Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials.

Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development.

Nutrition in cirrhosis and chronic liver disease.

Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.

Review of treatment options for nonalcoholic fatty liver disease.

Although the future of NAFLD and NASH treatment has many promising agents, clinicians are currently faced with limited options with an emphasis on lifestyle modification. Figs. 1 and 2 summarize current practices for the diagnosis and treatment of NAFLD with the understanding that each patient's treatment must be customized to their comorbidities, exercise tolerance, and willingness to comply with therapy.

NAFLD: Predictive value of ALT levels for NASH and advanced fibrosis.

With expanding waistlines, the prevalence of NAFLD has burgeoned to become the leading cause of chronic liver disease in the USA. A subset of patients with NAFLD meet criteria for NASH with its inherent risk of progression to cirrhosis. Verma et al.

Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes.

Killing two birds with one stone: screening for chronic hepatitis C at the time of colonoscopy in the baby boomer cohort.

Colonoscopy is a well-accepted colon cancer screening modality that is recommended by the United States Multi-Society Task Force on all individuals greater than 50 years of age. Chronic hepatitis C (CHC) is a common cause of chronic liver disease with notably increased rates of infection in individuals born between 1945 and 1965. The Centers for Disease Control recently recommended all individuals of this "Baby Boomer" cohort undergo one time screening for CHC.

Vitamin D and nonalcoholic fatty liver disease (NAFLD): is it more than just an association?

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations. Concomitantly, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease.

Physical activity: an essential component of lifestyle modification in NAFLD.

NAFLD encompasses a spectrum of liver diseases pertaining to fat accumulation in the liver in the absence of significant alcohol consumption. NASH is the most clinically relevant subset of NAFLD, and patients with NASH have an increased risk of progression to cirrhosis or developing liver cancer. No pharmacotherapy is currently approved for NAFLD, and lifestyle modification via diet and exercise is most commonly recommended.

Nonalcoholic fatty liver disease.

As the hepatic manifestation of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of asymptomatic liver enzyme elevations in Western nations. Although it is easy to diagnose NAFLD, a liver biopsy is currently required to diagnose nonalcoholic steatohepatitis (NASH). Patients with NASH are those at greatest risk of progression to cirrhosis and, thus, treatment efforts are targeted to these individuals.

Features, diagnosis, and treatment of nonalcoholic fatty liver disease.

As the global incidence of obesity has increased, nonalcoholic fatty liver disease (NAFLD) has become a worldwide health concern. NAFLD occurs in children and adults of all ethnicities and includes isolated fatty liver and nonalcoholic steatohepatitis (NASH). Patients with NASH are at risk for developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma and have increased all-cause mortality.

Nonalcoholic steatohepatitis and noncirrhotic hepatocellular carcinoma: fertile soil.

Nonalcoholic fatty liver disease (NAFLD) is easily the most common cause of chronic liver disease in the United States (U.S.) as the hepatic manifestation of the metabolic syndrome.

Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis.

Unlabelled: Coffee caffeine consumption (CC) is associated with reduced hepatic fibrosis in patients with chronic liver diseases, such as hepatitis C. The association of CC with nonalcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to correlate CC with the prevalence and severity of NAFLD.

Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: a 12-month randomized, prospective, open- label trial.

Unlabelled: Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for (NASH). The aim of this randomized, open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan, compared to rosiglitazone alone, after 48 weeks of therapy. A total of 137 subjects with biopsy-proven NASH were enrolled and randomly assigned to receive either 4 mg twice-daily of rosiglitazone, 4 mg of rosiglitazone and 500 mg of metformin twice-daily, or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks.

Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study.

Background & Aims: Prevalence of nonalcoholic fatty liver disease (NAFLD) has not been well established. The purpose of this study was to prospectively define the prevalence of both NAFLD and nonalcoholic steatohepatitis (NASH).

Methods: Outpatients 18 to 70 years old were recruited from Brooke Army Medical Center.

Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy.

Unlabelled: Elevated low-density lipoprotein (LDL) levels and statin use have been associated with higher sustained virological response (SVR) rates in patients receiving chronic hepatitis C therapy. However, these relationships have not been well characterized in randomized controlled trials. Furthermore, little is known about the relationship between high-density lipoprotein (HDL) and virological response.

Induction pegylated interferon alfa-2b in combination with ribavirin in patients with genotypes 1 and 4 chronic hepatitis C: a prospective, randomized, multicenter, open-label study.

Background & Aims: Standard of care (SOC) treatment for chronic hepatitis C (CHC) involves weekly pegylated (PEG) interferon plus weight-based ribavirin with resultant sustained virologic response (SVR) rates at or near 50% for genotypes 1 and 4 virus. Induction therapy with higher doses of PEG interferon may improve first-phase viral kinetics and thus improve the overall SVR in genotypes 1 and 4 patients.

Methods: This multicenter, randomized, open-label trial enrolled treatment-naive genotypes 1- and 4-infected CHC patients to either initial induction therapy versus SOC.