Steatosis Group Research Articles

Diagnostic significance of the newest biomarkers of steatosis progression in patients with stable coronary heart disease, combined with nonalcoholic fatty liver disease

The purpose was to determine the diagnostic value of selenoprotein P and M30 fragments of cytokeratin 18 in conjunction with proinflammatory cytokines for early diagnosis and progression of non-alcoholic fatty liver disease (NAFLD) in patients with stable coronary heart disease (CHD). Materials and methods. 140 patients with NAFLD and stable CHD of II-III functional classes were examined: 89 patients with non-alcoholic steatosis (Group I); 51 patients with non-alcoholic steatohepatitis (Group II). General-clinical examination, electrocardiography, coronary angiography, echocardiography, liver ultrasound, determination of cytokeratin 18 M30, selenoprotein P, TNF-alpha, interleukin-6, high-sensitivity C-reactive protein serum levels were performed to all patients. Results. The presence of liver steatosis of different degrees was established in all examined patients. However, the majority of the patients of Group I had steatosis of 1 and 2 degrees; in group 2 – steatosis of 3 degree prevailed. Selenoprotein P level in patients with steatosis of 1 degree was on 39.6 % higher compared with 0 degree; at 2 degree – it was by 2.8 times higher vs. its level in the control group and by 1.9 times vs. its level at steatosis of 1 degree (P < 0.05). Cytokeratin 18 M30 level at steatosis of 1 degree was by 1.8 times higher than its value in the control group; at 2 degree – it exceed this value by 2.3 times; at 3 degree – it reached its highest value (P < 0.05). TNF-alpha level at 1 degree of steatosis was by 2.5 times higher than its value in the control group; at 2 degree – it exceed this value by 3.7 times; at 3 degree – it was by 5.4; 2.2 and 1.5 times higher vs. its value at steatosis 0, 1 and 2 degrees (P < 0.05). Similar patterns were observed by IL-6 and hsCRP levels. Positive correlation relationships between serum selenoprotein P, cytokeratin 18 M30 and proinflammatory cytokines levels were revealed. Conclusion. Increasing of serum selenoprotein P and cytokeratin 18 M30 levels next to proinflammatory cytokines at liver steatosis of 1 degree indicates their independent diagnostic and prognostic value at the early stages of NAFLD development in patients with stable CHD.

Pathogenesis of non-alcoholic fatty liver disease mediated by YAP.

This study aimed to investigate the mechanism of the interaction between Yes-associated protein (YAP) and transforming growth factor-β (TGF-β)/Smad signaling pathways in the development of non-alcoholic fatty liver disease (NAFLD). Serum samples of monkeys with biopsy-proven NAFLD and healthy normal monkeys were used to measure fasting plasma glucose (FPG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG) and albumin (ALB) with the BECKMAN CX5 PRO. Hematoxylin-eosin staining (H&E) was used for pathologic analysis, Masson trichrome staining was used to assess for fibrosis staging, and Oil Red O staining was used to detect lipid droplet deposition. According to an NAFLD activity score of <4 points and >4 points, the samples were divided into groups: the steatosis group and fibrosing NASH group. Furthermore, monkeys with a fibrosis stage <2 were assigned to the mild fibrosis group, while monkeys with fibrosis stage ≥2 were assigned to the significant fibrosis group. Moreover, the fibrosis stage was subdivided as follows: stages 1a, 1c and 2-3. Immunohistochemistry and real-time quantitative PCR were used to quantify protein and gene expression, respectively. In the present study, 54 monkeys with NAFLD and 23 normal monkeys were recruited. Serum FPG and TG levels were higher in fibrosing NASH monkeys compared with simple steatosis and normal monkeys, and differences between simple steatosis and normal monkeys were not statistically significant (p>0.05). YAP increased in NAFLD, which mainly localized in the nuclei of hepatocytes, perivascular cells and bile duct cells; the accumulation of YAP correlated with the severity of hepatocyte injury. Compared with normal monkeys, the expression of TGF-β, α-smooth muscle actin (α-SMA), Drosophila mothers against decapentaplegic protein 3 (Smad3) and connective tissue growth factor (CTGF) in the liver of simple steatosis monkeys significantly increased (p<0.01). Compared with simple steatosis monkeys, the expression of TGF-β, α-SMA, Smad3 and CTGF in fibrosing NASH significantly increased (p<0.01). However, the expression of Drosophila mothers against decapentaplegic protein 7 (Smad7) in the liver of fibrosing NASH monkeys significantly decreased (p<0.01). With the severity of liver fibrosis, the expression of TGF-β, α-SMA, Smad3 and CTGF gradually increased, and the difference was statistically significant (p<0.01). However, there was no significant difference in the expression of Smad3 between fibrosis stage 1a and 1c. Compared with normal monkeys, the expression of Smad7 in the liver of monkeys with fibrosis significantly decreased (p<0.01), but was significantly higher at fibrosis stage 1c than at fibrosis stage 1a and 2. The YAP and TGF-β signaling pathways and the interaction between them promote the development and progression of NAFLD.

Association of total testosterone, free testosterone, bioavailable testosterone and sex hormone–binding globulin with hepatic steatosis and the ratio of aspartate aminotransferase to alanine aminotransferase

Several articles have shown the inverse association between total testosterone (TT) or sex hormone-binding globulin (SHBG) and hepatic steatosis. No articles report associations of TT, SHBG, free testosterone (FT), and bioavailable testosterone (BioT) with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratios. Therefore, we investigated the associations of TT, FT, BioT and SHBG with hepatic steatosis and AST/ALT ratios. A total of 218 men were enrolled. We diagnosed hepatic steatosis by ultrasound. TT and SHBG showed a reduced risk for hepatic steatosis when analyzed with or without adjusting for age, smoking, alcohol consumption and physical activity. Compared with the lowest quartile, the ORs for hepatic steatosis in the third and fourth quartiles (0.32 [95% CI: 0.14-0.75] and 0.27 [95% CI: 0.10-0.73], respectively) of SHBG were significantly lower after adjustments. The OR for hepatic steatosis in the fourth quartile of TT (0.41 [95% CI: 0.17-0.95]) was significantly lower than in the lowest quartile after adjustments. The mean AST/ALT ratios in men with hepatic steatosis were lower than those without hepatic steatosis (0.83 and 1.04, respectively), due to the elevated ALT levels in hepatic steatosis groups. Furthermore, TT and SHBG were positively associated with AST/ALT ratios with and without adjustments. In conclusion, higher TT and SHBG levels in men are associated with the reduced risk of hepatic steatosis and elevated AST/ALT ratios, independent of age, smoking, alcohol consumption and physical activity.

Assessment of alteration in liver 18F\u2013FDG uptake due to steatosis in lymphoma patients and its impact on the Deauville score

AimOur aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on 18F–FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders.MethodsOver a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n = 143), interim (n = 79) and end-of-treatment (EoT, n = 136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SULmax were recorded on the liver and the tumour target lesion. DS were then computed.ResultsPrevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p = 0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SULmax values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66 ± 0.36 versus 2.15 ± 0.27) and EoT (1.67 ± 0.29 versus 2.17 ± 0.30) PET. CT density was found to be an independent factor that correlated with liver SULmax, while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SULmax, all DS4 steatotic patients on interim (n = 1) and EoT (n = 2) PET moved to DS3.ConclusionsSteatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%.

Dynamic thiol-disulfide homeostasis is disturbed in patients with non-alcoholic fatty liver disease

AbstractBackground:Oxidative stress has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Plasma thiols are major defense mechanisms against oxidative stress and undergo oxidation to form disulfides under oxidative conditions. This study was conducted to investigate thiol-disulfide homeostasis in NAFLD patients.Methods:Thirty patients with biopsy proven non-alcoholic steatohepatitis (NASH), 40 patients with simple steatosis and 50 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentration were measured using the Erel and Neselioglu’s method.Results:The mean serum total thiol concentrations in the NASH, simple steatosis and control groups were 415±64 μmol/L, 447±38 μmol/L and 480±37 μmol/L, respectively (p&lt;0.001). The mean serum native thiol concentrations in the NASH, simple steatosis and control groups were 378±62 μmol/L, 416±41 μmol/L and 451±36 μmol/L, respectively (p&lt;0.001). The mean serum disulfide concentrations in the NASH, simple steatosis and control groups were 18.5±6.3 μmol/L, 15.5±4.8 μmol/L and 14.9±3.6 μmol/L, respectively (p=0.005). The native thiol/total thiol ratio was significantly lower and the disulfide/total thiol and disulfide/native thiol ratios were significantly higher in the NASH group than in the simple steatosis and control groups.Conclusions:Thiol-disulfide homeostasis is disturbed and shifted toward disulfide side in NAFLD and NASH patients.

Effect of transforming growth factor-β1 on HBV replication and antigen synthesis in HepG2.2.15 cells with steatosis

Objective: To investigate the effect of transforming growth factor-β1 (TGF-β1) on HBV replication and protein expression in HepG2.2.15 cells with steatosis, as well as the association of TGF-β1 with suppressor of cytokine signaling-3 (SOCS-3) mRNA and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA during the steatosis of HepG2.2.15 cells. Methods: The cells were divided into HepG2/HepG2.2.15 cell control groups (C1/C2 groups) and HepG2/HepG2.2.15 cell steatosis groups (F1/F2 groups). 5 ng/ml TGF-β1 was added to the two cell systems for intervention to establish TGF-β1 intervention groups (T1/T2 groups) and steatosis+TGF-β1 intervention groups (TF1/TF2 groups). A time-resolved fluorescence analyzer was used to measure HBsAg and HBeAg, and quantitative real-time PCR was used to measure HBV DNA, SOCS-3 mRNA, and SREBP-1 mRNA. A one-way analysis of variance and a factorial analysis were used for the statistical analysis of data. Results: TGF-β1 significantly reduced the level of HBeAg in C2 group (P = 0.034) and the levels of HBsAg (P < 0.001) and HBeAg (P = 0.004) in F2 group. There was an interaction between steatosis and TGF-β1 in inhibiting HBsAg. In addition, TGF-β1 significantly reduced the mRNA expression of SOCS-3 in C1, F1, C2, and F2 groups (P < 0.05) and significantly increased the mRNA expression of SREBP-1c in C1, F1, C2, and F2 groups (P < 0.05), suggesting that there was an interaction between steatosis and TGF-β1 in downregulating the mRNA expression of SOCS-3 and upregulating the mRNA expression of SREBP-1c. Conclusion: TGF-β1 does not affect HBV duplication in HepG2.2.15 cells and can inhibit the expression of HBsAg and HBeAg. TGF-β1 can downregulate the mRNA expression of SOCS-3 and upregulate the mRNA expression of SREBP-1c.

Value of Acoustic Radiation Force Impulse Imaging in the Diagnosis of Early Non-alcoholic Steatohepatitis.

Objective To evaluate the value of acoustic radiation force impulse(ARFI)imaging in the diagnosis of early non-alcoholic steatohepatitis(NASH).Methods Totally 32 SD rats were randomly divided into high-fat diet group(n=24)and normal-diet group(n=8)by using the random number table. At the end of the 4th,8th,12th,and 16th week,six rats from the high-diet group and two rats from the normal-diet group were selected blindly for weighting,blood biochemical test,conventional ultrasound,and ARFI imaing. HE staining was used for pathological observation. Results None of the 32 rats developed liver fibrosis. Based on the pathological results,these rats were divided into M1 [mild-to-moderate simple fatty liver(SS)],M2(severe SS),M3(severe SS with early NASH),and C groups(normal control). Early NASH was seen only in the severe hepatic steatosis groups,and its distribution had a significant difference(P=0.006). The diagnostic accuracy of conventional ultrasound based on histological results was 34.4%(11/32). The ARFI value of M3 group was significantly lower than that of M2 group [(1.16±0.04)m/s vs.(1.22±0.05)m/s;t=2.301,P=0.04),and the low-density lipoprotein of M3 group was significantly higher than M2 group [(1.53±0.07)mmol/L vs.(1.21±0.22)mmol/L;t=3.075,P=0.01),while other clinical indicators had no statistical difference between these two groups. Conclusions The development of early NASH is associated with the severity of hepatic steatosis. ARFI value can provide important information to identify early NASH in patients with severe hepatic steatosis.

Changes of suppressors of cytokine signaling-3 and sterol regulatory element binding proteins-1c pathway in steatosis HepG2/HepG2.2.15 cells

Objective To investigate the effects of HepG2 and HepG2.2.15 cells steatosis on the mRNA and protein expressions of suppressors of cytokine signaling-3(SOCS-3) and sterol regulatory element binding proteins (SREBP-1c). Methods The cell model of chronic hepatitis B (CHB) combined with nonalcoholic fatty liver disease (NAFLD) was successfully constructed using an oleic acid-induced HepG2 and HepG2.2.15 cells steatosis. Cells were divided into HepG2 cell control group (HepG2 cell control group), HepG2.2.15 cell control group (HepG2.2.15 cell control group), HepG2 cell steatosis group (HepG2 cell steatosis group) and HepG2.2.15 cell steatosis group (HepG2.2.15 cell steatosis group). The expression levels of SOCS-3 and SREBP-1c mRNA were detected by real-time quantitative polymerase chain reaction (PCR). Changes in protein expressions of SOCS-3 and SREBP-1c were measured by western blot. Results SOCS-3 mRNA expression level in HepG2.2.15 cell control group was significantly lower than that in HepG2 cell control group (P<0.01). The level in HepG2 cell steatosis group was also significantly lower than that in HepG2 cell control group (P<0.01). However, the level of SOCS-3 mRNA in HepG2.2.15 cell steatosis group was lower than HepG2.2.15 cell control group with no statistical significance (P=0.173). There was interaction between cells and steatosis (F=25.547, P<0.01). The expression of SREBP-1c mRNA in HepG2.2.15 cell control group was significantly lower than that in HepG2 cell control group (P<0.01), and was significantly higher in HepG2.2.15 cell steatosis group than that in HepG2.2.15 cell control group (P<0.01). There was no significant difference between HepG2 cell steatosis group and HepG2 cell control group (P=1.000). There was interaction between cells and steatosis (F=5.04, P<0.05). Western blot analysis showed that protein levels of SOCS-3 and SREBP-1c in steatosis cells at 48 h and 72 h were significantly higher than those in non-alcoholic steatosis cells. Conclusions Protein expressions of SOCS-3 and SREBP-1c are up-regulated in both steatosis groups. Factorial analysis shows that there is interaction between cells and steatosis. HBV gene could inhibit SOCS-3 mRNA expression and promote the expression of SREBP-1c mRNA in steatosis cells. Key words: Hepatitis B; Fatty liver; SOCS-3; SREBP-1c

Ex vivo study of acoustic radiation force impulse imaging elastography for evaluation of rat liver with steatosis

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in developed countries. Accurate, noninvasive tests for diagnosing NAFLD are urgently needed. The goals of this study were to evaluate the utility of acoustic radiation force impulse (ARFI) elastography for determining the severity grade of steatosis in rat livers, and to investigate the changes in various histologic and biochemical characteristics. Steatosis was induced in the livers of 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Liver mechanics were measured ex vivo using shear wave velocity (SWV) induced by acoustic radiation force. The measured mean values of liver SWV ranged from 1.33 to 3.85m/s for different grades of steatosis. The area under the receiver operative characteristic curve (⩾S1) was equal to 0.82 (95% CI=0.69, 0.96) between the steatosis group and the normal group, and the optimal cutoff value was 2.59 with sensitivity of 88% and specificity of 76%. However, there are no significant differences in SWV measurements between the steatosis grades. SWV values did not correlate with the early grade of inflammation. In conclusion, ARFI elastography is a promising method for differentiating normal rat liver from rat liver with steatosis, but it cannot reliably predict the grade of steatosis in rat livers. The early grade of inflammation activity did not significantly affect the SWV measurements.

Role of endoscopic ultrasound in the diagnosis of pancreatic intraductal papillary mucinous neoplasms

Type 2 diabetes mellitus, obesity and hepatic steatosis showed a strong correlation with metabolic syndrome. However, data on the influence of pancreatic steatosis on metabolic syndrome are lacking.Our aim is to perform the prevalence of pancreatic steatosis in adults and its association with metabolic syndrome in a Chinese population.This was a cross-sectional study, randomly selected. A total of 1190 health examination subjects were recruited. Pancreatic steatosis or hepatic steatosis was diagnosed via trans-abdominal sonography. The clinical and metabolic parameters were compared between the two groups, and their associations with pancreatic steatosis were examined.The prevalence of pancreatic steatosis was 30.7%. The presence of pancreatic steatosis was significantly increased by age, gender, central obesity, hepatic steatosis, hypertriglyceridemia and hyperglycemia. In the logistic regression analysis, age (P < 0.05), central obesity (P < 0.01), diabetes (P < 0.05), hypertriglyceridemia (P < 0.05) and hepatic steatosis (P < 0.01) were independently associated with pancreatic steatosis. The number of the parameters of the metabolic syndrome in pancreatic steatosis group was more than that in non-pancreatic steatosis group [(2.5 ± 1.1) vs (1.4 ± 1.2)] (P < 0.01).The pancreatic steatosis is strongly associated with the parameters of metabolic syndrome, such as central obesity, diabetes, and hepatic steatosis.

Diagnostic accuracy of hepatorenal index in the detection and grading of hepatic steatosis.

The objectives of our study were to assess the accuracy of hepatorenal index (HRI) in detection and grading of hepatic steatosis and to evaluate various factors that can affect the HRI measurement. Forty-five patients, who had undergone an abdominal sonographic examination within 30 days of liver biopsy, were enrolled. The HRI was calculated as the ratio of the mean brightness levels of the liver and renal parenchymas. The effect of the measurement technique on the HRI was evaluated by using various sizes, depths, and locations of the regions of interest (ROIs) in the liver. The measurements were obtained by two observers. The HRI was compared with the subjective grading of steatosis. The optimal HRI cutoff to detect steatosis was 2.01, yielding a sensitivity of 62.5% and specificity of 95.2%. Subjective grading had a sensitivity of 87.5% and specificity of 62.5%. HRIs of the hepatic steatosis group were statistically different from the no-steatosis group (p < 0.05). However, there was no statistically significant difference between mild steatosis and no-steatosis groups (p value = 0.72). There was a strong correlation between different HRIs based on variable placements of ROIs, except when the ROIs were positioned randomly. Interclass correlation coefficient for measurements performed by two observers was 0.74 (confidence interval: 0.58-0.86). The HRI is an effective tool for detecting hepatic steatosis. It provides similar accuracy for different methods of ROI placement (except for random placement) and has good interobserver agreement. It, however, is unable to effectively differentiate between absent and mild steatosis. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:580-586, 2016.

Fluoride Intensifies Hypercaloric Diet-Induced ER Oxidative Stress and Alters Lipid Metabolism.

The role of fluoride (F) in oxidative stress is well reported, but its effects on the lipid metabolism has not been completely exploredBackgroundHere, we evaluated the relationship of diet and F-induced oxidative stress to lipid metabolism in the liver of rats eating normocaloric or hypercaloric diets for two time periods (20 or 60 days).MethodsSeventy-two 21-day-old Wistar rats were divided into 2 groups (n = 36) based on the type of diet they were eating; each of these groups was then further divided into another two groups (n = 18) based on the time periods of either 20 or 60 days, for a total of four groups. Each of these was divided into 3 subgroups (n = 6 animals/subgroup), dependent on the dose of F administered in the drinking water (0 mg/L(control), 15 mg/L or 50 mg/L). After the experimental period, blood samples and the liver were collected. Plasma samples were analyzed for HDL, cholesterol and triglycerides. Western blots were performed to probe for GRP78, Erp29, SOD2, Apo-E and SREBP in hepatic tissues.ResultsAs expected,the expression of target proteins involved in oxidative stress increased in the F-treated groups, especially in liver tissue obtained from animals eating a hypercaloric diet. Most changes in the lipid levels and pathological conditions were seen earlier in the time period, at day 20. The morphometric analyses showed a reduction in steatosis in groups on ahypercaloric diet and treated with 50 mg F/L compared to the control, while no changes were obtained in normocaloric-fed rats. Accordingly, plasma TG was reduced in the F-treated group. The reduced expression of Apo-E in a time- and diet-dependent pattern may account for the particular decrease in steatosis in hypercaloric-fed F-treated rats.ConclusionsThese results suggest that F changes liver lipid homeostasis, possibly because of the induction of oxidative stress, which seems to be higher in animals fed hypercaloric diets.

Follicle‐stimulating hormone is associated with non‐alcoholic fatty liver disease in Chinese women over 55 years old

Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability. Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55-89 years were selected. The degrees of fatty liver were categorized into mild and moderate-severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence. A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate-severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors (all P < 0.05). After adjusting for age, estradiol, and total testosterone, increased quartiles of FSH were associated with significantly decreased odds ratios of mild and moderate-severe groups (both P for trends <0.05). After further adjustment for waist circumference and HOMA-IR, FSH was no longer associated with mild hepatic steatosis. The association of FSH with moderate-severe hepatic steatosis was attenuated by waist circumference and HOMA-IR but persisted in the fully adjusted model (P for trend <0.01). Follicle-stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate-severe hepatic steatosis with FSH.

The Risk of Cardiovascular Disease, Diabetes, Liver-Related Outcomes, and Death Over 10 Years in HIV/HCV-Coinfected Patients With and Without Steatosis.

Coinfection with HIV/HCV is associated with more severe liver disease, including increased frequency of steatosis and significant fibrosis, compared to patients mono-infected with HCV or HIV. We sought to explore the impact of steatosis on cardiovascular disease (CVD), liver-related outcomes, and survival. An IRB-approved, single-center retrospective cohort study was undertaken to analyze 10-year clinical outcomes in HIV/HCV-coinfected patients. Liver biopsy was performed at study entry for the evaluation of HCV disease; a study pathologist graded samples for fibrosis and steatosis. Clinical outcomes, including cardiac events, liver function with FIB-4, AST to Platelet Ratio Index, and survival were assessed over 10 years. At cohort entry N = 105, mean age 45 ± 7 years, 70% male, and 56% had steatosis present on biopsy. During the 10-year follow-up, no association was found between incident CVD, changes in noninvasive liver fibrosis measures, or survival in the steatosis group compared to nonsteatosis group. However, nonsignificant trends were noted. Overall, mortality for this coinfected population was 25% over 10 years, with liver disease as the most common cause of death. Given the prevalence of steatosis in approximately half of coinfected patients, larger studies are warranted to determine if steatosis is associated with cardiac disease, diabetes, or liver disease progression in this population. Furthermore, 10-year mortality for this population was very high, underscoring the importance of HCV treatment and need for a better understanding of other variables responsible for decreased survival in this population.

Steatosis after liver transplantation: Is it really benign?

Steatosis after liver transplantation: Is it really benign?

The correlation between pancreatic steatosis and metabolic syndrome in a Chinese population

BackgroundType 2 diabetes mellitus, obesity and hepatic steatosis showed a strong correlation with metabolic syndrome. However, data on the influence of pancreatic steatosis on metabolic syndrome are lacking. ObjectiveOur aim is to perform the prevalence of pancreatic steatosis in adults and its association with metabolic syndrome in a Chinese population. MethodsThis was a cross-sectional study, randomly selected. A total of 1190 health examination subjects were recruited. Pancreatic steatosis or hepatic steatosis was diagnosed via trans-abdominal sonography. The clinical and metabolic parameters were compared between the two groups, and their associations with pancreatic steatosis were examined. ResultsThe prevalence of pancreatic steatosis was 30.7%. The presence of pancreatic steatosis was significantly increased by age, gender, central obesity, hepatic steatosis, hypertriglyceridemia and hyperglycemia. In the logistic regression analysis, age (P < 0.05), central obesity (P < 0.01), diabetes (P < 0.05), hypertriglyceridemia (P < 0.05) and hepatic steatosis (P < 0.01) were independently associated with pancreatic steatosis. The number of the parameters of the metabolic syndrome in pancreatic steatosis group was more than that in non-pancreatic steatosis group [(2.5 ± 1.1) vs (1.4 ± 1.2)] (P < 0.01). ConclusionThe pancreatic steatosis is strongly associated with the parameters of metabolic syndrome, such as central obesity, diabetes, and hepatic steatosis.

The correlation between fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B

Objective To investigate the correlation between non-alcoholic fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B (CHB). Methods Clinical and laboratory data from patients with CHB who received liver biopsy from 2009 to 2015 were collected. Patients were divided into steatosis and non-steatosis groups based on the presence of steatosis in liver biopsies. Propensity score matching (PSM) was conducted to adjust the confounding bias including age, sex, body mass index (BMI), total cholesterol (TC) and triglyceride (TG). Correlation of liver fatty and viral parameters was compared between steatosis and non-steatosis groups. Student t test, χ2 test, rank sum test and Pearson correlation test were employed to analyze the data. Results A total of 874 patients with a mean age of (37.0±10.1) years were enrolled in the study, with 690 males and 184 females, and 270 (30.9%) patients were diagnosed with steatosis by liver biopsy. Age, gender, BMI, TC and TG were significantly different between the two groups before PSM (all P 0.05). Serum hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) level, proportion of hepatitis B e antigen (HBeAg) positivity, HBsAg and hepatitis B core antigen (HBcAg) immunohistological staining in liver tissue were not significantly different between steatosis and non-steatosis groups after PSM (all P>0.05). Patients in steatosis group were stratified into two groups according to the degree of steatosis confirmed by liver biopsies: mild steatosis group (F1) and medium to severe steatosis group (F2-F4). The serum alanine aminotransferase (ALT), HBV DNA, HBsAg level, proportion of HBeAg positivity, immunohistological HBsAg and HBcAg staining in liver tissue between those two groups showed no differences (all P>0.05). The mean rank of liver inflammation and fibrosis in F1 group were 129.9 and 128.2, respectively, which were both significantly higher than those in F2-F4 group (105.9 and 108.5, respectively; both P<0.05). Steatosis was negatively correlated with either inflammatory grade (r=-0.183, P=0.005) or fibrosis stage (r=-0.150, P =0.020). Conclusions There is no correlation between serum viral factors and hepatic steatosis. Hepatic steatosis is not associated with the expressions of HBsAg and HBcAg in liver tissue. The severity of steatosis is negatively correlated with both liver inflammation and fibrosis. Key words: Hepatitis B, chronic; Fatty liver; Liver biopsy; Propensity score matching

Interactions of a PPARGC1A Variant and a PNPLA3 Variant Affect Nonalcoholic Steatohepatitis in Severely Obese Taiwanese Patients.

The patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant is associated with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, the role of genetic variations of the peroxisome proliferator-activated receptor gamma coactivator-1-alpha gene (PPARGC1A) and glucokinase regulatory (GCKR) gene on NASH in obese patients remains unclear. We studied the effects and interaction of these genetic polymorphisms on NASH in severely obese Taiwanese patients.The genotypes of PPARGC1A rs8192678, PNPLA3 rs738409, and GCKR rs780094 were determined in 177 severely obese patients who underwent bariatric surgery. NASH was evaluated by liver histopathology.Of 177 patients, 29 (16.4%), 57 (33.2%), and 91 (51.4%) were in the non-NAFLD, steatosis, and NASH groups, respectively. We found that the PPARGC1A and PNPLA3 variants, but not the GCKR variant, were associated with NASH. The PPARGC1A rs8192678 GA/AA genotype was associated with higher steatosis grade and presence of ballooning degeneration. The PNPLA3 rs738409 GG genotype was associated with higher severity in all histologic features except for fibrosis. In multivariate analysis, both the PPARGC1A rs8192678 GA/AA genotype (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.08–4.98; P = 0.031) and the PNPLA3 rs738409 GG genotype (OR 4.05; 95% CI 1.24–13.23; P = 0.021), and also body mass index were independent risk factors for NASH. Further, there was an additive effect of the PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype on the presence of NASH (OR 6.83; 95% CI 1.61–29.01; P = 0.009).The PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype had an additive effect on NASH in severely obese Taiwanese patients.

Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors.

Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.

Intrahepatic Fat Content and Markers of Hepatic Fibrosis in Obese Children.

Aim. We evaluated both direct and indirect hepatic fibrosis markers in obese children and their relationship with intrahepatic fat (IHF) content. We also aimed to investigate the possible roles of IHF and fibrosis markers in metabolic syndrome (MS). Methods. 189 obese children were divided into simple obese (SOB), simple steatosis (SS), and nonalcoholic steatohepatitis (NASH) groups according to their IHF and blood alanine transaminase (ALT) levels. They were also scored for the MS components. IHF was assessed as a continuous variable by proton magnetic resonance spectroscopy (1H-MRS). In addition, 30 nonobese children were enrolled as controls and their direct hepatic fibrosis markers and IHF were assessed. Results. Age was related to IHF, NFS, and FIB-4. Both NFS and APRI were related to IHF more significantly than the direct markers. In the estimation of liver function impairment, indirect markers had greater AUROC than direct markers. In MS, IHF and all the fibrosis markers showed similar AUROC. Conclusions. Both direct and indirect markers played a valuable role in evaluating MS. Indirect markers were more effective in distinguishing fatty hepatitis. Age is an important factor underlying hepatic steatosis and fibrosis even in children.