No abstract

No abstract

To investigate the relationship among circulating cytokines, inflammation in the liver, and kind of response to interferon-alpha (IFN-alpha) in hepatitis C, we studied 63 consecutive patients (38 male, 25 female), treated with IFN for up to 1 year. Serum tumor necrosis factor-alpha (TNF-alpha) was measured at baseline and after 3 months of treatment. Transient (TR) or sustained response (SR) was observed in 29 and 16 patients, respectively. Baseline levels of TNF < or = 22 ng/L were observed in 69% of patients with SR, 55% of patients with TR, and 22% of nonresponders (p < 0.01). There was a significant correlation between baseline TNF levels and histologic grading score of hepatitis (p < 0.01). After 3 months of treatment, TNF levels >22 ng/L were observed in 63% of patients with SR, 69% of patients with TR, and 83% of nonresponders (p NS). Independent of the treatment outcome, TNF levels were lower at baseline and increased significantly with treatment in patients with lower histologic grading (p < 0.005). In conclusion, in patients with chronic hepatitis C, circulating TNF levels correlate with the degree of inflammation in the liver. Response to IFN is accompanied by an inflammatory response involving the release of TNF.

C-terminal peptide of procollagen I, N-terminal peptide of procollagen III, collagen IV and serum prolyl hydroxylase were measured in 100 patients with cirrhosis and 71 patients with noncirrhotic chronic liver disease. Patients with cirrhosis had significantly higher mean values of prolyl hydroxylase, collagen IV, N-terminal peptide of procollagen III and C-terminal peptide of procollagen I as compared to noncirrhotic patients. This difference was maintained for collagen products even after stratification for alcohol intake, although all markers of fibrosis were higher in alcoholics. Stepwise logistic regression analysis showed that collagen IV, and N-terminal peptide of procollagen III were independently associated with cirrhosis. Receiver-operating characteristic (ROC) curves showed that collagen IV and N-terminal peptide of procollagen III perform more efficiently than C-terminal peptide of procollagen I and prolyl hydroxylase in identifying cirrhosis.

SUMMARYTo differentiate intraluminal from peritubular factors in mediating the glomerulotubular balance, single nephron filtration rate (SNGFR) and reabsorption were measured by total collection from the last proximal segment before, and during, externally applied mechanical compression of an early proximal convolution of ninety-three rat nephrons. SNGFR fell from 55 6 + 2 3 nl min-' during control conditions to 34 5 + 2.0 nl min' during compression (P < 0 0001) in sixty tubules ('responders'). Absolute reabsorption fell from 41 8 + 2.0 to 28.4 + 1 8 nl min-' (P < 0.0001), while percentage reabsorption rose from 75 + 2 to 82 + 2 % (P < 0.0001). These effects were reversible and independent of whether the compression was applied before or after the control collection. In thirty-three proximal tubules the compression procedure was not successful ('nonresponders'), SNGFR remaining unchanged (36.1 + 2 9 vs. 36-9 + 2 9 nl min-1, P > 0 3).Absolute and percentage reabsorptions rose slightly, albeit significantly, from 26 1 + 2 1 to 30 7 + 2 4 nl min-1 (P < 0 0001) and from 75 + 3 to 85 + 2 % (P < 0.0001). Thus, the response of reabsorption to changes in intraluminal flow is composed of two different adaptive mechanisms. The slowing of flow is present in both sets of tubules and causes a slight increase in resorption; the change in filtration per se is present only in the first set of responders, and causes an SNGFRdependent consensual change in resorption.