frank Tacke and Alexander Wree

Diagnostics 2021, 11(4), 629; https://doi.org/10.3390/diagnostics11040629 - 31 Mar 2021

Cited by 3 | Viewed by 2811

Abstract

Liver affection of Alpha1-antitrypsin deficiency (AATD) can lead to cirrhosis and hepatocellular carcinoma (HCC). A noninvasive severity assessment of liver disease in AATD is urgently needed since laboratory parameters may not accurately reflect the extent of liver involvement. Preliminary data exist on two-dimensional [...] Read more.

Liver affection of Alpha1-antitrypsin deficiency (AATD) can lead to cirrhosis and hepatocellular carcinoma (HCC). A noninvasive severity assessment of liver disease in AATD is urgently needed since laboratory parameters may not accurately reflect the extent of liver involvement. Preliminary data exist on two-dimensional shear wave elastography (2D-SWE) being a suitable method for liver fibrosis measurement in AATD. AATD patients without HCC were examined using 2D-SWE, shear wave dispersion imaging (SWD) and transient elastography (TE). Furthermore, liver steatosis was assessed using the controlled attenuation parameter (CAP) and compared to the new method of attenuation imaging (ATI). 29 AATD patients were enrolled, of which 18 had the PiZZ genotype, eight had PiMZ, two had PiSZ and one had a PiZP-Lowell genotype. 2D-SWE (median 1.42 m/S, range 1.14–1.83 m/S) and TE (median 4.8 kPa, range 2.8–24.6 kPa) values displayed a significant correlation (R = 0.475, p < 0.05). 2D-SWE, ATI (median 0.56 dB/cm/MHz, range 0.43–0.96 dB/cm/MHz) and CAP (median 249.5 dB/m, range 156–347 dB/m) values were higher in PiZZ when compared to other AATD genotypes. This study provides evidence that 2D-SWE is a suitable method for the assessment of liver disease in AATD. The newer methods of SWD and ATI require further evaluation in the context of AATD. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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14 pages, 1021 KiB

Open AccessArticle

Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees

by Kenichiro Murayama, Michiaki Okada, Kenichi Tanaka, Chika Inadomi, Wataru Yoshioka, Yoshihito Kubotsu, Tomomi Yada, Hiroshi Isoda, Takuya Kuwashiro, Satoshi Oeda, Takumi Akiyama, Noriko Oza, Hideyuki Hyogo, Masafumi Ono, Takumi Kawaguchi, Takuji Torimura, Keizo Anzai, Yuichiro Eguchi and Hirokazu Takahashi

Diagnostics 2021, 11(1), 132; https://doi.org/10.3390/diagnostics11010132 - 16 Jan 2021

Cited by 23 | Viewed by 3415

Abstract

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual [...] Read more.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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19 pages, 869 KiB

Open AccessArticle

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study

by Cristina Galarregui, Bertha Araceli Marin-Alejandre, Nuria Perez-Diaz-Del-Campo, Irene Cantero, J. Ignacio Monreal, Mariana Elorz, Alberto Benito-Boillos, José Ignacio Herrero, Josep A. Tur, J. Alfredo Martínez, M. Angeles Zulet and Itziar Abete

Diagnostics 2020, 10(11), 917; https://doi.org/10.3390/diagnostics10110917 - 8 Nov 2020

Cited by 8 | Viewed by 2937

Abstract

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or [...] Read more.

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT). Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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11 pages, 1272 KiB

Open AccessArticle

The Appropriate Opportunity for Evaluating Liver Fibrosis by Using the FIB-4 Index in Patients with Nonalcoholic Fatty Liver Disease in Japan

by Yuya Seko, Kota Yano, Aya Takahashi, Shinya Okishio, Seita Kataoka, Keiichiroh Okuda, Atsushi Umemura, Kanji Yamaguchi, Michihisa Moriguchi, Saiyu Tanaka and Yoshito Itoh

Diagnostics 2020, 10(10), 842; https://doi.org/10.3390/diagnostics10100842 - 19 Oct 2020

Cited by 3 | Viewed by 2033

Abstract

In patients with nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the predictive factor for liver-related events and prognosis. This retrospective study aimed to evaluate longitudinal changes in the FIB-4 index and to determine a strategy for diagnosing and following patients with NAFLD [...] Read more.

In patients with nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the predictive factor for liver-related events and prognosis. This retrospective study aimed to evaluate longitudinal changes in the FIB-4 index and to determine a strategy for diagnosing and following patients with NAFLD using this index. We analyzed the FIB-4 index at baseline and after 1 and 5 years in 272 consecutive patients with biopsy-proven NAFLD. Of these, 52 patients underwent serial biopsies. The change in the FIB-4 index was correlated with changes in the fibrosis stage among these patients (p = 0.048). The median FIB-4 index was 1.64 at baseline, 1.45 at 1 year, and 1.74 at 5 years. The negative predictive value for advanced fibrosis at a low cutoff point was 90.4/90.1 at baseline/1 year. Its specificity at a high cutoff point increased from 65.0% at baseline to 82.3% at 1 year. Multivariate analysis identified the FIB-4 index at 1 year as a predictive factor for a FIB-4 index > 2.67 at 5 years. A FIB-4 index < 1.30 was acceptable for excluding advanced fibrosis at baseline. In contrast, to evaluate and predict advanced liver fibrosis with the FIB-4 index at a high cutoff point, we should use the index at 1 year after appropriate therapy. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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13 pages, 1143 KiB

Open AccessArticle

An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials

by Wei-Qiang Leow, Pierre Bedossa, Feng Liu, Lai Wei, Kiat-Hon Lim, Wei-Keat Wan, Yayun Ren, Jason Pik-Eu Chang, Chee-Kiat Tan, Aileen Wee and George Boon-Bee Goh

Diagnostics 2020, 10(9), 643; https://doi.org/10.3390/diagnostics10090643 - 28 Aug 2020

Cited by 13 | Viewed by 4505

Abstract

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are [...] Read more.

Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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Review

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11 pages, 242 KiB

Open AccessReview

Diagnostic Accuracy of FibroScan and Factors Affecting Measurements

by Satoshi Oeda, Kenichi Tanaka, Ayaka Oshima, Yasue Matsumoto, Eisaburo Sueoka and Hirokazu Takahashi

Diagnostics 2020, 10(11), 940; https://doi.org/10.3390/diagnostics10110940 - 12 Nov 2020

Cited by 59 | Viewed by 9278

Abstract

Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is [...] Read more.

Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

12 pages, 235 KiB

Open AccessReview

Complications of Non-Alcoholic Fatty Liver Disease in Extrahepatic Organs

by Wataru Tomeno, Kento Imajo, Takuya Takayanagi, Yu Ebisawa, Kosuke Seita, Tsuneyuki Takimoto, Kanami Honda, Takashi Kobayashi, Asako Nogami, Takayuki Kato, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Hiroyuki Kirikoshi, Yasunari Sakamoto, Masato Yoneda, Satoru Saito and Atsushi Nakajima

Diagnostics 2020, 10(11), 912; https://doi.org/10.3390/diagnostics10110912 - 7 Nov 2020

Cited by 19 | Viewed by 4127

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

17 pages, 1131 KiB

Open AccessReview

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

by Yoshio Sumida, Masashi Yoneda, Yuya Seko, Hiroshi Ishiba, Tasuku Hara, Hidenori Toyoda, Satoshi Yasuda, Takashi Kumada, Hideki Hayashi, Takashi Kobayashi, Kento Imajo, Masato Yoneda, Toshifumi Tada, Takumi Kawaguchi, Yuichiro Eguchi, Satoshi Oeda, Hirokazu Takahashi, Eiichi Tomita, Takeshi Okanoue, Atsushi Nakajima and Japan Study Group of NAFLD (JSG-NAFLD) Show full author list Hide full author list

Diagnostics 2020, 10(8), 579; https://doi.org/10.3390/diagnostics10080579 - 10 Aug 2020

Cited by 27 | Viewed by 6053

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability. Full article

(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)

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