Serum Leptin Levels Correlate With Hepatic Steatosis in Chronic Hepatitis C

Romero–Gómez, Manuel; Castellano-Megias, Victor M.; Grande, Lourdes; Irles, J. A.; Cruz, Marina; Nogales, M.C.; Alcón, Juan Carlos; Robles, Antonio Gianluca

doi:10.1111/j.1572-0241.2003.07450.x

Cited by 98 publications

(67 citation statements)

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“…[39][40][41] A major impediment to interpreting these data include small sample size (n Յ 100), 27,29,31-35,37-40 heterogeneous 27 failure to study the effects on IR, 13,[27][28][29][30][32][33][34][35]38 lack of histological correlation, 15,27,37 and failure to examine all cytokines in the same cohort in order to determine independent effects. 13,15,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] In contrast, the present study used a large cohort of well-characterized subjects closely matched with controls in the characteristics which modulate IR, with the principal aim of characterizing the independent effects of the four adipocytokines as well as other host and viral factors in relation to IR and hepatic pathology in chronic HCV infection. While TNF␣ and IL6 levels were elevated over 2-fold in HCV-infected patients compared to controls, these were not associated with markers of IR.…”

Section: Discussionmentioning

confidence: 99%

“…Further, there is no consensus in the literature on whether alterations in these adipocytokines contribute to liver cell injury and inflammation in chronic HCV infection. 13,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] In the present study, we tested the hypothesis that TNF␣, IL6, leptin, and adiponectin contribute to the development of HCV-induced IR and liver injury in a prospectively enrolled, well-characterized cohort of untreated non-diabetic, male subjects with chronic HCV infection. We did not assess the serum levels of resistin as its association with obesity, IR, and T2DM in humans is unclear.…”

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Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

et al. 2007

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The role of tumor necrosis factor ␣, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCVinfected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P ‫؍‬ 0.01), TNF␣ (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P ‫؍‬ 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. C hronic hepatitis C virus (HCV) infection is associated with the development of hepatic steatosis 1-5 and unique, virus-specific alterations in host metabolism leading to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). [6][7][8][9] We and others have shown that chronic HCV infection is associated with the development of IR in the absence of overt T2DM, irrespective of the presence or absence of cirrhosis. 6,10 Further, IR as assessed by the homeostasis model (HOMA-IR) 11 was independently associated with virally-mediated portal inflammation and an increased rate of fibrosis progression, indicating that IR is a cause rather than a consequence of hepatic fibrosis in HCV infection. 6 Despite recent recognition of the important role of IR in the progression of liver injury in HCV infection [12][13][14] and the response to antiviral therapy, 12,14,15 the mechanism of HCV-induced IR is not known. There is an abundance of literature to suggest that adipose tissue-derived cytokines (adipocytokines) may play a key role in the development of obesity-related IR. 16,17 TNF␣, IL6 and leptin are proinflammatory cytokines that can directly alter glucose and lipid metabolism. [16][17][18] In contrast, adiponectin, the most abundant of all the adipocytokines has an opposite effect, increasing insulin sensitivity [16][17][18] and having anti-steatotic, 19 anti-inflammatory 20 and antifibrotic effects. 21 In nonalcoholic fatty liver disease, it has been shown that serum levels of the various adipocyto-

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

et al. 2007

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“…31 In CHC genotype 1 patients there appears to be a correlation between serum leptin levels, steatosis, and fibrosis. 32 …”

Section: Increased Fibrosismentioning

confidence: 99%

Steatosis and Chronic Hepatitis C Infection: Mechanisms and Significance

Harrison

2005

Clinical Gastroenterology and Hepatology

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“…A role for obesity-related alterations in serum leptin levels in chronic HCV remains controversial. 43,46,47 Although in NASH, lower levels of the protective adipokine, adiponectin, are associated with higher grades of steatosis and necroinflammatory activity, 48,49 the contribution of adiponectin to disease progression in HCV has not been determined.…”

Section: Potential Pathogenic Roles Of Steatosis and Obesity In Hepatmentioning

confidence: 99%

Steatosis: Co-factor in Other Liver Diseases *

2005

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The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol-and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells. In conclusion, active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis. (HEPATOLOGY 2005;42:5-13.)

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Serum Leptin Levels Correlate With Hepatic Steatosis in Chronic Hepatitis C

Abstract: Hepatic steatosis was related to genotype, fibrosis degree, and serum leptin levels. Genotype 3 seems to have a viral specific steatogenic effect. Leptin seems to be a link between obesity and steatosis development in CHC genotype 1-infected patients.

Cited by 98 publications

References 35 publications

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

Steatosis and Chronic Hepatitis C Infection: Mechanisms and Significance

Steatosis: Co-factor in Other Liver Diseases *

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