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The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Patients: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. Results: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. Conclusion: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance. [ABSTRACT FROM AUTHOR]

Lu J-Y, Chuang L-M, Yang W-S, Tai T-Y, Lai M-Y, Chen P-J, Kao J-H, Lee C-Z, Lee H-S. Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-α therapy. Liver International 2005: DOI: 10.1111/j.1478-3231.2005.0. © Blackwell Munksgaard 2005 The study was designed to survey the change of adiponectin levels before and after interferon-α (IFN-α) therapy in patients with chronic hepatitis B and C infections. Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-α for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-α therapy. Insulin suppression test was conducted before and within 1 week after IFN-α therapy. The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-α treatment (−4.8±2.2 vs. 0.5±1.0 μg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-α ( P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9±3.2 vs. 10.8±3.0 μg/ml, P=0.02, n=4) and HBV responders (17.7±4.1 vs. 9.2±1.0 μg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6±1.8–11.7±1.2 mmol/l, P=0.03), but not in non-responders (12.3±1.1–11.0±1.0 mmol/l, P=0.20), after IFN-α therapy. IFN-α resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-α treatment, contributes to the lowering of adiponectin levels needs to be further investigated. [ABSTRACT FROM AUTHOR]

Lin C-L, Liao L-Y, Wang C-S, Chen P-J, Lai M-Y, Chen D-S, Kao J-H. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B.Liver International: 2005: 25: 564–570.© Blackwell Munksgaard 2005The long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are distinct from those in HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of hepatitis B virus (HBV) genotypes as well as precore/basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic hepatitis B in Taiwan.HBV genotypes and sequences of precore and basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease.HBV carriers with older age (>50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22–25,P<0.001) and basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41–12.03,P=0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30–14.52,P=0.02).The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan. [ABSTRACT FROM AUTHOR]

Liaw Y-F, Leung N, Guan R, Lau GKK, Merican I, McCaughan G, Gane E, Kao J-H, Omata M for the Asian-Pacific consensus update working party on chronic hepatitis B. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update.Liver International 2005: 25: 472–489.© Blackwell Munksgaard 2005.A large amount of new data on the treatment of chronic hepatitis B has become available such that the 2003 consensus statement requires revision and update.New data were presented, discussed and debated in an expert pre-meeting to draft a revision. The revised contents were finalized after discussion in a general meeting of APASL.Conceptual background, including the efficacy and safety profile of currently available and emerging drugs, was reviewed. Nineteen recommendations were formed and unresolved issues and areas for further study were suggested.The current therapy of chronic hepatitis B is modestly effective but not satisfactory. The development of new drugs and new strategies is required to further improve the outcomes of treatment. [ABSTRACT FROM AUTHOR]

Mah Y-H, Kao J-H, Liu C-J, Chen C-L, Chen P-J, Lai M-Y, Chen D-S. Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan.Liver International DOI: 10.1111/j.1478-3231.2005.01055.x.© Blackwell Munksgaard 2005The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan.H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease.All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B-related liver cirrhosis (6%) and hepatitis C-related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49–20.5,P=0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19–28.5,P=0.52).Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan. [ABSTRACT FROM AUTHOR]

Background/aim: Accurate histological assessment of liver fibrosis is essential in the management of chronic hepatitis B (CHB). Although semi- quantitative scoring systems describe well the pathological patterns of hepatic structure, they produce fibrosis evaluation that is not very precise. Image analysis or morphornetry has the theoretical advantage of providing truly quantitative data. Patients and methods: The present study aimed at validating a new image analysis system, Bioquant Nova Prime, in estimating collagen content in liver biopsy samples from patients with CHB. The biopsies were stained with picrosirius red and the areas of collagen were measured. The results were correlated with laboratory parameters and Ishak modified histological scores. Discriminative reliability of morphornetry was determined using receiver operating characteristics (ROC) analysis. Results: There was excellent interobserver agreement (r = 0.84-0.94, P< 0.01) in the morphornetric analysis. Significant correlations between the quantitative m orphornetric data and the semi-quantitative score (Spearman' s r = 0.68-0.78, P<0.001) were also demonstrated. Excellent discriminative power of morphornetry in differentiating mild from advanced fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis. Conclusions: Our results validated the use of Bioquant Nova Prime in estimating collagen content in liver biopsies. We showed that morphometry is a sensitive method of liver fibrosis quantification in CHB and complements semi-quantitative histological scoring system. This tool, with its reliable intraassay variability, could be of special value in assessing histological response to treatment after anti-viral or anti-fibrotic therapy. [ABSTRACT FROM AUTHOR]

Fotiadu A, Tzioufa V, Vrettou E, Koufogiannis D, Papadimitriou CS, Hytiroglou P. Progenitor cell activation in chronic viral hepatitis. Liver International 2004: 24: 268–274. © Blackwell Munksgaard 2004 Oval cell proliferation is known to occur in experimental models of hepatic regeneration and carcinogenesis. Recent studies have suggested that activation of progenitor cells, representing the human counterpart of oval cells, may play a role in hepatic diseases. Therefore, we evaluated putative progenitor cells in chronic viral hepatitis. Forty-one needle liver biopsy specimens from patients with chronic hepatitis B and 43 specimens from patients with chronic hepatitis C were examined histologically. The grade (histological activity index (HAI)) and stage (degree of fibrosis) were determined on routinely stained sections. The number of progenitor cells was assessed semiquantitatively on cytokeratin 7- (CK 7-) stained sections. In both aetiological categories of chronic viral hepatitis, progenitor cell numbers were found to increase in parallel to the HAI, as well as to the stage of disease. Features suggestive of hepatocytic differentiation of progenitor cells were also noted on immunohistochemical stains for CK 7 and ‘hepatocyte-specific’ antigen. In chronic hepatitis B and chronic hepatitis C, progenitor cell activation is correlated with the grade and stage of disease. Proliferating progenitor cells may play a role in hepatic regeneration occurring in this setting. [ABSTRACT FROM AUTHOR]

Firstly, the authors did not mention hepatitis B virus (HBV) infection status in 734 HCV-positive patients. It was reported that CHC patients with OBI co-infected were more likely to develop cirrhosis and HCC than those who are negative, as well as short survival time.2 Therefore, the HBV status in CHC patients might influence the development of HCV-related HCC and comprised the results. Some concerns about "PDCD1 and IFNL4 genetic variants and risk of developing hepatitis C virus-related diseases". [Extracted from the article]

MRI-defined sarcopenia predicts mortality in patients with chronic liver disease To the editor: We read with interest the study by Beer et al1 where the authors explored the association between sarcopenia defined by magnetic resonance imaging (MRI) and the mortality in patients with chronic liver disease (CLD). Actually, previous studies have shown that gender differences have a crucial impact on the prognosis of CLD patients.2,3 Therefore, gender differences might explain, at least in part, why sarcopenia is associated with higher mortality in CLD patients. [Extracted from the article]

Are inflammation-based models feasible tools in predicting the outcome of patients with hepatocellular carcinoma? Keywords: HCC; inflammation; prognosis EN HCC inflammation prognosis 1498 1498 1 06/04/20 20200601 NES 200601 We read with interest the paper "Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy" published in an upcoming issue of Liver International.[1] It is an elegant study that specifically looked at the feasibility of 8 inflammation-based prognostic models in predicting the outcome in patients with post-resection early recurrence of hepatocellular carcinoma (HCC). Firstly, as most HCC patients in China had chronic hepatitis B as the major etiology of cancer, the status of viral loads was not mentioned in these patients at the time of early recurrence. [Extracted from the article]

A letter to the editor is presented which discusses a study which evaluates long-term histological results in chronic hepatitis B Asian patients treated with entecavir.

A response from the author of the article "A model to predict antiviral treatment in HBeAg negative chronic hepatitis B with alanine aminotransferase ≤2 upper limit of normal," in the 2014 issue is presented.