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Genetics of Viral Hepatitis:

Differential Gene Expression of Liver Tissue and Blood From Individuals With Chronic Viral Hepatitis: The purpose of this ongoing study is to find the genes that are expressed in both the circulating white blood cells and the liver of patients with varying degrees of liver damage of different causes. We anticipate that results from Differential Gene Expression (DGE) analysis will allow us to make predictions about likelihood of disease progression and/or response to treatment - http://clinicaltrials.gov/ct/gui/show/NCT00160940;jsessionid=86DC7605CA07D755E8BD1D1CDD17D308?order=38

Amplification of Full-Length Hepatitis B Virus Genomes from Samples from Patients with Low Levels of Viremia: Frequency and Functional Consequences of PCR-Introduced Mutations: Hepatitis B virus (HBV) sequence variability is increasingly recognized as a factor which modulates the course and outcome of HBV infection. Variants with disturbed hepatitis B e antigen (HBeAg) synthesis, large deletions in the nucleocapsid gene, or novel hepatocyte nuclear factor 1 binding sites in the core promoter were found to be associated with severe liver disease. This study aimed at estimating the number of mutations introduced during amplification of genomes from samples from patients with low levels of viremia and their influence on replication and antigen expression. The study concluded that many of the replication-competent HBV genomes from a clinical specimen will retain their replication and antigen expression phenotypes even after extensive amplification with Taq-Pwo polymerases. It is also stated that since replication competence is highly sensitive to random mutations, it is the best marker for the identification of HBV genomes with few or no PCR-introduced mutations - http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=9466771

Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes: Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15564741&dopt=Citation

Molecular Epidemiology of Hepatitis B Virus Variants in Nonhuman Primates: We characterized hepatitis B virus (HBV) isolates from sera of 21 hepatitis B virus surface antigen-positive apes, members of the families Pongidae and Hylobatidae (19 gibbon spp., 1 chimpanzee, and 1 gorilla). Sera originate from German, French, Thai, and Vietnamese primate-keeping institutions. To estimate the phylogenetic relationships, we sequenced two genomic regions, one located within the pre-S1/pre-S2 region and one including parts of the polymerase and the X protein open reading frames. By comparison with published human and ape HBV isolates, the sequences could be classified into six genomic groups. Four of these represented new genomic groups of gibbon HBV variants. The gorilla HBV isolate was distantly related to the chimpanzee isolate described previously. To confirm these findings, the complete HBV genome from representatives of each genomic group was sequenced. The data given in this study suggests that HBV infections are indigenous in the different apes. One event involving transmission between human and nonhuman primates in the Old World of a common ancestor of human HBV genotypes A to E and the ape HBV variants might have occurred - http://jvi.asm.org/cgi/content/full/74/11/5377

A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness: Genotypically, HBV genomes have been classified into six groups, designated A–F, based on an intergroup divergence of 8% or more in the complete nucleotide sequence. In this study, the authors report the HBV genotype prevalence in Atlanta (Georgia, USA) and Lyon (France) and describe a complete genome sequence of a new human HBV genotype, provisionally named genotype G. This genotype was found in patients chronically infected with HBV - http://vir.sgmjournals.org/cgi/content/full/81/1/67

A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients: This article describes a method which allows sensitive amplification and simplified functional analysis of full-length HBV genomes with or without prior cloning. The results demonstrate the potential of the established method for the structural and functional characterization of heterogeneous populations of complete virion-encapsidated HBV DNAs and suggest that HBV genomes with C gene deletions can have a selective advantage in immunosuppressed patients - http://www.pubmedcentral.gov/picrender.fcgi?artid=189390&blobtype=pdf

Heterogeneity and Common Features of Defective Hepatitis B Virus Genomes Derived from Spliced Pregenomic RNA: Defective hepatitis B virus (HBV) genomes derived from packaging and reverse transcription of spliced RNA pregenomes were reported to be associated with progression to chronic infection. Since only two types with similarly spliced regions were characterized so far we reasoned that additional "spliced" genome variants may exist. The data given in this article demonstrates substantial and HBV genotype-dependent diversity of spliced genomes. These genomes and the encoded proteins may play a role in the viral life cycle, persistence, and pathogenesis -

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WXR-45M902Y-P-1&_cdi=7165&_user=126770&_orig=search&_coverDate=11%2F24%2F1997&_qd=1&_sk=997619997&view=c&wchp=dGLbVtz-zSkWA&md5=b073579a4b962d199041ba96706c34d9&ie=/sdarticle.pdf

Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases: The aim of this study was to determine whether parenchymal cells or hepatic cytochrome P450 protein was changed in chronic liver diseases, and to compare the difference of CYP3A4 enzyme and its gene expression between patients with hepatic cirrhosis and obstructive jaundice, and to investigate the pharmacologic significance behind this difference. study demonstrated that, hepatic levels of individual P450s and its CYP3A4 isoform activity can selectively change in different chronic liver diseases. The hepatic microsome proteins and total P450 content remained unchanged in patients with hepatic cirrhosis and obstructive jaundice , but CYP3A4 activity and its protein level in liver tissue among patients with cirrhosis were evidently lowered. This change was not seen in obstructive jaundice group, and the cause of this change may be the lowered expression of CYP3A4 mRNA. These findings may have practical implications for the use of drugs in patients with liver diseases and emphasize the need to understand the metabolic fate of therapeutic compounds - http://www.wjgnet.com/1007-9327/9/359.asp

Relationship between clinical and pathologic findings in patients with chronic liver diseases: The aim of this study was to explore the relationship between clinical findings of patients with chronic liver diseases and the pathologic grading and staging of liver tissues. The study concluded that viral replication parameters such as HBeAg and HBV DNA have no correlation with the severity of inflammation and fibrosis. We compared the inflammatory and fibrotic severity in patients with positive markers of hepatitis B only (141 cases) and in those with positive markers of both hepatitis B and C (10 cases), but no statistical difference was found between them. However, as the patients suffering from co-infection of hepatitis B and C were very few in the study, the conclusion needs to be verified by larger sample studies - http://www.wjgnet.com/1007-9327/9/2796.asp

Subclinical Hepatic Encephalopathy Impairs Daily Functioning: Subclinical hepatic encephalopathy (SHE) is defined by the presence of at least one abnormal psychometric test and/or abnormal slowing of the EEG. The aim of this study was to determine the influence of SHE on the quality of life. Two psychometric tests with age-related normal values (NCT-A and DST) and automated EEG analysis were selected to be used as neuropsychological and neurophysiological screening tests for SHE. The influence of cirrhosis and SHE on patients' daily functioning was assessed using the Sickness Impact Profile (SIP) questionnaire. The study found a diminished level of functioning in patients with SHE, as reflected by significantly more impairments in all 12 categories of the SIP. Highest scores were found on the categories of social interactions, alertness, emotional behavior, mobility, sleep/rest, home management, and recreation and pastimes. These are all items that are expected to be affected in cognitive disorders. Although the severity and etiology of liver disease could have influenced the total SIP scores, multivariate analysis showed that only the presence of SHE independently accounts for the total SIP score result - http://hepatitis-central.com/hcv/symptoms/encephalopathy/subclinical.html

Hepatitis C Virus Genotypes - http://hepatitis-central.com/hcv/genotype/explained.html

Measures:

Medical Tests and Procedures in context of viral hepatitis - http://www.hon.ch/Library/Theme/HepB/tests.html

Hepatitis B Virus Test - Test Overview - http://www.webmd.com/hw/hepatitis/hw201572.asp

Test for HBsAg - American Association for Clinical Chemistry - http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html

Special Considerations in Interpreting Liver Function Tests: A number of pitfalls can be encountered in the interpretation of common blood liver function tests. These tests can be normal in patients with chronic hepatitis or cirrhosis. The normal range for aminotransferase levels is slightly higher in males, nonwhites and obese persons. Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis. Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase and gamma-glutamyltransferase levels do not become elevated for several days. Asymptomatic patients with isolated, mild elevation of either the unconjugated bilirubin or the gamma-glutamyltransferase value usually do not have liver disease and generally do not require extensive evaluation. Overall hepatic function can be assessed by applying the values for albumin, bilirubin and prothrombin time in the modified Child-Turcotte grading system - http://www.aafp.org/afp/990415ap/2223.html

Guidelines for Laboratory Testing and Result Reporting of Antibody to Hepatitis C Virus: Testing for the presence of antibody to hepatitis C virus (anti-HCV) is recommended for initially identifying persons with hepatitis C virus (HCV) infection. Substantial variation in reflex supplemental testing practices exists among laboratories, and an anti-HCV–positive laboratory report does not uniformly represent a confirmed positive result. These guidelines expand recommendations for anti-HCV testing to include an option for reflex supplemental testing based on screening-test– positive signal-to-cut–off (s/co) ratios. Use of s/co ratios minimizes the amount of supplemental testing that needs to be performed while improving the reliability of reported test results. Adoption of these guidelines by all public and private laboratories that perform in vitro diagnostic anti-HCV testing will improve the accuracy and utility of reported anti-HCV test results for counseling and medical evaluation of patients by health-care professionals and for surveillance by public health departments - http://www.cdc.gov/mmwr/PDF/rr/rr5203.pdf

Transmission of human hepatitis C virus from patients in secondary cells for long term culture: Infection by human hepatitis C virus (HCV) is the principal cause of post-transfusion hepatitis and chronic liver diseases worldwide. A reliable in vitro culture system for the isolation and analysis of this virus is not currently available, and, as a consequence, HCV pathogenesis is poorly understood. We report here the first robust in vitro system for the isolation and propagation of HCV from infected donor blood. This system involves infecting freshly prepared macrophages with HCV and then transmission of macrophage-adapted virus into freshly immortalized B-cells from human fetal cord blood. Using this system, newly isolated HCV have been replicated in vitro in continuous cultures for over 130 weeks - http://www.virologyj.com/content/2/1/37

Chronic liver disease questionnaire: Translation and validation in Thais: Quality of life (QOL) is a concept that incorporates many aspects of life beyond “health”. The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL. The objectives of this study were to translate and validate a liver specific questionnaire, the CLDQ - http://www.wjgnet.com/1007-9327/10/1954.pdf

COLORADO DEPARTMENT OF PUBLIC HEALTH & ENVIRONMENT - Acute Hepatitis C Questionnaire - http://www.cdphe.state.co.us/dc/hepatitis/hepc/AcuteHepCQuestionnaire.pdf

Document Provenance and History

Document Author: Dr. Fazal Danish

Document Created: 13th March 2006

Document Edits:

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