Animals ; Carcinoma, Hepatocellular ; genetics ; virology ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Neoplasms ; genetics ; virology ; Neoplasm Recurrence, Local ; genetics ; Point Mutation ; Telomerase ; metabolism

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

<b>OBJECTIVEb>To study the clinical features of liver disease patients with abnormal glucose metabolism.

<b>METHODSb>Liver functions and levels of FPG, PPG, FINS, PINS, FCP, and PCP in 91 chronic hepatitis B patients with abnormal glucose metabolism (62 had liver cirrhosis) were analyzed.

<b>RESULTSb>(1) The incidence of hepatogenic impaired glucose tolerance (IGT) and of diabetes mellitus (DM) in hepatitis B patients with liver cirrhosis (20.53%; 24.11%) were higher than those without cirrhosis (3.82%; 1.64%; P<0.05, P<0.01). (2) There were no diabetic symptoms among any of the hepatogenic IGT and DM patients. 12 of 19 chronic hepatitis B patients with primary DM and 6 of 12 hepatitis B associated liver cirrhosis patients with primary DM had diabetic symptoms. (3) The levels of FPG and PPG in chronic hepatitis B patients with hepatogenic IGT and DM were lower than those in the patients with primary DM (P<0.05), but the levels of PINS and PCP in chronic hepatitis B patients with hepatogenic IGT and DM were higher than those in the patients with primary DM (P<0.05). (4) There were no differences in the levels of FPG and PPG between the hepatitis B associated liver cirrhosis patients with hepatogenic DM and those with primary DM (P<0.05). The levels of FINS, PINS, FCP, and PCP were higher in the hepatitis B associated liver cirrhosis patients with hepatogenic DM than those in the hepatitis B associated liver cirrhosis patients with primary DM (P<0.05). The levels of FPG and PPG in the hepatogenic DM patients were higher than those in the hepatogenic IGT patients (P<0.05), but their levels of FINS, PINS, FCP and PCP were lower than those in the hepatogenic IGT patients (P<0.05, P<0.01).

<b>CONCLUSIONb>Hepatogenic IGT and DM are always secondary in severe liver cirrhosis patients, who always showed no diabetic symptoms. The chronic hepatitis B patients with hepatogenic DM had increased insulin secretion, while the hepatitis B associated liver cirrhosis patients with hepatogenic DM had decreased insulin secretion.

Blood Glucose ; metabolism ; Diabetes Mellitus ; epidemiology ; etiology ; metabolism ; Female ; Glucose Intolerance ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; complications ; metabolism ; Male

PURPOSE: Using FibroScan(R) to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer's recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). MATERIALS AND METHODS: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. RESULTS: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages > or =F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong's method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. CONCLUSION: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.
Adult ; Alanine Transaminase/metabolism ; Female ; Hepatitis B, Chronic/*complications/metabolism ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis/*diagnosis/etiology/metabolism ; Male ; Middle Aged ; Prospective Studies

MicroRNA polymorphisms may be associated with carcinogenesis or immunopathogenesis of infection. We evaluated whether the mircoRNA-604 (miR-604) polymorphism can affect the persistence of hepatitis B virus (HBV) infection, and the development to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 subjects, who have either past or present HBV infection, were enrolled and divided into four groups (spontaneous recovery, chronic HBV carrier without cirrhosis, liver cirrhosis and HCC). We genotyped the precursor miR-604 genome region polymorphism. The CC genotype of miR-604 rs2368392 was most frequently observed and T allele frequency was 0.326 in all study subjects. The HBV persistence after infection was higher in those subjects with miR-604 T allele (P=0.05 in a co-dominant and dominant model), which implied that the patients with miR-604 T allele may have a higher risk for HBV chronicity. In contrast, there was a higher rate of the miR-604 T allele in the chronic carrier without HCC patients, compared to those of the HCC patients (P=0.03 in a co-dominant model, P=0.02 in a recessive model). The T allele at miR-604 rs2368392 may be a risk allele for the chronicity of HBV infection, but may be a protective allele for the progression to HCC in chronic HBV carriers.
Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Carcinoma, Hepatocellular/etiology/*genetics/pathology ; Case-Control Studies ; Demography ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genotype ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/metabolism ; Hepatitis B, Chronic/complications/*genetics/virology ; Humans ; Liver Neoplasms/etiology/*genetics/pathology ; Male ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors

<b>OBJECTIVEb>The aim of this study was to explore the diagnostic value of liver stiffness measurement combined with serum high-sensitivity C-reactive protein detection in HBV-related cirrhosis patients complicated with primary liver cancer.

<b>METHODSb>A total of 156 previously untreated chronic hepatitis B-related cirrhosis patients and 50 healthy subjects were included in this study. The 156 patients were divided into two groups: those with primary liver cancer (67 cases) and without liver cancer (89 cases). The 50 healthy subjects were considered as normal control group. Liver stiffness measurement (LSM) was conducted and serum high-sensitivity C-reactive protein (CRP) level was assayed in all the 156 patients and 50 normal individuals, and their measurement values were statistically compared and analyzed.

<b>RESULTSb>The LSM value was (39.72±29.05) kPa in the liver cancer patients, significantly higher than the (27.81±18.46) kPa in the cirrhosis alone patients and (4.25±0.74) kPa in the healthy controls (P<0.01 for both). Serum hs-CRP levels in the liver cancer patients was 5.81mg/L, significantly higher than 1.78 mg/L in the cirrhosis alone patients and 0.38mg/L in healthy controls, (P<0.01 for both). The higher the grade of LSM values was, the positive rate of CRP was higher in the cirrhosis patients complicated with primary liver cancer. In patients with LSM values ≥27.6 kPa, the serum CRP positive rate was 64.2% in patients with primary liver cancer, significantly higher than the 38.0% in patients with cirrhosis alone (P<0.01). In the 67 HBV-related cirrhosis patients complicated primary liver cancer, the LSM value and serum hs-CRP level in AFP-positive patients were (48.95±28.59) kPa and 4.91 mg/L, respectively, higher than those in the AFP-negative patients (28.64±26.83) kPa and 4.16 mg/L, but with a non-significant difference (P>0.05).

<b>CONCLUSIONb>Liver stiffness measurement combined with serum high-sensitivity C-reactive protein detection may have potential diagnostic implications as a marker of primary liver cancer occurrence in patients with HBV-related cirrhosis.

Biomarkers ; C-Reactive Protein ; metabolism ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B, Chronic ; complications ; metabolism ; Humans ; Liver Cirrhosis ; etiology ; metabolism ; virology ; Liver Neoplasms

<b>OBJECTIVEb>To study the pathogenesis of abnormal bone metabolism in patients with HBV liver cirrhosis.

<b>METHODSb>NM-300 signal-energy X-ray absorptiometry system was used to measure the bone mineral density (BMD) in 61 liver cirrhosis patients and 30 age-matched healthy controls. The serum levels of 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), bone gamma-carboxyglutamic acid-containing protein (BGP), IL-1beta, IL-6, tumor necrosis factor (TNF)alpha and urine crosslaps were also detected in these patients.

<b>RESULTSb>BMD in patients with HBV liver cirrhosis was lower than those of the controls. The serum levels of 1,25(OH)2D3 and BGP in cirrhosis patients were lower than those in the controls, and they were much lower in the osteoporosis (OP) group than in the non-osteoporosis (NOP) group. The PTH and CT were higher significantly in the patients than in the controls. The changes of serum 1,25(OH)2D3 and BGP were correlated with the changes of BMD. The serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps in cirrhosis patients were higher than those of the controls, and they were much higher in the OP group than in the NOP group. We also found that the serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps had a negative correlation with BMD.

<b>CONCLUSIONSb>These data suggest that bone formation is weakened and bone resorption is increased in patients with HBV liver cirrhosis, 1,25(OH)2D3 plays an important role in abnormal bone formation. Elevation of serum IL-1beta, IL-6, TNFalpha can accelerate bone resorption and cause hepatic bone disease (HBD). Taking 1,25(OH)2D3 and reducing the level of IL-1beta, IL-6, TNFalpha may be very important in preventing and treating HBD.

Adult ; Bone Density ; Bone and Bones ; metabolism ; Calcitriol ; pharmacology ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Osteoporosis ; etiology

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Bone Density ; drug effects ; Creatinine ; blood ; Hepatitis B, Chronic ; complications ; drug therapy ; metabolism ; Humans ; Male ; Organophosphonates ; therapeutic use ; Pain ; etiology ; Phosphorus ; blood

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis.
Apoptosis/genetics ; Carcinoma, Hepatocellular/pathology/*virology ; Cell Cycle ; DNA Mismatch Repair ; Hepatitis B virus/genetics/*pathogenicity ; Hepatitis B, Chronic/*complications ; Humans ; Liver Neoplasms/pathology/*virology ; Neovascularization, Pathologic/genetics/virology ; Telomere/genetics ; Trans-Activators/*metabolism ; Transcription, Genetic

<b>OBJECTIVEb>To investigate the relationship between hemostatic changes in liver cirrhosis patients with different degrees of their liver lesions.

<b>METHODSb>Forty-three patients (35 men, 8 women; age: 25 to 71 yr) with liver cirrhosis were divided into three subgroups (A, B, and C) on the basis of Child-Pugh classification. Among the patients, 13 were classified as Child-Pugh class A, 15 were class B, 15 were class C. 16 healthy individuals served as controls. A series of hemostatic tests and parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), factors II, V, VII, VIII, IX, X, vWF assay, antithrombin-III (AT-III), protein C (PC), D-dimer, tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor activity (PAI) were performed on 43 patients and the 16 healthy controls.

<b>RESULTSb>PT and APTT were progressively prolonged from A to B and then to C. In comparison to the controls there was a significant difference. Fibrinolytic activity and the activities of factors II, V, VII, IX, X were progressively decreased from A to B and then to C. In comparison to the controls there was a significant difference . AT-III and PC activity were progressively decreased from A to B and then to C. In comparison to the controls there was a significant difference. D-dimer and t-PA-antigen were progressively increased from A to B and then to C. In comparison to the controls there was significant difference. PAI activity did not display significant changes in the four groups.

<b>CONCLUSIONb>We found that there is a close relationship between the severity of cirrhosis and the hemostatic changes. Because the deterioration of the coagulation function and increasing fibrinolytic activity parallel the severity of liver cirrhosis, adequate treatment for cirrhotic bleeding should not only correct the coagulation defects, but also lower the increased fibrinolytic activity.

Adult ; Aged ; Antithrombins ; metabolism ; Blood Coagulation Factors ; metabolism ; Female ; Fibrinogen ; metabolism ; Hemostasis ; Hepatitis B, Chronic ; blood ; complications ; Humans ; Liver Cirrhosis ; blood ; diagnosis ; etiology ; Male ; Middle Aged ; Prothrombin Time ; Severity of Illness Index