Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis.

BACKGROUND: Macrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF). AIMS: This study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis. METHODS: This prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls. RESULTS: Circulating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002-1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000-1.004, p = 0.041), Child-Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan-Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001). CONCLUSIONS: Higher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg·kg body weight-1·day-1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin.

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg · kg body weight(-1) · day(-1)) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX-3 index.

HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR > or = F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 +/- 0.081 (0.909, when adjusted by DANA). Values < or =4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 +/- 0.053 vs 0.762 +/- 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.

Anti-hepatitis C virus-positive blood donors: are women any different?

We sought to assess clinical, epidemiological, biochemical, serological and histological characteristics of anti-hepatitis C virus (HCV)-positive female blood donors and compare them with men. As women are frequently the minority among blood donors, studies evaluating this population usually reflect characteristics of male gender. This retrospective study included 380 blood donors with confirmed positive anti-HCV. The mean age was 36.9 +/- 11.3 years and 33.2% were women. Compared with men, female donors showed higher prevalence of prior transfusion of blood products (P = 0.031) and lower prevalence of intravenous drug use (P = 0.001) and alcohol abuse (P < 0.001). Women exhibited lower medians of alanine aminotransferase (P < 0.001) and gamma-glutamyltransferase (P < 0.001). They also showed higher platelet count (P < 0.001) and prothrombin activity (P = 0.049), and a lower frequency of antibody against core antigen of hepatitis B virus (anti-HBc) positivity (P = 0.032). A higher proportion of spontaneous viral clearance (P = 0.001) and a lower frequency of viraemia (P < 0.001) were observed among women. On liver biopsy, women had lower prevalence of fibrosis stage > or = 2. Multivariate analysis identified age (OR = 1.050, 95% CI: 1.019-1.081, P = 0.001) and anti-HBc positivity (OR = 2.184, 95% CI: 1.010-4.722, P = 0.047) as independent predictors of significant fibrosis. Female blood donors presented higher prevalence of spontaneous viral clearance as well as biochemical and histological evidence of less advanced liver disease. These findings could be because of intrinsic characteristics of female gender or secondary to associated factors such as younger age or anti-HBc positivity.

Serum levels of YKL-40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is highly prevalent among end-stage renal disease (ESRD) patients undergoing haemodialysis and it is an important cause of morbidity and mortality in this population. The aim of this study was to evaluate the diagnostic value of YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in 185 ESRD HCV-infected patients. Significant liver fibrosis was defined as METAVIR F2, F3 or F4 stages. Significant fibrosis was observed in 45 patients (24%). By univariate analysis, higher levels of YKL-40, HA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as well as reduced platelet count were associated with fibrosis. However, by multivariate analysis, only AST (P = 0.001), platelet count (P = 0.004) and HA (P = 0.042) were independently associated with significant fibrosis. For the prediction of significant fibrosis, the areas under receiver operating characterictic curve (AUROC) of the regression model (0.798) was significantly higher than the AUROC of YKL-40 (0.607) and HA (0.650). No difference was noted between the AUROC of the regression model and AST to platelet ratio index (APRI) (0.787). Values <8.38 of the regression model showed a negative predictive value of 94% and scores >or=9.6 exhibited a positive predictive value of 65%. If biopsy indication was restricted to scores in the intermediate range of the regression model, it could have been correctly avoided in 61% of the cases. In conclusion, APRI and a model based on AST, platelet count and HA showed better accuracy than YKL-40 and HA (when used solely) for the prediction of significant fibrosis in ESRD HCV-infected patients.