OBJECTIVETo explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).

METHODSOne hundred and eighty-five chronic HBV carriers in ITP, seen in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to December 2010, were admitted in an observational study under the guidance of CM. Patients' CM symptoms and signs, demographics, liver biochemistries, and qualitative HBV DNA were recorded in the questionnaires. CM syndromes were then differentiated to 15 detailed types and analyzed by generalization. Lastly, the location, pathogenic factors and nature of the disease were also assessed.

RESULTSWhen CM syndrome patterns were differentiated to 15 types, there were 27 (15%) no syndrome cases, 94 (50%) single syndrome cases and 64 (35%) compound syndromes cases. The main detailed syndromes included Liver (Gan)-qi depression (LQD), Kidney (Shen)-qi deficiency (KQD), Spleen (Pi)-qi deficiency (SQD) and Kidney-yang deficiency (KYAD). After CM syndromes generalized to five types, their frequency was Spleen-Kidney deficiency (SKD)>LQD>inner dampness-heat retention (IDHR)>Liver-Kidney deficiency (LKD)>blood stasis blocking collateral (BSBC). SKD and LQD occupied 64%. The disease location included Liver, Gallbladder (Dan), Spleen, Stomach (Wei) and Kidney. The pathogenic factors were mainly qi stagnation, qi deficiency, yang deficiency, concurrently dampness-heat and blood stasis. The deficiency syndrome was more than excess syndrome in its nature.

CONCLUSIONSMost of chronic HBV carriers in ITP have their CM syndrome, and the most common types are SKAD, LQD. This study suggests that the natural history may be improved through breaking the state of immune tolerance or shorten the time of ITP by strengthening Spleen-Kidney and reliving Liver qi.

Adolescent ; Adult ; Biopsy ; Carrier State ; immunology ; Child ; Child, Preschool ; Female ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Humans ; Immune Tolerance ; Liver ; immunology ; pathology ; virology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Syndrome ; Viscera ; pathology ; Young Adult

BACKGROUND: The aim of this study was to evaluate oxidative stress in various clinical forms of hepatitis B infection and to investigate its role in the development of the chronic form of the disease. METHODS: Ninety-three patients with inactive hepatitis B surface antigen (HbsAg) carrier state (IHBCS), 65 patients with chronic hepatitis B infection (CHB), and 42 healthy adults were included in the study. The following values were measured and compared in patient groups: total antioxidant status (TAS), total oxidative stress (TOS), oxidative stress index (OSI), sulfhydryl (SH), lipid peroxidation (LOOH), catalase (CAT), and ceruloplasmin. In patients with chronic hepatitis B, these values were compared with HBV DNA and fibrosis levels. RESULTS: ALT, TOS, LOOH, and OSI levels were higher in the CHB group compared to the other groups (P<0.001). Catalase levels increased in the CHB and IHBCS groups compared to the control group (P<0.001). Total aminooxidant and ceruloplasmin levels were found to be lowest in the CHB group and highest in the control group (P<0.001). Sulfhyrdyl was higher in the control group compared to the other groups (P<0.001). In the CHB group, there was no correlation between the HBV DNA and OSI (P>0.05). CONCLUSIONS: These finding suggested that oxidative stress is associated with hepatitis B activity.
Adolescent ; Adult ; Aged ; Alanine Transaminase/blood ; Antioxidants/metabolism ; Carrier State ; Catalase/blood ; DNA, Viral/*analysis ; Female ; Fibrosis ; Hepatitis B/*metabolism/pathology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*genetics ; Hepatitis B, Chronic/metabolism/pathology ; Humans ; Lipid Peroxidation ; Male ; Middle Aged ; *Oxidative Stress ; Sulfhydryl Compounds/blood ; Young Adult

OBJECTIVEIn China, liver failure is also termed as severe hepatitis in whom chronic severe hepatitis B (CSHB) is most common. The aim of this study was to assess whether CSHB based on different liver injury extent can meet the international definition of acute-on-chronic liver failure(ACLF)criteria, according by their clinical and pathological feature.

METHODSA total of 91 patients with CSHB were involved in the study. The clinical findings, laboratory data and liver pathology features were retrospectively analyzed and grouped by hepatitis virus B carrier state (HBC), chronic hepatitis B (CHB) or liver cirrhosis (LC) before they started liver failure.

RESULTS74 out of the 91 patients were male and 17 were female, the mean age was 40.6+/-11.2 years. 9.9%, 7.7% and 82.4% of the patients were based on HBC, CHB and LC respectively. The ages of HBC group were youngest. The mean age of HBC group (years) (25.8+/-6.6) was significantly lower than that of CHB group (36.9+/-9.0) and LC group (42.0+/-10.5)with P values of 0.032 and 0.001 respectively. Most cases presented with sub-acute liver failure characterized by high icterus and ascites. Predisposing factors included exertion, superinfection, virus variation, drugs or alcoholic injury. No difference found between PTA (F = 0.906, P = 0.408) and TBil (F = 0.839, P = 0.436) among the above three groups. The Alb and CHE levels in LC group were (30.3+/-5.1) g/L and (2926.8+/-1471.1) U/L respectively, which were lower than both HBC group [Alb (35.6+/-5.1) g/L, CHE (4363.5+/-2063.2) U/L] and CHB group [Alb (37.4+/-5.0) g/L, CHE (5167.1+/-1522.1) U/L] (F = 9.450; F = 9.297; P value less than 0.01).The level of CHO (1.8+/-1.0) mmol/L in LC group was lower than that of HBC group (2.9+/-1.0mmol/L, P = 0.034), while serum HBV DNA level of HBC group [(6.8+/-1.7) log10copies/ml] was higher than that of LC group [(4.2+/-2.6) log10copies/ml]. The liver tissue in HBC and CHB group showed massive or submassive necrosis which distribute evenly in different parts of liver and similarly in slides, most like acute/subacute severe hepatitis. The chronic lesion was easily covered by extensive necrosis in CSHB based on CHB, with portal fibrosis can be seen by masson stain. Characteristic picture of LC group were massive or submassive necrosis with some nodules were intact or only patchy necrosis of the parenchyma, disparity of extent and stage of necrosis existed in slides, which were the major difference in histopathological change in HBC and CHB group.

CONCLUSIONMost of CSHB cases were based on liver cirrhosis, which match with the international definition of ACLF, while small part of CSHB cases based on HBC and CHB are identical to acute/subacute liver failure.

Adult ; Carrier State ; pathology ; virology ; Female ; Hepatitis B, Chronic ; pathology ; Humans ; Liver Cirrhosis ; pathology ; virology ; Liver Failure ; etiology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVESTo study the relationship between liver pathology and clinical characters of chronic HBV carriers.

METHODSAnalyze the age, sex, grade of liver inflammation and stage of liver fibrosis among patients with chronic HBV carriers (n = 58) and non-active HBsAg carriers (n = 32), and compare the grade of liver inflammation and stage of liver fibrosis in different groups according to age, ALT levels and with/without HBeAg. The data was processed by using t test or Chi-square test for statistical analysis, respectively.

RESULTS(1) No differences existed in gender composition ratio between chronic HBV carriers and non-active HBsAg carriers. However, the ages of non-active HBsAg carriers group (35.2+/-7.6) were much older than that of the HBV carriers group (24.7+/-4.8) (t = 2.576, P = 0.017). (2) The stage of liver fibrosis in non-active HBsAg carriers group was more aggravated than that of the chronic HBV carriers group (Chi-square = 23.231, P less than 0.01), whereas no significant differences existed between these 2 groups (Chi-square = 0.058, P = 0.972). (3) As to the grade of liver inflammation and the stage of liver fibrosis, significant differences existed between the groups with higher level of serum ALT (20-40 U/L) and lower level ( is less than or equal to 20 U/L) (Chi-square = 7.827, P = 0.008; Chi-square = 14.303, P = 0.001), and similar results also existed between elder group (more than 40) and younger group (is less than or equal to 40) (Chi-square = 10.949, P = 0.001; Chi-square = 21.271, P less than 0.01); (4) Among the chronic HBV carriers, significant differences existed in grade of liver inflammation between groups with HBeAg positive and negative patients (Chi-square = 10.275, P = 0.002), and the latter was more aggravated; however, there was no difference in stage of liver fibrosis between them (Chi-square test = 3.457, P = 0.178).

CONCLUSIONLiver histopathology can be recommended to guide the clinical diagnosis and treatment, especially for the chronic HBV carriers, with elder age, ALT close to normal and HBeAg negative.

Adolescent ; Adult ; Age Factors ; Biopsy ; Carrier State ; pathology ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo compare the liver pathohistological and clinical features between chronic HBV carriers and chronic hepatitis B patients with mild elevated in ALT.

METHODS128 patients were divided into 3 groups according to the ALT: group A: ALT is less than or equal to 0.5*ULN, group B: 0.5*ULN less than ALT is less than or equal to 1*ULN, group C: 1*ULN less than ALT less than 2*ULN. The age, sex, serum HBV DNA, HBeAg status, expression of HBcAg in liver, thickness of spleen, breadth of portal vein ,blood stream speed of protal vein, right liver obliqua diameter, grade of liver inflammation and stage of liver fibrosis were compared in the three groups.

RESULTSAmong 128 patients, 57(44.5%) patients had G1 hepatitis and 71 (55.5%) had G2 hepatitis, no G0 hepatitis was found in these patients; 72 patients (56.3%) had S1 fibrosis, 30 (23.4%) patients had S2 fibrosis, and 26 (20.3%) patients did not have liver fibrosis. The liver inflammation in group C was more aggravated than that in group A (P less than 0.05). And there were significant differences in thickness of spleen and right liver obliqua diameter between group C and group A, as well as between group C and B (P all less than 0.01). With the aggravating of liver inflammation, the serum ALT, thickness of spleen, breadth of portal vein and expression of HBcAg in liver were increased obviously (P less than 0.05). With the aggravating of liver fibrosis, the thickness of spleen, breadth of portal vein, right liver obliqua diameter and HBeAg negative patients were increased obviously, while the blood stream speed of portal vein was decreased obviously (P less than 0.01).

CONCLUSIONAmong the chronic HBV infection patients whose ALT less than 2*ULN, there were 55.5% patients had G2 of liver inflammation and 23.4% patients had S2 of liver fibrosis. The serum ALT, thickness of spleen, breadth and blood stream speed of portal vein, right liver obliqua diameter and expression of HBcAg in liver are associated with pathohistological changes in these patients.

Adult ; Alanine Transaminase ; blood ; Biopsy, Needle ; Carrier State ; blood ; pathology ; virology ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; metabolism ; pathology ; virology ; Liver Cirrhosis ; pathology ; Male ; Polymerase Chain Reaction ; methods ; Retrospective Studies ; Virus Replication

OBJECTIVETo investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL).

METHODSHBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were examined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy).

RESULTSSubjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9+/-1.4) vs (4.1+/-1.1) log(10)copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HAI) > or = to 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAI) > or = to 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, x(2)=0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r=0.626, 0.592, P < 0.01; BCP: r=0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F > or = 3) (AUC = 0.905, 95% CI: 0.771-1.039, P < 0.05) with the cutoff value of 4.5 log(10) copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA is > or = to 10(4) copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 log(10)copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes.

CONCLUSIONSVirus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting significant fibrosis (F > or = 3).

Adult ; Alanine Transaminase ; blood ; Base Sequence ; Carrier State ; pathology ; virology ; DNA, Viral ; blood ; genetics ; Female ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis C, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Male ; Middle Aged ; Mutation ; Promoter Regions, Genetic ; genetics ; Viral Load

Adolescent ; Adult ; Carrier State ; metabolism ; pathology ; Collagen Type III ; blood ; Collagen Type IV ; blood ; Female ; Hepatitis B, Chronic ; complications ; metabolism ; pathology ; Humans ; Interleukin-17 ; metabolism ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; etiology ; metabolism ; pathology ; Male ; Middle Aged ; Severity of Illness Index ; Young Adult

OBJECTIVESTo understand the hepatic pathology, hepatitis B reactivation rates and serological changes in chronic HBV carriers.

METHODSA 5 year dynamic observation and survey of 220 chronic HBV carriers in Wuxi district was taken, analyzing their clinical symptoms, liver histopathology, virology and HBV immunological markers.

RESULTSThirty-five of the 220 (15.9%) patients, showed hepatitis B reactivation. The hepatitis B reactivation rate of patients with obvious hepatic tissue inflammation (> or = G2) was 27.0% (33/122) and the rate of the patients with mild hepatic tissue inflammation (G0-G1) was 2.0% (2/98), showing significant differences (x2=25.41, P less than 0.01). The reactivation rate of patients with high inflammation was clearly higher than those with mild inflammation. Twenty-seven of the 35 hepatitis B reactivation cases were older than 40 years, showing a significant association between the ages of the patients and hepatitis B reactivation rates (x2=6.72, P less than 0.01), moreover there was no relationship between sex and the hepatitis B reactivation rate. There were differences in the inflammation grades and fibrosis stages between HBeAg positive and anti-HBe positive group cases (Kruskal-Wallis Test, x2=8.68, P less than 0.01, x2=6.84, P less than 0.01), showing inflammation grades and fibrosis stages of the anti-HBe positive group were higher than those of the HBeAg positive group. There were no obvious differences about the inflammation grade between age less than 40 years old and > or = 40 years old group cases (x2=0.62, P more than 0.05), but there were significant statistical differences about the fibrosis stage (x2=7.37, P less than 0.01), showing fibrosis stage of more than 40 years old group cases was clearly higher than the less than 40 years old group cases. Fifty-six cases received a liver biopsy for a second time and 23 for a third time. We found those whose hepatic tissues were normal in their first liver biopsies, then their liver histology continued remaining stable for several years while those with abnormal ones hardly or only recovered slightly. The rate of HBsAg turning to negativity per year was 1.55% and for HBeAg was 5.4%.

CONCLUSIONThe hepatic tissue pathology for most chronic HBV carriers (55%) had significant abnormalities (inflammation grade > or = G2), and the rates of hepatitis B reactivation were highly relevant to the liver inflammation grades and the ages of the patients.

Adolescent ; Adult ; Carrier State ; virology ; Child ; Female ; Follow-Up Studies ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Inflammation ; Liver ; pathology ; virology ; Male ; Middle Aged ; Virus Activation ; Virus Replication ; Young Adult

OBJECTIVETo evaluate the causes of alanine aminotransferase (ALT) level elevation in HBsAg-positive chronic hepatitis B (CHB) patients with low HBV DNA loads.

METHODSOne hundred nineteen HBsAg positive CHB patients with both serum HBV DNA loads less than 1000 copies/ml and ALT more than 1.25 upper limits of normal (ULN) lasting for at least 6 months were enrolled in this study. Patients co-infected with hepatitis C virus or HIV or suffering from other liver diseases were not included. HBV DNA loads were assayed by PCR. Serological biochemistry and liver biopsy histopathological changes and clinical characteristics of the patients were analyzed.

RESULTSOf the 119 patients 102 were males and 17 were females. The mean age of the patients was (33.9+/-9.7) years and their body mass index (BMI) was (23.4+/-3.7) kg/m2. Mean ALT levels were (150.0+/-166.6) U/L and AST levels were (102.4+/-193.2) U/L. Liver biopsies showed hepatic steatosis in 26.9 % (32/119) of the cases, chronic hepatitis in 53.8% (64/119), non-specific changes in 12.6% (15/119), and 1 without any change. However, hepatic steatosis was more frequently seen in patients taking nucleoside analogs (56.7%), x2=10.394, Probability value less than 0.01. BMI, apolipoprotein B (APO-B), triglyceride, cholesterol and uric acid were all significantly higher in patients with hepatic steatosis than those without (t values were 5.369, 4.276, 3.216, 4.223 and 2.438 respectively, all P less than 0.05) while ALT, AST and apolipoprotein A were much lower in those with steatosis than those without (t values were -2.234, -3.877 and -2.956 respectively, all P less than 0.05). Obesity, dyslipidemia and hyperuricemia were more frequently seen in patients with steatosis than in patients without it (x2 value 3.829, 7.659, 13.389, 0.549, all P less than 0.05). The severity of inflammation and fibrosis were also more significant in patients with steatosis (x2 value 20.978, 17.550, all P less than 0.05). As compared to those patients without specific changes, serum levels of ALT, AST, GGT in patients with chronic hepatitis were obviously higher, all P less than 0.05. In contrast, there were no significant differences in mean age, BMI, male preference, obesity, diabetes, dyslipidemia or hyperuricemia, and the levels of triglyceride, cholesterol, and fasting plasma glucose between the two groups.

CONCLUSIONOur data indicate that hepatic steatosis might be a factor associated with elevated ALT levels in HBsAg-positive CHB patients with low HBV DNA loads, especially in patients treated with nucleoside analogs.

Adult ; Alanine Transaminase ; blood ; Carrier State ; Fatty Liver ; physiopathology ; virology ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; virology ; Hepatocytes ; pathology ; Humans ; Male ; Viral Load ; Young Adult

OBJECTIVETo study of serum level of cortisol and peripheral T lymphocyte subsets state in the hepatitis B virus (HBV) carriers.

METHODSSixty chronic HBV carriers and ten healthy controls were all enrolled in this present study. Serum expression of cortisol was determined by radioimmunoassay, and also flow cytometry was performed to evaluate peripheral blood T lymphocyte subset.

RESULTSCompared with those in normal controls, the serous levels of cortisol in chronic HBV carriers were significantly elevated, while there was no distinct difference in the proportion of CD4+ T lymphocytes ( P > 0.05) with the decreased odds of CD4+/CD8+ lymphocytes( P < 0.05) and obvious higher proportion of CD8+ T lymphocytes( P < 0.05). In comparison between HBeAg positive group and HBeAg negative group, the serous levels of cortisol of the former group were significantly higher ( P < 0.05), and so proportion of CD8+ T was too ( P < 0.05). However, there is no significant differences in the proportion of CD4+ T lymphocyte ( P > 0.05).

CONCLUSIONThe elevated serum cortisol and increased CD8+ T lymphocytes subsets in the chronic HBV carriers, suggested that there was disturbance of endocrine-immune response in the chronicity of HBV infection.

Adult ; Carrier State ; immunology ; pathology ; virology ; Female ; Hepatitis B ; blood ; immunology ; metabolism ; pathology ; Hepatitis B virus ; immunology ; Humans ; Hydrocortisone ; blood ; immunology ; Male ; T-Lymphocyte Subsets ; immunology