Conference Reports for NATAP

7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV November 13-17, 2005 Dublin, Ireland Back

Hepatic steatosis: the common denominator for insulin resistance in obese and lipoatrophic subjects       Abstract presented at the 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-16 November 2005, Dublin, Ireland Antiviral Therapy 2005; 10:L2   Note from Jules Levin: Below in this report are two presentations on fatty liver made at the 7th Lipodystrophy Workshop. Concerns regarding the development of fatty liver or steatosis (also called NASH: nonalcoholic steatosis hepatitis) have been high on my radar. Not only are HIV+ individuals at risk for developing fatty liver now but over time as we age risk will increase. HIV+ individuals often have the important risk factors for fatty liver and fatty liver can have serious consequences. If a person has hepatitis + HIV coinfection, fatty liver is a greater concern, fatty liver can harm the liver & reduce response rates to pegIFN/RBV. If After having been a lone voice rigorously raising this concern at the Lipodystrophy Workshop for years, Workshop organizers finally brought in an expert speaker on the topic. I did not attend the meeting since I was at the AASLD liver conference, which was a landmark meeting due to the presentations regarding about 10 new HCV drugs in various stages of development, and the development of new drugs for HBV & the extensive attention HBV also received at AASLD. But I was told after the Lipo Wksp that the talk on steatosis was excellent and appeared to invigorate interest, although we'll see if it receives attention or is put on the back burner. Meanwhile, people with HIV are at risk for fatty liver, but a controversy appears to be that some HIV doctors and HIV researchers do not agree that the risk is any more than for the general population. I disagree and a number experts in the field of lipids, hepatitis, HIV, & lipodystrophy agree with me. At the very least HIV & lipodystrophy researchers should agree there is a concern & take a better look with properly designed studies at this question. Several studies have been presented at HIV/hepatitis conferences over the past 2 years showing a correlation between developing fatty liver for people with HIV who have risk factors for steatosis. Risk factors include elevated lipids and insulin resistance. Following is the abstract of the talk at the Workshop & links to numerous articles & studies on this topic on the NATAP website:   ABSTRACT FOR TALK AT WORKSHOP   H Yki-Jarvinen University of Helsinki, Helsinki, Finland   Insulin normally inhibits the production of both glucose and triglycerides (VLDL) from the liver. If the liver is fatty, these inhibitory actions of insulin are impaired. This results in mild hyperglycaemia (leading to hyperinsulinaemia) and hypertriglyceridaemia. The amount of fat in the liver, rather than the amount of subcutaneous fat, seems to determine the degree of insulin resistance, as both individuals with too little fat (lipoatrophy) and too much subcutaneous fat (obesity) have an increased amount of fat in the liver and are insulin resistant. Hyperinsulinaemia is a consequence rather than cause of fat accumulation in the liver (this is controversial--which causes which-see study in links), since chronic hyperinsulinaemia induced by insulin therapy decreases liver fat content.   An increase in liver fat content has been shown to predict, independent of other cardiovascular risk factors, type 2 diabetes and cardiovascular disease. This is easily explained by the fact that the liver, once fatty, overproduces most of the known cardiovascular risk factors. These include in addition to VLDL and glucose, CRP, PAI- 1, fibrinogen and coagulation factors. Liver fat content can be non-invasively accurately quantified by proton magnetic resonance spectroscopy. The exact causes of variation in liver fat content are poorly understood. The amount of visceral fat is correlated with liver fat but does not, even in patients with markedly increased visceral fat, explain more than a minor fraction of variation in liver fat content.   Despite marked differences in adipose tissue mass between obese and lipoatrophic individuals, these two groups are characterized by in part similar alterations in adipose tissue metabolism. In both groups, the number of macrophages is increased. TNFa expression and production from macrophages are increased. TNFa induces insulin resistance in adipose cells. One mechanism via which this occurs is downregulation of adiponectin expression. Serum levels of adiponectin are low in both insulin-resistant obese and lipoatrophic subjects. Genetic causes in variation in liver fat content have been sparsely studied. Liver fat content can be decreased by weight loss and by a low as compared to a high fat diet. In addition, treatment of both lipodystrophic and type 2 diabetic patients with PPARg agonists but not metformin decreases liver fat content and increases serum adiponectin levels.   The fatty liver may help to explain why some, but not all, obese individuals are insulin resistant and why even lean individuals lacking subcutaneous fat are insulin resistant, and thereby at risk of developing type 2 diabetes and cardiovascular disease.   Hepatic steatosis and insulin resistance in HIV infection   Abstract presented at the 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-16 November 2005, Dublin, Ireland ABSTRACT 47 Antiviral Therapy 2005; 10:L30   J Liebau1, R Andersen1, S Grinspoon1, N Holalkere 2, D Sahani 2 and C Hadigan1 1Program in Nutritional Metabolism, Massachusetts General Hospital, Boston, MA, USA; 2Department of Radiology, Massachusetts General Hospital, Boston, MA, USA   Objectives: HIV-infected patients have a number of potential risk factors that may predispose them to the development of hepatic steatosis, including increased visceral fat, hyperlipidaemia, insulin resistance, HCV co-infection and drug toxicities. The aim of the study was to evaluate HIV-infected men and women for hepatic steatosis using noninvasive MR spectroscopy (MRS) and to evaluate the relationship between liver fat content, insulin resistance and other associated risk factors.   Methods: We examined 28 consecutively recruited HIV-infected subjects (21 men and 7 women) without specific referral for liver disease from community-based organizations. Subjects with alcohol abuse within 3 years were excluded. The primary clinical measures were homeostatic model for assessment of insulin resistance (HOMA-IR) calculated from fasting insulin and glucose, liver fat content measured by MRS and visceral abdominal fat area (VAT) measured by computed tomography.   Results: Steatosis (defined as liver % fat >5) was found in 13 (46%) subjects.   Subjects with steatosis were older [48 (3) vs 42 (2) years, P=0.04], more likely to be male [male/female ratio 12/1 vs 9/6, P=0.04] and had higher-   mean HOMA-IR [2.9 (0.6) vs 1.5 (0.2), P=0.03], alanine aminotransferase [64 (7) vs 43 (3) U/L, P=0.005], and VAT [17 249 (2532) vs 9852 (1123) mm2, P=0.01] compared to subjects without steatosis.   We identified a strong positive correlation between liver % fat and VAT (r=0.71, P<0.0001) and liver % fat and HOMA-IR (r=0.58, P=0.0014).   A positive history of HCV co-infection or past alcohol abuse was not associated with increased steatosis. There was no difference in CD4 T cell count between subjects with and without steatosis.   In a multivariate regression model, abdominal VAT was the strongest independent predictor of liver % fat (P<0.005).   Discussion: We identify a high prevalence of steatosis among HIV-infected subjects. Subjects with steatosis had significantly greater insulin resistance and increased visceral adipose tissue, and these variables were tightly correlated with the degree of hepatic steatosis. Further studies are needed to determine the prevalence and extent of steatosis in the general population of HIV-infected patients. Our data suggest that hepatic steatosis is a common finding and we show strong correlations between steatosis and risk factors known to be associated with fatty liver in the general population.   Useing the search Engine on the NATAP website will bring you to many more articles & studies on this topic than what you see below.   CRYOGLOBULINEMIA IS ASSOCIATED WITH STEATOSIS AND FIBROSIS IN ... Risk factors for fibrosis and steatosis were assessed. ... Steatosis higher than 10% was associated with a higher body mass index (p<0.001), HCV genotype 3 ... www.natap.org/2005/AASLD/aasld_26.htm   Steatosis in chronic hepatitis C: Relative contributions of ... Steatosis has emerged as a histologic finding of importance to the progression ... However, most studies of HCV-associated steatosis have excluded alcohol ... www.natap.org/2002/september/090102_3.htm   Hepatic steatosis with stavudine in HIV/hepatitis C virus co-infection With interest we read the study on hepatic steatosis in subjects co-infected with ... They detected hepatic steatosis in 40% of patients who had received ... www.natap.org/2005/HCV/091405_06.htm   Fatty Liver By Howard Worman, MD (Fatty liver is called steatosis) Fatty liver is called steatosis, and fatty liver with liver inflammation is ... Steatosis and steatohepatitis can be caused by alcohol and other drugs and ... www.natap.org/2000/june/fatty_liver_by060500.htm   Insulin resistance is a cause of steatosis and fibrosis ... Independent risk factors for steatosis were insulin resistance in genotype 1 ... It has been suggested that insulin resistance may result from steatosis, ... www.natap.org/2005/HCV/091405_01.htm   abstract 179. INFLUENCE OF STEATOSIS ON CHRONIC HEPATITIS C ... editorial note: Steatosis can be defined as the accumulation of fat globules within the ... Steatosis is a frequent feature of HCV chronic hepatitis and may ... www.natap.org/2001/aasld2/day32.htm   Liver Steatosis Common in HIV+ Hepatic steatosis, a common histological finding in hepatitis C virus ... Hepatic steatosis, a frequent histopathologic finding on liver biopsy in the ... www.natap.org/2005/HCV/110905_02.htm   IS THERE A CORRELATION BETWEEN HEPATIC STEATOSIS, FIBROSIS, BODY ... A correlation with hepatic steatosis (fat accumulation in liver), ... We sought to determine a potential association between hepatic steatosis, fibrosis, ... www.natap.org/2000/ddw/rpt_04.htm   Fatty Liver Accelerates Liver Disease: Steatosis, Co-factor in ... Fatty Liver Accelerates Liver Disease: Steatosis, Co-factor in other liver ... 13 Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis ... www.natap.org/2005/HCV/070105_01.htm   Leptin reverses insulin resistance and hepatic steatosis in ... This disease is associated with hypertriglyceridemia, hepatic steatosis, ... These alterations were associated with severe hepatic steatosis in all of the ... www.natap.org/2002/may/053102_1.htm - 19k -   Hispanics Developed Cirrhosis More Quickly Due to the presence of ... Prevalence of obesity (52%) and hepatic steatosis (77%) was highest in Hispanics vs NHW (22% and 47%) and Others (31% and 47%), p<0.004. ... www.natap.org/2005/AASLD/aasld_29.htm   Fat in the Liver Reduces Response to HCV Therapy Steatosis, also called fatty liver, is the accumulation of fat in hepatocytes (liver ... More advanced fatty liver is called NASH, alcoholic steatosis. ... www.natap.org/2003/DDW/day7.htm   Fatty Liver Is Worse in HIV Fatty Liver Is Worse in HIV "IMPACT of HIV COINFECTION on the DEVELOPMENT of STEATOSIS (FATTY LIVER) in PATIENTS with Chronic HCV Infection" ... www.natap.org/2005/HIV/053105_03.htm   Hepatic steatosis and antiretroviral drug use among adults ... Hepatitis C Articles (HCV). Back · grey_arrow_rt.gif. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus ... www.natap.org/2005/HCV/040905_08.htm   Fat in the Liver Reduces Response to HCV Therapy Steatosis, also called fatty liver, is the accumulation of fat in ... Liver biopsies evaluated for steatosis by two investigators (k=0.84, p<0.005). ... www.natap.org/2003/may/052703_1.htm   Interplay between hepatitis C, liver steatosis and antiretroviral ... Hepatitis C Articles (HCV). Back · grey_arrow_rt.gif. Interplay between hepatitis C, liver steatosis and antiretroviral therapy in HIV-infected patients ... www.natap.org/2005/HCV/040905_02.htm   12th CROI HCV Report Steatosis was absent (31%), minimal (23%), mild (28%), and moderate to severe (19%). Patterns of steatosis were macrovesicular (4%), microvesicular (17%), ... www.natap.org/2005/CROI/croi_35.htm   Prevalence of hepatic steatosis (fatty liver) in an urban ... Back · grey_arrow_rt.gif. Prevalence of hepatic steatosis (fatty liver) in an urban population in the United States: Impact of ethnicity ... www.natap.org/2004/HCV/121304_03.htm   Lipids/Diabetes & HCV Liver disease Whatever the cause, liver steatosis may contribute to progression of fibrosis in patients with HCV. Indeed, obesity with a BMI >30 kg/m2, liver steatosis of ... www.natap.org/2005/HCV/110205_01.htm   Different mechanisms of steatosis in hepatitis C virus genotypes 1 ... Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 ... Summary This study reports evidence that hepatocellular steatosis, a frequent ... www.natap.org/2004/HCV/092204_06.htm   PILOT STUDY OF PIOGLITAZONE IN NONALCOHOLIC STEATOHEPATITIS Liver histology was scored for degree of steatosis, cellular injury, parenchymal and portal inflammation, Mallory bodies and fibrosis. ... www.natap.org/2003/DDW/day16.htm   Concluding remarks: metabolic syndrome, liver and HCV Hepatic steatosis is a well-documented histological feature during hepatitis C virus (HCV) infection.1619 There is clear evidence that HCV itself (through ... www.natap.org/2005/HCV/110505_01.htm   New CDC HIV Prevention Funding Emphasizes Effectiveness, Focuses ... "Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a ... Steatosis accelerates activity and progression of CHC, ... www.natap.org/2003/dec/122903_9.htm   Hepatology Highlights Hepatology, January 2003, Volume 37, Number ... Steatosis (fat in the liver) and Genotype 3 Although steatosis has long been known to be a concomitant of non-A, non-B/HCV infection, only recently has a ... www.natap.org/2003/Jan/010803_2.htm   BENEFIT OF SUSTAINED WEIGHT LOSS AND EXERCISE IN OVERWEIGHT ... Thirty-one patients (NAFLD, n=13; HCV and steatosis, n=18) completed a 15 month lifestyle intervention consisting of a 3 month weight loss program followed ... www.natap.org/2003/AASLD/day2_3.htm   High body mass index is an independent risk factor for nonresponse ... Steatosis leads to an increase in lipid deposits within cells25 that may cause ... It has also been shown that HCV genotype 3a is associated with steatosis ... www.natap.org/2003/oct/102403_8.htm   Weight Reduction May Improve Fibrosis, ALT, Insulin ... Steatosis was graded from 1-3 and HAI/fibrosis scored by modified Knodell. ... There was a mean reduction in grade of steatosis of 1.3, necroinflammatory ... www.natap.org/2000/nov/weight_reduction112200.htm   PDF The prevalence of steatosis in patients with chronic hepatitis C differs ... The pathogenic significance of steatosis likely differs according to its origin ... www.natap.org/2004/jan/steatosis_CurrHepRep.htm   Metabolic syndrome cardiovascular disease risk and more This increasingly recognized condition, including a wide spectrum of lesions from simple steatosis to end stage liver disease, has relation to insulin ... www.natap.org/2005/HCV/110505_02.htm   Effect of treatment with peginterferon or interferon alfa-2b and ... Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C ... www.natap.org/2003/june/063003_3.htm