Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.
Promoter Regions (Genetics)/*genetics ; Polymorphism, Genetic/*genetics ; Middle Aged ; Male ; Humans ; Hepatitis B virus/*physiology ; Hepatitis B/complications/*genetics/therapy/*virology ; Haplotypes/genetics ; Female ; Chemokine CCL2/*genetics ; Carcinoma, Hepatocellular/epidemiology/etiology/genetics/virology ; Aged, 80 and over ; Aged ; Adult

Amino Acid Motifs ; genetics ; Female ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; drug therapy ; virology ; Humans ; Lamivudine ; therapeutic use ; Liver Cirrhosis ; drug therapy ; etiology ; virology ; Male ; Point Mutation ; RNA-Directed DNA Polymerase ; genetics ; Reverse Transcriptase Inhibitors ; therapeutic use

<b>OBJECTIVEb>To investigate the distribution of HBV genotypes in Changzhou area and to clarify the genotype-related difference in the liver function, the level of HBV DNA and the long-term effect of lamivudine in the pathogenicity of HBV.

<b>METHODSb>Nested PCR and sequence analysis were conducted in 14 acute hepatitis (AH), 104 chronic hepatitis (CH), and 28 liver cirrhosis or hepatocellular carcinoma (LC/HCC) patients.

<b>RESULTSb>One hundred and forty six samples were positive for HBV DNA, and 51 samples were classified as genotype B (34.9%), 95 samples were classified as genotype C, serum ALT value was 383.8 +/- 335.7 IU in patients with HBV genotypes B, and 364.3 +/- 333.7 IU in genotypes C, HBV DNA value was 10(7.795 +/- 1.22) copies/ml in genotypes B and 10(7.69 +/0- 1.19) copies/ml in genotypes C, and there were 36 and 64 HBeAg positive cases in patients with genotypes B and C; there were no significant difference on the level of ALT, HBV DNA and the expression of HBeAg (P>0.05), but genotype C in LC/HCC was higher than CH (P<0.01). Twenty three genotype B and forty five genotype C patients received lamivudine treatment, after 48 weeks, 18 genotype B and 14 genotype C patients had higher ALT or HBV DNA positive.

<b>CONCLUSIONSb>These results indicate that genotype B and C existing Changzhou area; genotype C is associated with the development of severe liver disease and better therapeutic effect could be obtained in the patients with genotype C.

Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; genetics ; Female ; Genotype ; Hepatitis B ; complications ; drug therapy ; Hepatitis B virus ; genetics ; Humans ; Lamivudine ; therapeutic use ; Liver Cirrhosis ; etiology ; virology ; Liver Neoplasms ; etiology ; virology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Treatment Outcome

<b>OBJECTIVEb>To analyze antiviral effects of entecavir in patients with hepatitis B virus-related cirrhosis.

<b>METHODSb>104 patients of hepatitis B virus-related cirrhosis with no previous history of antiviral therapy were treated with entecavir 0.5 mg once daily. 37 patients were taken hepatic histologic examination before and after the treatment.

<b>RESULTSb>Mean reductions of serum HBV DNA was 5.1 log10 96 weeks after the treatment, HBV DNA became undetectable in 98.1% patients, and ALT became normal in 80.7% patients; HBeAg seroconversion occurred in 13.9% of the 72 HBeAg positive patients; 61.5% of these patients were infected with genotype C HBV, and 26.9% were infected with genotype B HBV. The genotype of HBV was not associated with the therapeutical effect. Child-pugh score was associated with the progression of the disease: the proportion of patients with disease progression was highest in Child-Pugh C grade patients and lowest in Child-Pugh A grade patients. The level of the HBV DNA load was positively correlated with Knodell HAI score at the baseline and 96 weeks after the treatment.

<b>CONCLUSIONb>Entecavir treatment results in suppression of HBV replication and delayed progression of fibrosis in patients with hepatitis B virus-related cirrhosis.

Adult ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Genotype ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; isolation & purification ; Hepatitis B, Chronic ; complications ; drug therapy ; virology ; Humans ; Liver Cirrhosis ; drug therapy ; etiology ; virology ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Virus Replication ; drug effects

<b>OBJECTIVEb>To study the incidence and the predictive factors of HBV polymerase YMDD variation among patients with chronic hepatitis B and liver cirrhosis during lamivudine therapy.

<b>METHODSb>The clinical data and serial sera of 313 chronic HBV infected patients (249 chronic hepatitis B and 64 liver cirrhosis) treated with lamivudine were collected. YMDD variations were determined by mispairing PCR-RFLP assay. The data were analyzed using SPSS software.

<b>RESULTSb>The cumulative rates of variation among patients with chronic hepatitis B and liver cirrhosis were 8.84% and 17.19%, 20.91% and 32.40%, 26.92% and 39.56%, 26.92% and 58.79% after 12, 24, 36 and 48 months of lamivudine treatment, respectively. The results of log-rank test and Cox's proportional hazard model analysis indicated that lamivudine monotherapy, low ALT level, high HBV DNA level, and the patients with liver cirrhosis at baseline were significantly related to an occurrence of YMDD variation.

<b>CONCLUSIONb>This study suggests that lower ALT and higher HBV DNA levels at baseline before lamivudine treatment, lamivudine monotherapy without combining alpha-interferon, and the patients with liver cirrhosis seem to be statistically significant for predicting the occurrence of YMDD variation.

Adolescent ; Adult ; Aged ; Amino Acid Motifs ; genetics ; Antiviral Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; genetics ; DNA-Directed DNA Polymerase ; genetics ; Female ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; drug therapy ; genetics ; Humans ; Lamivudine ; therapeutic use ; Liver Cirrhosis ; drug therapy ; virology ; Male ; Middle Aged ; Mutation

<b>OBJECTIVEb>To evaluate the efficacy and safety of adefovir dipivoxil in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine therapy.

<b>METHODSb>The disease relapsed in 14 hepatitis B patients with decompensated liver cirrhosis during lamivudine treatment due to the YMDD motif mutation. All 14 patients had positive HVBDNA and active hepatitis, and were evaluated as Child-Pugh Score C (CPS-C). The patients were treated with lamivudine 50 mg/d and adefovir dipivoxil 10 mg/d for 6 months.

<b>RESULTSb>One patient signed off due to non-hypoxemic hyperlactacidemia; other 13 patients showed decreased serum HBVDNA. All patients had serum HBVDNA < or =10(5) copies/ml and 7 patients had HBVDNA < or =10(4) copies/ml. Six patients regained normal serum ALT level and Child-Pugh scores decreased in all patients.

<b>CONCLUSIONb>Adefovir dipivoxil has satisfied efficacy and safety in treatment of decompensated liver cirrhosis patients with YMDD motif mutation during lamivudine treatment.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Aged ; Amino Acid Motifs ; genetics ; Antiviral Agents ; therapeutic use ; DNA-Directed DNA Polymerase ; genetics ; Female ; Hepatic Encephalopathy ; drug therapy ; genetics ; virology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; complications ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Liver Cirrhosis ; drug therapy ; genetics ; virology ; Male ; Middle Aged ; Mutation ; Organophosphonates ; adverse effects ; therapeutic use ; Protein Structure, Tertiary ; genetics ; Recurrence ; Reverse Transcription ; genetics

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

<b>METHODSb>One 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.

<b>RESULTSb>Comprehensive 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.

<b>CONCLUSIONb>GXR 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

BACKGROUND/AIMS: Viral breakthrough has been considered a major limitation of lamivudine in the treatment of hepatitis B virus related chronic liver disease. Its clinical meaning has not been thoroughly assessed. METHODS: 64 patients who showed viral breakthrough during lamivudine treatment were retrospectively reviewed. We evaluated the rate of HBeAg seroconversion and hepatic decompensation after viral breakthrough. RESULTS: After viral breakthrough, serum alanine transaminase (ALT) elevation more than 1.2X upper limit of normal (ULN) was noticed in 40 patients (62.5%). Acute flare (serum ALT elevation >X5 ULN, or serum bilirubin >3 mg/dL) occured in 15 patients (23.4%). During the period of follow up (15.0 +/- 9.7 months; range, 0-31 months) since viral breakthrough, decreased serum HBV-DNA level to below the detection limit and serum ALT normalization was seen in 15 patients (23.4%). HBeAg seroconversion was noticed in 7 (13.7%) of a total of 51 HBeAg positive patients at base line; in 4 (15.4%) of 26 patients with non-hepatic failure (chronic hepatitis or Child-Pugh class A liver cirrhosis) at base line; and in 2 (40.0%) of 5 patients with non-hepatic failure at base line and acute flare after viral breakthrough. During this period, terminal hepatic decompensation (Child-Pugh class C) or death was noticed in 9 (90.0%) of 10 patients who had hepatic decompensation (Child-Pugh class B or C) at baseline and acute flare after viral breakthrough. CONCLUSIONS: Acute flare after viral breakthrough seemed to continue during HBeAg seroconversion and rarely developed into terminal hepatic decompensation or death in patients with non-hepatic decompensation at baseline. Its incidence is not only high but lethal to most patients with hepatic decompensation at baseline.
Acute Disease ; Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; English Abstract ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/complications/drug therapy/*virology ; Humans ; Lamivudine/*therapeutic use ; Male ; Middle Aged ; Reverse Transcriptase Inhibitors/*therapeutic use

BACKGROUND/AIMS: Relapse has been reported after stopping nucleos(t)ide (NUC) therapy in the majority of chronic HBeAg negative hepatitis patients. However, the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not well known. We investigated the frequency of relapse in HBeAg negative CHB patients receiving NUC therapy. METHODS: The NUC therapy was discontinued at least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients. Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal range. Virological relapse was defined as HBV DNA >2,000 IU/mL. RESULTS: Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virological relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1 year sustained response. Of these factors, cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year virological relapse rate. Baseline HBV DNA and total treatment duration tended to be associated with virological relapse. CONCLUSIONS: Virological relapse developed in the majority (73.3%) of HBeAg negative CHB patients and clinical relapse developed in the half (53.3%) of patients at 1 year off therapy. Cirrhosis may be associated with the low rate of virological relapse.
Adult ; Age Factors ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Aspartate Aminotransferases/blood ; DNA, Viral/analysis ; Drug Administration Schedule ; Female ; Hepatitis B e Antigens/*analysis ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/diagnosis/etiology ; Male ; Middle Aged ; Nucleotides/*therapeutic use ; Recurrence ; Sex Factors