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

This study examined endogenous cannabinoid (ECB)-anandamide (AEA) and its cannabinoid receptors (CBR) in mice liver with the development of schistosoma japonicum. Mice were infected with schistosoma by means of pasting the cercaria onto their abdomens. Liver fibrosis was pathologically confirmed nine weeks after the infection. High performance liquid chromatography (HPLC) was employed to determine the concentration of AEA in the plasma of mice. Immunofluorescence was used to detect the expression of CBR1 and CBR2 in liver tissue. Morphological examination showed typical pathological changes, with worm tubercles of schistosoma deposited in the liver tissue, fibrosis around the worm tubercles and infiltration or soakage of inflammatory cells. Also, CBR1 and CBR2 were present in hepatocytes and hepatic sinusoids of the two groups, but they were obviously enhanced in the schistosoma-infected mice. However, the average optical density of CBR1 in the negative control and fibrosis group was 13.28+/-7.32 and 30.55+/-7.78, and CBR2 were 28.13+/-6.42 and 52.29+/-4.24 (P<0.05). The levels of AEA in the fibrosis group were significantly increased as compared with those of the control group. The concentrations of AEA were (0.37+/-0.07) and (5.67+/-1.34) ng/mL (P<0.05). It is concluded that the expression of endocannabinoids AEA and its cannabinoid receptor CBR were significantly increased in schistosoma-infected mice. Endogenous endocannabinoids may be involved in the development of schistosoma-induced liver fibrosis.
Arachidonic Acids/*metabolism ; Endocannabinoids/*metabolism ; Liver Cirrhosis/etiology ; Liver Cirrhosis/*metabolism ; Liver Cirrhosis/parasitology ; Polyunsaturated Alkamides/*metabolism ; Random Allocation ; Receptor, Cannabinoid, CB1/*metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Schistosomiasis japonica/*complications ; Schistosomiasis japonica/metabolism

The lymphatic system is part of the circulatory system and plays a key role in normal vascular function. Its failure plays a crucial role in the development and maintenance of various diseases including liver diseases. Lymphangiogenesis (the growth of lymphatic vessels) and changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. Therefore, how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases are largely unknown. This article summarizes: 1) the lymphatic vascular system; 2) its role in liver tumors, liver fibrosis/cirrhosis and portal hypertension; and 3) its role in ascites formation.
Ascites/*etiology ; Humans ; Hypertension, Portal/complications/pathology ; Liver Cirrhosis/complications/pathology ; Liver Diseases/complications/*pathology ; Liver Neoplasms/complications/pathology ; Lymphangiogenesis ; Lymphatic Vessels/metabolism/physiopathology

BACKGROUND/AIMS: Nonalcoholic steatohepatitis can develop from nonalcoholic fatty liver and progress to severe liver disease such as cirrhosis. The mechanism determining the progression from fatty liver to steatohepatitis is unknown. Iron is suspected to enhance hepatic damage associated with nonalcoholic fatty liver disease (NAFLD). The aims of this study were to evaluate the relationship of serum iron indices and hepatic iron deposition with hepatic fibrosis or inflammation, and to assess whether the increased hepatic iron deposition is an independent predictor of progression to liver injury. METHODS: The biochemical and histopathological data of thirty-nine patients with NAFLD were analyzed. Liver biopsy findings were graded according to the method described by Brunt, et al. Hepatic iron concentration was available in 29 of 39 patients. RESULTS: The mean hepatic iron concentration and hepatic iron indices were 1,349+/-1,188 microgram/g dry weight and 0.9+/-0.7 microgram/g/age. Serum ferritin and body mass indices were associated with hepatic inflammation (p=0.001, p=0.006) and fibrosis (p=0.005, p=0.013). Hepatic iron concentration and hepatic iron index were not associated with hepatic inflammation and fibrosis. Multivariate analysis did not identify serum ferritin or body mass index as an independent predictor of liver injury. CONCLUSIONS: Hepatic iron deposition shows no association with the degree of hepatic inflammation or fibrosis. Hepatic iron is not an independent predictor of hepatic injury in patients with NAFLD.
Adolescent ; Adult ; Fatty Liver/complications/*metabolism ; Female ; Ferritins/blood ; Humans ; Inflammation ; Iron/blood/*metabolism ; Liver/*metabolism/pathology ; Liver Cirrhosis/*etiology/metabolism/pathology ; Male ; Middle Aged

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.
Acute-On-Chronic Liver Failure/complications/mortality/*pathology ; Age Factors ; Cytokines/metabolism ; Hepatitis, Alcoholic/complications ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Sepsis/complications ; Severity of Illness Index ; Survival Rate

PURPOSE: Using FibroScan(R) to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer's recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). MATERIALS AND METHODS: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. RESULTS: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages > or =F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong's method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. CONCLUSION: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.
Adult ; Alanine Transaminase/metabolism ; Female ; Hepatitis B, Chronic/*complications/metabolism ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis/*diagnosis/etiology/metabolism ; Male ; Middle Aged ; Prospective Studies

Adult ; Cytokines ; metabolism ; Female ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; immunology ; metabolism ; pathology ; virology ; Liver Failure ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Th1 Cells ; metabolism

OBJECTIVETo study the clinical features of liver disease patients with abnormal glucose metabolism.

METHODSLiver functions and levels of FPG, PPG, FINS, PINS, FCP, and PCP in 91 chronic hepatitis B patients with abnormal glucose metabolism (62 had liver cirrhosis) were analyzed.

RESULTS(1) The incidence of hepatogenic impaired glucose tolerance (IGT) and of diabetes mellitus (DM) in hepatitis B patients with liver cirrhosis (20.53%; 24.11%) were higher than those without cirrhosis (3.82%; 1.64%; P<0.05, P<0.01). (2) There were no diabetic symptoms among any of the hepatogenic IGT and DM patients. 12 of 19 chronic hepatitis B patients with primary DM and 6 of 12 hepatitis B associated liver cirrhosis patients with primary DM had diabetic symptoms. (3) The levels of FPG and PPG in chronic hepatitis B patients with hepatogenic IGT and DM were lower than those in the patients with primary DM (P<0.05), but the levels of PINS and PCP in chronic hepatitis B patients with hepatogenic IGT and DM were higher than those in the patients with primary DM (P<0.05). (4) There were no differences in the levels of FPG and PPG between the hepatitis B associated liver cirrhosis patients with hepatogenic DM and those with primary DM (P<0.05). The levels of FINS, PINS, FCP, and PCP were higher in the hepatitis B associated liver cirrhosis patients with hepatogenic DM than those in the hepatitis B associated liver cirrhosis patients with primary DM (P<0.05). The levels of FPG and PPG in the hepatogenic DM patients were higher than those in the hepatogenic IGT patients (P<0.05), but their levels of FINS, PINS, FCP and PCP were lower than those in the hepatogenic IGT patients (P<0.05, P<0.01).

CONCLUSIONHepatogenic IGT and DM are always secondary in severe liver cirrhosis patients, who always showed no diabetic symptoms. The chronic hepatitis B patients with hepatogenic DM had increased insulin secretion, while the hepatitis B associated liver cirrhosis patients with hepatogenic DM had decreased insulin secretion.

Blood Glucose ; metabolism ; Diabetes Mellitus ; epidemiology ; etiology ; metabolism ; Female ; Glucose Intolerance ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; complications ; metabolism ; Male

Bone Density ; Bone and Bones ; metabolism ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; metabolism ; Male ; Tumor Necrosis Factor-alpha ; analysis

Animals ; Elasticity Imaging Techniques ; Extracellular Matrix ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; diagnosis ; drug therapy ; etiology ; Liver Diseases ; complications ; Mice ; Retrospective Studies