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Little is known about the role of hepatitis B virus (HBV) factors in the long-term prognosis of hepatocellular carcinoma (HCC) after resection. The objective of the present study was to identify the changing patterns of HBV levels and its effect on outcome after resection. This study recruited 188 patients with HBV-related HCC who underwent curative resection. Among the 188 patients, 115 were alive without recurrence at 12 months, and had serial measurements of viral levels. The mean age was 53 years and the mean follow-up period was 48.5 months. With multivariate analysis, tumor size > 5 cm ( P = 0.047), Child-Pugh class B ( P = 0.017), vascular invasion ( P = 0.028), and HBV DNA > 10 copies/mL at the time of resection ( P = 0.003) were independently predictive of HCC recurrence for the entire population. For the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV DNA > 10 copies/mL at resection, and the absence of sustained HBV DNA level < 10 copies/mL, the presence of cirrhosis, and elevated aminotransferase levels (> 40 IU/L) were marginally or significantly associated with HCC recurrence and overall survival. However, on multivariate analysis, sustained HBV DNA level < 10 copies/mL was the only factor for both low recurrence ( P = 0.002; odds ratio [OR] 3.13; 95% confidence interval [CI] 1.55-6.35) and longer survival ( P = 0.002; OR 3.76; 95% CI 1.61-8.78). A high HBV replication state is among the most important predictors of adverse outcome after resection of HBV-related HCC. The sustained suppression of HBV below 10 copies/mL is a strong protective factor for long-term recurrence-free and overall survival. [ABSTRACT FROM AUTHOR]

Background/Aims: In patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria, the recurrence rate after liver transplantation is over 50%. We investigated pretransplant factor(s) that could predict recurrence after living donor liver transplantation (LDLT) in patients with HCC exceeding the Milan criteria. Methods: Pre-operative imaging showed that, of the 111 HCC patients who underwent LDLT between June 1995 and January 2006, 37 exceeded the Milan criteria. Clinical factors before LDLT were evaluated. Results: The 1- and 3-year cumulative recurrence rates were 35 and 55% respectively. Pretransplant risk factors for HCC recurrence were large tumour size (>6 cm, P=0.001), tumour exposed to the liver surface ( P=0.014) and progressive disease after pretransplant treatment ( P=0.038). The 2-year HCC recurrence rates in patients with 0, 1, 2 and 3 factors were 0% (0/4), 9% (1/16), 80% (8/10) and 100% (7/7) respectively ( P<0.001). The 2-year survival rate was significantly higher in patients with 0 or 1 factor than in patients with two or more factors ( P=0.022). Conclusions: In patients with HCC exceeding the Milan criteria, the three pretransplant factors that may be useful for identifying those with high HCC recurrence potential after LDLT are tumour size >6 cm, progressive disease after pretransplant treatment and tumour exposed to the liver surface. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the impact of hepatitis B viral (HBV) load on recurrence after complete necrosis in patients with hepatocellular carcinoma (HCC) who receive transarterial chemolipiodolization. The study involved several patients who had HBV-related HCC. Risk factors including viral load for posttreatment recurrence were analyzed. The study found that most of the patients developed a recurrence during the study period. Additionally, high HBV viral load was among the most important risk factors for posttreatment recurrence.

Background and Aims: The topographical distribution of hepatitis B core antigen (HBcAg) is related to the pathogenesis of liver damage caused by hepatitis B virus (HBV) infection. β-catenin plays an important role in both intracellular adhesion and Wnt signaling transduction pathways. This study investigated the intrahepatic expression of HBcAg and β-catenin in chronic HBV infection, and correlated the results with the degree of liver damage and viral replication. Method: Liver sections from 73 patients with chronic HBV infection were examined immunohistochemically for HBcAg and β-catenin. Results: The distribution of HBcAg could be classified into four types: only nucleus (C-1), both nucleus and cytoplasm (C-2), only cytoplasm (C-3) and all negative for nucleus and cytoplasm (C-4). Significant differences in serum aminotransferase level, HBV DNA and necroinflammatory score were observed among the different distribution types, and as the distribution of HBcAg changed from C-1 to C-4, fibrosis stage and hepatitis B e antigen (HBeAg) negative/anti-HBe positive rate increased concurrently. The distribution of β-catenin could be classified into two types: only membrane (B-1) and membrane with nucleus or cytoplasm (B-2). B-2 showed higher serum aminotransferase level and necroinflammatory score than B-1. Between B-1 and B-2, there was no significant difference in serum HBV DNA level or fibrosis stage. Conclusions: In chronic HBV infection, HBcAg distribution may change from C-1 to C-4 gradually, and in correlation with serum aminotransferase, and HBV DNA and HBeAg negative/anti-HBe positive rate. Nuclear or cytoplasmic distribution of β-catenin, compared with exclusive membranous distribution of β-catenin, is related to active hepatitis, but not viral replication. [ABSTRACT FROM AUTHOR]

Background and Aim: This study investigated the clinical variables that predict hepatitis B e antigen (HBeAg) loss in lamivudine-resistant patients receiving adefovir therapy. Methods: Fifty-six consecutive HBeAg-positive patients treated with adefovir for at least 12 months were enrolled in this study. All had serum alanine aminotransferase (ALT) levels over twice the upper limit of normal (ULN) as a result of lamivudine resistance. Predictors of HBeAg loss after switching from lamivudine to adefovir were examined. Results: During the follow-up period, 18 (32.1%) of 56 patients showed a loss of HBeAg. The estimated rates of HBeAg loss at 6, 12, and 18 months were 11.5%, 26.8%, and 42.9%, respectively. Univariate analysis revealed that pretreatment ALT levels >10 × ULN ( P = 0.029), a viral load at 3 months of therapy ( P = 0.017), and viral decline by >3 log10 from baseline at 3 months ( P < 0.001) were significantly associated with the loss of HBeAg within 12 months of therapy. With multivariate analysis using the stepwise logistic regression model, pretreatment ALT > 10 × ULN (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.09–19.44; P = 0.044) and viral suppression >3 log10 at 3 months (OR, 10.39; 95% CI, 1.86–58.07; P = 0.008) were identified as the two independent predictors of HBeAg loss. Conclusions: Pretreatment ALT levels and the initial pattern of post-treatment viral decline are the strongest predictors of the early achievement of HBeAg loss following treatment with adefovir in lamivudine-resistant patients. These results may provide useful information for the optimal timing of adefovir rescue as well as for better monitoring after treatment. [ABSTRACT FROM AUTHOR]

Adefovir dipivoxil (ADV) has demonstrated clinical activity against both wild‐type and lamivudine‐resistant hepatitis B virus (HBV). We analyzed the evolution of viral load and the changes of polymerase and precore/core promoter sequences in lamivudine‐resistant virus during ADV therapy. The authors studied 14 patients who had breakthrough hepatitis after lamivudine therapy. Serial sera were obtained prior to adefovir administration and at 3, 6 and 12 months after ADV therapy. Nucleotide sequences of polymerase and the precore/core promoter from the hepatitis B virus were analyzed. The median serum HBV DNA decrease with adefovir treatment was 4.35 log10 copies/mL at 12 months. Tyrosine‐methionine‐aspartate‐aspartate (YMDD) mutants were found in 12 patients among the 14 patients with lamivudine resistance. The YMDD mutant viruses reversed to the wild‐type in 6 patients out of the 12 patients after 3–6 months of ADV after discontinuing lamivudine therapy. In the analysis of the nucleotide sequences of the precore/core promoter gene, core promoter mutants in 12 patients were replaced by wild‐type virus in three patients (25%), while precore mutants in four patients were replaced by the wild‐type in three patients (75%). The results demonstrate the patterns of polymerase and precore/core promoter mutations in lamivudine‐resistant hepatitis B viruses and the reversion from the mutant to the wild‐type in some patients. In addition, despite several mutations in the polymerase during ADV therapy, ADV effectively suppressed HBV replication without the emergence of resistant viral mutants. J. Med. Virol. 79:902–910, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Background and Aim: Studies from hepatitis B virus endemic areas have shown less durable lamivudine-induced responses and have raised issues about the management of a post-treatment relapse. Methods: From January 2000 to June 2004, all 51 patients (43 HBeAg-positive and eight HBeAg-negative) were retreated with lamivudine for at least 12 months. All had a post-treatment relapse after HBeAg responses (HBeAg loss/seroconversion) during the first therapy. Results: During retreatment, HBeAg seroconversion occurred more frequently in those patients with HBeAg seroconversion than in those with HBeAg loss alone during prior lamivudine therapy ( P = 0.001). On multivariate analysis, prior HBeAg seroconversion and early virological response (EVR) (≤ 2 months of retreatment) independently predicted HBeAg seroconversion ( P = 0.012 and P = 0.004, respectively). With regard to virological breakthrough, only the time to virological response (> 2 months of retreatment) remained significant ( P = 0.048). Among the HBeAg-negative patients, virological breakthrough occurred in only one patient with a late virological response. Conclusions: EVR is a major predictor in determining a favorable response to lamivudine retreatment. Our observations suggest that lamivudine retreatment will provide more therapeutic gains in those patients with a prior HBeAg seroconversion than in those with HBeAg loss alone. [ABSTRACT FROM AUTHOR]

Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population. Methods: One hundred and thirty-seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules. Results: In class I antigens, the frequencies of HLA-A3 (relative risk (RR)=3.5, P<0.04), HLA-B35 (RR=2.0, P<0.03), and HLA-B46 (RR=2.5, P<0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1*0803, DQB1*0601 and DQB1*0604 were significantly higher in chronic HCV carriers than in controls (RR=2.5, P<0.005; RR=1.8, P<0.05; RR=1.9, P<0.04, respectively). On the other hand, the frequencies of DRB1*0301, DQA1*0501 and DQB1*0201 were significantly lower in chronic HCV carriers than in normal controls (RR=0.2, P<0.03; RR=0.4, P<0.004; RR=0.5, P<0.02, respectively). The haplotype DRB1*0803−DQB1*0601 significantly increased (RR=2.5, P<0.02) while the DQA1*0501−DQB1*0201 significantly decreased (RR=0.2, P<0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1*0803 and DQB1*0601 were associated with HLA-B46, particularly in patients with chronic HCV carriers. Conclusions: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population. [ABSTRACT FROM AUTHOR]

Background: Few clinical trials have investigated the use of lamivudine (LAM) in patients with decompensated cirrhosis related to chronic hepatitis B. The aim of the present study was to evaluate the efficacy of extended LAM treatment and to determine the timing of LAM administration in patients with decompensated cirrhosis. Methods: A total of 17 patients were treated with LAM 100 mg/day. The mean duration of follow up was 28 ± 8.4 months (range: 14–42 months). All patients were evaluated for evidence of clinical, biochemical and serologic replication of hepatitis B virus (HBV) infection. There were 12 patients with Child class B and five with Child class C. Results: Ten of 17 patients (58.2%) responded to LAM treatment. Of the breakthrough patients, six (86%) had YMDD motif variants. Clinical improvement was observed in nine out of 10 responders (90%), six of the seven breakthrough patients (86%) and five of six patients with YMDD variant DNA. Mean time to achieve a 2-point reduction in Child–Pugh–Turcotte score was 14 months in patients with Child class C, compared with 5.9 months in those with Child class B ( P < 0.001). Mean time required to gain a 0.5 g/dL increment in albumin was 14 months in Child class C and 5.8 months in Child class B. Hepatitis B e antigen (HBeAg) seroconversion was achieved in five of 13 HBeAg-positive patients at the last follow up and during the follow-up period. Conclusion: Long-term administration of LAM for patients with decompensated cirrhosis is effective. Earlier LAM administration in Child class B patients led to improved clinical outcomes. © 2005 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

Choi JY, Bae SH, Yoon SK, Cho SH, Yang JM, Han JY, Ahn BM, Chung KW, Sun HS, Kim DG. Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation – a pilot study. Liver International 2005: 25: 740–745. © Blackwell Munksgaard 2005 The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade ≥2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT. [ABSTRACT FROM AUTHOR]