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Insulin resistance is extremely common and frequently is associated with comorbid conditions such as cardiovascular disease, hypertension, obesity, infertility, and neurodegeneration. In addition, insulin resistance is the driving force for type 2 diabetes mellitus. Interestingly, co-existence of insulin resistance and chronic hepatitis C occurs more often than predicted by chance, with recent estimates indicating that 30% to 70% of patients with chronic hepatitis C display some evidence of insulin resistance. Recent research revealed several molecules, including tumor necrosis factor alpha, suppressor of cytokine signaling 1 and 3 proteins, insulin-receptor substrates 1 and 2, and other adipocytokines, potentially are involved in the development of insulin resistance in patients with chronic hepatitis C. Unfortunately, baseline insulin resistance has a negative impact on treatment outcomes in patients with chronic hepatitis C. However, successfully managing insulin resistance or diabetes mellitus in these patients may improve patients' likelihoods of successful outcomes with antiviral therapy. Likewise, eradication of hepatitis C virus in patients with insulin resistance or diabetes mellitus appears to improve glucose metabolism. Although adjunctive therapies such as insulin sensitizers and weight loss often are recommended, their ability to improve antiviral treatment response in patients with chronic hepatitis C is unproven. Studies are under way to determine whether improving insulin sensitivity results in better outcomes in patients receiving pegylated interferon alfa plus ribavirin therapy for chronic hepatitis C.
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PMID:Insulin resistance among patients with chronic hepatitis C: etiology and impact on treatment. 1858 70

In hepatitis C virus (HCV) infection, significant hepatic steatosis or superimposed nonalcoholic steatohepatitis is associated with disease severity and poor response to antiviral therapy. Nonalcoholic fatty liver disease (NAFLD) and HCV are common causes of chronic liver disease in Western countries and are strongly linked to concurrent obesity, insulin resistance, and the metabolic syndrome. With the escalating prevalence of obesity in North America, insulin resistance and the metabolic syndrome are major public health problems that have a significant impact on morbidity and mortality associated with NAFLD and HCV. This article focuses on the current understanding of the interplay between host and viral factors that are involved in the interaction between NAFLD and HCV.
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PMID:Hepatitis C infection and nonalcoholic fatty liver disease. 1862 29

Emerging attention has been paid to metabolic syndrome, which comprises several metabolic disorders including visceral obesity, diabetes mellitus, dyslipidemia, and hypertension. Whether the severity of each disease is mild to moderate, the comorbidity of these metabolic disorders has a serious impact on the development of atherosclerosis. Nonalcoholic fatty liver disease (NAFLD) is the major hepatic disorder in patients with metabolic syndrome, and indeed it is the most common cause of abnormal liver function tests in the working population in industrialized countries. In recent years, it has become recognized that NAFLD is no longer just a trivial disease, and a rather considerable proportion of the patients develop liver cirrhosis. Furthermore, chronic infection of hepatitis C virus also develops a pathological feature of steatohepatitis, and extended hepatic steatosis has a serious impact not only on the progression of hepatic fibrosis but also on the antiviral efficacy of interferon therapy. Emerging lines of studies indicated that insulin resistance, abnormal lipid metabolism, and dysregulation of cytokines/adipokines (e.g., tumor necrosis factor-alpha, adiponectin, and leptin) are profoundly involved in the pathogenesis of NAFLD. This review aims to integrate the reported evidence and to provide the current point of view for comprehensive understanding of the pathophysiology of steatohepatitis.
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PMID:Liver diseases and metabolic syndrome. 1864 37

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this disease.
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PMID:The epidemiology of nonalcoholic fatty liver disease: a global perspective. 1895 90

Hepatic fibrosis is an integral part in the progression of chronic liver disease, ultimately leading to cirrhosis and hepatocellular carcinoma. Globally, alcohol consumption, hepatitis B (HBV) and hepatitis C (HCV) have been the main causes of cirrhosis. More recently, the increasing prevalence of obesity and the metabolic syndrome has resulted in increasing incidence of cirrhosis secondary to nonalcoholic fatty liver disease (NAFLD), especially in developed countries. Chronic liver disease and cirrhosis are important causes of morbidity and mortality in the world. Moreover, the burden of chronic liver disease is projected to increase, due in part to the increasing prevalence of end-stage liver disease and HCC secondary to NAFLD and HCV.
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PMID:The global impact of hepatic fibrosis and end-stage liver disease. 1898 63

Narcotic analgesics are commonly prescribed drugs in patients with chronic hepatitis C (CHC) infection. In vitro data have shown that morphine enhances hepatitis C virus replication in human hepatic cells, however the effect of narcotics on hepatitis C virus disease progression remains uncertain. The aim of this study was to evaluate the potential effects of narcotic analgesic use on the progression of hepatic fibrosis in patients with CHC infection. We identified CHC patients who had been seen at our institution and had undergone a liver biopsy between 1990 and 2005. Their charts were reviewed for the presence of narcotic analgesic and known risk factors for progression of hepatic fibrosis including male sex, age > or =40, obesity, diabetes, and alcohol abuse. All biopsy were reviewed and fibrosis scores were standardized using the Batts and Ludwig scoring system (stage 0 to 4). A total of 1147 evaluable patients were identified and 171 of these had narcotic analgesic use. In univariate analysis, narcotic analgesic use was associated with the presence of alcohol abuse (P<0.001), obesity (P=0.02), and advanced fibrosis defined as stage 3 to 4 fibrosis (P=0.02), but not with male sex or diabetes. In multivariate logistic regression analysis, obesity [odds ratio (OR) 1.68 (confidence interval (CI), 1.21-2.33)], alcohol abuse [OR 1.45 (CI, 1.04-2.02)], age > or =40 [OR 1.85 (CI, 1.22-2.89)], and diabetes [OR 2.43 (CI, 1.41-4.14)] all independently predicted advanced liver fibrosis but narcotic analgesic use did not [OR 1.71 (CI, 0.99-2.89)]. As the amount of narcotic analgesic use increased from no use, to <3 months use, to > or =3 months use, the frequency of obesity, alcohol abuse, and advanced fibrosis increased accordingly (P=0.005), suggesting that it is difficult to separate these known risk factors from narcotic use as the cause for advanced fibrosis in this population.
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PMID:Narcotic analgesics and progression of fibrosis in patients with chronic hepatitis C. 1903 42

New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.
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PMID:New-onset diabetes mellitus after solid organ transplantation. 1904 Apr 89

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent liver diseases in the Western world. NAFLD represents a wide spectrum of histologic subgroups, with nonalcoholic steatohepatitis as the most aggressive form. The risk of developing NAFLD is strongly associated with metabolic syndrome and insulin resistance. The pathogenesis of NAFLD is a multiple-hit process resulting from hepatic fat deposition that is related to several conditions, including insulin resistance and central obesity. Additional hits, such as oxidative stress or adipocytokines produced by white adipose tissue, can further enhance liver damage leading to nonalcoholic steatohepatitis or fibrosis. Although NAFLD is often the primary liver disease of metabolic conditions, it can also exacerbate other liver diseases such as hepatitis C (HCV); indeed, more than 50% of patients with HCV have hepatic steatosis. Hepatic steatosis can be related to host factors (e.g., obesity, metabolic syndrome or insulin resistance) or to the genotype of virus (e.g., HCV genotype 3). Increasing evidence suggests that hepatic steatosis, insulin resistance and obesity in the setting of HCV have a negative impact on the efficacy of treatment and hepatic progression of fibrosis.
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PMID:Interaction of metabolic syndrome, nonalcoholic fatty liver disease and chronic hepatitis C. 1907 56

Candidates for liver transplantation undergo a thorough medical, surgical, psychosocial and financial evaluation prior to listing for transplantation. Prioritization for allocating livers is based upon the model for end-stage liver disease score and waiting-time mortality with the fundamental concept of giving organs to the sickest first. In the upcoming years the allocation system may be modified to include other factors associated with mortality, such as serum sodium, and may incorporate both pre- and post-transplant mortality. Strategies to expand the donor pool include utilizing livers from donors after cardiac death, split liver transplantation and living donor liver transplantation. Future challenges for liver transplantation will include the obesity epidemic and the prevention and treatment of recurrent disease, particularly hepatitis C.
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PMID:Current concepts in the evaluation of patients for liver transplantation. 1907 23

The incidence of liver cancer is high in all low-resource regions of the world, with the exception of Northern Africa and Western Asia. The estimated worldwide number of new cases of liver cancer in 2002 is 600,000, of which 82% are from developing countries. Given the poor survival from this disease, the estimated number of deaths is similar to that of new cases. Hepatocellular carcinoma (HCC) is the main form of liver cancer. A part from chronic infections with Hepatitis B and Hepatitis C viruses, which are the main causes of HCC, contamination of foodstuff with aflatoxins, a group of mycotoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is an important contributor to HCC burden in many low-income country. Alcoholic cirrhosis is an important risk factor for HCC in populations with low prevalence of HBV and HCV infection, and the association between tobacco smoking and HCC is now established. Diabetes is also related to an excess risk of HCC and the increased prevalence of overweight and obesity likely contributes to it. The second most important type of liver cancer is cholangiocarcinoma, whose main known cause is infestation with the liver flukes, Opistorchis viverrini and Clonorchis sinensis, which is frequent in some areas in South-East Asia. Angiosarcoma is a rare form of liver cancer whose occurence is linked to occupational exposure to vinyl chloride.
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PMID:Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. 1909 58


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