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PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n=52) or without hepatic steatosis (CHB group, n=47) and non-CHB subjects with (HS group, n=37) or without hepatic steatosis (normal group, n=45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027–3.105; P=0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P=0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD)., Methods: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA., Results: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05)., Conclusion: Four linked SNPs of PNPLA3 (rs738409, rs3747206, rs4823173, and rs2072906) are correlated with susceptibility to NAFLD, NASH, liver fibrosis, and HBV dynamics in CHB 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.

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.

Objective: To study changes of glycolipid metabolism and adipocyte function in an catch-up growth intrauterine growth retardation (IUGR) rat model., Methods: IUGR rat model was established by maternal nutrition restriction during pregnancy. Newborn IUGR pups were used as IUGR group, and normal newborn pups were used as control group (appropriate for gestational age, AGA group). At age of 12 weeks, plasma samples were collected for the test of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), adiponectin and acylation stimulating protein (ASP). Oral glucose tolerance test (OGTT) was performed for the test of glucose and insulin levels, and insulin resistance index (IRI) was calculated. Expression of glucose transfer 4 (GLUT-4) in adipocytes was examined by confocal microscopy., Results: Body weight and BMI in the IUGR group were significantly higher than in the AGA group by 12 weeks (P<0.01), and plasma TC, TG and LDL-C levels in the IUGR group were higher than in the AGA group, but HDL-C was lower (P<0.05). In the OGTT test, blood glucose level and IRI score in the IUGR group were higher than in the AGA group (P<0.05). Compared with the AGA group, the IUGR group had a higher ASP level (P<0.05) and a lower adiponection level (P<0.05). GLUT4 expression in the adipocytes was significantly lower in the IUGR group than in the AGA group (P<0.05)., Conclusions: Catch-up growth may be obviously noted in IUGR rats after birth. Both hyperlipidaemia and insulin resistance occur at age of 12 weeks. Dysfunction of adipocytes decreased expression of GLUT-4 may be risk factors for insulin resistance in IUGR rats.

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.

Objective: To investigate the expression of RUNX3 mRNA and protein in hepatic cell carcinoma (HCC) and surrounding normal tissue, to analyze the relationship between RUNX3 expression and clinical pathological parameters., Methods: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to detect the expression of RUNX3 mRNA and protein in HCC and surrounding normal tissue respectively, and their relationship with clinical pathological parameters were analyzed., Results: The relative expression value of RUNX3 mRNA found in 51 cases HCC was 0.4509 +/- 0.0963, and that did in 51 cases surrounding normal tissue was 0.9147 +/- 0.0222. The difference of RUNX3 mRNA expression between two kinds of samples was statistically significant (t = 33.6087, P < 0.001). The positives rate of RUNX3 protein expression found in 51 cases HCC tissue was 49.02% (25/51) and that did in 51 cases surrounding normal tissue was 82.35% (42/51). The difference of RUNX3 protein expression between two kinds of samples was statistically significant (chi2 = 12.5706, P < 0.005). The difference of RUNX3 mRNA and protein expression in some clinical pathological parameters involving differentiation degree, invasion, cancer thrombus and diversion in liver were statistically significant (P < 0.05). However that were not in another clinical pathological parameters involving gender, cancer diameter, cancer location as well as hemorrhage and necrosis of cancer, histotype (P > 0.05)., Conclusion: The expression of RUNX3 mRNA and protein in HCC were significantly lower than that in surrounding normal tissue. The lower expression of runx3 protein in the HCC probably plays an important role in the tumorigenesis and development of HCC. The RUNX3 gene may be an anti-oncogene of HCC.

Objective: This study examined the effects of PI3K inhibitor LY294002 on the differentiation of mouse preadipocytes and the expression of CCAAT enhancer binding protein α (C/EBPα) and peroxisome proliferation activated receptor γ (PPARγ), in order to study the possible roles of insulin receptor substrate (IRSs)/PI3K signal pathway in the differentiation of preadipocytes., Methods: The mouse 3T3-L1 cells were cultured normally and divided into experimental and control groups. 3T3-L1 cells in the experimental group were treated with PI3K inhibitor LY294002 (25 μmol/L) and those in the control group were treated with DMSO culture medium. 3-isobutyl-1-methylxanthine (IBMX) (0.5 mmol/L), dexamethasone (10-6 mol/L) and insulin (5 μg/mL) were used to induce the differentiation of 3T3-L1 preadipocytes in both groups. Before culture, and 2, 4 and 8 days after culture, the cells were collected to detect the expression of C/EBPα and PPARγ by real-time PCR and Western blot assays. The lipid droplets of 3T3-L1 preadipocytes were observed by oil-red O staining., Results: PI3K inhibitor LY294002 did not affect the expression of C/EBPα and PPARγ in un-induced 3T3-L1 preadipocytes (P>0.05), but decreased the expression of C/EBPα and PPARγ during the in vitro induced differentiation of 3T3-L1 preadipocytes compared with the control group (P<0.05 or 0.01). The lipid droplets count was greatly reduced by LY294002., Conclusions: PI3K inhibitor LY294002 can inhibit the differentiation of mouse 3T3-LI preadipocytes and the expression of C/EBPα and PPARγ in the differentiation of 3T3-LI preadipoeytes, suggesting that IRSs/PI3K signal pathway may play an important role in the differentiation of 3T3-L1 preadipocytes by regulating the expression of C/EBPα and PPARγ.

Objective: To investigate the expression of RUNX3 protein in hepatic cell carcinoma (HCC) and its relationship with the clinicopathological factors of HCC., Methods: Immunohistochemistry was performed to detect the expression of RUNX3 protein in HCC and the surrounding normal tissues, and the relation of RUNX3 with the clinicopathological factors of HCC was analyzed., Results: The positivity rate of RUNX3 protein expression was 49.02% (25/51) in HCC tissues, significantly lower than that in the surrounding normal tissues [82.35% (42/51), Χ(2)=12.5706, P<0.01). RUNX3 protein expression varied significantly with such pathological factors as the differentiation degree, cancer-associated thrombosis in the portal vein and intrahepatic metastasis (P<0.05), but not with tumor diameter, location, tumoral hemorrhage, necrosis or histotypes of the tumor (P>0.05)., Conclusion: RUNX3 protein expression is lowered in HCC as compared with that in the surrounding normal tissue, suggesting an important role of RUNX3 in the tumorigenesis and development of HCC and the possible identity of RUNX3 gene as an anti-oncogene of HCC.

Objective: To investigate the correlation between nonalcoholic fatty liver disease (NAFLD) and three anthropometric indices, namely waist to hip ratio (WHR), body mass index (BMI) and waist to height ratio (WHtR)., Methods: This retrospective case-control study involved 77 NAFLD patients and 50 patients without such disease, and their data of the 3 anthropometric indices were collected. Risk correlation analysis and Mantel-Haenszel chi-square test were used for correlation analysis., Results: NAFLD was significantly correlated to WHR (chi(2)(MH)=59.609, P<0.001; odds ratio=30.522, 95% CI 12.815-72.695), WHtR (chi(2)(MH)=45.316, P<0.001; odds ratio=21.037, 95% CI 8.665-51.072) and showed a dose-response relationship with BMI (chi(2)=25.017, P<0.001)., Conclusion: These results support a close correlation between NAFLD and the 3 anthropometric indices, indicating that BMI, WHR and WHtR can be significant predictors of NAFLD and have potential value for evaluating and predicting NAFLD.

Objective: Preparing rat model of non-alcoholic fatty liver disease by fat-rich diet to observe the expression and the role of LXR-alpha in rat nonalcoholic fatty liver disease., Methods: Thirty-six SD rats were randonmized into basic diet-control group and high-fat diet group. Each of the two groups was subdivided into 3 subgroups (4, 8, 12 weeks). Changes in animal weight, liver exponent and the level of TG and TC in serum and liver were observed dynamically. Meanwhile,the expression of hepatocyte LXR-alpha and SREBP-1c were assayed by Reverse transcript-polymerase chain reaction at 4, 8, 12 weeks. The level of steatosis was observed under light microscope after haematoxylon-eosin (HE) staening., Results: Compared with control group, body weight, liver exponent, TG and Tc in serum and liver were increased dynamically in model groups. Compared with control group, the mRNA of LXR-a and SREBP-1c were obviously increased dynamically in model groups (P < 0.05) ., Conclusion: The increase of LXR-alpha and SREBP-1c in liver may be concered with energy disorder and closely associated with the activity of inflammation and the severity of the liver damage in NAFLD rats.

Objective: To investigate the effects of interferon -alpha1b (IFN-alpha1b) on hepatic intercellular adhesion molecule-1 (ICAM-1) expression and serum HBV DNA in patients with chronic hepatitis B., Methods: Before and 6 months after IFN-alpha1b treatment, liver biopsy was performed in patients with chronic hepatitis B to detect the expression of ICAM-1 in the liver tissues using immunohistochemistry. Serum HBV load was detected with real-time fluorescence polymerase chain reaction., Result: CAM-1 expression in the liver tissue was significantly down-regulated after IFN treatment in patients with severe and moderate chronic hepatitis B (P<0.05). No significant variation was noted in the expression of ICAM-1 in the livers of patients with mild chronic hepatitis B after the treatment (P>0.05). In the patients weakly positive for ICAM-1 expression (+), serum HBV DNA varied scarcely after the treatment (P>0.05), while in the patients with strong ICAM-1 positivity (++, +++, or ++++), significant variation of serum HBV DNA occurred after the treatment (P<0.05 or P<0.01)., Conclusion: The therapeutic effect of IFN-alpha1b is associated with the expression of ICAM-1 in the hepatocytes, and its expression might enhance the effects of IFN on HBV DNA in patients with chronic hepatitis B.

Objective: To study the pathological and clinical features of nonalcoholic fatty liver disease (NAFLD)., Methods: Grades and stages of liver lesions in 41 patients with NAFLD were analyzed. The relationships between pathohistological features of the livers, serum biochemical parameters, ultrasound examination and other clinical data of the patients were studied., Results: Among the 41 patients with NAFLD (there were 21 with their liver fatty degeneration in grade 1, 15 in grade 2, and 5 in grade 3). There were 2 of grade 0, grade 1 had 25, grade 2 had 10, grade 3 had 3, and grade 4 had 1. Stage 0 of fibrosis was 20, stage 1 was 14, stage 2 was 4, stage 3 was 2, and stage 4 was 1. Degree of fatty degeneration was not positively associated with the body mass index (BMI) of the patients and the ultrasound findings in their livers. Grading of the inflammation was positively related to the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and ultrasound findings in their livers, but negatively to the platelet counts. Staging of fibrosis of the livers was positively related to the blood ALT, AST, GGT, and ALP, and negatively to triglyceride levels and platelet counts., Conclusions: Degree of liver fatty degeneration was not associated with grades of inflammation and staging of fibrosis of the liver. BMI, ALT and AST level, platelet counts, and ultrasound grades of fatty liver were associated with the liver histopathological changes of NAFLD patients. Liver biopsy is the essential way to make a diagnosis of NAFLD.

Objective: To investigate the clinicopathological features of nonalcoholic steatohepatitis (NASH) and elucidate its diagnosis and differential diagnosis., Methods: Liver biopsy tissues and clinical data of 32 patients with NASH were collected and the clinicopathological findings by HE and Masson staining were evaluated for NASH grading., Results: Ballooning degeneration of the liver cells and fibrosis around hepatic sinusoid was scarce in mild NASH cases and increased in moderate to severe cases. Steatotic and inflammatory cells in the liver lobes decrease in liver cirrhosis related to seatohepatitis., Conclusion: Ballooning degeneration of the liver cells and fibrosis around the hepatic sinusoid have important value in differential diagnosis of mild from moderate to severe NASH, and correct histological grading benefits clinical intervention and prognostic evaluation of NASH.

Objective: To study histological changes of the livers in patients with chronic viral hepatitis B treated with bicyclol tablets., Methods: Thirty one patients with chronic viral hepatitis B were divided into two groups and were treated with bicyclol orally at doses of 150 mg daily or 75 mg daily for 36 weeds. The histological changes of the livers were observed before and after the treatment., Results: Compared with pre-treatment findings, there were significant differences in histological activity index in each group (P < 0.01, P < 0.05), there were also significant differences between the two groups (P < 0.05). Decreased inflammatory reaction was also seen (P < 0.05)., Conclusion: Daily use of 150 mg and 75 mg bicyclol tablets are effective in improving liver histological changes in chronic hepatitis B patients. Bicyclol 150 mg daily was better.