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Fatty Liver Syndrome
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Fatty Liver Syndrome

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (25 August 2020) | Viewed by 30903

Special Issue Editor

Dr. Yoshio Sumida

E-Mail Website
Guest Editor
Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
Interests: nonalcoholic steatohepatitis; oxidative stress; hepatic fibrosis; diabetes mellitus; liver cirrhosis; hepatocellular carcinoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fatty liver disease is the most prevalent chronic liver disease worldwide. Fatty liver disease is induced by a variety of factors, such as alcohol intake, obesity, diabetes, hepatic virus C infection, endocrine disorder (growth hormone deficiency, testosterone deficiency, hypothyroidism), operation (pancreatoduodenectomy, ilio-cecal bypass), drugs (tamoxifen, methotrexate, steroids, etc.), and genetic polymorphism (PNPLA3, TM6SF2 etc.). Accumulating evidence has established that PNPLA3 SNP is closely associated with fibrosis progression or HCC development in FLS. The term “nonalcoholic fatty liver disease” (NAFLD) was coined by Schaffner, and has been used for a few decades. We do not know how obese patients that are mild drinkers (210~300 g/wk) showing steatohepatitis should be categorized. Both associated steatohepatitis (BASH) has been suggested in this case. It is time to abandon the term “NAFLD and AFLD”. Therefore, we would like to suggest that fatty liver disease can be called “fatty liver syndrome” (FALIS). This Special Issue welcomes original research and review paper regarding FALIS.

Suggested topics:

  • Mechanisms of insulin resistance and hepatic steatosis/fibrosis;
  • The role of alcohol in FLS;
  • The role of SNPs with disease severity in FLS;
  • The role of microbiota in FLS;
  • Endocrine disorder in FLS;
  • Drug-induced FLS;
  • The role of iron metabolism in FLS;
  • Antifibrotic agents in FLS;
  • How can we stop HCC development in FLS?
  • Mechanisms of cardiac/renal disease and FLS;
  • Treatment strategy or pipelines for FLS;
  • Noninvasive tests (NITs) of hepatic fibrosis in FLS;
  • Liver transplantation for FLS.

You may choose our Joint Special Issue in Gastroenterology Insights.

Assoc. Prof. Dr. Yoshio Sumida
Guest Editor

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Published Papers (6 papers)

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Research

Jump to: Review

12 pages, 1067 KiB  
Article
Association between Activity and Brain-Derived Neurotrophic Factor in Patients with Non-Alcoholic Fatty Liver Disease: A Data-Mining Analysis
by Ryuki Hashida, Dan Nakano, Sakura Yamamura, Takumi Kawaguchi, Tsubasa Tsutsumi, Hiroo Matsuse, Hirokazu Takahashi, Lynn Gerber, Zobair M. Younossi and Takuji Torimura
Life 2021, 11(8), 799; https://doi.org/10.3390/life11080799 - 7 Aug 2021
Cited by 10 | Viewed by 2429
Abstract
Reduction in activity links to the development and progression of non-alcoholic fatty liver disease (NAFLD). Brain-derived neurotrophic factor (BDNF) is known to regulate an activity. We aimed to investigate the association between reduction in activity and BDNF in patients with NAFLD using data-mining [...] Read more.
Reduction in activity links to the development and progression of non-alcoholic fatty liver disease (NAFLD). Brain-derived neurotrophic factor (BDNF) is known to regulate an activity. We aimed to investigate the association between reduction in activity and BDNF in patients with NAFLD using data-mining analysis. We enrolled 48 NAFLD patients. Patients were classified into reduced (n = 21) or normal activity groups (n = 27) based on the activity score of the Chronic Liver Disease Questionnaire-NAFLD/non-alcoholic steatohepatitis. Circulating BDNF levels were measured using an enzyme-linked immunoassay. Factors associated with reduced activity were analyzed using decision-tree and random forest analyses. A reduction in activity was seen in 43.8% of patients. Hemoglobin A1c and BDNF were identified as negative independent factors for reduced activity (hemoglobin A1c, OR 0.012, p = 0.012; BDNF, OR 0.041, p = 0.039). Decision-tree analysis showed that “BDNF levels ≥ 19.1 ng/mL” was the most important classifier for reduced activity. In random forest analysis, serum BDNF level was the highest-ranked variable for distinguishing between the reduced and normal activity groups (158 valuable importance). Reduced activity was commonly seen in patients with NAFLD. Data-mining analyses revealed that BNDF was the most important independent factor corresponding with the reduction in activity. BDNF may be an important target for the prevention and treatment of NAFLD. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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17 pages, 1365 KiB  
Article
Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD
by Jessica Binetti, Laia Bertran, David Riesco, Carmen Aguilar, Salomé Martínez, Fàtima Sabench, Jose Antonio Porras, Javier Camaron, Daniel Del Castillo, Cristóbal Richart and Teresa Auguet
Life 2020, 10(10), 245; https://doi.org/10.3390/life10100245 - 16 Oct 2020
Cited by 12 | Viewed by 3216
Abstract
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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10 pages, 3112 KiB  
Article
Plasma Long Noncoding RNA LeXis is a Potential Diagnostic Marker for Non-Alcoholic Steatohepatitis
by Jung Gil Park, Gyeonghwa Kim, Se Young Jang, Yu Rim Lee, Eunhye Lee, Hye Won Lee, Man-Hoon Han, Jae Min Chun, Young Seok Han, Jun Sik Yoon, Min Kyu Kang, Young Oh Kweon, Won Young Tak, Soo Young Park and Keun Hur
Life 2020, 10(10), 230; https://doi.org/10.3390/life10100230 - 3 Oct 2020
Cited by 14 | Viewed by 2726
Abstract
Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in [...] Read more.
Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0–14.9); 4.6 (4.0–6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590–0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25–395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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11 pages, 4526 KiB  
Article
Fatty Liver, and Not Visceral Fat, Is More Associated with Liver Fibrosis and Diabetes in Non-Obese Japanese Individuals: A Cross-Sectional Study
by Noriyo Urata, Miwa Kawanaka, Ken Nishino, Katsunori Ishii, Tomohiro Tanikawa, Mitsuhiko Suehiro, Takako Sasai, Ken Haruma, Hirofumi Kawamoto, Jun Nakamura, Noriaki Manabe and Tomoari Kamada
Life 2020, 10(9), 175; https://doi.org/10.3390/life10090175 - 4 Sep 2020
Cited by 6 | Viewed by 2497
Abstract
Asians are known to be more likely than Westerners to develop fatty liver and lifestyle-related diseases in spite of their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat [...] Read more.
Asians are known to be more likely than Westerners to develop fatty liver and lifestyle-related diseases in spite of their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat and hepatic fat in participants with a normal body mass index (BMI) and examine their characteristics during a medical checkup. This cross-sectional study was conducted on 663 of 1142 patients who underwent abdominal ultrasonography and who had an alcohol intake (converted to ethanol) of <30 g/day for males and <20 g/day for females and a BMI of <25 kg/m2 during a health checkup. Participants were classified into four groups: group A, visceral fat accumulation (VFA) (−) and fatty liver (FL) (−) (n = 549); group B, VFA (+) and FL (−) (n = 32); group C, VFA (−) and FL (+) (n = 58); and group D, VFA (+) and FL (+) (n = 24). The frequencies of lifestyle-related disease complications, liver function tests, and liver fibrosis were evaluated among the four groups. Compared with group A (control), groups B, C, and D had a higher number of males, BMI, abdominal circumference, ALT, AST, γ-GTP, triglyceride, uric acid, fasting blood sugar levels, and incidence of hyperlipidemia. Groups C and D had higher ALT, HbA1c, cholinesterase, and triglyceride levels, FIB4 index, and the number of patients with diabetes mellitus (DM) than groups A and B; however, there was no difference between groups A and B. FL is a risk factor of DM and liver fibrosis in non-obese Japanese individuals; however, VFA only is not a risk factor of DM and liver fibrosis. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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Review

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20 pages, 1161 KiB  
Review
FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic
by Yoshio Sumida, Masashi Yoneda, Katsutoshi Tokushige, Miwa Kawanaka, Hideki Fujii, Masato Yoneda, Kento Imajo, Hirokazu Takahashi, Yuichiro Eguchi, Masafumi Ono, Yuichi Nozaki, Hideyuki Hyogo, Masahiro Koseki, Yuichi Yoshida, Takumi Kawaguchi, Yoshihiro Kamada, Takeshi Okanoue, Atsushi Nakajima and Japan Study Group of NAFLD (JSG-NAFLD)
Life 2021, 11(2), 143; https://doi.org/10.3390/life11020143 - 14 Feb 2021
Cited by 34 | Viewed by 10034
Abstract
The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of [...] Read more.
The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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16 pages, 891 KiB  
Review
Noninvasive Tests (NITs) for Hepatic Fibrosis in Fatty Liver Syndrome
by Ma Ai Thanda Han
Life 2020, 10(9), 198; https://doi.org/10.3390/life10090198 - 13 Sep 2020
Cited by 13 | Viewed by 8494
Abstract
Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease’s advancement to cirrhosis and liver-related complications, it is important to assess the severity of the [...] Read more.
Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease’s advancement to cirrhosis and liver-related complications, it is important to assess the severity of the disease, which is typically done via a liver biopsy. Due to the limitations and risks of liver biopsy, the role of noninvasive tests is essential and evolving to stratify the stage of the liver disease, predict the outcomes, and/or monitor the treatment response. This review is focused on noninvasive tests, including the use of serum-based biomarkers, ultrasound-based shear wave elastography, transient elastography, and magnetic resonance elastography in both clinical and research settings. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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