There are few data evaluating plasma and/or peripheral blood monocyte cytokine concentrations/production or attempts to manipulate proinflammatory cytokines in nonalcoholic steatohepatitis (NASH). A pilot project in a general clinical research center evaluated the effects of a step 1 American Heart Association diet plus aerobic exercise with or without 800 IU of vitamin E daily on cytokine profiles and liver enzyme levels in 16 patients with biopsy-proven NASH. Biochemical assessment of liver function, lipid profiles, and body mass index significantly improved during the first 6 weeks of therapy and remained stable during the following 6 weeks. Plasma hyaluronic acid (HA) concentrations decreased in parallel with weight loss. Plasma tumor necrosis factor (TNF) concentrations were significantly elevated in patients with NASH and similar to patients with stable alcoholic cirrhosis but not as elevated as in patients with acute alcoholic steatohepatitis (AH). Although plasma TNF, interleukin 8 (IL-8), and IL-6 concentrations were all significantly elevated compared with control values, only plasma IL-6 levels significantly decreased with therapy. Peripheral blood monocyte TNF, IL-8, and IL-6 production was significantly elevated in patients with NASH but did not significantly decrease. Independent effects of vitamin E were not observed in this small sample. In conclusion, patients with NASH have dysregulated cytokine metabolism similar to, but less pronounced than abnormalities documented in AH. Cytokine values generally did not decrease significantly with weight loss with or without vitamin E over the duration of the study. Lifestyle modifications (low-fat diet and exercise) were associated with improvement in liver enzymes, cholesterol, and plasma HA levels in patients with NASH, whereas the level of vitamin E supplementation used in this short-term pilot study provided no apparent added benefit. (HEPATOLOGY 2003;38:413-419.)

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with earlystage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (Nl), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. Copyright r 1997 by the American Association for the Study of Liver Diseases C onventional liver tests (serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) do not quantitate hepatic function but only assess the presence or absence of hepatobiliary injury. 1 Chronic liver disease, especially early cirrhosis, is characterized by a compensated phase (Child' s class A) where clinical findings and standard routine biochemical parameters are relatively stable despite progression of the liver disease. During this phase some patients experience significant worsening of functional hepatic reserve and are at risk for clinical decompensation. For these reasons, we determined in a small group of cirrhotic patients whether quantitative tests could identify the degree of impairment in hepatic reserve and whether those with the greatest impairment had clinical progression in their liver disease.A number of model compounds have been shown to be useful in assessing the severity of liver disease: aminopyrine, antipyrine, phenacetin, caffeine, erythromycin, galactose, indocyanine green, lidocaine, and bile acids. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] These studies suggest that hepatic drug clearance offers more precise quantitation of hepatic function and reserve when compared with standard liver blood tests. Hepatic clearance of these model compounds is dependent on two major physiological variables: the rate of delivery of the drug to the liver and the intrinsic hepatic clearance. For compounds with a high intrinsic hepatic clearance, such as cholate, clearance is limited by liver blood flow. For compounds with a low intrinsic hepatic clearance, such as antipyrine and caffeine, clearance is relatively independent of liver blood flow but dependent upon hepatic metabolism.The specific aims of this study were to define the degree of functional hepatic impairment by comparing clearances of caffeine, antipyrine, and cholate in patients with early-stage cirrhosis to those of controls. In addition, we determined whether the

Reduced food consumption is a major manifestation of zinc (Zn) deficiency. Many manifestations of Zn deficiency are complications of anorexia nervosa and bulimia nervosa. We evaluated serum and 24-hour urinary Zn values in 12 healthy volunteers and 33 eating disorder patients before and after hospitalization which included either Zn supplementation (75 mg Zn/day) or placebo. Bulimics had depressed serum Zn concentrations (p < 0.025). Admission urinary Zn was lower in bulimics (258 +/- 44 micrograms/day), and significantly depressed in anorexics (196 +/- 36 micrograms/day, p < 0.005) vs controls (376 +/- 45 micrograms/day). During hospitalization, serum Zn concentrations increased in all supplemented patients vs no change with placebo. Urinary Zn excretion increased in supplemented bulimics (p < 0.001) and placebo (p < 0.05). Urinary Zn excretion markedly increased in supplemented anorexics (179 +/- 65 to 1052 +/- 242 micrograms/day); however, placebo values fell or remained unacceptably low (admission 208 +/- 48 micrograms/day; discharge 160 +/- 17 micrograms/day). By dietary history, controls consumed the Recommended Dietary Allowance (RDA) for Zn (11.95 +/- 1.25 mg/day); anorexics 6.46 +/- 1.14 mg/day; and bulimics 8.93 +/- 1.29 mg/day. We suggest that Zn deficiency may act as a "sustaining" factor for abnormal eating behavior in certain eating disorder patients.