No abstract

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

Sweat contains ammonia. However, neither its source nor factors affecting its concentration in the sweat are known. The aim of this study was to examine the effect of plasma concentrations of ammonia and urea on the concentration of ammonia in the sweat. Four groups of male volunteers were examined: one control, two after ingestion of ammonium chloride, three cirrhotic, hyperammonaemic, four uraemic. Sweat was collected from each subject from the palmar side of the forearm using gauze pads, after previous iontophoresis of pilocarpine. Ammonia and urea concentrations were determined in the sweat and in the plasma. It was found that elevated plasma ammonia concentration in healthy subjects after ingestion of ammonium chloride as well in the cirrhotic patients resulted in an increase of ammonia concentration in the sweat. High plasma and sweat urea concentration in the uraemic subjects did not affect the concentration of ammonia in the sweat. It was concluded that plasma ammonia was the principal source of ammonia in the sweat.

The results confirm the negative association between chronic HCV and DQB1*0301 and identify two novel genetic associations. In particular, the DRB1*0701-DQA1*0201-DQB1*02 haplotype is associated with both chronic infection and response to alpha-interferon. Interestingly, the same haplotype is reportedly associated with non-response to hepatitis B vaccination.

Background and aim: The aim of this study was to assess the diagnostic performance of new morphology-related indices and Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores during hospitalization in predicting the onset of bacterial infection in patients with liver cirrhosis. Material and methods: A total of 171 patients (56.9% males; median age 59 years; total number of hospitalizations 209) with liver cirrhosis were included in this observational study. The diagnosis of cirrhosis was made on the basis of clinical, biochemical, ultrasonic, histological, and endoscopic findings. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), modified aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), Fibrosis-4 index (FIB-4), platelet-to-lymphocyte ratio (PLR), neutrophil-to-monocyte ratio (NMR), and CTP and MELD scores were calculated for the cases of patients with cirrhosis. Results: Bacterial infection was diagnosed in 60 of the 209 (28.7%) hospitalizations of patients with cirrhosis. The most common infections were urinary tract infection (UTI), followed by pneumonia and sepsis. The more severe the liver failure, the greater the bacterial infection prevalence and mortality. Patients with decompensated liver cirrhosis were infected more often than subjects with compensated cirrhosis (50.0% vs. 12.9%, p = 0.003). The calculated MELD score, CTP, NLR, LMR, AAR, monocyte count, and C-reactive protein (CRP) concentration were also related to the bacterial infection prevalence, and mortality areas under the curve (AUC) were 0.629, 0.687, 0.606, 0.715, 0.610, 0.648, and 0.685, respectively. The combined model with two variables (LMR and CTP) had the best AUC of 0.757. The most common bacteria isolated from patients with UTI were Escherichia coli, Enterococcus faecalis, and Klebsiella pneumonia. Gram-negative bacteria were also responsible for spontaneous bacterial peritonitis (SBP), and together with gram-positive streptococci and staphylococci, these microorganisms were isolated from blood cultures of patients with sepsis. Significant differences were found between CTP classification, MELD score, NLR, LMR, AAR, CRP, and PLR in patients with cirrhosis with, or without, bacterial infection. Conclusions: Bacterial infection prevalence is relatively high in patients with liver cirrhosis. Although all analyzed scores, including the LMR, NLR, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), CRP, CTP, and MELD, allowed the prediction of bacterial occurrence, the LMR had the highest clinical utility, according to the area under the curve (AUC) and odds ratio (OR).