Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy ...(CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes.
In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb (n = 67) or CRRT alone (n = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics.
At the start of therapy, CytoSorb-treated patients had higher lactate levels (p < 0.001), lower mean arterial pressure (p = 0.007) and higher levels of noradrenaline (p < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 (n = 67) was 75% (95%CI 71-79%), while the actual 28-day mortality rate was 48% (mean difference - 27%, 95%CI - 38 to - 15%, p < 0.001). For CRRT, based on a SOFA of 12.8 (n = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference - 16.9% 95%CI - 32.6 to - 1.2%, p = 0.035). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio aOR 5.47, p = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p = 0.031) and older age (aOR per 10 years 1.67, p = 0.034).
CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.
MAFLD often cooccurs with excessive alcohol consumption, while its prognostic value in this group remains unclear. We aimed to study the mortality risk of MAFLD in relation to excessive alcohol ...consumption and its potential interactions.
We analyzed persons 25-74 years old enrolled in the National Health and Nutrition Examination Survey III cohort with available steatosis and alcohol data. Participants with viral hepatitis, body mass index < 18.5, and missing data on age or follow-up were excluded, leaving 12,656 participants for analysis with a median follow-up of 22.9 20.9-24.8 years. MAFLD was defined as steatosis on ultrasound in the presence of metabolic dysfunction. Daily alcohol intake of ≥10 g in females and ≥20 g in males was considered excessive alcohol consumption. We quantified mortality risk with multivariate Cox regression for MAFLD and excessive alcohol consumption. Models were adjusted for age, age squared, sex, race, marital status, education, and smoking. MAFLD was present in 31% and excessive alcohol consumption in 13% and were both independently and simultaneously associated with increased mortality risk in fully adjusted models (adjusted HR aHR, 1.21; 95% CI, 1.13-1.30 and aHR, 1.14; 95% CI, 1.04-1.26, respectively). Similarly, MAFLD was associated with increased mortality risk in participants with and without excessive alcohol consumption. Participants with both MAFLD and excessive alcohol consumption (4.0%) expressed the highest mortality risk (aHR, 1.47; 95% CI, 1.28-1.71). Results were consistent using the initial 10 years of follow-up, a stringent definition of excessive alcohol, and propensity score weighting.
MAFLD increases mortality risk independent of excessive alcohol consumption. This underscores the importance of MAFLD, even in patients with excessive alcohol consumption.
Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long‐term therapy may be required. We investigated whether adding on pegylated interferon (Peg‐IFN) to ETV therapy enhances ...serological response rates. In this global investigator‐initiated, open‐label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg‐IFN add‐on therapy (180 µg/week) from week 24 to 48 (n = 85) or to continue ETV monotherapy (n = 90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16 of 85 (19%) patients allocated to the add‐on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg‐IFN add‐on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6‐14.0; P = 0.004). Eleven (13%) of the add‐on‐treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 8) of those who discontinued ETV (P = 0.014). At week 96, 22 (26%) patients assigned add‐on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (P = 0.036). Peg‐IFN add‐on led to significantly more decline in hepatitis B surface antigen, HBeAg, and HBV DNA (all P < 0.001). Combination therapy was well tolerated. Conclusion: Although the primary endpoint was not reached, 24 weeks of Peg‐IFN add‐on therapy led to a higher proportion of HBeAg response, compared to ETV monotherapy. Add‐on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence, Peg‐IFN add‐on therapy may facilitate the discontinuation of nucleos(t)ide analogs. (Hepatology 2015;61:1512–1522)
Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C ...virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV.
This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed.
In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).
Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.
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