Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH) and ultimately may lead to cirrhosis. Hepatic ...steatosis or fatty liver is defined as increased accumulation of lipids in hepatocytes and results from increased production or reduced clearance of hepatic triglycerides or fatty acids. Fatty liver can progress to NASH in a significant proportion of subjects. NASH is a necroinflammatory liver disease governed by multiple pathways that are not completely elucidated. This review describes the main mechanisms that have been reported to contribute to the pathophysiology of NAFLD and NASH.
Hereditary hemochromatosis (HH) is one of the most common genetic disorders among persons of northern European descent. There have been recent advances in the diagnosis, management, and treatment of ...HH. The availability of molecular diagnostic testing for HH has made possible confirmation of the diagnosis for most patients. Several genotype-phenotype correlation studies have clarified the differences in clinical features between patients with the C282Y homozygous genotypes and other HFE mutation patterns. The increasing use of noninvasive tests such as MRI T2* has made quantification of hepatic iron deposition easier and eliminated the need for liver biopsy in most patients. Serum ferritin of <1,000 ng/mL at diagnosis remains an important diagnostic test to identify patients with a low risk of advanced hepatic fibrosis and should be used routinely as part of the initial diagnostic evaluation. Genetic testing for other types of HH is available but is expensive and generally not useful in most clinical settings. Serum ferritin may be elevated among patients with nonalcoholic fatty liver disease and in those with alcoholic liver disease. These diagnoses are more common than HH among patients with elevated serum ferritin who are not C282Y homozygotes or C282Y/H63D compound heterozygotes. A secondary cause for liver disease should be excluded among patients with suspected iron overload who are not C282Y homozygotes. Phlebotomy remains the mainstay of therapy, but emerging novel therapies such as new chelating agents may have a role for selected patients.
MicroRNAs in Common Human Diseases Li, Yu; Kowdley, Kris V.
Genomics, Proteomics & Bioinformatics/Genomics, proteomics and bioinformatics
10, Issue:
5
Journal Article
Peer reviewed
Open access
MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that have attracted tremendous attention from the biological and biomedical research communities over the past decade. With over 1900 ...miRNAs discovered in humans to date, many of them have already been implicated in common human disorders. Facilitated by high-throughput genomics and bioinformatics in conjunction with traditional molecular biology techniques and animal models, miRNA research is now positioned to make the transition from laboratories to clinics to deliver profound benefits to public health. Herein, we overview the progress of miRNA research related to human diseases, as well as the potential for miRNA to becoming the next generation of diagnostics and therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this preliminary study, a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin was effective for the treatment of HCV genotype 1 infection.
Hepatitis C virus ...(HCV) infection is a leading cause of cirrhosis, liver cancer, and liver transplantation. Peginterferon-free regimens of direct-acting antiviral agents have the potential to improve both the safety and efficacy of HCV therapy, as compared with the current standard treatment of peginterferon and ribavirin with telaprevir or boceprevir.
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Interferon is associated with substantial toxicity, and many patients with HCV infection are not eligible for interferon therapy owing to coexisting medical or psychiatric conditions or adverse events related to interferon, or they decline such therapy.
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There is also a large population of HCV-infected patients in whom interferon . . .
Nonalcoholic fatty liver disease is a common cause of chronic liver disease in the general population. Nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease, is ...associated with an increased risk of liver‐related mortality and cardiovascular disease. At present, a liver biopsy is the only generally acceptable method for the diagnosis of NASH and assessment of its progression toward cirrhosis. Although several treatments have shown evidence of efficacy in clinical trials of varying design, there are no approved treatments for NASH, and published trials are often too divergent to allow meaningful comparisons. There is thus a lack of established noninvasive, point‐of‐care diagnostics and approved treatment on one hand and a substantial population burden of disease on the other. These provide the rationale for developing consensus on key endpoints and clinical trial design for NASH. Conclusion: This article summarizes the consensus arrived at a meeting of the American Association for the Study of Liver Diseases on the key endpoints and specific trial design issues that are germane for development of diagnostic biomarkers and treatment trials for NASH. (HEPATOLOGY 2011;)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nonalcoholic steatohepatitis (NASH) and the metabolic syndrome (MetS) are highly prevalent in the Western population. Their pathogenesis is closely linked to insulin resistance, which serves as a ...therapeutic target for the management of these conditions. This review article reviews the research supporting the influence of MetS on NASH and includes studies supporting their similar epidemiology, pathogenesis, and treatment.
MicroRNAs are a group of intracellular noncoding RNA molecules that have been implicated in a variety of human diseases. Because of their high stability in blood, microRNAs released into circulation ...could be potentially utilized as noninvasive biomarkers for diagnosis or prognosis. Current microRNA isolation protocols are specifically designed for solid tissues and are impractical for biomarker development utilizing small-volume serum samples on a large scale. Thus, a protocol for microRNA isolation from serum is needed to accommodate these conditions in biomarker development. To establish such a protocol, we developed a simplified approach to normalize sample input by using single synthetic spike-in microRNA. We evaluated three commonly used commercial microRNA isolation kits for the best performance by comparing RNA quality and yield. The manufacturer’s protocol was further modified to improve the microRNA yield from 200μl of human serum. MicroRNAs isolated from a large set of clinical serum samples were tested on the miRCURY LNA real-time PCR panel and confirmed to be suitable for high-throughput microRNA profiling. In conclusion, we have established a proven method for microRNA isolation from clinical serum samples suitable for microRNA biomarker development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Primary sclerosing cholangitis is a chronic cholestatic liver disease that can shorten life and may require liver transplantation. The cause is unknown, although it is commonly associated with ...colitis. There is no approved or proven therapy, although ursodeoxycholic acid is used by many on an empiric basis. Complications including portal hypertension, fat-soluble vitamin deficiency, metabolic bone diseases, and development of cancers of the bile duct or colon can occur.
Estimates of the prevalence of chronic hepatitis B (CHB) in the United States differ significantly, and the contribution of foreign‐born (FB) persons has not been adequately described. The aim of ...this study was to estimate the number of FB persons in the United States living with CHB by their country of origin. We performed a systematic review for reports of HBsAg seroprevalence rates in 102 countries (covering PubMed from 1980 to July 2010). Data from 1,373 articles meeting inclusion criteria were extracted into country‐specific databases. We identified 256 seroprevalence surveys in emigrants from 52 countries (including 689,078 persons) and 1,797 surveys in the general populations of 98 countries (including 17,861,035 persons). Surveys including individuals with lower or higher risk of CHB than the general population were excluded. Data were combined using meta‐analytic methods to determine country‐specific pooled CHB prevalence rates. Rates were multiplied by the number of FB living in the United States in 2009 by country of birth from the U.S. Census Bureau to yield the number of FB with CHB from each country. We estimate a total of 1.32 million (95% confidence interval: 1.04‐1.61) FB in the United States living with CHB in 2009; 58% migrated from Asia and 11% migrated from Africa, where hepatitis B is highly endemic. Approximately 7% migrated from Central America, a region with lower CHB rates, but many more emigrants to the United States. This analysis suggests that the number of FB persons living with CHB in the United States may be significantly greater than previously reported. Assuming 300,000‐600,000 U.S.‐born persons with CHB, the total prevalence of CHB in the United States may be as high as 2.2 million. (Hepatology 2012)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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