Background/Aims
: Transmission of hepatitis B virus (HBV) in countries of intermediate endemicity, such as Italy, is thought to be primarily horizontal and, to a lesser extent, vertical. Most chronic ...carriers therefore become infected in infancy or at a very young age. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, with whom the affected person is in close contact.
Methods
: We studied a number of Italian families with multiple members chronically infected with HBV. The precore/core region of the virus was amplified from serum derived HBV-DNA, and the sequences subjected to phylogenetic tree analysis. In addition, the extent of amino-acid variation within the core region was correlated to HLA type, determined by allele-specific PCR.
Results
: The phylogenetic tree analysis provided strong evidence of intra-familial transmission of the virus. Analysis of amino-acid substitutions in the core region in relation to HLA class II alleles from members of the same family showed that these substitutions were restricted in siblings with concordant, and more diverse in those with discordant HLA haplotypes.
Conclusions
: This is consistent with major histocompatibility complex class II mediated selection pressure on the virus.
Surfactant protein D (SP-D) is a collagenous glycoprotein, a collectin, which functions as a pathogen-associated molecular pattern (PAMP) recognition receptor in the innate immune response. Although ...originally identified in the lung as a component of surfactant, SP-D also occurs in the gastric mucosa at the luminal surface and within gastric pits of mucus-secreting cells. Infection with the gastroduodenal pathogen Helicobacter pylori up-regulates expression of SP-D in human patients with gastritis, and its influence on colonization has been demonstrated in a Helicobacter SP-D-deficient (SP-D—/ —) mouse model. SP-D binds and agglutinates H. pylori cells in a lectin-specific manner, and has been shown to bind H. pylori lipopolysaccharide. Furthermore, evidence indicates that H. pylori varies LPS O-chain structure to evade SP-D binding which is speculated aids persistence of this chronic infection.
Treatment strategies in chronic hepatitis B (CHB) are evolving as more potent oral antivirals become available. However, drug resistance remains a major challenge and policy guidelines on management ...are limited by the evidence base. This study aims to review the implications of the National Institute for Health and Clinical Excellence (NICE) guidelines in a cohort of unselected CHB patients in the United Kingdom and to evolve a management algorithm for their treatment.
In total, 783 unselected hepatitis B surface antigen-positive patients, were assessed of whom 212 (27%) underwent liver biopsy. Age, alanine aminotransferase, hepatitis B virus DNA and necroinflammatory score were analysed to determine their value as predictors of fibrosis. Patients with biopsy evidence of fibrosis were offered treatment and followed longitudinally. Six-month on-treatment virologic response was evaluated to determine the validity of this strategy in predicting the early emergence of resistance.
Age, gender and necroinflammatory score were predictors of fibrosis in CHB patients, whereas age > 40 years was a predictor of cirrhosis in both hepatitis B e antigen (HBeAg)-positive (P < 0.03) and HBeAg-negative patients (P < 0.003). A total of 81% of HBeAg-positive and 65% of HBeAg-negative CHB patients who required adefovir add-on therapy were identifiable after 6 months of lamivudine monotherapy, by continuing HBV DNA positivity (P < 0.002 and P < 0.0001, respectively).
Advanced liver disease was present in patients falling outside current treatment guidelines, highlighting the importance of liver histology in identifying fibrosis and the need for antiviral therapy. While 6 month on-treatment virologic response as a trigger for instituting add-on therapy may be an improvement on the current recommendations, such a strategy should be integrated into any new treatment algorithm, likely to consist of entecavir and tenofovir.
The cellular responses of host defenses against microbial invasion require pathogen-associated molecular pattern (PAMPs) recognition molecules. Surfactant proteins (SP) SP-A and SP-D, members of the ...collectin family, recognize PAMPs and act as important mediators of the immune system. Both SP-A and SP-D interact with various microorganism- and pathogen-derived components by binding to complex carbohydrate structures of bacterial, viral, and fungal cells. The binding occurs via the surfactant carbohydrate recognition domain and leads to the agglutination and enhancement of pathogen clearance by specialized immune cells. In addition to their interaction with bacterial cells, SP-A and SP-D have a direct effect on immune cell function. This chapter discusses the structure, biosynthesis, ligands, and functions of SP-A and SP-D. Furthermore, the possible clinical applications for both SP-A and SP-D are highlighted.
Surfactant protein D (SP-D) is a collagenous glycoprotein, a collectin, which functions as a pathogen-associated molecular pattern (PAMP) recognition receptor in the innate immune response. Although ...originally identified in the lung as a component of surfactant, SP-D also occurs in the gastric mucosa at the luminal surface and within gastric pits of mucus-secreting cells. Infection with the gastroduodenal pathogen Helicobacter pylori up-regulates expression of SP-D in human patients with gastritis, and its influence on colonization has been demonstrated in a Helicobacter SP-D-deficient (SP-D super(-/-)) mouse model. SP-D binds and agglutinates H. pylori cells in a lectin-specific manner, and has been shown to bind H. pylori lipopolysaccharide. Furthermore, evidence indicates that H. pylori varies LPS O-chain structure to evade SP-D binding which is speculated aids persistence of this chronic infection.
The precore stop‐codon variant of hepatitis B virus (HBV) has been implicated in fulminant hepatitis. The precore/core regions of such variants from two sets of patients with interpartner ...transmission resulting in fulminant hepatitis in the contact, were sequenced to establish whether further sequence variations in the core region are specifically associated with the fulminant disease. In both sets of patients, there was sequence diversity of the precore/core region from the wild type, leading to numerous amino acid substitutions in the core region. Between the infecting source and the contact, there was only one amino acid change in one set of patients and none in the other. In addition, in the second set of patients, serum samples from four different time points were investigated. Sequence data showed no variation in each patient at the nucleotide level in the core region, even in the case of the source, who was followed for 3 years. In this same pair of subjects, the remainder of the genome was sequenced and was identical at the nucleotide level. Therefore, it appears that, at least in some cases of fulminant hepatitis caused by infection with the precore variant, the nucleotide sequence of the patient with fulminant hepatitis is identical to that observed in the asymptomatic source of infection. These data indicate that the severity and outcome of infection in such cases are unrelated to any additional variation in the entire HBV genome, and that the changed clinical picture is dependent on host factors, possibly the HLA environment. HLA typing of both the contact and source in the two sets of patients revealed that the contacts with fulminant hepatitis had one or more alleles at the HLA class II locus, previously shown to be associated with an acute hepatitis sufficient to clear the virus. (Hepatology 1995; 22:1628‐1634).
Infection with the hepatitis B or hepatitis C viruses may result in a number of different outcomes, ranging from asymptomatic self-limited (‘‘acute’’) infection to persistent (‘‘chronic’’) infection ...with liver cirrhosis, liver failure, or hepatocellular carcinoma. Therapeutic intervention in patients with persistent viral infection may lead to complete resolution of the infection and the associated liver disease, may fail, or may even exacerbate the liver disease. While it is clear that environmental and viral variables play an important role in determining some of these outcomes, it is also evident that host genetic background is a major factor particularly in determining which individuals develop persistent infection.
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