Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin.

BACKGROUND & AIMS: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. RESULTS: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637-7.101), low (<400,000 IU) viremia (OR 2.907; CI 2.111-4.004), F0-F2 fibrosis (OR 1.631; CI 1.122-2.372) and type 2 diabetes (OR 0.528; CI 0.286-0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274-9.208), IL28B CC genotype (OR 3.306; CI 2.301-4.751), low viremia (OR 2.175; CI 1.542-3.070), and F0-F2 fibrosis (OR 1.506; CI 1.012-2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. CONCLUSIONS: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin.

Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.

BACKGROUND & AIMS: In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. RESULTS: In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction. CONCLUSION: In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.

Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies.

CONTEXT: For patients with borderline resectable pancreatic cancer, the benefit of neoadjuvant therapy remains to be defined. OBJECTIVE: We did a systematic search of the literature on this topic. METHODS: Prospective studies where chemotherapy with or without radiotherapy was given before surgery to patients with borderline resectable cancer, were analyzed by a meta-analytical approach. MAIN OUTCOME MEASURES: Primary outcome was surgical exploration and resection rates; tumor response, therapy-induced toxicity, and survival were secondary outcomes. Data were expressed as weighted pooled proportions with 95% confidence intervals (95% CI). RESULTS: Ten studies with 182 participants were included. Following treatment, 69% of patients (95% CI: 56-80%) were brought to surgery and 80% (95% CI: 66-90%) of surgically-explored patients were resected. Eighty-three percent (95% CI: 74-90%) of resected specimens were deemed R0 resections. The weighted fractions of resected patients alive at 1 and 2 years were 61% (95% CI: 48-100%) and 44% (95% CI: 32-59%), respectively. At restaging following neoadjuvant therapy, weighted frequencies for complete/partial response were 16% (95% CI: 9-28%), 69% (95% CI: 60-76%) for stable disease, and 19% (95% CI: 13-25%) for progressive cancer. Treatment-related grade 3-4 toxicity was 32% (95% CI: 21-45%). CONCLUSION: This meta-analysis shows that downstaging of the lesion following neoadjuvant therapies is uncommon for patients with borderline resectable pancreatic cancer. A clear benefit of this regimen could be to spare surgery to patients with progressive disease during the frame-time chemo-radiotherapy is being delivered.

False-positive results of SARS-CoV-2 IgM/IgG antibody tests in sera stored before the 2020 pandemic in Italy.

OBJECTIVES: Aside from the outbreak of the coronavirus disease 2019 (COVID-19), serological tests are not well known for their diagnostic value. We assessed the performance of serological tests using stored sera from patients with a variety of pathologic conditions, collected before the 2020 pandemic in Italy. METHODS: Rapid lateral flow tests and Enzyme-Linked Immunosorbent Assays (ELISA) that detect Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were carried out using 1150 stored human serum samples that had been collected in 2018 and 2019. The tests were also run using samples from 15 control patients who had positive or negative oral swab test results, as assessed using real-time reverse transcription-polymerase chain reaction (rRT-PCR). The urea dissociation test was employed to rule out false-positive reactivity in the two antibody detection methods. RESULTS: The lateral flow tests revealed 21 positive samples from the stored sera: 12 for IgM, four for IgG, and five for IgM/IgG. Among the nine rRT-PCR- positive controls, six individuals presented IgG and three IgM/IgG positivity. Using the urea (6 mol/L) dissociation test, two of the twelve stored samples that had shown IgM positivity were confirmed to be positive. The ELISA test detected four IgM-positive and three IgG-positive specimens. After treatment with 4 mol/L urea, the IgM-positive samples became negative, whereas the IgG positivity persisted. All of the rRT-PCR-positive controls were found to retain IgM or IgG positivity following the urea treatment. CONCLUSIONS: Our findings highlight the limited utility of serological testing for the SARS-CoV-2 virus based on the results of specimens collected before the outbreak of the infection.