Background: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-α and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. Methods: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. Results: The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low γ-glutamyltransferase (γ-GT) serum activities, a low pretreatment γ-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5–4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1–16.7, p < 0.001), low pretreatment γ-GT/ALT ratio (OR = 2.5, CI: 1.7–3.3, p < 0.001), age (OR = 0.96, CI: 0.94–0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85–8.65, p < 0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment γ-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10–71.1, p < 0.0001). Conclusion: The pretreatment γ-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-α-based combination therapy in a nontriaged ordinary setting.
IL28B genotypes and virological response within 4 weeks are predictors of sustained virological response in patients infected with chronic hepatitis C virus (HCV) genotype 1 treated with antiviral dual combination therapy. The predictive value of "early" anemia (within 4 weeks) alone or in combination with the two other predictors has not been studied yet. A total of 305 pegylated interferon-α and ribavirin-treated patients with HCV genotype 1 were included in this study. Hemoglobin values at week 0, 4, 8, and 12 as well as the predictive efficiency of early anemia (hemoglobin value below the gender-specific lower limit: female < 11.5; male < 13.5 g/dl) during therapy were assessed with IL28B genotypes and rapid virological response. Forty-eight percent of treated patients developed early anemia. In both females and males (64%), a decrease of hemoglobin concentration of 3 g/dl (female: 14.7 ± 1.1 to 11.4 ± 1.3; male: 15.2 ± 1.2 to 12.2 ± 1.5) significantly correlated with sustained virological response. 64% of IL28B-CC patients showed a sustained virological response. Seventy-eight percent of patients with rapid virological response definitively eliminated the virus. Early anemia (81:48:41%) and rapid virological response (83:91:92%) increased the predictive efficiency of IL28B rs12979860 genotype distribution (CC:CT:TT). IL28B-CC and early anemia as well as IL28B-CC and rapid virological response had an Odds ratio of 42.4 or 75 to achieve a sustained virological response compared to TT without early anemia or rapid virological response. This finding may help to early identify responders to standard PEG-IFN-α and ribavirin treatment even within those with unfavorable IL28B genotype.
Still little is known about the effect of cardiac surgery on neonatal hepatic tissue. We examined the effect of cardiopulmonary bypass (CPB) and the effect of deep hypothermic circulatory arrest (DHCA) on neonatal hepatic tissue. Liver biopsies of neonatal piglets were taken after CPB (n = 4), after DHCA (n = 5), and after surgery without CPB (non-CPB; n = 3). Additionally, findings were compared to those of control piglets (n = 9). The liver specimens were fixed, stained with hematoxylin and eosin, and scored regarding inflammatory reaction, hepatocellular edema, and apoptosis. Inflammation score of treated groups was higher than in control; CPB 2.5 ± 0.5, DHCA 1.6 ± 0.4, non-CPB 1.2 ± 0.6, control 0.4 ± 0.3 (P < 0.001 CPB and DHCA vs. control; P < 0.05 non-CPB vs. control). Hepatic cell edema was more evident after DHCA (score 2.0 ± 0.4 vs. 0.2 ± 0.3 in control and 0.6 ± 0.5 after CPB; P < 0.001 and P < 0.05, respectively). The highest apoptotic cell count was in the non-CPB group (22.3 ± 6.3 vs. 11.4 ± 3.6 in control and 8.9 ± 5.4 after CPB; P < 0.05). The present study showed that (i) surgical trauma induces hepatic cell apoptosis; (ii) CPB increases hepatic inflammatory reaction; and (iii) DHCA amplifies hepatic cell edema.
BackgroundAKI frequently develops in sepsis patients, significantly decreasing the overall prognosis. There are currently no diagnostic markers available which reliably predict the prognosis of sepsis-associated AKI. Recently, ATP content of CD4+ T cells (ATP_CD4) has been shown to correlate with survival in sepsis. The aim of the study was to determine ATP_CD4 in sepsis-associated AKI.MethodsThirty-three patients with sepsis were prospectively analyzed for ATP_CD4 at three different time points. Results were related to survival, renal recovery, and further clinical/laboratory findings.ResultsATP_CD4 tended to lower in concentration at 48 h after onset of sepsis in those patients with complete renal recovery. There were no differences between patients with no AKI and those with AKI of different severity (AKIN 1-3). Urinary NGAL did not correlate with renal prognosis.ConclusionATP_CD4 may serve as risk predictor in sepsis-associated AKI. Lower concentrations may indicate a higher chance of complete renal recovery in sepsis.
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