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

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

OBJECTIVETo analyze the clinicopathologic characteristics of well-differentiated hepatocellular carcinoma (WD-HCC), and to find clues for its pathologic diagnosis and differential diagnosis.

METHODSSeventy-three cases of WD-HCC were studied with clinical data analysis, gross and microscopic examination.

RESULTSAmong the 73 cases, the prevalence of HBV (+) and/or HCV (+) was 94.5% (69/73), liver cirrhosis was 80.8% (59/73), increased hepatic cell density was 95.9% (70/73), dilated and irregular hepatic sinus was 89.0% (65/73), prominent trabecularism was 89.0% (65/73), increased cytoplasmic eosinophilia or basophilia was 90.4% (66/73), glandular-like structure was 16.4% (12/73, and fatty degeneration was 42.4% (31/73) .

CONCLUSIONSThere are important clinicopathologic features associated with WD-HCC. These features are useful in the differential diagnosis of WD-HCC with dysplastic nodule (DN), focal nodular hyperplasia (FNH) and hepatocellular adenoma.

Adenoma, Liver Cell ; pathology ; Carcinoma, Hepatocellular ; pathology ; virology ; Cell Count ; Diagnosis, Differential ; Focal Nodular Hyperplasia ; pathology ; Hepacivirus ; Hepatitis B virus ; Humans ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; virology

OBJECTIVETo investigate whether gene expression profiles can be used to determine risk genes and predict HBV-related cirrhosis progression to liver carcinoma using Significance Analysis of Microarray (SAM) and Prediction Analysis of Microarray (PAM) methods.

METHODSThe Affymetrix GeneChip was used to establish the gene expression profiles of liver tissues from 15 patients with chronic hepatitis B and cirrhosis or hepatocellular carcinoma (HCC). Differentially expressed genes (fold-change more than 2; P value less than 0.01) were selected by GeneSpring GX software. Risk genes related to cirrhosis and liver carcinoma were generated by SAM and PAM methods. Real-time PCR was used to verify the expression of risk genes in the liver tissues.

RESULTSSamples were clustered into the cirrhosis subgroup (n =15) or the HCC subgroup (n =15). A total of 497 differentially expressed genes were identified, SAM identified 162 significant genes, including 18 up-regulated genes and 144 down-regulated genes (fold-change:-1.46 to 1.28). PAM identified 22 genes with a "poor risk signature" (defined with a threshold of 5.5), which were associated with classifying cirrhosis and liver carcinoma; of these risk genes, 4 were down-regulated and 18 were up-regulated in the HCC group compared to the cirrhosis group (fold-change: 2.038 to 7.897, P value less than 0.01). The correction of classification was more than 80% . FOXP1, SPINK1 and KCNJ16 were verified by real-time PCR as differently expressed in the two subgroups (P value =0.011, 0.002 and 0.004, respectively).

CONCLUSIONThe altered gene profiles of carcinogenesis in HBV-related cirrhosis involves hundreds of genes. The combination of three "poor risk genes" may represent potential targets for diagnosis and prediction of liver carcinoma progression.

Adult ; Carcinoma, Hepatocellular ; genetics ; pathology ; Female ; Gene Expression Profiling ; Hepatitis B, Chronic ; complications ; genetics ; pathology ; Humans ; Liver Cirrhosis ; genetics ; pathology ; virology ; Liver Neoplasms ; genetics ; pathology ; Male ; Microarray Analysis ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Transcriptome

OBJECTIVETo evaluate the clinicopathological features and prognosis of primary hepatic lymphoma (PHL).

METHODSThirty-five patients with PHL who underwent surgical resection and were confirmed by pathology in our hospital from 1982 to 2012 were re-evaluated for clinicopathological data, including their symptoms, radiological features, recurrence interval, histopathological properties and prognosis.

RESULTSOf the 35 patients, 25 were men (71.4%) and 10 were women (28.6%), with an average age of 52.6 years old (range, 17-79 years). Presented symptoms were epigastric phymatosis, abdominal pain and low-grade fever. In the present study, 21 (60.0%) patients were positive for HBsAg, 1(2.9%) patient was positive for anti-HCV, 3 patients were positive for AFP, 12 patients and 2 patients were complicated by cirrhosis and hepatocellular carcinoma, respectively. Pathologically, 35 PHL were classified into 19 DLBCL (54.3%), 13 T cell-lymphoma (37.1%), and 3 MALT lymphoma (8.6%). Patients with DCBCL showed better postoperative survival than patients with T cell-lymphoma (31.7 ± 3.2) months vs. (22.9 ± 2.2) months (P < 0.05).

CONCLUSIONSHepatitis B virus (HBV) infection may contribute to the pathogenesis of Chinese patients with PHL. Surgical resection followed by comprehensive therapy is the first-line option for PHL. The prognosis of patients with PHL is associated with PHL subtypes.

Adolescent ; Adult ; Aged ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Hepatocellular ; pathology ; therapy ; virology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis C Antibodies ; metabolism ; Humans ; Leukocyte Common Antigens ; metabolism ; Liver Cirrhosis ; complications ; Liver Neoplasms ; pathology ; therapy ; virology ; Lymphoma ; pathology ; therapy ; virology ; Lymphoma, B-Cell, Marginal Zone ; pathology ; therapy ; virology ; Lymphoma, Large B-Cell, Diffuse ; pathology ; therapy ; virology ; Lymphoma, T-Cell ; pathology ; therapy ; virology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult ; alpha-Fetoproteins ; metabolism

BACKGROUND/AIMS: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. METHODS: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. RESULTS: The epsilon3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the epsilon2, epsilon3, and epsilon4 alleles, respectively. Significantly more of those patients carrying the epsilon3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. CONCLUSIONS: The ApoE epsilon3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.
Adult ; Aged ; Aged, 80 and over ; Alleles ; Apolipoproteins E/*genetics/metabolism ; Carcinoma, Hepatocellular/*metabolism/pathology ; Case-Control Studies ; Child ; Chronic Disease ; Cohort Studies ; Female ; Gene Frequency ; Genotype ; Hepatitis B/complications/metabolism/virology ; Hepatitis B virus/*physiology ; Humans ; Liver Cirrhosis/etiology/*metabolism ; Liver Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the expression level and intracellular localization of APOBEC3G in peripheral blood mononuclear cells (PBMCs) and liver tissues of chronic HBV patients.

METHODSThe expression level and intracellular localization of APOBEC3G in PBMCs and liver tissues were detected using the western blot and confocal laser scanning microscope (CLSM).

RESULTSWestern-blot showed that the expression level of APOBEC3G in PBMCs of healthy controls was very low. The relative expression levels of APOBEC3G in PBMC of patients with chronic hepatitis B, chronic severe hepatitis, liver cirrhosis, or liver cancer were 4.12+/-0.21, 4.07+/-0.28, 4.16+/-0.36 or 4.21+/-0.39 respectively, which were higher than that in the healthy controls. However, there was no significant difference in APOBEC3G expression among different chronic HBV patients (q = 0.931, 0.744, 1.675, 1.675, 2.606 or 0.931, respectively, all P values more than 0.05). In addition, there was no significant difference on APOBEC3G in liver tissues between chronic hepatitis B patients and hepatocellular carcinoma patients (4.40+/-0.34 vs 4.34+/-0.43, q = 0.588, P more than 0.05). CLSM indicated that the localization of APOBEC3G protein was in cytoplasm of PBMCs and hepatocytes.

CONCLUSIONAPOBEC3G is upregulated in the PBMCs of chronic hepatitis B patients.

APOBEC-3G Deaminase ; Blotting, Western ; Case-Control Studies ; Cytidine Deaminase ; genetics ; metabolism ; Cytoplasm ; metabolism ; Hepatitis B, Chronic ; metabolism ; pathology ; virology ; Humans ; Leukocytes, Mononuclear ; metabolism ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; virology ; Liver Neoplasms ; metabolism ; pathology ; virology ; Microscopy, Confocal ; methods ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo explore the relationship of hepatitis B virus (HBV) infection and cirrhosis with liver metastasis in colorectal cancer.

METHODSClinical date of 1176 colorectal cancer patients undergone surgical treatment in the Peking University School of Oncology between January 1999 and August 2004 were analyzed retrospectively to investigate the impact of HBV infection and cirrhosis on the occurrence of liver metastasis and prognosis of patients.

RESULTSThe incidence of liver metastasis was 8.8% (10/114) in the HBV infection group and 23.9% (254/1062) in the non-infection group (P<0.01). The 5-year survival rates of these two groups were 54.2% and 60.7% ( P>0.05). The incidence of liver metastasis was 3.8% (1/26) in the cirrhotic group and 22.9% (263/1150) in the non-cirrhotic group (P<0.05). The 5-year survival rates of these two groups were 60.9% and 59.9% ( P>0.05).

CONCLUSIONBoth hepatitis B virus infection and cirrhosis are associated with less liver metastasis in colorectal cancer, but have no impact on the survival.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; pathology ; virology ; Female ; Hepatitis B ; complications ; Hepatitis B virus ; Humans ; Liver Cirrhosis ; complications ; Liver Neoplasms ; secondary ; virology ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Survival Rate ; Young Adult

Adult ; Cytokines ; metabolism ; Female ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; immunology ; metabolism ; pathology ; virology ; Liver Failure ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Th1 Cells ; metabolism

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