Stepwise application of fibrosis index based on four factors, red cell distribution width-platelet ratio, and aspartate aminotransferase-platelet ratio for compensated hepatitis B fibrosis detection.

BACKGROUND AND AIM: Fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width-platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB-4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis. METHODS: A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut-offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB-4, and APRI were statistically analyzed. RESULTS: The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB-4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume-platelet ratio, respectively. The proportion of patient determined as cirrhosis or non-cirrhosis was 65.9% by transient elastography, 36.9% by FIB-4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB-4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively. CONCLUSIONS: In source-limited settings without transient elastography, stepwise applying FIB-4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.

Combining routine markers improves the accuracy of transient elastography for hepatitis B cirrhosis detection.

BACKGROUND AND AIM: Vibration Controlled Transient Elastography (VCTE) is a non-invasive test for liver fibrosis and cirrhosis but may be inaccurate in some patients, especially in those with chronic hepatitis B. This study aims at improving the accuracy of VCTE in cirrhosis detection by combining ultrasound and routine blood parameters. METHODS: Hepatitis B patients with liver biopsies samples ≥20mm underwent VCTE, ultrasound and blood tests, and were divided into training set (n=170) and validation set (n=75). RESULTS: An algorithm consisting of VCTE, international normalization ratio (INR), ultrasonic hepatic vessel and platelet count (CIR-4) and a VCTE-based cirrhosis six-index score (CIR-6) comprised VCTE, INR, platelet, albumin, ultrasonic hepatic vessel and liver parenchyma were derived. In training set, area under receiver operating characteristics curve of CIR-6 and CIR-4 to detect cirrhosis was 0.946 and 0.945, respectively, which was superior to that of VCTE 0.907. CIR-4 could save more liver biopsies. In validation set, CIR-6 detected cirrhosis with accuracy similar to that in training set. However, the sensitivity of CIR-4 and VCTE in validation set lowered to 0.538 and 0.846, respectively. CONCLUSIONS: Combining routine markers improve the accuracy of VCTE for cirrhosis detection in hepatitis B patients. CIR-6 may be more valuable.

Up-regulating CYP3A4 expression in C3A cells by transfection with a novel chimeric regulator of hPXR-p53-AD.

Most hepatoma cell lines lack proper expression and induction of CYP3A4 enzyme, which limits their use for predicting drug metabolism and toxicity. Nuclear receptor pregnane X receptor (PXR) has been well recognized for its critical role in regulating expression of CYP3A4 gene. However, its physiological activity of binding to the particular site of promoter is significantly weakened in hepatic cell lines. To address this problem, we created "chimeric PXR" constructs by appending a strong activation domain (AD) from p53 subunit to either N- or C- termini of the human PXR (hPXR), that is, hPXR-p53 and p53-hPXR. C3A, a hepatoma cell line, was used as the cell model to test the regulation effect of chimeric hPXR over wild type (WT) hPXR on CYP3A4 expression at gene, protein, and metabolism levels, respectively. Compared with C3A cells transiently transfected with WT hPXR, the activity of CYP3A4.XREM.luc reporter gene in C3A cells transfected with hPXR-p53 or p53-hPXR increased 5- and 9-fold respectively, and the levels of CYP3A4 mRNA expression increased 3.5- and 2.6-fold, respectively. C3A cells stably transfected with hPXR-p53-AD exhibited an improved expression of CYP3A4 at both gene (2-fold) and protein (1.5-fold) levels compared to WT C3A cells. Testosterone, a CYP3A4-specific substrate, was used for detecting the metabolism activity of CYP3A4. No testosterone metabolite could be detected in microsomes from WT C3A cells and WT C3A cells-based array, while the formation of 6ß-hydroxytestosterone metabolite in the transfected cells was 714 and 55 pmol/mg protein/min, respectively. In addition, all the above expression levels in the transfected cell models could be further induced with additional treatment of Rifampicin, a specific inducer for CYP3A4. In conclusion, our study established a proof-of-principle example that genetic modification with chimeric hPXR-p53-AD could improve CYP3A4 metabolism ability in hepatic cell line.

Hepatitis B Virus Genotype B and High Expression of Interferon Alpha Receptor ß Subunit are Associated With Better Response to Pegylated Interferon Alpha 2a in Chinese Patients With Chronic Hepatitis B Infection.

BACKGROUND: Hepatitis B virus (HBV) is one of leading causes of various hepatic diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hundreds of million people worldwide are infected by HBV, chronically. OBJECTIVES: This study in conducted to investigate the influence of Hepatitis B virus (HBV) genotypes and type I IFN-αreceptor ß subunit (IFNAR2) expression in liver on response to treatment with pegylated IFN-α-2a (Peg-IFN-α-2a) for chronic hepatitis B infection. PATIENTS AND METHODS: In this study, 65 eligible patients with chronic hepatitis B disease were enrolled. HBV genotypes of these patients were analyzed by using PCR-RFLP of the surface gene of HBV. The expression of IFNAR2 in the liver was immune histochemically investigated using anti-IFNAR2 antibody. All immune histochemical slides were read semi-quantitatively by image analysis. Chronic hepatitis B patients were treated with Peg-IFN-α2a therapy for a 48-week period and followed up for 24 weeks. Baseline characteristics and sustained viral response (SVR) to Peg-IFN-α-2a therapy were evaluated. RESULTS: 55 % of patients exhibited HBV genotype B and 31.7 % patients exhibited HBV genotypes C infections. After treatment with Peg-IFN-α-2a, SVR was achieved in 66.7 % of patients with HBV genotype B and in 26.3 % of patients with HBV genotype C (P = 0.009). Semiquantitative and the image analysis indicated by gray level values revealed a higher IFNAR2 expression in the group with severe inflammation (P < 0.001). Patients' high IFNAR2 protein expression had a significant impact on SVR to Peg-IFN-α-2a therapy (P = 0.028). CONCLUSIONS: HBV genotype B and high expression of IFNAR2 in the liver of chronic hepatitis B patients are closely associated with better response to Peg-IFN-α-2a therapy in chronic hepatitis B disease.

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Although larger biopsies sample had been recommended for the study of non-invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re-evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. METHODS: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. RESULTS: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838-0.909) in total patients, 0.880 (0.844-0.917) in length ≥ 15 mm, 0.897 (0.863-0.932) in length ≥ 20 mm and 0.911 (0.874-0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860-0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824-0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. CONCLUSIONS: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non-AF and obviated them from liver biopsies.

Improving transient elastography performance for detecting hepatitis B cirrhosis.

BACKGROUND: Transient elastography is a well-established method for detecting cirrhosis. AIM: To improve the performance of transient elastography in detecting hepatitis B cirrhosis by alanine aminotransferase (ALT)-stratified cutoffs, bilirubin normalization and transient elastography-based algorithms. METHODS: A total of 315 compensated patients were analysed following liver biopsies, transient elastography, ultrasonography and blood tests. RESULTS: The area under the receiver operating characteristics (ROC) curve of transient elastography for predicting cirrhosis was 0.88 (95% confidence interval 0.84-0.92). The cutoffs to exclude and confirm cirrhosis were 10.4 kPa and 17.3 kPa in patients with ALT <5 × upper limit of normal range, 13.7 kPa and 25.0 kPa in ALT ≥5 × upper limit of normal range, respectively. With ALT-stratified cutoffs, 68.6% of patients did not require liver biopsies. Areas under the ROC curve in patients with normal or abnormal bilirubin was 0.90(0.85-0.95) and 0.84(0.77-0.92), respectively. In patients with normal bilirubin, the cutoffs for excluding and confirming cirrhosis were 10.6 kPa and 16.9 kPa, respectively. By transient elastography screening, 78.3% of patients with normal bilirubin would not need a liver biopsy. Areas under the ROC curves between transient elastography and transient elastography-based algorithm including transient elastography-splenomegaly-platelet index [0.90(0.86-0.94)] and ultrasonic score-transient elastography index [0.91(0.86-0.96)] were not significantly different. CONCLUSIONS: Amongst ALT-stratified cutoffs, bilirubin normalization and transient elastography-based algorithm, bilirubin normalization was especially important for improving performance of transient elastography for compensated hepatitis B cirrhosis detection.

[Hepatitis B virus P22(e) inhibit hepatocyte apoptosis via nuclear factor kappa B].

OBJECTIVE: To test whether nuclear factor kappa B plays an important role in the apoptosis-inhibitory effect of hepatitis B virus (HBV) P22(e) protein. METHODS: 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. RESULTS: 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. CONCLUSION: This study indicates that HBV P22(e) protein inhibits apoptosis of hepatocyte via the NF-kappa B signaling pathway.

[Diagnosis of liver pathologies based on apparent diffusion coefficient of magnetic resonance diffusion-weighted imaging in a rabbit model of liver fibrosis].

OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

B-cell clonality in the liver of hepatitis C virus-infected patients.

AIM: The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B-cell lymphoma remains controversial. In patients with HCV infection, B-cell clonal expansions have been detected in peripheral blood and bone marrow, and a high prevalence of B-cell non-Hodgkin's lymphomas has been documented. Liver biopsies in chronic HCV infection frequently show portal lymphoid infiltrates with features of B follicles, whose clonality has not yet been investigated. The object of this study was to determine the frequency of liver-infiltrating monoclonal B-cells in 40 patients with HCV infection. METHODS: Eight hundred and forty-eight patients were studied prospectively, including 40 HCV-positive patients and 808 patients with chronic hepatitis B virus (HBV) infection. Immunohistochemical study for B- and T-cell markers was performed on the paraffin-embedded liver tissue sections. The clonality of lymphoid B-cells was tested using a polymerase chain reaction (PCR) approach designed to identify immunoglobulin heavy chain gene (IgH) rearrangements. RESULTS: Liver-infiltrating monoclonal B-cells were detected in the liver for 4 (10%) of 40 HCV-positive patients but were present in only 3 (0.37%) of 808 liver biopsy specimens with chronic HBV infection. Chi-square testing showed that the monoclonal B-cells infiltration in the liver was more frequent in the HCV-infected patients (P = 0.000). A clonal IgH rearrangement was detected in 5 (71.4%) of 7 liver biopsy specimens with monoclonal B-cells infiltration. In 2 of 5 patients with both a clonal B-cell expansion and monoclonal B-cells infiltration in the liver, a definite B-cell malignancy was finally diagnosed. CONCLUSION: Liver-infiltrating monoclonal B-cells are detected in the liver of patients with chronic HCV and HBV infection. A high percentage of patients with monoclonal B-cells infiltration and B-cell clonality in the liver were finally diagnosed as having a definite B-cell malignancy.

[Ultrasonic scores combined with blood indexes for screening and predicting compensated liver cirrhosis in chronic hepatitis B patients].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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%.

Model consisting of ultrasonographic and simple blood indexes accurately identify compensated hepatitis B cirrhosis.

BACKGROUND AND AIM: Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis. METHODS: A total of 653 patients with chronic hepatitis B who underwent liver biopsies, ultrasonographic scanning, and routine blood tests were retrospectively analyzed. The patients were divided into the model set and validation set. Blood tests and ultrasonographic indexes were analyzed statistically. An ultrasonographic scoring system consisting of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly was introduced. RESULTS: There were significant differences between cirrhosis and other fibrosis stages in ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly. Ultrasonographic scores were significantly different between F4 and other fibrosis, and significantly correlated with fibrosis stage. Apart from alanine aminotransferase and alkaline phosphatase, blood tests and patients' age were correlated with fibrosis, and were significantly different between patients with and without cirrhosis. The model for cirrhosis indexes consisting of ultrasonographic score, patient's age, and variables, including platelet, albumin, and bilirubin predicted cirrhosis with area under receiver-operator curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut-off values, nearly 81% patients could be accurately assessed for the absence or presence of cirrhosis. CONCLUSION: The model consisting of ultrasonographic score, patients' age, blood variables of platelet, albumin, and bilirubin can identify hepatitis B cirrhosis with a high degree of accuracy. The application of this model would greatly reduce the number of biopsies.

[Expression of IFN-alpha/beta receptor in the PBMCs and liver of patients with hepatitis B and its clinical significance].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[The influence of HBV/P22 protein on the apoptosis of HepG2 cells: an experimental study].

OBJECTIVE: To study the influence of HBV/P22 protein on the induced apoptosis of HepG2 cells. METHODS: 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. RESULTS: 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). CONCLUSION: HBV/P22 protein could inhibit the induced apoptosis of HepG2 cells both in vitro and in vivo.

[Hepatitis B virus P22e protein inhibits human hepatocellular carcinoma HepG2 cell apoptosis in vitro].

OBJECTIVE: To investigate the effects of the hepatitis B virus (HBV) P22e protein on the apoptosis of human hepatocellular carcinoma HepG2 cells. METHODS: 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. RESULTS: 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). CONCLUSION: The introduction and expression of extraneous gene HBVP22e significantly inhibits the apoptosis of HepG2 cells.

[Affects of HBV genotypes (B/C) on the levels of serum and intrahepatic HBsAg].

OBJECTIVE: To observe the effects of HBV genotypes on the level of HBsAg in serum and hepatocytes in chronic hepatitis B patients without antiviral therapy. METHODS: Seventy-six chronic hepatitis B inpatients were enrolled into this study, and liver biopsies and histologic diagnosis were performed, and serum samples were collected at the time point of liver biopsy. PCR-RFLP method was adopted to determine the genotype of hepatitis B virus and Abbott Architect HBsAg assay was used to quantify the serum HBsAg. Immunostaining for antigens in liver tissues with monoclonal antibody (for HBsAg) or polyclonal antibodies (for HBcAg) was carried out in consecutive slides. The percentages of hepatocytes for HBsAg stain, hepatocytes for HBcAg nuclear stain and hepatocytes for HBcAg cytoplasm stain were estimated in the ranges of 0 (negative), < or = 1%, 1+; 2% - 5%, 2+; 6% - 25%, 3+; 26% - 50%, 4+; and > 50%, 5+. The distributions of positive cells in slides are described as single or isolated, cluster or widespread. Surface gene was directly sequenced with the serum HBV DNA from 6 patients with genotype B and 8 with genotype C HBV infection, respectively. RESULTS: Four HBV genotypes were detected in 76 patients: 47 patients with B, 21 with C, 3 with D and 5 were infected by genotype B mixed with C HBV infection. Age, gender, serum HBV DNA level, ALT, AST or histological evaluation (grades and stages scores) were not different between the patients infected with genotype B or C HBV. The level of serum HBsAg was not significantly different between the patients infected with genotype B or C HBV, but the proportions of hepatocytes stained with HBsAg was greater in patients with C type HBV infection than B (P < 0.01). In the liver slides from the patients infected HBV genotype B, HBsAg was stained frequently in single or isolated hepatocytes (22/47), and widespread HBsAg-positive hepatocytes were often seen in the patients with C type HBV (8/21), P < 0.01. In the patients with B type HBV, serum HBsAg was positively correlated with serum HBV DNA (r = 0.674, P = 0.000), proportion of hepatocytes with HBcAg in nucleus (r = 0.534, P = 0.000) and in cytoplasm (r = 0.405, P = 0.004). In the patients with C type HBV infection, serum HBsAg had positive correlation only with serum HBV DNA (r = 0.503, P = 0.017). Proportion of HBsAg positive hepatocytes was positively correlated only with the proportion of HBcAg cytoplasm positive hepatocytes in the patients with B type HBV (r = 0.318, P = 0.029) and no correlation with serum HBsAg, HBV DNA, or proportions of hepatocytes with HBcAg in nucleus. Analysis of the first 40 amino acid sequences of surface antigen showed that variations most existed at amino acid 3, 4, 5 and 8. CONCLUSION: Proportion of HBsAg in hepatocytes is significantly greater in the patients with C type HBV than those with B type HBV. Positive correlation between serum HBsAg and viral replication was seems to be more significant in the patients with HBV genotype B infection.

[An ultrasonographic scoring system for screening compensated liver cirrhosis in patients with chronic hepatitis B and C virus infection].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

[A comparison of clinical and virological characteristics of 1686 cases of HBeAg-negative and HBeAg-positive chronic hepatitis B].

OBJECTIVE: To investigate the clinical characteristics of HBeAg-negative and HBeAg-positive chronic hepatitis B (CHB). METHODS: A total of 1686 hospitalized CHB cases were analyzed retrospectively. The serum ALT values, HBV DNA levels and hepatic inflammation and fibrosis were analyzed by their serum HBeAg status. RESULTS: Among the 1686 cases, 628 (37.3%) were HBeAg-negative and 1058 (62.7%) were HBeAg-positive. Compared with HBeAg-positive group, HBeAg-negative group had a lower serum ALT and HBV DNA levels. However, hepatic necroinflammation grading and fibrosis staging in HBeAg-negative group were more advanced than that of HBeAg-positive group. Irrespective to serum HBeAg status, patients with serum HBV DNA less than 10(5)copies/ml, had a lower hepatic necroinflammation activity. CONCLUSIONS: HBeAg-positive CHB is still the predominant form of CHB in Chinese patients. Compared with patients with low HBV replication, patients with active HBV replication had a higher hepatic necroinflammation activity. The liver histological grading and staging in HBeAg-negative CHB patients were more advanced than that in HBeAg-positive patients.