Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence,outcomes and implications of a change in name

Nonalcoholic fatty liver disease (NAFLD) affects about a third of the world’s adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a “positive” diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.     

Serum lipocalin-2 is a potential biomarker for the clinical diagnosis of nonalcoholic steatohepatitis

Background/AimsNonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression.MethodsA mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited.ResultsInflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis.ConclusionsLCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.     

非酒精性脂肪肝患者血清AFP水平及其应用价值

目的 检测非酒精性脂肪肝（NAFLD）患者血清AFP水平,并探讨其应用价值.方法 对97例患者进行评估,患者通过做腹部超声诊断确定为脂肪肝,并分成3个组.无脂肪肝患者作为对照组.所有患者和对照组进行体格检查、肝功能检测、稳态模型法评估胰岛素抵抗指数（HOMA-IR）检测.结果 体质指数、AST、ALT、血糖、HOMA-IR等在NAFLD患者中高于对照组.TG、总胆固醇、LDL-C、HDL-C水平在NAFLD中高于对照组.AFP水平在NAFLD中比对照组显著升高（5.43±2.65 IU/mL vs 2.33±0.99 IU/mL,P＜0.05）.三级NAFLD AFP水平显著高于一级NAFLD （6.69±2.36 IU/mLVS 3.56±1.60 IU/mL,P＜0.05）和二级NAFLD AFP水平（6.69±2.36 IU/mL VS 4.27±1.79 IU/mL,P＜0.05）.另外,二级NAFLD AFP水平显著高于一级NAFLD（P＜0.05）.ALT、AST与其无相关性.结论 NAFLD患者AFP水平高于非脂肪肝患者,AFP水平与脂肪病分级有关,NAFLD分级与血清AFP水平的相关性独立于其它因素.     

Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid

We report a case of hepatocellular carcinoma (HCC) arising in nonalcoholic steatohepatitis (NASH). The patient, a 64-year-old man, was incidentally found to have multiple tumors in the liver when admitted for pneumonia. He had been obese, had been receiving a standard dose of valproic acid since clipping surgery for subarachnoid hemorrhage 17 years previously, and had not consumed any alcohol since the surgery. Laboratory data revealed moderate hyperlipidemia and no evidence of diabetes mellitus, hepatitis B or C infection. The patient died of hepatic insufficiency, and an autopsy was performed. A tumor, a maximum of 13 cm in diameter, grossly occupied the entire left lobe and one third of the right lobe of the liver. Histologically, moderately differentiated HCC was found with foci of poorly differentiated HCC. The non-tumorous area showed NASH with moderate bridging fibrosis, without interface hepatitis, hemochromatosis, or copper accumulation. In this patient, obesity, hyperlipidemia, and long-term treatment with valproic acid could have all been associated with induction of NASH. The present case suggests that HCC could develop in non-cirrhotic NASH liver, and that chronic inflammation in itself could be an important risk factor in the development of HCC.     

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/Aims

The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.

Methods

One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.

Results

According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.

Conclusions

Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.     

Ultrasonographically detected hepatosteatosis independently predicts the presence and severity of coronary artery disease

BackgroundNonalcoholic fatty liver disease (NAFLD) has shown to be associated with coronary artery disease (CAD)ObjectivesThe aim of our study was to evaluate the association between the presence and severity of CAD and NAFLD.MethodsThe study group consisted of 153 patients who underwent coronary angiographies. Patients were categorized into CAD and non-CAD groups. CAD severity was determined by the number of CAD-involved arteries and the vessel score multiplied by Gensini score, the latter judging CAD severity. Fatty liver was diagnosed by abdominal ultrasonography (USG), with the patients being categorized by the degree of hepatosteatosis, as Grade 0, Grade 1, and Grade 2–3.ResultsAmong the whole study population, 47.1% of patients (n=72) were female and 52.9% of patients (n=81) were male. Forty-three patients had normal coronary arteries; 27 patients had non-critical CAD and side branch disease; and 83 patients had clinically significant CAD (stenosis>50%). The rate of CAD and Gensini score were significantly different between Grade 0, 1 and 2–3 hepatosteatosis groups (p<0.05). Patients with CAD had a significantly higher AST level than those without (p< 0.05).ConclusionsUltrasonographically detected hepatosteatosis independently predicts the presence and severity of CAD.     

中医防治非酒精性脂肪性肝病研究进展

非酒精性脂肪性肝病是以肝实质脂肪贮积以及细胞变性为特征,且无过量饮酒史的临床病理综合征,它与遗传易感和胰岛素抵抗有密切相关性。在中医古籍中,该病则属于“肝癖”、“肝著”、“痞满”等范畴。随着现代生活水平不断的提高,非酒精性脂肪性肝病的发病率迅速攀升,占据我国慢性肝病的主导地位之一,对人们的健康造成严重威胁。中医在诊治非酒精性脂肪性肝病的领域中,展现了独特的优势,对非酒精性脂肪性肝病进行分类和早期干预,充分体现了“不治已病治未病”及“救治于后不若摄生于先”的思想。     

Development and validation of a simple index system to predict nonalcoholic fatty liver disease

Background/Aims

Abdominal ultrasonography is useful for the detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). The aims of this study were to establish a predictive model for the selection of subjects for abdominal ultrasonography for the diagnosis of NAFLD and to assess validity of the model.

Methods

The subjects included 901 people who visited the health examination center of the Busan Medical Center. We conducted multiple logistic regression analyses of potential risk factors to identify independent risk factors for NAFLD, and developed an index system.

Results

Four independent risk factors were identified. The index system was developed by assigning 1 clinical scoring point to approximately 0.7 logistic regression coefficients to each factor as follows: alanine aminotransferase/aspartate aminotransferase ratio >1.5 (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.21-4.07; P=0.010), 1 point; γ-glutamyl transpeptidase >50 (OR, 2.15; 95% CI, 1.13-4.07; P=0.019), 1 point; triglyceride >150 mg/dL (OR, 1.92; 95% CI, 1.14-3.24; P=0.015), 1 point; 23 kg/m²≤BMI<25 kg/m² (OR, 3.68; 95% CI, 2.05-6.63; P<0.001), 2 points; and BMI 25 kg/m² (OR, 7.65; 95% CI, 4.29-13.62; P<0.001), 3 points. The area under the receiver operating characteristics curve was 0.797 (95% CI, 0.751-0.842), and when 3 points was used as a cut-off value, the sensitivity and specificity were 71.7% and 75.9%, respectively.

Conclusions

NAFLD can be predicted through the clinical application of the index system established herein. If abdominal ultrasonography is used for high-risk patients, NAFLD will be diagnosed and managed in its early stage.     

慢性乙型肝炎合并非酒精性脂肪性肝病 中医辨治的研究进展

慢性乙型肝炎是我国三大肝病之一,近年来随着人们生活习惯及饮食方式等改变,非酒精性脂肪性肝病患病率明显增高,两者并存于同一个体的现象较为普遍,病情更加复杂,治疗难度增大。中医药在促进肝脏脂肪代谢、提高抗病毒疗效、抗纤维化进展等方面展现了独特的优势。本文通过收集相关文献从中医学理、法、方药、非药物治疗等几个方面作为切入点,浅述慢性乙型肝炎合并非酒精性脂肪性肝病患者中医辨治的研究进展。     

Nonalcoholic Fatty Liver Disease Is Associated with the Presence and Morphology of Subclinical Coronary Atherosclerosis

Purpose

In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease.

Materials and Methods

We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques.

Results

Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis.

Conclusion

Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis.     

Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study

Background/Aims

Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome.

Methods

A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85).

Results

The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period.

Conclusions

Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.     

Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods

Background/AimsTo develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model.MethodsThis prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10–14 weeks and screened them for GDM at 24–28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks.ResultsAmong 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1–4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563–0.697 in settings 1–3 vs. 0.740–0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719–0.819 in setting 5, P=not significant between settings 4 and 5).ConclusionsWe developed an early prediction model for GDM using machine learning. The inclusion of NAFLD-associated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02276144","term_id":"NCT02276144"}}NCT02276144)     

Psychosocial Predictors of Work Ability in Morbidly Obese Patients: Results of a Cross-Sectional Study in the Context of Bariatric Surgery

BackgroundObesity is associated with a higher risk of work disability and premature early retirement.ObjectiveThe aim of this study was to examine psychosocial predictors for work ability prior to surgery.MethodsBased on a sample of 197 surgery-seeking obese patients (preoperative body mass index [BMI] above 35 kg/m²) from a German bariatric surgery unit, the present cross-sectional study examined based on standardized self-rating measures whether depressive symptoms, dysfunctional eating behaviors, relationship satisfaction, and life satisfaction have a predictive value for work ability.ResultsConsiderable impairment of work ability was found in 51.8% of morbidly obese participants (n = 102). Multiple regression analyses revealed that older age, greater depressive symptoms, and lower life satisfaction were significant predictors of preoperative work ability. BMI, gender, relationship satisfaction, and dysfunctional eating behaviors did not predict work ability.ConclusionsOur findings might indicate the use of further psychosocial measures following bariatric surgery to increase work ability.     

血清APN及CG水平对非酒精性脂肪肝肝纤维化患者的诊断价值

目的：研究脂联素（APN）与甘胆酸（CG）的水平对非酒精性脂肪肝肝纤维化（NAFLD）诊断。方法：采用ELISA检测NAFLD患者和正常对照组的血清APN水平及放免法检测CG水平,并以NEFLD和正常对照组作比较。结果：NAFLD组APN水平显著低于正常对照组（P〈0.05）,CG水平显著高于正常对照组（P〈0.05）,APN水平与CG水平呈显著负相关（P〈0.05）。结论：NAFLD患者血清APN水平降低,APN的表达在NAFLD患者肝纤维化进程中可能起重要作用。