BACKGROUND/AIMS: The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined . The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naive chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy. METHODS: This study included 364 treatment-naive CHB patients treated with ETV for > or =48 weeks and who received continuous ETV monotherapy for > or =96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log10 IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48. RESULTS: Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for > or =96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up. CONCLUSIONS: Long-term ETV monotherapy is effective for achieving a VR in treatment-naive CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Administration Schedule ; Female ; Genotype ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy/pathology/virology ; Humans ; Liver Cirrhosis/etiology/radiography/ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

BACKGROUND/AIMS: To screen for serum protein/peptide biomarkers of hepatitis B virus (HBV)-associated chronic hepatic lesions in an attempt to profile the progression of HBV-associated chronic hepatic lesions using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) techniques. METHODS: Using SELDI-TOF MS, serum protein/peptide profiles on the CM10 ProteinChip arrays were obtained from a training group including 26 HBV-associated hepatocellular carcinoma patients with liver cirrhosis (LC), 30 HBV-associated LC patients, 85 patients at different stages of liver fibrosis, and 30 asymptomatic HBV carriers. The most valuable SELDI peak for predicting the progression to LC in HBV-infected patients was identified. RESULTS: A SELDI peak of M/Z 5805 with value for predicting LC in HBV-infected patients was found and was identified as a peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1. CONCLUSIONS: The peptide of the C-terminal fraction of the fibrinogen alpha-chain precursor, isoform 1 with M/Z 5805, may be a serological biomarker for progression to LC in HBV-infected patients.
Adult ; Aged ; Biomarkers/*blood ; Carcinoma, Hepatocellular/*virology ; Disease Progression ; Female ; Hepatitis B virus ; Hepatitis B, Chronic/*blood/complications ; Humans ; Liver Cirrhosis/*blood/pathology/virology ; Liver Neoplasms/*virology ; Male ; Middle Aged ; Protein Array Analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult

OBJECTIVETo explore clinical and pathological features of chronic hepatitis B (CHB) with hepatic steatosis.

METHODSRetrospective analysis of hepatic steatosis in patients with liver biopsy-proven CHB between January 2005 and June 2008. Detailed clinical, laboratory and pathological data of CHB patients with steatosis were compared with those in sex-, age- matched CHB patients without steatosis. Patients co-infected hepatitis C virus or HIV or suffering from liver diseases of other causes were excluded.

RESULTSHistological hepatic steatosis was found in 33.4% of the 1263 CHB patients. The prevalence of steatosis was increased with time in the study period (20.3%, 28.2%, 32.6%, 65.4%, in trend analysis, P values less than 0.05). Body mass index, fasting plasma glucose, serum triglyceride and total cholesterol level in CHB patients with hepatic steatosis (n = 114) were significantly higher than those in 113 patients without steatosis (t values were 6.811, 2.733, 3.063, 2.340, respectively, P values less than 0.01 or 0.05). Compared to patients without steatosis, serum hepatitis B virus DNA titer in patients with steatosis was significantly lower (x2 = 6.154, P less than 0.05) and reduced sharply with the increased degree of hepatic steatosis (x2 = 4.941, P less than 0.05). There were no differences in liver biochemical test (t values were 0.744, 1.390, -0.029, -1.175, 1.393, respectively, P values more than 0.05), hepatic inflammation grade and fibrosis stage between CHB patients with and without steatosis (x2 = 1.434, 0.106, respectively, P more than 0.05), and these parameters were not associated with different degree of hepatic steatosis (x2 = 2.447, 2.911, respectively, P more than 0.05).

CONCLUSIONSHepatic steatosis is common in patients with CHB, and is related to metabolic disorders. Hepatic steatosis does not affect the severity of CHB. The reverse association of hepatitis B virus titer with the degree of hepatic steatosis needs further investigation.

Alanine Transaminase ; blood ; Biomarkers ; blood ; Body Mass Index ; Cholesterol ; blood ; DNA, Viral ; blood ; Fatty Liver ; epidemiology ; etiology ; pathology ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Liver Cirrhosis ; epidemiology ; etiology ; pathology ; Male ; Obesity ; complications ; Retrospective Studies ; Risk Factors ; Severity of Illness Index

OBJECTIVETo investigate the relationship between the serum HBV DNA loads normalized to hepatic parenchyma cell volume and the liver histopathologic inflammation gradings in the immune clearance phase during the natural history of hepatitis B.

METHODSSerum HBV DNA loads were detected by fluorescence polymerase chain reaction and normalized to hepatic parenchyma cell volume. The association between normalized HBV DNA loads and liver inflammation histopathologic grade were analyzed.

RESULTSThe serum HBV DNA loads in patients with liver inflammation histopathologic grading 1, 2, 3 and 4 were 8.20*10(5)+/-9.11*10, 1.36*10(6)+/-5.96*10, 8.12*10(5)+/-8.01*10 and 2.08*10(6)+/-3.69*10 copies/ml, respectively (P more than 0.05). But the serum HBV DNA loads normalized to hepatic parenchyma cell volume in their located fibrosis stage were 9.24*10(8)+/-935, 5.33*10(9)+/-756, 1.06*10(10)+/-1770 and 3.31*10(11)+/-518 copies/ml, respectively (P less than 0.05).

CONCLUSIONThe serum HBV DNA load normalized to hepatic parenchyma cell volume in patients with different fibrosis stages is associated with liver histopathologic inflammation gradings.

Adult ; Automatic Data Processing ; Biopsy, Fine-Needle ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; immunology ; isolation & purification ; Hepatitis B, Chronic ; blood ; immunology ; pathology ; virology ; Humans ; Inflammation ; pathology ; virology ; Liver Cirrhosis ; pathology ; virology ; Male ; Polymerase Chain Reaction ; methods ; Severity of Illness Index ; Viral Load ; 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

Adiponectin ; blood ; metabolism ; Antiviral Agents ; therapeutic use ; Aspartate Aminotransferases ; blood ; Fatty Liver ; blood ; pathology ; Female ; Genotype ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Hepatitis C, Chronic ; blood ; drug therapy ; virology ; Humans ; Insulin Resistance ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; blood ; pathology ; Male ; Metabolic Syndrome ; blood ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Viral ; blood ; Receptors, Adiponectin ; genetics ; metabolism

BACKGROUND: Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients. METHODS: From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, alpha-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months). RESULTS: Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died. CONCLUSION: The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.
Carrier State ; Female ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/*blood/immunology ; Hepatitis B virus/*immunology ; Hepatitis B, Chronic/drug therapy/pathology/*virology ; Humans ; Incidence ; Korea ; Liver Cirrhosis/pathology/virology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Seroepidemiologic Studies ; Time Factors ; *Treatment Outcome

BACKGROUND/AIMS: Serum alpha-fetoprotein (AFP) is frequently used for the diagnosis of hepatocellular carcinoma (HCC). Most available data concerning AFP came from studies of patients with chronic hepatitis B or mixed etiologies. Studies concerning the diagnostic value of AFP for HCV-related liver cirrhosis (LC) are limited. We evaluated the factors influencing AFP elevation in the absence of HCC and analyzed the diagnostic value of serum AFP in HCC surveillance of HCV-related LC patients. METHODS: We enrolled 55 patients of HCV-related LC with HCC and 62 patients without HCC as a case-control study were analyzed. The sensitivity and specificity were calculated and the clinical and biochemical factors influencing serum AFP levels. RESULTS: The sensitivities and specificities of serum AFP for the detection of HCC in HCV-related LC were 72.7% and 59.7% for AFP> or =20 ng/mL, and 47.3% and 92.5% for AFP> or =100 ng/mL, respectively. Elevated serum AST was independently associated with elevated serum AFP level in HCV-related LC. In cases of AST< or =2 x upper limit of normal (ULN), the specificity of AFP> or =100 ng/mL for the diagnosis of HCC was 100%. However, in case of AST>2 x ULN, the specificity was 85.0% for AFP> or =100 ng/mL and 95.0% for AFP> or =200 ng/mL. CONCLUSIONS: Serum AST levels influence serum AFP level in HCV-related LC. In cases of AST< or =2 x ULN, AFP greater than 100 ng/mL highly indicates HCC in HCV-related LC, but not in case of AST>2 x ULN.
Aged ; Carcinoma, Hepatocellular/complications/*diagnosis/pathology ; Diagnosis, Differential ; Female ; Hepatitis C/*complications/immunology/virology ; Humans ; Liver Cirrhosis/*virology ; Liver Neoplasms/complications/*diagnosis/pathology ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Tumor Markers, Biological/*blood ; alpha-Fetoproteins/*analysis

BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI=1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.
Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/*blood ; Female ; Hepatitis B, Chronic/blood/enzymology/*pathology ; Humans ; Liver/pathology ; Liver Cirrhosis/*pathology/virology ; Male ; *Platelet Count ; Sensitivity and Specificity

OBJECTIVETo evaluate the clinical efficacy of Ganxian recipe (GXR) and lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB).

METHODSOne hundred and twenty patients with CHB were randomly divided into the combinedly treated group (combined group) of 40 CHB patients who were treated with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone (WM group), and still another 40 CHB patients were treated with GXR alone (TCM group). All these cases were randomly controlled and observed for two years.

RESULTSComprehensive efficacy: Total effective rate of the combined group (complete response and partial response) was 92.5%, while that of the WM group was 67.5% and TCM group 57.5%, respectively, with the difference between them was significant (P < 0.01); after treatment, the hepatic functions (AST, ALT, SB) of the three groups were all reduced, and the reduction in the combined group was particularly significant in comparison with the WM group or TCM group, P < 0.05 or P < 0.01 respectively, suggesting that the effect in the combined group was better than that in the other two groups; the rate of tyrosine-methionine-aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group, 40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement parameter: after treatment, the results in the combined group got better than those in the other two groups.

CONCLUSIONGXR could inhibit the appearance of YMDD after long-term application of LVD, and combined use has marked synergism.

Adolescent ; Adult ; Female ; Gene Frequency ; Genes, Viral ; Hepatitis B Antibodies ; blood ; Hepatitis B e Antigens ; blood ; immunology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; physiopathology ; therapy ; virology ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Liver ; physiopathology ; Liver Cirrhosis ; pathology ; virology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Mutation ; Phytotherapy ; adverse effects ; Plant Preparations ; adverse effects ; therapeutic use ; Reverse Transcriptase Inhibitors ; adverse effects ; therapeutic use ; Treatment Outcome