Hepatitis B virus P22(e) inhibit hepatocyte apoptosis via nuclear factor kappa B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To test whether nuclear factor kappa B plays an important role in the apoptosis-inhibitory effect of hepatitis B virus (HBV) P22(e) protein.</p><p><b>METHODS</b>HepG2 cells were transfected with recombination plasmid pEGFP-HBVP22(e). The Act-D and TNF alpha were used to induce apoptosis. NF-kappa B inhibitor ALLN were used to inhibit the signaling pathway. The activation of NF-kappa B was EMSA, and the nulear translocation of NF-kappa B was determined by immuno-staining.</p><p><b>RESULTS</b>Laser scanning confocal microscopy and EMSA indicated that HBV P22(e) protein enhanced the nuclear translocation of NF-kappa B after apoptosis induction. ALLN treatment inhibited the nuclear translocation of NF-kappa B, and blocked the apoptosis-inhibiting effect of HBV P22(e) protein.</p><p><b>CONCLUSION</b>This study indicates that HBV P22(e) protein inhibits apoptosis of hepatocyte via the NF-kappa B signaling pathway.</p>

Diagnosis of liver pathologies based on apparent diffusion coefficient of magnetic resonance diffusion-weighted imaging in a rabbit model of liver fibrosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of apparent diffusion coefficient (ADC) of magnetic resonance diffusion-weighted imaging (MR-DWI) for diagnosis of the liver pathologies in rabbit model of liver fibrosis.</p><p><b>METHOD</b>MR-DWI with four different b values (200, 500, 300 and 600 s/mm(2)) was performed in 4 normal New Zealand white rabbits and 13 rabbits with experimental liver fibrosis. For each rabbit, 4 ADC values were obtained in the left and right lobes of the liver. According to the ISHAK criteria of liver histopathological scoring and fibrosis staging system, all the liver specimens were histopathologically graded (scores 1-6 for grade I, 7-12 for grade II, and 13-18 for grade III) and assessed for fibrosis staging (stages I to VI). The variation of ADC values were analyzed based on the results of histopathological grading and fibrosis staging.</p><p><b>RESULTS</b>The 4 ADC values were obviously lower in rabbits with liver fibrosis than in the normal control rabbits. Statistical analysis showed significant differences in the ADC values between the normal control and liver fibrosis groups, and between the rabbits with different histopathological grades and fibrosis stages (P=0.000).</p><p><b>CONCLUSIONS</b>Liver fibrosis results in significantly lowered ADC values of the liver depending on the histopathological grades and fibrosis stages. The pathological basis for these changes lies in reduced water content and restricted Brownian motion of water in the liver due to hepatocyte degeneration and swelling, inflammatory cell infiltration, and collagen fiber deposition in the interstitial space.</p>

Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of interferon (IFN)-alpha/beta receptor beta subunit (IFNAR2) in the patients' response to IFN-alpha therapy as influenced by the grade of chronic hepatic inflammation, and understand the relation of IFNAR2 expression in the peripheral blood mononuclear cells (PBMCs) with HBV infection.</p><p><b>METHODS</b>Liver tissue specimens were obtained from 21 patients with chronic hepatitis B for examination of the hepatic inflammation, and PBMCs were isolated from another 16 patients with chronic hepatitis B and 15 health control subjects. Both the hepatic tissues and PBMCs were examined for IFNAR2 expression using immunohistochemistry.</p><p><b>RESULTS</b>The 21 patients with chronic hepatitis B were divided into 3 groups according to the severity of hepatic inflammation, namely G(1) (n=3), G(2) (n=7) and G(3) (n=11) groups. The patients in G(3) group showed had significantly higher IFNAR2 expressions in liver (25.1307-/+7.0700) than those of the G(1) (5.6913-/+1.8422) and G(2) (7.4706-/+5.3572) groups (P=0.000). The IFNAR2 levels in the PBMCs, however, did not show significant difference between patients with chronic hepatitis B and the healthy control subjects.</p><p><b>CONCLUSION</b>In patients with chronic hepatitis B, IFNAR2 expression level is positively correlated to the severity of hepatic inflammation, and increased IFNAR2 expression in severe hepatic inflammation is therefore likely to result in increased response rate to INF-alpha therapy. The expression of IFNAR2 in the PBMCs is not associated with HBV infection.</p>

Ultrasonic scores combined with blood indexes for screening and predicting compensated liver cirrhosis in chronic hepatitis B patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the correlation between ultrasonic scores, routine blood tests and stages of hepatic fibrosis in patients with chronic hepatitis B (CHB), and identify non-invasive indexes to establish a diagnostic model for liver cirrhosis.</p><p><b>METHODS</b>A retrospective analysis of 428 patients with CHB undergoing liver biopsies was conducted. The patients' hematology, serum biochemical indexes, serum alpha fetal proteins (AFP), serum HBeAg status and ultrasonic scores were statistically analyzed. A diagnostic model was established by stepwise discriminant analysis, and aspartate aminotransferase (AST) to platelet ratio index (APRI) was used to estimate the diagnostic value.</p><p><b>RESULTS</b>Partial correlation analysis indicated that platelet, serum albumin, bilirubin, AST, ratio of AST to alanine aminotransferase, prothrombin time and ultrasonic scores were correlated to the stages of liver fibrosis, and significantly differed between patients with and without liver cirrhosis. Logistic regression analysis identified ultrasonic scores, platelet, serum bilirubin, albumin and AST as indexes affecting the diagnosis of compensated cirrhosis. The area under receiver operation curve of model was 0.907. The cirrhosis index (CI) of -0.94 for this model was suitable for screening, with specificity of 85.0%, sensitivity of 81.7%, and accuracy of 84.3%. About 56.2% of the patients' CI was lower than -2.0 with the negative predictive value of 97.0% and the rate of missed diagnosis of 3.0%. About 18.2% of the patients' cirrhosis probabilities were above 0.15, with positive predictive value of 77.3%, and only 2.7% of the patients had mild fibrosis (F2), suggesting that nearly 75% of the patients did not have to receive liver biopsies.</p><p><b>CONCLUSION</b>This diagnostic model integrates the ultrasonic scores, platelet, serum bilirubin, albumin and AST to enable effective screening and prediction of compensated cirrhosis, and can reduce the number of patients required to undergo liver biopsy by about 75%.</p>

The influence of HBV/P22 protein on the apoptosis of HepG2 cells: an experimental study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the influence of HBV/P22 protein on the induced apoptosis of HepG2 cells.</p><p><b>METHODS</b>In vitro, two HepG2 strains were transfected with pcDNA3.1+ and pcDNA3.1+HBV/P22 respectively and the cells were exposed to Act D and TNF alpha for 6h and then the induced apoptosis was detected by flow cytometry (FCM) and TUNEL technique. Supernatant HBeAg was detected by Abbott reagent. The intracellular expression of HBV/P22 protein was measured by Western blot and immunochemistry. In vivo, three cell groups were inoculated into nude mice by subcutaneous injections. After two weeks, Act D and TNF alpha were injected into the tumors and then the induced apoptosis in the tissues was detected by TUNEL technique. The expression of HBV/P22 protein in the tumor tissues was detected by immunochemistry.</p><p><b>RESULTS</b>In vitro, in HepG2- pcDNA3.1+HBV/P22 cells, supernatant HBeAg was positive and intracellular HBV/P22 protein was positively expressed. The apoptosis proportion of HepG2-pCDNA3.1+HBV/P22 cells was markedly lower than HepG2 and HepG2-pcDNA3.1+ cells (P < 0.05). In vivo, HBV/P22 protein was expressed in the tumor tissues, and the apoptosis proportion in the group injected with HepG2-pcDNA3.1+HBV/P22 cells was markedly lower than those injected with HepG2 and HepG2-pcDNA3.1+cells (P < 0.05).</p><p><b>CONCLUSION</b>HBV/P22 protein could inhibit the induced apoptosis of HepG2 cells both in vitro and in vivo.</p>

Hepatitis B virus P22e protein inhibits human hepatocellular carcinoma HepG2 cell apoptosis in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of the hepatitis B virus (HBV) P22e protein on the apoptosis of human hepatocellular carcinoma HepG2 cells.</p><p><b>METHODS</b>HepG2 cells were transfected with recombinant plasmid pEGFP-HBVP22e and exposed to Act-D and tumor necrosis factor alpha (TNFalpha) treatment to induce cell apoptosis. Flow cytometry was performed to determine the proportion of cells containing sub-G1 DNA to represent the number of apoptotic cells. Laser scanning confocal microscopy was used to observe the nuclear alterations in the apoptotic cells.</p><p><b>RESULTS</b>HepG2EGFP-C2HBVP22e cell strain showed a much delayed apoptosis as well as obviously lowered apoptotic rate in comparison with the HepG2 strain (P<0.01).</p><p><b>CONCLUSION</b>The introduction and expression of extraneous gene HBVP22e significantly inhibits the apoptosis of HepG2 cells.</p>

An ultrasonographic scoring system for screening compensated liver cirrhosis in patients with chronic hepatitis B and C virus infection / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation between the stage of hepatic fibrosis and ultrasonographic findings of the liver, spleen and gallbladder and establish a sensitive ultrasonographic semi-quantitative scoring system for screening compensated liver cirrhosis.</p><p><b>METHODS</b>Totalling 248 patients with chronic hepatitis B and hepatitis C virus infection underwent liver biopsy and ultrasonic examination. The images of the liver surface, parenchymal echo, intrahepatic vessels, gallbladder, spleen and diameter of portal vein were analyzed.</p><p><b>RESULTS</b>The stages of hepatic fibrosis were not correlated to ultrasonographic findings of the liver surface or diameter of portal vein, but hepatic fibrosis of different stages showed significant differences in parenchymal echo, intrahepatic vessels, gallbladder and splenomegaly. In cases with normal liver parenchymal, intrahepatic vessels, gallbladder and spleen, the negative predictive value of the ultrasonographic semi-quantitative scoring system for diagnosing compensated liver cirrhosis amounted to 96.3%. The sensitivity of a score not lower than 5 was 90% for detecting compensated cirrhosis. With a score not lower than 7, the diagnostic accuracy and specificity was 85.9% and 95.2%, respectively, but the sensitivity was lowered to 37.5%.</p><p><b>CONCLUSION</b>The ultrasonic images of the liver parenchyma, intrahepatic vessels, gallbladder and spleen in patients with compensated liver cirrhosis vary significantly in patients with hepatic fibrosis of different stages, and this ultrasonographic scoring system allows for a sensitive diagnosis of compensated cirrhosis.</p>

Efficacy of interferon-alpha therapy for HBeAg-negative chronic hepatitis B and its influencing factors / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B.</p><p><b>METHODS</b>Sixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response.</p><p><b>RESULTS</b>Rates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors.</p><p><b>CONCLUSION</b>Interferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.</p>