importance of hepatitis B virus genome diversity in basal core promoter region

Hepadnaviruses employ an unusual strategy for the production of enormous number of virions during replication which makes rapid and substantial genetic sequence changes and alterations. The pathogenesis and clearance of hepatitis B virus [HBV] infection are engaged by the selection and expression of viral mutants during virus-host interactions. Mutations in regulatory regions such as the basal core promoter [BCP] which is thought to be related to lower production of hepatitis B "e" antigen [HBeAg] directly affects the clinical presentation of liver disease. However, the molecular structure of these mutations in chronic carriers has not been adequately evaluated. In this review we evaluate the molecular aspect and pathologic basis of basal core promoter mutations

Histopathological study of chronic hepatitis B: a comparative study of Ishak and METAVIR scoring systems

Ishak and METAVIR scoring systems are among the most commonly used histopathological systems to evaluate chronic hepatitis. To assess the level of agreement between these two scoring systems in patients with chronic hepatitis B. Liver biopsy samples taken from 92 patients with chronic hepatitis B were considered as the training set; 57 more biopsy specimens were used as the validation set. In the training set, grade of necroinflammation and stage of fibrosis for each liver biopsy specimen were determined by two expert liver pathologists using both Ishak and METAVIR systems. Inter-observer variability between the two pathologists was evaluated. Biopsy specimens of the validation set were seen and scored by a third expert pathologist. In the training set, criteria were developed to categorize Ishak grading and staging systems separately to best fit with the METAVIR scoring system. The criteria found in the training set, was then tested in the validation set. The level of agreement between the two scoring systems was assessed by weighted kappa statistics. For the training set, agreement between the two pathologists was excellent. Using our proposed criteria in the training set, there was excellent level of agreement in grading [Kappa = 0.89] and staging [Kappa = 0.99] between Ishak and METAVIR systems. In the validation set, the criteria led to substantial correlation [Kappa = 0.61] in grading, and excellent correlation [Kappa = 0.94] in staging between the two systems. Using our proposed criteria, excellent or at least substantial concordance between Ishak and METAVIR scoring systems can be achieved for the degree of both necro-inflammatory changes and fibrosis

Treatment of chronic hepatitis B

The primary goal of therapy in patients with chronic hepatitis B is durable suppression of HBV DNA to the lowest possible level. The threshold of HBV DNA level to initiate therapy is >/= 10[5] copies /ml for patients with HBe antigen-positive and >/= 10[4] copies /ml for patients with HBe antigen-negative chronic hepatitis B. Interferon alpha2b, lamivudine and adefovir dipivoxil are PDA-approved and could all be used as an initial first-line therapy in chronic hepatitis B. It was shown that adding lamivudine to either conventional interferon or peg-interferon did not increase the efficacy of treatment. Also, addition of lamivudine to adefovir had no additional effect in compensated patients. Response rate is about 30-40% with first-line drugs. Peg-interferon, which recently received PDA approval, was associated with an increased response rate. Further long-term studies are required in order to use Peg-interferon as a wide-scale first-line treatment. Treatment strategy is changing towards using prolonged combination therapy with evolving nucleoside analogues with or without an immunomodulatory agent, aiming to eradicate cccDNA

Effect of eradicating Helicobacter pylori on gastroesophageal reflux disease

The effect of helicobacter pylori either in provoking or protecting GERD is unclear and the results of studies are conflicting. We aimed to study the effect of H.pylori eradication on GERD by 24-hour ph monitoring. 14 patients with duodenal ulcer or erosive duodenitis without any endoscopic and clinical evidences of GERD were enrolled. 24-hour ph monitoring were performed before and 12 month after H-Pylori eradication. The score was based on DeMeester scoring system. H.Pylori was diagnosed by rapid urease test before eradication and by urea breath test [UBT] after eradication. The mean age was 41.6..10.2 years. The mean scores of 24-hour ph monitoring were 6.8..4.3 and 5.4..3.9 before and after eradication, respectively. The differences were not statistically significant [NS]. Epigastric pain changed significantly before and after the therapy [p<0.01]. H.pylori eradication did not have any effect on scores of 24-hour esophageal ph monitoring. Epigastric pain significantly decreased after eradication