Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol.

OBJECTIVE: Because over 90% of serum cortisol is bound to albumin and corticosteroid-binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum-free and salivary cortisol concentrations. METHODS: We assessed basal (T0) and post-synacthen (T60) serum total cortisol, serum-free and salivary cortisol in 125 consecutive cirrhotics (95 non-septic and 30 septic patients with a Child>8). RESULTS: Serum total cortisol levels significantly decreased from the Child A-C non-septic group, as did albumin and CBG levels, with a non-significant rise in serum-free cortisol concentrations. Non-septic patients with low albumin (≤25 g/L) or CBG levels (≤35 mg/L) had lower T0 serum total cortisol levels than patients with near-normal albumin (303.4 vs. 382.6 nmol/L; P=0.0035) or with normal CBG levels (289.9 vs. 441.4 nmol/L; P<0.0001), respectively, despite similar serum-free cortisol or salivary cortisol concentrations. Subnormal T60 serum total cortisol concentrations (<510.4 nmol/L) were measured in 7.2% of all patients (Child C: 14.5% vs. Child A and B: 0%; P=0.0013) but no patients exhibited symptoms suggesting adrenal insufficiency. Patients with or without subnormal T60 total cortisol had similar T0 salivary cortisol and serum-free cortisol concentrations. A trend was observed towards high serum-free cortisol concentrations and mortality in multivariate analysis. CONCLUSIONS: Serum total cortisol levels overestimated the prevalence of adrenal dysfunction in cirrhotics with end-stage liver disease. Since serum-free cortisol cannot be measured routinely, salivary cortisol testing could represent a useful approach but needs to be standardized.

Relative impact of ribavirin monitoring and HIV coinfection on sustained virological response in patients with chronic hepatitis C.

BACKGROUND: In chronic hepatitis C, higher ribavirin (RBV) concentrations are associated with sustained virological response (SVR); target concentration cutoffs have been proposed. As RBV displays interindividual variability, monitoring of RBV plasma levels appears relevant. The impact of RBV therapeutic drug monitoring (TDM(RBV)) on SVR has not been explored in current practice. Our study aimed to assess this impact. METHODS: Three patient groups were defined as RBV cutoffs achieved at week 12 (group A1), not achieved (group A2), and one without RBV concentration assessment (group B). A predictive model assessed the group impact on SVR in multivariate analysis, while adjusting for additional predictive factors. A specific evaluation of HIV-HCV-coinfected patients was performed. RESULTS: A total of 122 patients were included. In group A1 (n=30, HIV-positive =18), SVR, relapse and non-response rates were 60%, 17% and 23%, respectively; in group A2 (n=32, HIV-positive =18), 25%, 19% and 56%, respectively; and in group B (n=60, HIV-positive =3), 52%, 33% and 15%, respectively (P=0.0004). The patient group was an independent predictor of SVR (P=0.01), along with baseline viral load and HCV genotype. HIV coinfection did not impede the SVR rate. The cutoffs were achieved in 62% and 28% (P=0.008) of patients, when TDM(RBV) was performed or not, respectively. CONCLUSIONS: The achievement of RBV cutoffs is a predictive factor of SVR independent of HIV coinfection. It makes it possible to reach high SVR rates, avoid relapse and obtain the same SVR rates in HIV-HCV-coinfected as in HCV-monoinfected patients. TDM(RBV) enables RBV concentration cutoffs to be reached more frequently and could thus be a useful tool to optimize hepatitis C treatment.