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Background & Aims We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD-resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy. Methods This study enrolled 72 patients with undetectable viral loads (≤12 IU/ml) and normal alanine aminotransferase levels after ADV add-on therapy for at least 6 months in LVD-resistant CHB patients. The enrolled patients were randomly assigned to continue with LVD–ADV combination therapy or switch to ADV monotherapy (n = 36 per group). Virological rebound was defined as HBV DNA detection at more than 12 IU/ml by quantitative polymerase chain reaction determined on two consecutive measurements. Results During 96 weeks of follow-up, 100% (36/36) of the patients in the LVD–ADV combination maintained group had persistently undetectable HBV DNA, compared with 94.4% (34/36) patients in the ADV monotherapy switched group. These two patients had undetectable HBV DNA after switching back to LVD–ADV combination therapy. There were no significant differences in the HBsAg levels between the two treatment groups during the 96-week follow-up period. Conclusions In our study, switching to ADV monotherapy resulted in sustained HBV DNA suppression in 94.4% of the patients for 96 weeks. Prior complete viral suppression with LVD–ADV combination therapy conferred a significant advantage in patients who switched to ADV monotherapy. LVD may be discontinued in patients who show a complete virological response to LVD–ADV combination therapy for at least 6 months.

Background The enhanced liver fibrosis (ELF) value is a non-invasive serum marker used for assessing liver fibrosis in chronic liver disease. To use the ELF value for the purpose of screening the general population and selecting subpopulations at high risk, it is important to know the normal range of ELF values as a prerequisite. Aims We aimed to define the normal range of ELF values by recruiting apparently healthy subjects and investigating factors influencing ELF values in subjects with minimal fibrotic burden. Methods ELF values were determined in a cohort of healthy subjects who underwent a health check-up and in healthy living liver donors who were screened for transplantation. None of subjects suffered from chronic heart disease, diabetes mellitus, metabolic syndrome, hepatitis B, hepatitis C, or human immunodeficiency virus infection, systemic autoimmune disease or liver dysfunction. Results Among 183 subjects analyzed, the normal ELF 5th through 95th percentile range was 5.95–8.73. Body mass index (P = 0.014) and male gender (P = 0.015) showed significant positive correlations with ELF value, whereas age did not. In multivariate linear regression analysis, platelet count was identified as the only independent factor influencing the ELF value (β=−0.006, P = 0.016). When considering the difference in ELF values between genders, the normal range of men was defined to be 6.72–8.93, this was slightly higher than that of women, 5.69–8.67. Conclusions We identified the normal range of ELF values and found that it can be significantly influenced by platelet count even in the healthy population.

BACKGROUND AND AIMS Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12. METHODS In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months. RESULTS Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17-0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83-0.95; P = 0.044). CONCLUSIONS Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

Hepatitis B virus surface antigen (HBsAg) quantification has been suggested to discriminate inactive carriers from hepatitis e antigen (HBeAg) negative chronic hepatitis, but it could be genotype-dependent. We studied the predictive value of HBsAg quantification in genotype C HBeAg-negative hepatitis B virus (HBV) carriers.We recruited 104 HBeAg-negative HBV carriers with HBV DNA levels 2,000 IU/ml and normal alanine aminotransferase (ALT) levels for at least 12 months and prospectively followed them for 36 months. Patients were classified into two groups: inactive carriers (IC) who showed HBV DNA levels 2,000 IU/ml and persistently ALT ≤ 40 IU/ml throughout the follow-up period and patients with HBeAg-negative chronic hepatitis (ENH).After follow-up, 73 patients were categorized into the IC group and 31 patients into the ENH group. HBsAg levels were significantly lower in the IC group than in the ENH group. The diagnostic accuracy of single-point HBsAg levels for predicting viral activation was favourable (AUROC = 0.710, P 0.001). Diagnostic accuracy improved when HBsAg was combined with baseline HBV DNA levels (AUROC = 0.750, P 0.001). The combination of HBsAg levels 850 IU/ml and HBV DNA 850 IU/ml predicted the reactivation of HBV replication with 84.6% diagnostic accuracy.Although it is inferior to other genotypes and to serum HBV DNA alone, single-point HBsAg level has a favourable diagnostic accuracy in genotype C HBeAg-negative HBV carriers and is expected to provide additional information for managing chronic hepatitis B.

Background: Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. Aim: To clarify the post-operative prognostic relevance of clinically significant PHT in Child–Pugh A cirrhotic patients. Methods: A total of 100 Child–Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). Results: Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P

To optimize management and predict long-term clinical courses in patients with chronic hepatitis B (CHB), noninvasive tests to determine the degree of hepatic fibrosis have been developed.This study aimed to validate a simple, noninvasive FIB-4 index, which was first derived from an HCV-HIV-co-infected population, in patients with CHB and to compare it with other noninvasive tests for predicting cirrhosis.From 2006-2008, a total of 668 consecutive CHB patients who underwent liver biopsies were enrolled. The fibrosis stage was assessed according to the Batts and Ludwig system by a single pathologist blinded to patients' data.For prediction of significant (For = 2) and severe (For = 3) fibrosis, and cirrhosis (F = 4), the area under the receiver-operating characteristic curves were 0.865, 0.910 and 0.926 respectively. In predicting cirrhosis, it demonstrated diagnostic values comparable to the age-spleen platelet ratio index (0.937, P=0.414) and age-platelet index (0.928, P=0.888), and better outcomes than spleen-platelet ratio index (0.882, P=0.007), aspartate aminotransferase (AST)-platelet ratio index (0.731, P0.001) and AST-alanine aminotransferase ratio index (0.730, P0.001). FIB-4 cut-offs of 1.6 and 3.6 provided 93.2% negative predictive value and 90.8% positive predictive value for detection of cirrhosis respectively. Based on these results, liver biopsy could be avoided in 70.5% of the study population. These cut-offs were validated internally using bootstrap resampling methods, showing good agreement.FIB-4 is a simple, accurate and inexpensive method of predicting cirrhosis, with outcomes comparable to other noninvasive tests and may reduce the need for liver biopsy in the majority of CHB patients.

Backgrounds: Periodic endoscopic screening for oesophageal varices (OVs) and prophylactic treatment for high-risk OVs (HOVs; medium/large OVs or small OVs plus red sign/decompensation) are currently recommended for all cirrhotic patients. However, if a simple, noninvasive test is available, many low-risk patients may reliably avoid endoscopy. Aims: We conducted a large-scale validation study of a simple, noninvasive test called P2/MS based on complete blood counts, (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)], and compared it with other predictive tests for HOVs in B-viral cirrhotic patients. Methods: From 2008 to 2009, we prospectively enrolled 318 consecutive B-viral cirrhotic patients. All underwent endoscopy and laboratory evaluation. Results: An area under the receiver operating characteristic curve of P2/MS was 0.941 for HOVs, comparable with those of the age–spleen platelet ratio index (0.922, P=0.317) and spleen–platelet ratio index (0.922, P=0.324), and better than those of age–platelet index (0.653, P

Aim To investigate the variability in liver stiffness measurement (LSM) values from the fifth, sixth and seventh intercostal space (ICS) and examine whether LSM better predicts significant fibrosis (F2-4) and cirrhosis when LSM is performed at the same site as liver biopsy (LB). Methods This study enrolled 91 consecutive patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) who underwent both LB and LSM between September 2007 and January 2009. Results The mean age of the patients was 45.4 years (66 men and 25 women). F1 fibrosis was noted in 12 patients (13.2%), F2 in 28 (30.7%), F3 in 15 (16.5%) and F4 in 36 (39.6%). The mean LSM values from the fifth, sixth and seventh ICS were 11.6, 11.1 and 10.9 kPa respectively. The mean LSM value from the same site as LB was 11.0 kPa. An interclass correlation analysis showed no significant difference in LSM values from the fifth, sixth and seventh ICS and the same site as LB. The area under the receiver operating characteristic curves of LSM values from the fifth, sixth and seventh ICS and the same site as LB for predicting significant fibrosis were 0.815, 0.838, 0.818 and 0.837, respectively, and those for cirrhosis were 0.919, 0.916, 0.907 and 0.913, respectively, with all overlapping confidence intervals. Conclusions Any LSM value from the fifth, sixth or seventh ICS can predict significant fibrosis and cirrhosis with considerable accuracy without statistical differences regardless of correspondence with LB site in patients with HBV-related CLD.

Background: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence. Patients and methods: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100 000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA ( 100 000copies/ml). Serum DNA level, biochemical tests, α-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. Results: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently. Conclusions: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.

Purpose: Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. Methods: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count ≥250/mm3. Results: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. Conclusion: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites.