Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). METHODS: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. RESULTS: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CONCLUSION: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients.

Clinical and virological characteristics of chronic hepatitis B patients with hepatic steatosis.

OBJECTIVE: This study aimed to explore clinical and virological characteristics of chronic hepatitis B (CHB) patients with hepatic steatosis in order to provide a theoretical basis for the prevention and control of hepatic steatosis. METHODS: A total of 360 CHB inpatients were recruited from Affiliated Dongnan Hospital of Xiamen University and divided into hepatic steatosis group and non-hepatic steatosis group. The body mass index (BMI), waist-to-hip ratio (WHR), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), hepatitis B e antigen (HBeAg), hepatitis B virus DNA (HBV DNA) and hepatic histological changes were detected and compared between the two groups. The association of these factors with hepatic steatosis was evaluated in CHB patients. RESULTS: BMI, FPG, TG, TC, GGT, AST and HBV DNA showed statistically significant differences between two groups (P<0.01). The patients with hepatic steatosis had markedly higher BMI, FBG, TG and TC than those without steatosis did. No significant differences were found in ALT and HBeAg between two groups (P>0.05). In male patients, there was marked difference in the WHR between two groups (P < 0.01), which was not found in female patients (P > 0.05). The severity of hepatic steatosis increased in patients with hepatic steatosis, compared to those without steatosis (P < 0.01), but the severities of inflammation and fibrosis in the non-hepatic steatosis group were dramatically higher than those in the hepatic steatosis group (P < 0.01). CONCLUSIONS: BMI, WHR, FBG, TG and TC appeared to be influencing factors of CHB combined with hepatic steatosis. Hepatic steatosis in CHB patients was closely related to changes in anthropometric indices and metabolic factors but not HBV. It is necessary to improve these factors to effectively prevent hepatic steatosis in CHB patients.

[Risk factors analysis of nonalcoholic fatty liver disease in Chinese men].

OBJECTIVE: To explore risk factors of nonalcoholic fatty liver disease (NAFLD) in men in order to provide a theoretical basis for developing more effective NAFLD prevention and control strategies. METHODS: One-hundred-and-two male patients (37.3+/-11.4 years old) hospitalized with NAFLD at the Dongnan Affiliated Hospital of Xiamen University between January 2009 and December 2010 were enrolled in the study, along with 23 age-matched healthy men (34.4+/-16.7 years old) to serve as the control group. The correlation(s) of body mass index (BMI; overweight defined as more than or equal to 22.717 kg/m2), waist circumference (WC), waist-to-hip ratio (WHR; central obesity defined as more than or equal to 0.866), fasting plasma glucose (FPG), triglyceride (TG), and total cholesterol (TC) with NAFLD was analyzed by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to select proper thresholds for classification. RESULTS: BMI, WC, WHR, FPG, TG, and TC were significantly different between the cases and controls (P less than 0.01). BMI, WC, WHR, TG and TC were identified as risk factors of NAFLD in these male cases (P less than 0.01). Relative to WC, TG and TC, both BMI and WHR had significant predictive value for NAFLD (odds ratio (OR) = 10.819 and 10.588, respectively). In addition, BMI had the highest diagnostic value for the prediction of NAFLD (area under the curve (AUC) = 0.931) followed by WHR (AUC = 0.879). CONCLUSION: BMI, WC, WHR, TG, and TC are risk factors of NAFLD in Chinese men. BMI and WHR are effective anthroposomatology indices of NAFLD and may be useful factors on which to base future prevention and early diagnosis strategies for NAFLD in males.

PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has now become the leading cause of chronic liver disease with its growing incidence worldwide. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C > G reflects one of the critical genetic factors that confers high-risk to NAFLD. However, the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain. Here, the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409 (PNPLA3 148M variant) are sensitive to therapies of lifestyle modification, dipeptidyl peptidase-4 inhibitors, and bariatric surgery. They exhibit much significant reduction of liver fat content, in concurrence with weigh loss and abolished insulin resistance, as compared to those of C-allele carriers. In contrast, patients bearing PNPLA3 rs738409 C-allele (PNPLA3 148I variant), instead of G-allele, demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention. Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409 related diversities in therapeutic efficacy. Therefore, PNPLA3 rs738409 underlies the response to a variety of treatments, which warrants a personalized, precise medicine in NAFLD on the basis of genotype stratification.

circRNA_0046366 inhibits hepatocellular steatosis by normalization of PPAR signaling.

AIM: To investigate micro (mi)R-34a-antagonizing circular (circ)RNA that underlies hepatocellular steatosis. METHODS: The effect of circRNA on miR-34a was recognized by the miRNA response element (MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in HepG2-based hepatocellular steatosis induced by free fatty acids (FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of miR-34a activity, peroxisome proliferator-activated receptor (PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the miR-34a/PPARα regulatory system. Both triglyceride (TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34a-dependent hepatosteatogenesis. RESULTS: Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of miR-34a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circRNA_0046366 up-regulation abolished the miR-34a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TG-specific lipolytic genes [carnitine palmitoyltransferase 1A (CPT1A) and solute-carrier family 27A (SLC27A)] among these showed significant increase in their expression levels. The circRNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis. CONCLUSION: Dysregulation of circRNA_0046366/miR-34a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circRNA_0046366 serves as a potential target for the treatment of hepatic steatosis.

circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis.

Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs). PPARα restoration led to the transcriptional activation of genes associated with lipid metabolism, including carnitine palmitoyltransferase 2 (CPT2) and acyl-CoA binding domain containing 3 (ACBD3), and then resulted in the steatosis resolution. Hepatotoxicity of steatosis-related lipid peroxidation, being characterized by mitochondrial dysfunction, growth arrest, and apoptosis, is resultantly prevented after the circRNA_0046367 administration. These findings indicate a circRNA_0046367/miR-34a/PPARα regulatory system underlying hepatic steatosis. Normalized expression of circRNA_0046367 may ameliorate the lipoxidative stress on the basis of steatosis attenuation. circRNA_0046367, therefore, is suggested to be potential approach to the therapy of lipid peroxidative damage.

Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients.

AIM: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis. METHODS: This was a multi-center prospective cohort study. Consecutive patients (aged ≥ 18 years) who had undergone percutaneous liver biopsy and CAP measurement were recruited from three Chinese liver centers. Steatosis was categorized as S0: < 5%; S1: 5%-33%; S2: 34%-66%; or S3: ≥ 67%, according to the nonalcoholic fatty liver disease (NAFLD) activity score. The FibroScan(®) 502 equipped with the M probe (Echosens, Paris, France) was used to capture both CAP and liver stiffness measurement values simultaneously. Receiver operating characteristic curves were plotted, and the areas under the curves were calculated to determine the diagnostic efficacy. The accuracy of the CAP values at the optimal thresholds was defined by maximizing the sum of sensitivity and specificity (maximum Youden index). RESULTS: A total of 152 patients were recruited, including 52 (34.2%) patients with NAFLD and 100 (65.8%) with chronic hepatitis B (CHB) virus infection. After adjustment, the steatosis grade (OR = 37.12; 95%CI: 21.63-52.60, P < 0.001) and body mass index (BMI, OR = 6.20; 95%CI: 2.92-9.48, P < 0.001) were found independently associated with CAP by multivariate linear regression analysis. CAP was not influenced by inflammation, fibrosis or aetiology. The median CAP values and interquartile ranges among patients with S0, S1, S2 and S3 steatosis were 211 (181-240) dB/m, 270 (253-305) dB/m, 330 (302-360) dB/m, and 346 (313-363) dB/m, respectively. The cut-offs for the CAP values in all patients with steatosis ≥ 5%, ≥ 34% and ≥ 67% were 253 dB/m, 285 dB/m and 310 dB/m, respectively. The areas under the curves were 0.92, 0.92 and 0.88 for steatosis ≥ 5%, ≥ 34% and ≥ 67%, respectively. No significant differences were found in the CAP values between the NAFLD group and the CHB group in each steatosis grade. CONCLUSION: CAP appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis, but is limited by BMI.

Role of Body Mass Index, Waist-to-Height and Waist-to-Hip Ratio in Prediction of Nonalcoholic Fatty Liver Disease.

Objective. To investigate the anthropometric indicators that can effectively predict the nonalcoholic fatty liver disease (NAFLD). Methods. The height, body weight, waist and hip circumference were measured, and body mass index (BMI), waist-to-height (WHtR) and waist-to-hip ratio (WHR) were calculated. M-H chi square test, logistic regression analysis, and receiver-operating characteristic (ROC) curve were employed for the analysis of risk factors. Patients or Materials. 490 patients were recruited, of whom 250 were diagnosed as NAFLD and 240 as non-NAFLD (control group). Results. Compared with the control group, the BMI, WHR, and WHtR were significantly higher in patients with NAFLD. Logistic regression analysis showed that BMI and WHR were effective prognostic factors of NAFLD. In addition, WHR plays a more important role in prediction of NAFLD by the area under curve. Conclusion. WHR is closely related to the occurrence of NAFLD. We assume that WHR is beneficial for the diagnosis NAFLD.

[Relationship between mannose-binding protein gene polymorphisms and disease progression and HBV DNA in patients with chronic HBV infection].

OBJECTIVE: To determine the influences of Mannose binding protein (MBP) gene polymorphisms on HBV DNA loads and on the progression of liver disease in patients with chronic HBV infection. METHOD: The Codons on 54 MBP gene polymorphisms and HBV DNA loads in a cohort of 395 patients with chronic HBV infection, including 244 with chronic hepatitis B (CHB), 151 with liver cirrhosis (LC) and 88 normal controls were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and fluorescent quantitative PCR (FQ-PCR). RESULT: The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC in CHB group showed no significant differences comparing to the normal control group (P > 0.05). The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC on CHB group (severe), compensation phase of LC group and decompensation phase of LC group were higher than those in the normal control group (P < 0.05), the genetic polymorphism of decompensation of LC was 36.5%, highest of all. The MBP genotype frequencies of GGC/GAC and alleles genetic frequencies of GAC of patients with chronic HBV infection were not changed with the differences of HBV-DNA loads. CONCLUSION: The codes on 54 MBP gene polymorphisms is not closely related to HBV DNA loads, but was associated with the progression of hepatitis B infection.