Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Lipidoses ; metabolism ; pathology ; Non-alcoholic Fatty Liver Disease

Biopsy ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Non-alcoholic Fatty Liver Disease/pathology*

Fatty Liver ; pathology ; Gonadal Steroid Hormones ; Humans ; Non-alcoholic Fatty Liver Disease

Animals ; Endoplasmic Reticulum ; metabolism ; Fatty Liver ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Non-alcoholic Fatty Liver Disease

Fatty Liver ; metabolism ; pathology ; Humans ; Inflammation ; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/pathology* ; Liver/pathology* ; Macrophages/metabolism* ; Liver Cirrhosis/complications* ; Disease Progression

A study conducted 15-year ago showed that only 13.5% of chronic alcoholics developed alcohol-induced liver damage, which misled some people to believe a lack of relationship between the amount of alcohol and the occurrence of liver disease. However, it is true that a significant correlation exists between per capita consumption and the prevalence of cirrhosis. Alcoholic fatty liver is observed in most of chronic alcoholics even though the severity is not uniform. Abstinence remains the cornerstone of therapy for alcoholic liver disease (ALD). There is also consensus for the use of corticosteroids and pentoxifylline in severe alcoholic hepatitis maintaining good nutritional status to treat comorbidities in all forms of ALD, and liver transplantation in the end-stage ALD patients who can stop drinking for 6 months pre-transplantation period. Several clinical trials targeting tumor necrosis factor (TNF-alpha) and reducing oxidative stress have not been successful at this time. There is still a large field of alcohol research to explore in order to go farther in the area of pathophysiology. We need to understand a role of various cytokines and immune cells in the development of ALD to have more treatment tools to cope with ALD.
Alcohols/metabolism ; Cytochrome P-450 CYP2E1/metabolism ; Fatty Liver, Alcoholic/pathology/therapy ; Humans ; Liver Cirrhosis, Alcoholic/pathology/therapy ; Liver Diseases, Alcoholic/*etiology/pathology/therapy ; Oxidative Stress

Artificial intelligence (AI) refers to the use of computer programs to simulate and extend human intelligence, and has application prospects in the diagnosis and treatment of diseases. This review focuses on the research status of the screening and diagnosis of NAFLD and nonalcoholic steatohepatitis using artificial intelligence technology, electronic health record data, multi-omics prediction models, image recognition technology based on liver imaging and pathological biopsy, and new drugs research and development, with a view to provide new ideas for the diagnosis and treatment.
Artificial Intelligence ; Biopsy/methods* ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Neoplasms/pathology* ; Non-alcoholic Fatty Liver Disease/pathology*

OBJECTIVE: To investigate the relationship between serum 25(OH) vitamin D and liver fat content in nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 120 patients with NAFLD admitted in our hospital between June and August, 2017 were enrolled and divided into 4 groups with different serum 25 (OH) vitamin D levels: >75 nmol/L (group A, =25), 50-75 nmol/L (group B, =35), 25-50 nmol/L (group C, =32), and < 25 nmol/L (group D, =28). For all the patients, serum 25 (OH) vitamin D level was measured by ELISA, and liver fat content was determined using in-phase opposed-phase TWI sequences. The measurement data were compared among the 4 groups to assess the association between serum 25(OH) vitamin D level and liver fat content. RESULTS: The liver fat content appeared to be higher in group B (28.66±6.45%) and group C (38.74±11.47%) than in group A (22.79 ± 6.10%), but the difference was not statistically significant (>0.05); the liver fat content in group D (54.79 ± 5.28%) was significantly higher than that in the other 3 groups (>0.05). Liver fat content increased significantly as serum 25(OH) vitamin D level decreased, showing an inverse correlation between them in these patients ( < 0.05, =-0.125). CONCLUSIONS In patients with NAFLD, a decreased serum 25(OH) vitamin D level is associated with an increased liver fat content, suggesting the value of serum 25(OH) vitamin D as a predictor of NAFLD.
Humans ; Liver ; pathology ; Non-alcoholic Fatty Liver Disease ; blood ; pathology ; Vitamin D ; blood

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*