Saturday, November 20, 2010

Hepatitis C Wellness: Fatty Liver Disease

By Meghan Lewit on November 17, 2010 8:05 AM

Two studies from the Childhood Obesity Research Center at the Keck School of Medicine of USC have found evidence that Hispanic children and adolescents are genetically predisposed to developing fatty liver disease — a condition that can lead to cirrhosis, cardiovascular disease and diabetes.

The studies, recently published in the journals Diabetes and the American Journal of Clinical Nutrition, found that Hispanic children who carry the PNPLA3 gene variant (GG) have increased liver fat. Children who carry the variant also are more susceptible to developing liver fat when consuming a high sugar diet.
Previous research has shown that Hispanics particularly are susceptible to the accumulation of fat in the liver, and reports suggest that nearly four of 10 obese Hispanic children and adolescents have nonalcoholic fatty liver disease.

“Collectively these findings demonstrate that Hispanics are genetically susceptible to the negative health effects of high sugar consumption and that this effect is manifested early in life,” said principal Investigator Michael Goran, professor of preventive medicine, physiology and biophysics and pediatrics, and director of the USC Childhood Obesity Research Center at the Keck School of Medicine. “This is a major public health concern, especially in the face of massive marketing of sugary beverages to children.”

The researchers conducted cross-sectional studies of more than 300 Hispanic youth (ages 8-18) in the Los Angeles area, using metabolic, diet and genetic measures. They found that GG carriers have almost double the amount of liver fat content as noncarriers. The effects are strongest in Hispanics because the frequency of the variant is much higher (49 percent) than in whites (23 percent) or African Americans (17 percent), said Jaimie Davis, assistant professor of preventive medicine at the Keck School of Medicine and a lead author on the studies.
The findings suggest that obese Hispanic children with the variant have an increased capacity for fat storage and decreased hepatic lipid mobilization (breakdown of stored fats), among those whose diets are high in sugar, she said.

Sugar intake is high among youth in Los Angeles and accounts for nearly half of all daily carbohydrate intake and 25 percent of energy intake. However, because the link between high sugar diets and liver fat accumulation was only evident among children who had the GG variant, the findings could have important implications for treating nonalcoholic fatty liver disease, Davis said.

“Specific dietary interventions based on the genetic predisposition may lead to more effective therapeutic outcomes in children with fatty liver disease,” she said. “I think the studies really highlight the need to test such diet and genotyping interventions.”
The work done by Goran and his team is at the interface of personalized and community health, said D. Brent Polk, professor and chair of the Department of Pediatrics and director of the Saban Research Institute at the Keck School of Medicine and Childrens Hospital Los Angeles.
“While we know that this genetic variant is overrepresented in Hispanic people, the findings help us identify individuals with increased susceptibility to worse disease,” he said. “Now we can ask does early intervention in this group prevent their progression to the complications of fatty liver disease?”

The studies were supported by the National Institute of Cancer, the USC Center for Transdisciplinary Research on Energetics and Cancer, the National Institute of Child Health and Human Development, the Minority Research Center of Excellence, the National Heart, Lung and Blood Institute, the Dr. Robert C. and Veronica Atkins Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the MGM Mirage Fund at USC.
Michael Goran, director of the USC Childhood Obesity Research Center at the Keck School of Medicine of USC
Fatty liver is a disease mostly seen among those who consume excessive alcohol or are obese and can lead to a form of hepatitis. It is a major cause of illness and death in the United States.
Previous reports have shown Hispanics are particularly susceptible to accumulation of fat in the liver, and reports suggest that nearly four of 10 obese Hispanic children have nonalcoholic fatty liver disease continue reading.........
January 31, 2010

No doubt, obesity is a massive public health issue here in America, as welll as rest of the developed world. We think about diabetes, heart disease, and chronic lung disease when we talk about the obesity related health complications. Now we can add chronic hepatitis C, and the increased rate of progression related to obesity. There have been numerous recent articles published regarding these two diseases.
James E. Everhart and colleagues published an excellent article in the journal, Gastroenterology, looking at the weight-related effects on disease progression in hepatitis C. They found the following:
This study showed an association of several weight-related features to increased rates of liver disease progression among patients with advanced chronic hepatitis C. In particular, insulin resistance and histologic features of fatty liver disease at baseline were strongly associated with progressive liver disease. Of greatest clinical significance, weight change during the trial was associated with liver disease outcomes. Although this study was performed among a selected group of patients with treatment-resistant hepatitis C, it is likely that the findings would extend to other patients with hepatitis C. In addition, the relations of weight-related features and outcomes were consistent for the 2 randomized groups, with the exception of HOMA2-IR, which was strongly associated with disease progression among untreated patients but not among patients assigned to treatment.

Several large cross-sectional studies, including the baseline of HALT-C, have documented an association of the degree of hepatic steatosis and fibrosis severity[8], [9], [10], [11], [12] and [13] up to cirrhosis, at which point steatosis was less common.[14] and [15] At least one study did not find an association of steatosis and fibrosis.16 Such associations have generally been made among patients without advanced liver disease. Cross-sectional studies neither offer compelling evidence of the influence of a risk factor on disease severity nor can they quantify the risk of disease progression.
In contrast to the cross-sectional studies, relatively small paired biopsy studies of patients with untreated hepatitis C either did not show a relation of steatosis on first biopsy to progression of fibrosis or did not report the result.[17] and [18] Of importance, a relation of steatosis to clinical outcomes has not been reported among a large cohort of patients with chronic hepatitis C. The current study has shown a complex yet clinically significant relation of steatosis and progressive liver disease, one that differed between patients with bridging fibrosis and with cirrhosis. No other factor showed an interaction with fibrosis stratum and outcome. In addition, in a secondary analysis limited to clinical outcomes, the interaction persisted such that the importance of the degree of steatosis on clinical progression was modulated by the severity of fibrosis. Most significantly, among patients with bridging fibrosis, steatosis was strongly associated with progression of liver disease. It is possible that greater steatosis would be a risk factor for fibrosis progression not only among patients with advanced fibrosis but also in patients with hepatitis C and a lesser degree of fibrosis.
In contrast to bridging fibrosis, clinical outcomes occurred less commonly among patients with cirrhosis and greater steatosis. Although steatosis may stimulate fibrosis progression, once cirrhosis develops, lack of histologic fat might reflect greater disease severity. In a separate analysis of this cohort, a decline in steatosis was associated with progression to cirrhosis, supporting the concept that less steatosis might be a marker of more severe disease in patients with cirrhosis.19 In the current analysis, baseline steatosis was not associated with other indicators of liver disease such as thrombocytopenia and esophageal varices (Table 4). Nevertheless, taken together, these data indicate that the failure to find fat in cirrhotic biopsies in hepatitis C appears to be an adverse prognostic sign and is quite different from patients with steatosis and less severe fibrotic liver disease. Two other markers of fatty liver disease were also evaluated. The presence of Mallory bodies was associated with disease progression for the entire cohort, but the relation was stronger among patients with bridging fibrosis. Interestingly, pericellular (zone 3) fibrosis was not associated with disease progression in either fibrosis stratum. The Ishak fibrosis scale does not consider pericellular fibrosis in its staging, which appears justified by the current study.

Although commonly found in hepatitis C–related liver disease, features of fatty liver disease have not been considered as measures of severity and are not scored in the standard grading and staging systems.7 The presence of fatty liver is not specific to hepatitis C and has not always been recognized as clinically significant. Because of their prognostic significance, histologic characteristics of fatty liver, particularly degree of steatosis and the presence of Mallory bodies, should be recorded in biopsy readings of patients with hepatitis C, and consideration should be given to their incorporation into histologic scoring systems of chronic hepatitis. Note that patients whose baseline biopsies indicated severe steatohepatitis were excluded from the trial. It is possible that patients with severe steatohepatitis (alcoholic or nonalcoholic) and chronic hepatitis C would have had an even higher rate of outcomes.

Baseline median HOMA2-IR of 4.59 was much higher than norms in the general population, as was the 24.9% prevalence of diabetes.[20] and [21] Glucose homeostasis deteriorates with development of severe liver disease, so that diabetes is common with cirrhosis.22 Therefore, associations in cross-sectional studies cannot establish that diabetes and hyperinsulinemia result in severe liver disease. An advantage of the current study is that a strong association of HOMA2-IR to the risk of progressive liver disease was established prospectively, even though HOMA2-IR is not necessarily a good measure of true insulin resistance. In the presence of steatosis, it appears that indirect measures of insulin secretion such as HOMA2-IR are strongly affected by diminished hepatic insulin clearance as well as by insulin resistance.23 Irrespective of the mechanism of its elevation, increased HOMA2-IR was associated with significant liver disease progression.

Baseline BMI was associated with outcomes (at least in univariate analysis), as was weight change. Nearly half of the HALT-C cohort was obese, which may have contributed to the severity of liver disease and resistance to standard treatment before entering the randomized trial. For a population with severe hepatitis C that is resistant to available treatment, the association of weight change with outcomes is the most immediate clinically significant finding of this analysis. Until now, there has been indirect evidence only that overweight and obesity are associated with worse outcomes in hepatitis C. Even among patients with nonviral-related steatohepatitis, evidence that weight ameliorates clinical disease has been limited.24 As previously shown, weight loss in the HALT-C cohort was associated with decline in steatosis.19 A.S. Lok, J.E. Everhart and R.T. Chung et al., Evolution of hepatic steatosis in patients with advanced hepatitis C: results from the hepatitis C antiviral long-term treatment against cirrhosis trial (HALT-C) trial, Hepatology 49 (2009), pp. 1828–1837.19
Of comparable significance, the current report has shown that weight loss was associated with a decline in inflammation. The difference in the change in inflammation between patients who lost >5% of weight within a year of random assignment and those who gained >5% was comparable to the change in inflammation between treated and untreated patients.2 Such declines in both steatosis and inflammation with weight loss might slow disease progression, even in the presence of ongoing infection. It is possible that the weight-related associations with liver disease progression identified in the current study could apply to obesity-related fatty liver in the presence of other liver diseases not resulting from hepatitis C.

For patients resistant to or unable to take antiviral therapy for hepatitis C, body weight appears to be a significant modifiable risk factor for disease progression. In the absence of a long-term trial of weight loss and liver disease outcomes, the results of this study may provide the strongest evidence for a clinical benefit of weight loss among overweight or obese persons with chronic hepatitis C.

In thinking about hepatitis C, and the treatments available, while we talk about all of the new results with protease inhibitors, stepping on the scale seems just as important in the comprehensive approack the treatment of hepatitis C requires.
By Nancy on November 16, 2010

Triglycerides and cholesterol are two different types of lipids or fats that are found in your blood as plasma lipids. The body needs cholesterol for building and maintaining the cell parts like cell membrane and others, as well as for making some essential hormones. Triglycerides are the chemical form of chains of high-energy fatty acids that supplies energy for tissue functions.
The body obtains triglycerides and cholesterol from fats in the foods ingested or the body makes them from other energy sources like carbohydrates. The bloodstream transports these lipids to the liver. Up to eight hours after a meal, the liver takes the triglycerides and cholesterol in the bloodstream that came from digested food. The liver processes these lipids and these are distributed by the blood; to all the body tissues to be used for cell and tissue functions. The cholesterol and triglycerides do not dissolve in the bloodstream, but attach to certain proteins, called lipoproteins that help them circulate in the entire body.
The liver converts excess calories from carbohydrates and fats to triglycerides and stores them in fat cells. Hormones regulate the release of the triglycerides from the fat cells as an when the body requires energy between meals.

Just as high cholesterol levels are bad, so are excess triglycerides in the bloodstream. Excess triglycerides can indicate an underlying condition like untreated diabetes mellitus. This excess can cause coronary artery diseases, fatty liver and renal disease in people. Therefore, it is important to keep your triglyceride levels under check along with your cholesterol levels.
Rigorous exercise, Omega-3 rich foods and supplements, a healthy diet and avoiding high caloric foods are ways to cut triglyceride levels.

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