Very Low Hepatitis C Viral Loads in Treatment-naive Persons: Do They Compromise Hepatitis C Virus Antigen Testing?

BACKGROUND: Hepatitis C virus (HCV) antigen testing is less expensive than quantitative reverse-transcription polymerase chain reaction but has lower sensitivity for very low viral load (VLVL; HCV RNA ≤3000 IU/mL). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce. METHODS: We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing. RESULTS: We included 2533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female sex, and human immunodeficiency virus coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall, 33% of samples with VLVL were reactive by antigen testing. CONCLUSIONS: The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.

Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

Characteristics of Foreign-Born Persons in the Swiss Hepatitis C Cohort Study: Implications for Screening Recommendations.

BACKGROUND: Switzerland recommends individuals who originate from high-prevalence countries to be screened for hepatitis C virus (HCV) infection. However, not all these persons are equally at risk. We thus aimed to describe the number and characteristics of persons with HCV infection born outside of Switzerland. METHODS: We compared characteristics of anti-HCV-positive individuals in the Swiss Hepatitis C Cohort Study (SCCS) and of HCV cases reported to the Federal Office of Public Health (FOPH), with those of the general population in Switzerland. Persons who inject drugs (PWID) and persons who do not inject drugs (non-PWID) were compared by age groups for different countries of origin (represented by ≥1% of participants in the SCCS or FOPH). RESULTS: We included 4,199 persons from the SCCS and 26,610 cases from the FOPH. Both groups had similar characteristics. In both data sources non-PWID were more frequent in foreign-born than in Swiss-born persons (63% versus 34% in the SCCS). The only subgroup with a clearly higher proportion both in the SCCS and FOPH than in the general population were persons over 60 years from Italy and Spain, with a 3.7- and 2.8-fold increase in the SCCS. These persons were non-PWID (99%), less frequently HIV- and anti-HBc positive and more often female than PWID from Italy and Spain; cirrhosis at enrolment was frequent (31%). Their HCV genotypes were consistent with those observed in elderly non-PWID of their birth countries. In the FOPH a higher proportion than in the general population was also seen for cases from Georgia and Russia. CONCLUSION: The identification of subgroups in which HCV infection is particularly frequent might allow for better targeting HCV screening among foreign-born persons in Switzerland and elsewhere.