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Novel Insights into Non Alcoholic Fatty Liver Disease

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 12566

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Dr. Tadashi Namisaki

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Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Nara, Japan
Interests: liver fibrosis; diabetes mellitus; inflammation; steatosis
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Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) includes the entire spectrum of fatty liver disease, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Occurrence of HCC has been shown to be the strongest prognostic factor of NASH. To date, despite its high prevalence, no drugs have been approved for the treatment of NASH. NASH is frequently accompanied by metabolic disorders such as type 2 diabetes mellitus (T2DM). Nonetheless, specific pharmacological targets and treatments have yet to be found, leaving important medical needs still to be met. This Special Issue of the Journal of Clinical Medicine, entitled “Novel Insights into Non-Alcoholic Fatty Liver Disease”, will include a selection of original research papers and review articles on novel molecular and clinical targets for the prevention and treatment of NAFLD. This Special Issue will also include updated information on the management of liver fibrosis, inflammation, and steatosis.

Dr. Tadashi Namisaki
Guest Editor

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Keywords

fatty liver
steatosis
diabetes mellitus
liver fibrosis
inflammation
steatohepatitis
non-alcoholic fatty liver disease
hepatocellular carcinoma

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Published Papers (4 papers)

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Research

10 pages, 461 KiB

Open AccessArticle

Non Alcoholic Fatty Liver Disease Is Positively Associated with Increased Glycated Haemoglobin Levels in Subjects without Diabetes

by Roberta Zupo, Fabio Castellana, Francesco Panza, Marco Castellana, Luisa Lampignano, Raffaele Ivan Cincione, Vincenzo Triggiani, Gianluigi Giannelli, Vittorio Dibello, Rodolfo Sardone and Giovanni De Pergola

J. Clin. Med. 2021, 10(8), 1695; https://doi.org/10.3390/jcm10081695 - 15 Apr 2021

Cited by 12 | Viewed by 3544

Abstract

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m², not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study. Full article

(This article belongs to the Special Issue Novel Insights into Non Alcoholic Fatty Liver Disease)

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11 pages, 1067 KiB

Open AccessArticle

Accuracy of Fibrosis-4 Index in Identification of Patients with Cirrhosis Who Could Potentially Avoid Variceal Screening Endoscopy

by Koji Ishida, Tadashi Namisaki, Koji Murata, Yuki Fujimoto, Souichi Takeda, Masahide Enomoto, Hiroyuki Ogawa, Hirotetsu Takagi, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Masanori Furukawa, Yasuhiko Sawada, Koh Kitagawa, Shinya Sato, Norihisa Nishimura, Hiroaki Takaya, Kosuke Kaji, Naotaka Shimozato, Hideto Kawaratani, Kei Moriya, Takemi Akahane, Akira Mitoro and Hitoshi Yoshiji Show full author list Hide full author list

J. Clin. Med. 2020, 9(11), 3510; https://doi.org/10.3390/jcm9113510 - 29 Oct 2020

Cited by 6 | Viewed by 2703

Abstract

A potential restriction of the Baveno VI consensus, which helps to avoid unnecessary endoscopies, is the limited availability of FibroScan. We aimed to identify serum fibrosis indices that might aid in ruling out the presence of high-risk varices in cirrhotic patients. This retrospective study included 541 consecutive patients with cirrhosis who underwent endoscopy and had data available for nine serum fibrosis indices, including platelet count, hyaluronic acid, 7S fragment of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, fibrosis index based on four factors (FIB-4), aspartate transaminase/platelet ratio index and enhanced liver fibrosis score. Optimal index cutoffs for predicting high-risk varices were calculated in an estimation cohort (n = 127) and evaluated in a validation cohort (n = 351). The diagnostic performance of the indices was assessed by receiver operating characteristic curve analysis. In the estimation cohort, a FIB-4 cutoff of 2.78 provided the greatest diagnostic accuracy in predicting both all-grade and high-risk varices. FIB-4 had a negative predictive value of 1.00 for high-risk varices in both cohorts, and 21.3% (27/127) and 14.8% (52/351) of the estimation and validation cohorts, respectively, avoided esophagogastroduodenoscopy; no high-risk varices were missed in either cohort. FIB-4 correctly identifies the absence of high-risk varices in patients with cirrhosis. Therefore, those with a FIB-4 of ≥2.78 should undergo esophagogastroduodenoscopy, and FIB-4 determination should be recommended every 6–12 months concurrently with the other blood tests until the index value reaches 2.78 in those with a FIB-4 of <2.78. Full article

(This article belongs to the Special Issue Novel Insights into Non Alcoholic Fatty Liver Disease)

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10 pages, 532 KiB

Open AccessArticle

Association between Non-Alcoholic Fatty Liver Disease and Chronic Kidney Disease: A Cross-Sectional Study

by Takemi Akahane, Manabu Akahane, Tadashi Namisaki, Kosuke Kaji, Kei Moriya, Hideto Kawaratani, Hiroaki Takaya, Yasuhiko Sawada, Naotaka Shimozato, Yukihisa Fujinaga, Masanori Furukawa, Koh Kitagawa, Takahiro Ozutsumi, Yuki Tsuji, Daisuke Kaya, Akira Mitoro and Hitoshi Yoshiji

J. Clin. Med. 2020, 9(6), 1635; https://doi.org/10.3390/jcm9061635 - 28 May 2020

Cited by 15 | Viewed by 3050

Abstract

It is unclear whether the link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) is mediated by common risk factors. We aimed to elucidate the association between NAFLD and CKD using propensity score (PS)-matched analysis. We assessed 3725 Japanese individuals, excluding those with hepatitis B or C infection and men and women who consumed >30 and >20 g/day of alcohol, respectively. Of these, we enrolled 1097 Japanese subjects with NAFLD diagnosed by ultrasonography and 1097 PS-matched subjects without NAFLD. The prevalence of CKD was higher in subjects with NAFLD than in those without NAFLD before PS matching, but there was no significant difference between these groups in terms of CKD prevalence after PS matching. There was no difference in the prevalence of CKD between those with and without NAFLD in the subgroup analyses. Logistic regression analysis demonstrated that obesity, hypertension, and hyperuricemia were independent predictors of CKD, but NAFLD was not independently associated with CKD. In subjects with NAFLD, obesity, hypertension, and hyperuricemia were independent predictors of CKD. Thus, the link between NAFLD and CKD may be mediated by common risk factors. We recommend screening for CKD when patients with NAFLD have the aforementioned comorbidities. Full article

(This article belongs to the Special Issue Novel Insights into Non Alcoholic Fatty Liver Disease)

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11 pages, 920 KiB

Open AccessArticle

Increased Endotoxin Activity Is Associated with the Risk of Developing Acute-on-Chronic Liver Failure

by Hiroaki Takaya, Tadashi Namisaki, Shinya Sato, Kosuke Kaji, Yuki Tsuji, Daisuke Kaya, Yukihisa Fujinaga, Yasuhiko Sawada, Naotaka Shimozato, Hideto Kawaratani, Kei Moriya, Takemi Akahane, Akira Mitoro and Hitoshi Yoshiji

J. Clin. Med. 2020, 9(5), 1467; https://doi.org/10.3390/jcm9051467 - 14 May 2020

Cited by 8 | Viewed by 2606

Abstract

Acute-on-chronic liver failure (ACLF) leads to systematic inflammatory response syndrome and multiple organ failure. This study investigated the relationship between endotoxin (Et) and ACLF with the aim of determining whether Et activity (EA) is useful as a predictive biomarker of ACLF development and whether rifaximin treatment decreased the risk of ACLF development. Two hundred forty-nine patients with liver cirrhosis were enrolled in this study. Et concentration was determined in the whole blood by a semiquantitative EA assay. Predictive factors of ACLF development and the risk of ACLF development with and without rifaximin treatment were identified by univariate and multivariate analysis using Fine and Gray’s proportional subhazards model. EA level was higher in Child-Pugh class B than in class A patients, and class B patients had an increased risk of ACLF development compared with class A patients. Multivariate analysis showed that EA level was a predictive factor independently associated with ACLF development. Rifaximin decreased EA level and the risk of ACLF development in Child-Pugh class B patients. Et levels were associated with functional liver capacity and were predictive of ACLF development in cirrhotic patients. Rifaximin decreased Et level and the risk of ACLF development in advanced cirrhotic patients. Full article

(This article belongs to the Special Issue Novel Insights into Non Alcoholic Fatty Liver Disease)

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