The American Gastroenterological Association (AGA) standards for office-based gastrointestinal endoscopy were written in response to market changes in physician reimbursements for many endoscopic procedures that will continue to drive their performance into unregulated physician offices. The AGA believes that patient safety is best protected if these standards are adopted by sites that also comply with state/federal laws for licensure or are certified as an ASC and/or are accredited by a nationally recognized accreditation program (e.g., the Joint Commission on Accreditation of Healthcare Organization's [JCAHO] new Office-Based Surgery Standards). Heretofore, relevant practice standards for the performance of endoscopic procedures in these settings have not been available, a situation that the AGA believes puts patients at risk. These standards have been developed to reduce that risk.

Increasingly, studies of the relationship between common genetic variants and colorectal tumor risk are being proposed. To assess the evidence that any of these confers a risk, a systematic review and meta-analysis of published studies was undertaken.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association (AGA) Clinical Practice and Practice Economics Committee. The paper was approved by the Committee on March 20, 2001, and by the AGA Governing Board on April 18, 2001.

This document presents the official recommendations of the American Gastroenterological Association (AGA) on Hereditary Colorectal Cancer and Genetic Testing. It was approved by the Clinical Practice and Practice Economics Committee on March 20, 2001, and the AGA Governing Board on April 18, 2001.

Immunologic injury in the liver involves immigrant T and B lymphocytes and a resident lymphoid population that comprises distinct lymphocytic cells and accessory cells. The forerunner to autoimmunity is breaching of natural self-tolerance and hence the disruption of a fundamental property of the immune system. Such breaching occurs by processes that include inflammatory activation of immunocytes and macrophages, spillage of intracellular constituents, and epitope mimicry by constituents of microorganisms, with these acting on a genetically conditional phenotype; compounding factors include aberrations of apoptosis, whether insufficient or excess. The downstream end requires specifically directed inflammatory leukocyte traffic as an essential component of autoimmune expressions in the liver. The culmination is an orchestrated attack on hepatocytes or biliary epithelial cells by multiple effector pathways. Progress in type 1 autoimmune hepatitis still requires knowledge of a disease-specific autoantigen(s) involved in T-cell reactivity, although such knowledge in type 2 autoimmune hepatitis, in which the known autoantigen is cytochrome P4502D6, has not yet been integrated into a clearly defined scheme of pathogenesis. For PBC there has been a very promising amalgamation of molecular knowledge of the mitochondrial autoantigens. Future insights require deeper analysis of molecular, genetic, macroenvironmental, and microenvironmental elements in predisposition.

Acute flares in chronic hepatitis B are common and may be caused by a number of identifiable and potentially treatable factors. The common link for many of these exacerbation episodes is a change in the immunologic response to hepatitis B virus (HBV), and this may have no identifiable cause or be triggered by an increase in viral replication or genotypic change. It is important to keep in mind the clinical situations in which patients are at increased risk of reactivated infection and secondary exacerbations. Reactivation is frequently induced by medical treatments such as cancer chemotherapy, antirejection drugs used in organ transplantation, and corticosteroids. The immunologic flares that often result from sudden withdrawal of these medications can be life-threatening unless recognized and treated promptly with antivirals, and there is increasing experience that preemptive antiviral treatment can diminish their occurrence and improve the outcome. The experience with lamivudine and other nucleoside analogues has increased our understanding of the molecular events behind hepatitis flares that occur when chronic hepatitis B is treated with drugs that potently inhibit HBV DNA polymerase. However, not all flares are explainable by events related to HBV infection alone. Depending on the population studied, as many as 20%-30% of flares may be caused by infection with other hepatotropic viruses, and this situation may inhibit HBV replication. Proper understanding of the etiology and effective treatment of acute flares in chronic hepatitis B requires an appreciation of high-risk clinical situations, assessment of HBV replication status, and testing for other viruses when appropriate.

Synthesis of the hepatitis B virus (HBV) DNA genome occurs within the viral nucleocapsid in a mechanistically ordered fashion. The nucleocapsid contains small pores that permit influx of nucleotide triphosphates and metabolites of nucleoside analogues such as lamivudine for DNA synthesis. Lamivudine is a potent inhibitor of HBV and human immunodeficiency virus (HIV) reverse transcriptases, but substitutions of isoleucine or valine for methionine within the tyrosine-methionine-aspartate-aspartate (YMDD) motif are associated with virologic and clinical resistance to lamivudine therapy. Under lamivudine selection pressure, the high viral production rate and the low fidelity viral polymerase contribute to frequent development of the YMDD mutants. However, the pattern and dynamics of emergence of the mutant viruses over the wild-type virus are determined by multiple factors including replication efficiency, host immune response, and availability of replication space. Structural modeling of HIV reverse transcriptase has permitted key insights into the molecular basis of lamivudine resistance of HBV based on evolutionary relatedness of HIV and HBV. The side groups of isoleucine and valine of the YMDD mutants sterically prevent lamivudine from appropriately configuring into the nucleotide binding site of the reverse transcriptase. Aminotransferase flares are associated with lamivudine therapy and may signify clinical resistance with emergence of YMDD mutants. They may also herald the recovery phase with seroconversion and viral clearance. Reconstitution of the endogenous anti-HBV immune response may be equally important in the control of viral replication by lamivudine and other nucleoside analogues.