ABSTRACT
Background/Aims@#The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not be fully elucidated, and the lack of therapeutic strategies for NAFLD is an urgent health problem. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) participates in several biological processes, but its relationship with lipid metabolism and NAFLD has not yet been reported. We aimed to determine the function of GNAI3 in the development of NAFLD. @*Methods@#Mice were fed a methionine and choline-deficient diet to induce NAFLD. An NAFLD model in HepG2 cells was induced by free fatty acid treatment. GNAI3 levels in HepG2 cells were downregulated by shRNA. Protein levels of related proteins were evaluated by Western blotting, and mRNA levels were determined by quantitative reverse transcription polymerase chain reaction. Hematoxylin and eosin and Oil Red O staining were used to observe histological changes in liver tissue. @*Results@#The dysregulated hepatic lipid metabolism in the NAFLD mouse model was enhanced by GNAI3 knockout, which also provoked worse liver damage. In the NAFLD model in HepG2 cells, the downregulation of GNAI3 promoted cellular lipid accumulation and enhanced the changes in lipid metabolic enzyme levels. @*Conclusions@#This study demonstrates that GNAI3 participates in the development of NAFLD in both cellular and mouse models. The data indicate that GNAI3 is a potential new target for the treatment of NAFLD in humans.
ABSTRACT
<p><b>OBJECTIVE</b>To study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB).</p><p><b>METHODS</b>One hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury.</p><p><b>RESULTS</b>HBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%.</p><p><b>CONCLUSION</b>HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.</p>
Subject(s)
Humans , Alanine Transaminase , Area Under Curve , Biomarkers , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Inflammation , ROC Curve , Real-Time Polymerase Chain Reaction , Serologic TestsABSTRACT
Objective To evaluate the predictive effect of baseline hepatitis B surface antigen (HBsAg)on virological response in HBeAg -positive chronic hepatitis B patients treated with pegylated interferon (PEG -IFN ) α-2b. Methods The retrospective analysis compared the treatment efficacy of PEG -IFN α-2b in 55 cases of HBeAg -positive chronic hepatitis B patients with different baseline HBsAg levels.Serum HBV DNA load was measured at baseline and after 1 2,24,and 48 weeks of the therapy.Virological response was defined as HBV DNA <1 000 IU /ml.Serum HBsAg titers were quantitatively assayed at baseline,1 2 and 24 weeks.Results 1 8 patients had baseline HBsAg levels greater than 20 000 IU /ml(Group A),26 patients had baseline HBsAg levels between 1 500 and 20 000 IU /ml(Group B)and 1 1 patients had baseline HBsAg levels less than 1 500 IU /ml(Group C)after 48 weeks treatment with PEG -IFNα-2b.The achieved virological response rates of the three groups were 1 6.67%,42.31 % and 63.64% respectively with a statistically significant difference between group A and C (P <0.05).1 3 patients had HBsAg levels declined greater than 0.5 log1 0 and 30 patients had HBsAg levels declined less than 0.5 log1 0 at week 1 2 and the achieved virological response rates were 1 6.67%,46.2% and 33.3% respectively without statistically significant difference (P >0.05).1 6 patients with HBsAg <br> levels greater than 20 000 IU /ml after treatment of 24 weeks did not achieve virological response after treatment of 48 weeks.Conclusion Baseline HBsAg levels in combination with HBV DNA quantitative value may become an effective predictor for guiding optimal therapy with PEG -IFN α-2b against HBeAg -positive chronic hepatitis B.