Elevated Soluble Tumour Necrosis Factor Receptor Serum Concentrations and Short-Term Mortality in Liver Cirrhosis without Acute Infections

Abstract

Background: Serum concentrations of the soluble 75-kDa tumour necrosis factor receptor (sTNF-R 75) are elevated in patients with severe liver disease and may be linked to mortality as well as to prognostic markers related to clinical outcome and metabolic functions in patients with liver cirrhosis. Patients and Methods: We prospectively studied the relation of sTNF-R 75 to Child-Pugh score points and serum markers of bile acid (total serum bile acids and 7α-hydroxycholesterol), lignocaine (lignocaine metabolite (MEGX) liver function test results) and albumin metabolism (albumin and prealbumin) in 10 healthy individuals and 30 patients with cirrhosis, all free of acute infections. In patients with cirrhosis mortality was recorded for 15 months. Results: Soluble TNF-R 75 concentrations correlated with Child-Pugh score points (r = 0.440, p = 0.015), MEGX test results (r_S = –0.604, p < 0.001) and prealbumin (r_S = –0.527, p < 0.001) in cirrhosis. Nonsurviving patients had almost threefold higher median sTNF-R 75 concentrations (29 ng/ml) than survivors (11 ng/ml) (p = 0.003). Soluble TNF-R 75 serum concentrations with an optimal cut off > 14 ng/ml were significantly more accurate in predicting patient mortality than Child-Pugh score points in a receiver-operator characteristic curve analysis. Conclusion: Soluble TNF-R 75 serum concentrations appear to be a promising new risk factor for mortality in patients with cirrhosis without acute infections.

Elevated Soluble Tumor Necrosis Factor Receptor 75 Concentrations Identify Patients With Liver Cirrhosis at Risk of Death

“…21 The sTNF-R 75 c-statistic in our cohort collective was somewhat lower than the 0.96 found for prediction of 15-month survival in our pilot study. 15 This currently lower AUC might be due to the inclusion of a larger proportion of patients with decompensated liver disease (Ͼ80% CHILD B and C), compared with the pilot study (60%). 15 Sensitivity of risk factors depends largely on the priority probability of an event that in the current situation is dependent on disease severity of the included patients, an effect that has been described for other risk scores like MELD.…”

“…15 This currently lower AUC might be due to the inclusion of a larger proportion of patients with decompensated liver disease (Ͼ80% CHILD B and C), compared with the pilot study (60%). 15 Sensitivity of risk factors depends largely on the priority probability of an event that in the current situation is dependent on disease severity of the included patients, an effect that has been described for other risk scores like MELD. 22 Likewise, the c-statistics for MELD yielded 0.78, 0.78, and 0.79, which are somewhat lower than the values higher than 0.8 in most other studies on MELD.…”

“…In our pilot study elevated levels of 75-kd sTNF-R were more accurate in prediction of 15-month survival than the Child-Turcotte-Pugh (CTP) score. 15 Thus, we aimed to confirm our previous results and tested the prognostic value of sTNF-R 75 as single marker test for survival at 6, 15, and 24 months in patients with liver cirrhosis in a prospective single-center survival study. The predictive properties of sTNF-R 75 were compared with biochemical markers, common predictive risk scores (Model for End-Stage Liver Disease [MELD], CTP), and with the sTNF-R 75 to sTNF-R 55 ratio suggested as predictive in a previous study in patients with alcoholic hepatitis.…”

“…15,16 Thus, we expected 60% of our patients to be dead within 24 months. Assuming an increased relative risk of 2 in patients with high sTNF-R 75 levels (type I error, 0.05), our study has a power of 82% to detect a difference in survival (PS power and sample size program).…”

Gambogic Acid-Loaded Electrosprayed Particles for Site-Specific Treatment of Hepatocellular Carcinoma

“…PA is synthesized by hepatocytes, and lower PA values in the HCC model mice sensitively indicate the decreased synthetic function and reserve capacity of liver. 31 GGT is synthesized in the liver and excreted by the bile. In hepatoma cases, the synthesis of GGT is sthenic, permeation is increased, and excretion is blocked by biliary obstruction.…”