Impact of CD4+ T-cell count on sustained virologic response to direct-acting antivirals in hepatitis C virus monoinfected cancer patients: a prospective observational study.

Limited data are available on the use of CD4+ T-cell count and percentage to predict response to direct-acting antiviral (DAA) treatment outside the hepatitis C virus (HCV)-HIV coinfected population. We sought to determine the impact of CD4+ T-cell count and percentage on response to DAAs in cancer patients with HCV monoinfection. Patients treated with DAAs were enrolled in a prospective observational study. CD4+ T-cell count and percentage was measured at baseline, end of treatment (EOT), and 12 weeks after the EOT (SVR12). A total of 174 patients were enrolled. Most patients (155/174, 89%) achieved an SVR12. A multivariate logistic regression model found that patients with hepatocellular carcinoma, HCV-3 and previous DAA treatment were more likely to develop treatment failure. Neither univariate analysis nor multivariate logistic regression analysis did show any association between CD4+ T-cell count or percentage and SVR12. CD4 T-cell count or percentage does not appear to impact SVR rates in cancer patients with HCV monoinfection receiving DAAs.

Salvage therapy in cancer patients with hepatitis C without sustained virologic response after direct-acting antivirals-A prospective study.

BACKGROUND AND AIM: No information exists regarding direct-acting antivirals (DAAs) salvage therapy for Hepatitis C (HCV)-infected patients with any type of cancer. We prospectively evaluated the safety and efficacy (SVR12) of salvage therapy in these patients. METHODS: Patients who failed initial DAAs (01/2015-01/2018) were analyzed. Resistance-associated substitutions to NS5A and NS3 were investigated by population sequencing. RESULTS: Of 164 patients enrolled, 16 (10%) experienced treatment failure. Of these, 11 patients received salvage therapy. The majority (91%) were men; 55% had genotype 1a, 45% had cirrhosis, and 45% had hepatocellular carcinoma. Four patients failed the first salvage therapy, and two of them required a second salvage therapy. Overall, 9 of 11 (82%) patients achieved SVR12. All four patients treated with sofosbuvir/velpatasvir/voxilaprevir (+/- ribavirin) achieved SVR12. The presence of resistance-associated substitutions did not impact response. Seven patients developed grade 1/2 adverse events. No patient had grade 3/4 adverse events. No patient required interruption of DAA therapy because of clinical or laboratory abnormalities. CONCLUSIONS: This is the first prospective study in HCV-infected cancer patients failing DAAs. The efficacy of salvage therapy in this group appears to be lower than previously reported in non-cancer patients, but better response rates are observed with newer regimens. Salvage therapy is associated with minimal toxicity.

Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study.

BACKGROUND: Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease. METHODS: In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP). RESULTS: We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively). CONCLUSIONS: This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.