Nutrigenomics is a relatively new branch of nutrition science, which aim is to study the impact of the foods we eat on the function of our genes. Hepatosteatosis is strongly associated with hepatitis C virus infection, which is known to increase the risk of the disease progression and reduce the likelihood of responding to anti- virus treatment. It is well documented that hepatitis C virus can directly alter host cell lipid metabolism through nuclear transcription factors. To date, only a limited number of studies have been on the effect of human foods on the nuclear transcription factors of hepatitis C virus -induced hepatosteatosis.Three nutrients, selected among 46 different nutrients: beta-carotene, vitamin D2, and linoleic acid were found in a cell culture system to inhibit hepatitis C virus RNA replication. In addition, polyunsaturated fatty acids (PUFAs) especially arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) have been demonstrated to inhibit hepatitis C virus RNA replication. These PUFAs, in particular the highly unsaturated n-3 fatty acids change the gene expression of PPARa and SREBP, suppress the expression of mRNAs encoding key metabolic enzymes and hereby suppress hepatic lipogenesis and triglyceride synthesis, as well as secretion and accumulation in tissues. A recent prospective clinical trial of 1,084 chronic hepatitis C patients compared to 2,326 healthy subjects suggests that chronic hepatitis C patients may benefit from strict dietary instructions.Increasing evidence suggest that some crucial nuclear transcription factors related to hepatitis C virus -associated hepatosteatosis and hepatitis C virus RNA itself can be controlled by specific anti- hepatitis C virus nutrition. It seems important that these findings are taken into account and specific nutritional supplements developed to be used in combination with interferon as adjunctive therapy with the aim to improve both the early as well as the sustained virological response.

Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface hepatitis (based on histologic examination), hypergammaglobulinemia, and production of autoantibodies. Many clinical and basic science studies have provided important insights into the pathogenesis and treatment of AIH. Transgenic mice that express human antigens and develop autoantibodies, liver-infiltrating CD4(+) T cells, liver inflammation, and fibrosis have been developed as models of AIH. AIH has been associated with autoantibodies against members of the cytochrome P450 superfamily of enzymes, transfer RNA selenocysteine synthase, formiminotransferase cyclodeaminase, and the uridine diphosphate glucuronosyltransferases, whereas alleles such as DRB1*0301 and DRB1*0401 are genetic risk factors in white North American and northern European populations. Deficiencies in the number and function of CD4(+)CD25(+) (regulatory) T cells disrupt immune homeostasis and might be corrected as a therapeutic strategy. Treatment can be improved by continuing corticosteroid therapy until normal liver test results and normal liver tissue are within normal limits, instituting ancillary therapies to prevent drug-related side effects, identifying problematic patients early, and providing long-term maintenance therapy after patients experience a first relapse. Calcineurin inhibitors and mycophenolate mofetil are potential salvage therapies, and reagents such as recombinant interleukin-10, abatacept, and CD3-specific antibodies are feasible as therapeutics. Liver transplantation is an effective salvage therapy, even in the elderly, and AIH must be considered in all patients with graft dysfunction after liver transplantation. Identification of the key defects in immune homeostasis and antigen targets will direct new therapies.

Colorectal cancer is a significant cause of morbidity and mortality in the United States and throughout the world. The importance of this disease to gastroenterologists cannot be understated, given that screening and surveillance colonoscopy are dominant segments of clinical practice. The United States is the only country in the world where incidence and mortality rates from colorectal cancer are reported to be decreasing significantly, but health disparities in cancer screening, treatment, and survival persist. Health disparities are also evident worldwide, where the impact of this disease is staggering. In fact, rates of cancer are increasing in many parts of the world. Eliminating barriers to cancer screening and treatment could lead to substantial gains in quality and quantity of life and decrease the burden of colorectal cancer on public health. Programmatic and opportunistic screening programs have already had a measurable impact on disease burden, although the optimal screening strategy remains a matter of debate. Screening programs vary throughout the world, and further refinement will require a tailored approach because of differences in politics and fiscal reality among individual countries. Despite the strong impact of colorectal cancer on public health, there is cause for optimism and room for hope.

Treatment of colorectal cancer (CRC) has developed considerably over the past decade, especially in the areas of targeted therapeutics and biomarker development. Multiple cellular pathways influence the growth and metastatic potential of CRC. Targeted therapies have been designed to interfere with specific molecular events in pathways that mediate tumor growth and progression. Preclinical and clinical studies have shown that the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are valid therapeutic targets for patients with CRC. Monoclonal antibodies and tyrosine kinase inhibitors have been developed to target EGFR, VEGF, and VEGF receptors (VEGFRs) and are important additions to CRC treatment options. We review the most recent data on the VEGF and EGFR signaling pathways and therapeutic reagents designed to target them, provide insights into their mechanisms, and describe results from recent clinical trials.

First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. It is not clear if CD133 is a marker of colon CSCs-other cell surface markers, such as epithelial-specific antigen, CD44, CD166, Musashi-1, CD29, CD24, leucine-rich repeat-containing G-protein-coupled receptor 5, and aldehyde dehydrogenase 1, have been proposed. In addition to initiating and sustaining tumor growth, CSCs are believed to mediate cancer relapse after chemotherapy. How can we identify and analyze colon CSCs and what agents are being designed to kill this chemotherapy-refractory population?

Colon cancer screening is arguably the most important activity performed by gastroenterologists. Recent decreases in rates of death from colorectal cancer indicate that screening methods such as colonoscopy have a positive impact. There is still room for improvement, however, particularly in prevention of right-sided colon cancer. Practice issues, such as making colonoscopy more comfortable, safer, and less costly, are keys to continued success in cancer prevention. Colonoscopy techniques, technologies, and quality control measures have advanced to improve detection, classification, and removal of early neoplasias. In particular, slow, careful inspection of the colon by gastroenterologists who have been trained in lesion recognition has improved rates of detection of polypoid and flat neoplasias. Image enhancement methods such as chromoendoscopy have greatly improved neoplasia detection in patients with chronic colitis, but are not widely used because they are perceived as inconvenient. More convenient methods, such as "digital" chromoendoscopy, show promise but have had mixed results. Ultra-high magnification systems, including optical magnification and confocal endomicroscopy, can be used during the colonoscopy examination to evaluate small polyps, allowing physicians to make immediate diagnoses and decisions about whether to remove polyps. In patients with inflammatory bowel disease, improved imaging techniques could eliminate the needs for analysis of randomly selected biopsy samples and resection of all (neoplastic and non-neoplastic) polyps. It is important to maintain high standards of quality for colonoscopy examination, detection, and removal of high-risk lesions, as well as to make colon cancer screening more widely accepted and affordable for the entire at-risk population.

A variety of noninvasive molecular approaches to colorectal cancer screening are emerging with potential to improve screening effectiveness and user-friendliness. These approaches are based on the sensitive assay of molecular markers in stool, blood, and urine samples. New methods, especially next generation stool-based tests, have been shown to detect both colorectal cancers and precancerous lesions with high accuracy. Validation of these technologies in average-risk populations are needed to establish their role for general colorectal cancer screening. This review addresses the biological rationale, technical advances, recent clinical performance data, and remaining issues with molecular screening for colorectal cancer.

The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

The "serrated neoplastic pathway" describes the progression of serrated polyps, including sessile serrated adenomas and traditional serrated adenomas, to colorectal cancer. The recognition of this pathway during the last 15 years has led to a paradigm shift in our understanding of the molecular basis of colorectal cancer and significant changes in clinical practice. These findings are particularly relevant to prevention of interval cancers through colonoscopy surveillance programs-an important issue for colonoscopists. In the past, all serrated polyps were classified simply as hyperplastic polyps and were considered to have no malignant potential. Reappraisal of this view was largely driven by increasing recognition of the malignant potential of hyperplastic polyposis.

Microsatellite instability (MSI) is a hypermutable phenotype caused by the loss of DNA mismatch repair activity. MSI is detected in about 15% of all colorectal cancers; 3% are of these are associated with Lynch syndrome and the other 12% are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene, which occurs in tumors with the CpG island methylator phenotype. Colorectal tumors with MSI have distinctive features, including a tendency to arise in the proximal colon, lymphocytic infiltrate, and a poorly differentiated, mucinous or signet ring appearance. They have a slightly better prognosis than colorectal tumors without MSI and do not have the same response to chemotherapeutics. Discovery of MSI in colorectal tumors has increased awareness of the diversity of colorectal cancers and implications for specialized management of patients.

The acquisition of genomic instability is a crucial feature in tumor development and there are at least 3 distinct pathways in colorectal cancer pathogenesis: the chromosomal instability (CIN), microsatellite instability, and CpG island methylator phenotype pathways. Most cases of colorectal cancer arise through the CIN pathway, which is characterized by widespread imbalances in chromosome number (aneuploidy) and loss of heterozygosity. It can result from defects in chromosomal segregation, telomere stability, and the DNA damage response, although the full complement of genes underlying CIN remains incompletely described. Coupled with the karyotypic abnormalities observed in CIN tumors are the accumulation of a characteristic set of mutations in specific tumor suppressor genes and oncogenes that activate pathways critical for colorectal cancer initiation and progression. Whether CIN creates the appropriate milieu for the accumulation of these mutations or vice versa remains a provocative and unanswered question. The goal of this review is to provide an updated perspective on the mechanisms that lead to CIN and the key mutations that are acquired in this pathway.

Between 2% to 5% of all colon cancers arise in the setting of well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, and certain hamartomatous polyposis conditions. Each is associated with a high risk of colon cancer. In addition to the syndromes, up to one-third of colon cancers exhibit increased familial risk, likely related to inheritance. A number of less penetrant, but possibly more frequent susceptibility genes have been identified for this level of inheritance. Clarification of predisposing genes allows for accurate risk assessment and more precise screening approaches. This review examines the colon cancer syndromes, their genetics and management, and also the common familial colon cancers with current genetic advances and screening guidelines.

Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.

Molecular markers are used to characterize and track adult stem cells. Colon cancer research has led to the identification of 2 related receptors, leucine-rich repeat-containing, G-protein-coupled receptors (Lgr)5 and Lgr6, that are expressed by small populations of cells in a variety of adult organs. Genetic mouse models have allowed the visualization, isolation, and genetic marking of Lgr5(+ve) and Lgr6(+ve) cells and provided evidence that they are stem cells. The Lgr5(+ve) cells were found to occupy locations not commonly associated with stem cells in the stomach, small intestine, colon, and hair follicles. A multipotent population of skin stem cells express Lgr6. Single Lgr5(+ve) stem cells from the small intestine and the stomach can be cultured into long-lived organoids. Further studies of these markers might reveal adult stem cell populations in additional tissues. Identification of the ligands for Lgr5 and 6 will help elucidate stem cell functions and modes of intracellular signaling.

Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. There are no suitable preclinical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood. It is likely to arise from complex interactions among genetic, nongenetic host susceptibility, and environmental factors. Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. Alcohol consumption has been proposed as a risk factor for DILI from medications, but there is insufficient evidence to support this. Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. A genome-wide association study of flucloxacillin hepatotoxicity has yielded groundbreaking results and many similar studies are underway. Nonetheless, DILI is challenging to investigate because of its rarity, the lack of experimental models, the number of medications that might cause it, and challenges to diagnosis.

Complementary and alternative medicine (CAM) is increasingly used for treatment of inflammatory bowel disease (IBD). Acupuncture-type treatments are among the most popular options. Several studies have reported that moxibustion is effective in ulcerative colitis (UC). The objective of this review was to assess the clinical evidence for or against moxibustion as a treatment for UC.