2.An analysis of clinical features in HBeAg-negative and HBeAg-positive chronic hepatitis B.
Xiao-juan OU ; Xiao-ming WANG ; Bao-en WANG ; Tai-ling WANG ; Hong MA ; Hong YOU ; Ji-dong JIA
Chinese Journal of Hepatology 2007;15(6):428-430
<b>OBJECTIVESb>To analyze the frequency and the clinical and virological features of HBeAg-negative and HBeAg-positive chronic hepatitis B.
<b>METHODSb>Four hundred and seventeen chronic hepatitis B patients, 286 males and 131 females seen in our center were studied. Liver biopsies were taken from 83 patients.
<b>RESULTSb>The cases with HBeAg-negative chronic hepatitis B were 241 (57.8%), with an average age of 43.7+/-10.8 and a history of 16.8+/-8.5 years. HBeAg-positive chronic hepatitis B cases were 176 (42.2%), with an average age of 36.95+/-11 and a history of 12.3+/-8.0 years. HBeAg-negative patients were significantly older (P < 0.01) in age and had a longer disease history. ALT levels and the percentage of HBV DNA were higher than 10(5) copies/ml in HBeAg-negative patients and were significantly lower than those in the HBeAg-positive patients [(37.66+/-32.93) U/L vs. (82.09+/-107.57) U/L, 38.2% vs. 94.3%, P < 0.01]. Liver biopsies from 47 HBeAg-negative patients showed that the number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 27, 14, 1 and the number of cases with fibrosis scores of S1, S2, S3 and S4 were 10, 12, 5, 20, respectively. In the 36 HBeAg-negative patients the respective number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 14, 15, 2, and with fibrosis scores of S1, S2, S3, S4 were 8, 12, 6, 10. Although histopathological inflammation and fibrosis scores had no statistical difference between HBeAg-negative and positive patients (P > 0.05), 53.2% patients of HBeAg-negative group and 44.5% patients of HBeAg-positive group had a fibrosis score of >or= S3.
<b>CONCLUSIONb>Despite lower serum ALT and HBV DNA, HBeAg-negative chronic hepatitis B still has a significant disease progression. This observation may help to develop better clinical management in HBeAg-negative chronic hepatitis B patients.
Adult ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged
3.Histological changes in the livers of chronic hepatitis B patients with persistently normal serum alanine transaminase levels.
Hong-Lian GUI ; Qing XIE ; Hui WANG ; Wei CAI ; Zhi-Mei LIN ; Shan JIANG ; Pei XU ; Xia-Qiu ZHOU ; Qing GUO ; Hong YU
Chinese Journal of Hepatology 2007;15(12):881-885
<b>OBJECTIVEb>To study the histological changes in livers of chronic hepatitis B (CHB) patients with persistently normal serum ALT levels (PNAL).
<b>METHODSb>274 CHB patients who had percutaneous liver biopsies and had a detectable viral load (lower limit of detection is 10(3) copies/ml) in our department between October 2003 and February 2007 were included in this study. Among these patients, 139 had PNAL, group A, (with at least 3 normal serum ALT levels, with intervals of more than two months over a period of 12 or more months before the biopsy). The other 135 patients, group B, had abnormal serum ALT levels during the same period. The histological changes in the livers of the two groups of patients were compared.
<b>RESULTSb>Sixty-six (47.5%) patients with PNAL had normal liver histology, but significant pathohistological changes such as significant necroinflammation, fibrosis and/or cirrhosis were found in 33 (23.7%) patients. Thirteen (9.4%) had established cirrhosis. When compared to patients within (0-0.75)x upper limit of normal (ULN) ALT, patients within (0.76-1.00)x ULN ALT had higher scores of histological changes (43.5% vs. 19.8%, P < 0.05). In the PNAL group, scores of histological changes increased sharply in parallel with an age increase of older than 40 yrs. However neither viral loads nor HBeAg statuses of the PNAL patients had any predictive meaning to the scores of the histological findings.
<b>CONCLUSIONSb>23.7% of our CHB patients with PNAL, regardless of what their HBeAg statuses or viral load levels were, had significant liver pathohistological changes. Liver biopsies should be considered in CHB patients with PNAL, especially those older than 40 yrs and with a higher ALT within (0.76-1) x ULN.
Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; pathology ; physiopathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Young Adult
4.Characteristic of liver pathology in HBeAg-positive and HBeAg-negative chronic hepatitis B patients with mildly elevated ALT.
Shun-qing LIU ; Xiao-jun ZHU ; Xue-hua SUN ; Man LI ; Yue-qiu GAO
Chinese Journal of Hepatology 2012;20(5):348-352
<b>UNLABELLEDb>To analyse the live pathology characteristics in mild ALT-elevated (1 x ULN less than ALT less than 2 x ULN ) HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients, and to explore the influence of the age and HBV DNA level to liver pathology in different HBeAg status patients.
<b>METHODSb>All the patients who met the inclusion criteria form "eleventh five-year plan" National Science and Technology Major Project, the treatment program of integrative traditional and western medicine for CHB were enrolled in this study between October 2009 and March 2011 .B type ultrasound-guided liver biopsy was carried out in all patients and hepatitis B surface antigen (HBsAg) , HBeAg titer as well as HBV DNA level were detected at the same time. Hepatic tissue inflammation and fibrosis degree of patients according to HBeAg-positive and negative, age ( more than or equal to 40 years and less than 40 years), HBV DNA level (more than or equal to 10^5copy/ml and less than l0^5 copy/ml) were compared respectively. Chi-square test was used to compare the constitute percentage between the two samples. Multivariate logistic regression analysis was also performed to evaluate the correlation between different factors.
<b>RESULTSb>There were no significant difference in the grade of liver inflammation and the stage of liver fibrosis between 389 HBeAg positive and 126 HBeAg-negative patients (X2=4.326 and X2=3.464, respectively, P values were all more than 0.05). In the group of patients with age less than 40 years, the distribution of different liver inflammation and fibrosis had no significant difference between HBeAg-positive and negative patients (X2=2.543 and X2=5.024, respectively, P values were all more than 0.05). In the group of patient with age more than or equal to 40 years, the percentage of moderate and severe inflammation (G3, G4) HBeAg-positive patients(32.9%) owned is much higher than that of HBeAg-negative patients(16.4%), X2=8.777, P less than 0.05.But the stage of liver fibrosis in HBeAg-positive patients was not significantly different than that of HBeAg-negative ones (X2=0.977, P more than 0.5). In the group of patients with HBV DNA more than or equal to 10^5copy/ml, the percentage of mild inflammation in HBeAg-positive patients (17.5%) was much high than that of HBeAg-negative patients(7.3%), X2=8.851, P less than 0.05. The stage of liver fibrosis between HBeAg-positive and negative patients was no significant difference (X2=8.227, P more than 0.05).In the patients with HBV DNA less than 10^5 copy/ml, The percentage of HBeAg-negative patients(29.6%) with mild inflammation(G1) was much higher than HBeAg-positive patients (6.9%), X2=6.357, P less than 0.05. There was no significant difference in the stage of liver fibrosis between HBeAg-positive and negative patients (X2=4.061, P more than 0.05). The results of multivariate logistic regression analysis showed that age was the independent risk factor for different degree of liver inflammation and fibrosis seriousness.
<b>CONCLUSIONb>The status of HBeAg has no association with the grade of liver inflammation and the stage of liver fibrosis in CHB patients with mildly elevated ALT. The percentage of moderate and severe inflammation in the HBeAg-positive patients with age more than or equal to 40 years was significantly elevated. The grade of liver inflammation has significant difference between HBeAg-positive and negative patients with different HBV DNA levels as well.
Adolescent ; Adult ; Alanine Transaminase ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Young Adult
5.Relation between HBsAg levels during the immune clearance phase of hepatitis B virus infection and liver pathological stages of chronic hepatitis B.
Da-wu ZENG ; Jing DONG ; Li-hong CHEN ; Yue-yong ZHU ; Jing CHEN ; Qi ZHENG ; Yu-rui LIU ; Jia-ji JIANG
Chinese Journal of Hepatology 2012;20(10):746-750
<b>OBJECTIVEb>To investigate whether the level of hepatitis B surface antigen (HBsAg) represents the status of inflammation and stages of fibrosis in livers of patients with chronic hepatitis B (CHB) during the immune clearance phase (IC).
<b>METHODSb>Liver biopsy samples and sera were collected from 165 consecutive patients (136 males; 29 females) with CHB in IC who were treated in our hospital between March 2009 and June 2011. Routine biochemical tests were carried out to measure indicators of liver function. The relation between HBsAg level and liver pathological stages were determined by Spearman's rank correlation analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBsAg level for liver pathological stages. Binary logistic regression was used to analyze potentially relevant indicators, and liver pathology-predicting models were built and analyzed by the ROC method.
<b>RESULTSb>The mean values of HBsAg (IU/mL) were significantly different at the different liver inflammation stages: G1, 27 716.07+/-32 870.69; G2, 34 478.75+/-40 899.55; G3, 19 408.09+/-24 881.07; G4, 14 286.31+/-28 610.14. Likewise, the mean values of HBsAg (IU/mL) were significantly different at the different liver fibrosis stages: S1, 41 337.23+/-43 236.39; S2, 27 264.32+/-32 517.29; S3, 111 541.77+/-11 538.93; S4, 11 447.37+/-22215.44. Spearman's rank correlation analysis indicated a significant correlation between HBsAg level and liver inflammation stage (rs = -0.244) and fibrosis stage (rs = -0.365). ROC curve analysis of the diagnostic value of HBsAg for inflammation stages S more than or equal to 4 revealed that the area under the curve (AUC) was 0.70. The specificity of diagnosing S more than or equal to 4 was > 95.16% when HBsAg was less than or equal to 32995 IU/mL. Binary logistic regression analysis identified age, serum albumin, cholinesterase, and HBsAg as independent predictors of liver fibrosis.
<b>CONCLUSIONb>HBsAg level is negatively correlated with liver inflammation and fibrosis stages for patients with CHB in the IC phase, and might represent a useful noninvasive marker of the degree of hepatic fibrosis.
Adult ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; blood ; immunology ; pathology ; Humans ; Inflammation ; Liver ; immunology ; pathology ; Liver Cirrhosis ; immunology ; pathology ; Male ; Middle Aged ; Young Adult
6.Relationship among pathological changes in Liver tissues and level of serum HBV DNA, HBeAg and ALT of 194 patients with chronic hepatitis B.
Deng-yun ZHAO ; Ya-qin QIN ; Xing-ming TANG ; Gui-zhang LIU ; Wei ZHENG ; Hong-rong NONG ; Jia-jun SONG ; Qiu-yan XIE
Chinese Journal of Experimental and Clinical Virology 2007;21(1):35-37
<b>OBJECTIVEb>To study the relationships among pathological and immunohistochemical changes in liver tissues, and the HBeAg, HBV DNA, ALT level in the patients with chronic hepatitis B.
<b>METHODSb>Pathological and immunohistochemical examinations of liver tissue liver function tests, serum HBV and HBV DNA detection were performed in 194 patients with chronic hepatitis B.
<b>RESULTSb>There was significant difference between the serum HBeAg positive group and the negative group in G2, G3-4 S2, S3-4 in liver tissues; The serum HBV DNA level of the groups S0 and S1-4, and the hepatic activity index between the groups G0-1 and G2-4 were significantly different. And the hepatic HBcAg positive group and HBcAg negative group were significantly different too. There was no significant difference between the HBsAg level in liver tissues as "+" group and the "++ - +++" group. The pathological diagnosis as S1 or (and) G2 is respectively 28.57%, 53.33%, 80.15%, 77.88% among the four groups with normal-mild-moderate-severe elevated serum ALT level.
<b>CONCLUSIONb>Serum HBV DNA correlated with HBcAg expression in liver tissue; the HBsAg level in liver tissues have no relationship with the serum HBV DNA level. The patients with low serum HBV DNA level may have high index of hepatic activity and hepatic fibrosis. Asymptomatic carriers and patients with low serum ALT level should be encouraged to accept liver biopsy. It can determine the degree of liver inflammation and fibrosis and timing of treatment.
Adolescent ; Adult ; Alanine Transaminase ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; physiology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Young Adult
7.Relation of serological markers of hepatitis B virus and alanine transaminase to hepatic tissue pathology in patients with chronic hepatitis B.
Xiao-yun YANG ; Fan-yuan WEN ; Jing-li WU ; Hua-jian ZHOU
Journal of Southern Medical University 2006;26(6):892-893
<b>OBJECTIVEb>To investigate the association of serological markers of hepatitis B virus (HBV) and alanine transaminase (ALT) with hepatic tissue pathology in patients with chronic hepatitis B.
<b>METHODSb>The serological marker of HBV, liver function and liver biopsy of 133 patients with chronic hepatitis B were measured and evaluated. The patients were divided into 4 groups according to HBeAg and HBV DNA positivity. Hepatic necrosis/inflammation grade and hepatic fibrosis were compared between the groups.
<b>RESULTSb>Hepatic histological examination of all these patients showed inflammation, necrosis and different degrees of fibrosis. In patients with normal serum ALT, liver biopsy showed different degrees of inflammation, hepatic fibrosis, and even hepatocirrhosis. In patients with abnormal serum ALT negative for HBeAg, hepatic tissue inflammation and fibrosis were more serious. Hepatic tissue pathology was not paralleled with the level of HBV replication.
<b>CONCLUSIONb>Evaluation of the liver disease can not depend solely on serum ALT and viral loading in these patients. Hepatic tissue pathology in patients with chronic hepatitis B should be served as the most reliable evidence for evaluating hepatitis conditions and making the decision on antiviral therapy.
Adolescent ; Adult ; Alanine Transaminase ; blood ; Biopsy, Needle ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Viral Load
8.HBV DNA Levels, Aminotransferase and Histological Activity in Young Male Patients with HBeAg Positive Chronic Hepatitis B.
Seung Chul CHO ; Soong Hwan LEE ; Joon Jae SHINN ; Sung Hee HAN ; Byung Joo ROH ; Joo Hyun SOHN ; Dong Hoo LEE ; Choon Suhk KEE
The Korean Journal of Hepatology 2002;8(1):44-51
BACKGROUND/AIM: A significant correlation between HBV DNA and liver damage was found in precore mutant strains but there was no significant association between viral replication and liver damage in HBeAg positive patients. Laboratory tests are often requested to predict hepatitis activity (grade) and fibrosis (stage) in HBeAg positive chronic hepatitis B. We assessed ALT, AST, and HBV-branched DNA to find which is the best for predicting hepatitis activity and fibrosis. METHODS: Routine biochemical liver function tests and HBV DNA in sera were assessed in 119 young patients positive with HBsAg and HBeAg. The mean age of patients was 21+/-2 years. All patients were male. By logistic regression analysis the relationships between laboratory data, hepatitis activity, fibrosis, or risk of chronic active hepatitis were analyzed. RESULTS: There was a significant correlation between aminotransferase (AST, ALT) and hepatitis activity/ fibrosis. A significant inverse relationship between the HBV bDNA and hepatitis activity was demonstrated (Pearson's correlation coefficient: lobular activity,-0.305; porto-periportal activity, -0.410). But HBV bDNA was not correlated with severity of fibrosis. AST and HBV bDNA was the important test for predicting the more severe hepatitis activity (lobular activity and porto-periportal activity: score> or =3, respectively) CONCLUSION: The higher AST, but the lower HBV bDNA, in sera shows the more severe hepatitis activity. AST and HBV bDNA could be helpful for assessing the hepatitis activity in young male patients with HBeAg positive chronic hepatitis B if proper reference values are used.
Adult
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Alanine Transaminase/blood
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Aspartate Aminotransferases/blood
;
DNA, Viral/*analysis
;
English Abstract
;
Enzyme Tests
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Hepatitis B Virus/genetics/*isolation & purification
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Hepatitis B e Antigens/*blood
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Hepatitis B, Chronic/diagnosis/*pathology/virology
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Human
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Liver/pathology
;
Male
9.Treatment of chronic hepatitis B in children with prednisolone withdrawal followed by recombinant interferon alpha.
Hyo Sin KIM ; Je Woo KIM ; Ki Sup CHUNG
Yonsei Medical Journal 1998;39(4):309-316
Steroid withdrawal followed by interferon therapy is an alternative approach for treating chronic hepatitis B virus infection when there has been no therapeutic response to interferon alone. The effectiveness of steroid withdrawal followed by interferon therapy and factors predictive of the response were evaluated in 35 children with biopsy-proven chronic hepatitis B. Patients had received a 1-month course of prednisolone, 1 mg/kg per day orally, followed by a 2-week rest, and then were treated with interferon alpha 3 MU three times per week for 4-6 months. The serum aminotransferase values normalized in 80%, and negative seroconversion rates of HBeAg and HBV-DNA were 69% and 66%. The good response rate was associated with a pretreatment HBV-DNA level lower than 100 pg/ml and a posttreatment ALT level more than 200 IU/L. Normalization of ALT values usually took 5 months, and the clearance of HBV-DNA and HBeAg took 7.8 and 6.7 months, respectively. These results suggest that steroid withdrawal followed by interferon therapy is useful in the treatment of chronic hepatitis B in children, and that a good response rate can be expected in children with lower pretreatment HBV-DNA levels (< 100 pg/ml).
Adolescence
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Alanine Transaminase/blood
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Child
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Child, Preschool
;
DNA, Viral/analysis
;
Female
;
Hepatitis B, Chronic/virology
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Hepatitis B, Chronic/therapy*
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Hepatitis B, Chronic/pathology
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Human
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Infant
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Interferon Alfa-2a/therapeutic use*
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Male
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Prednisolone/therapeutic use*
10.Gene mutation in the areas of PreC/C and BCP of HBV DNA.
Cheng-long SUN ; Hui-min WANG ; Yue-guo WANG ; Dong-lei ZHANG ; Yue-ping WU ; Jian-long ZHAO
Chinese Journal of Experimental and Clinical Virology 2005;19(1):68-70
<b>OBJECTIVEb>To investigate the gene mutation in the areas of pre core/core (Pre C/C) and basic core promotor (BCP) of HBV DNA and its clinical significance.
<b>METHODSb>The nt 1 735-1 965 segment of HBV DNA was amplified with PCR in 54 cases with chronic hepatitis B and 10 cases with post-hepatitis cirrhosis. Then the PCR product was sequenced.
<b>RESULTSb>There were 168 site mutations in 48.5% (33/68) cases with hepatitis B. The first ten mutation sites were nt 1 764 (58.8%), 1 762 (48.5%), 1 799 (21.0%), 1 766 (14.7%), 1 896 (13.2%), 1 754 (8.8%), 1 899 (8.8%), 1 768 (7.4%), 1 814 (7.4%) and 1 913 (7.4%). Three rare mutations of nt 1907, 1 922 and 1 923 were also detected. The mutations of nt 1 896, 1 764 and 1 762 were found in 16.7%, 35.2% and 35.2% of chronic hepatitis, and in 30.0%, 60.0% and 60.0% respectively of post-hepatitis cirrhosis cases. There was statistical significance between the two groups (P < 0.01).
<b>CONCLUSIONb>The mutations in the areas of Pre C/C and BCP of HBV DNA might possibly be associated with liver fibrosis. There are many mutation sites in HBV DNA and mutation occurs frequently, therefore gene sequencing is helpful to the design of gene chip and to clinical application.
DNA, Viral ; blood ; genetics ; Gene Frequency ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Mutation ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length