Evolution of humoral immune response to SARS-CoV-2 mRNA vaccine in liver transplant recipients - a longitudinal study.

BACKGROUND AND AIM: Liver transplant recipients show suboptimal vaccine-elicited immune responses to severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccination. This study aimed to assess real-world data on SARS-CoV-2 antibodies after the second and third SARS-CoV-2 vaccination in liver transplant recipients in Switzerland. METHODS: We enrolled liver transplant recipients who attended regular follow-up visits between 01/07/2021 and 30/04/2022 at the outpatient clinic of the Department of Visceral Surgery and Medicine at Bern University Hospital, Switzerland. Following the Swiss Federal Office of Public Health recommendations, we measured SARS-CoV-2 anti-spike IgG antibodies in 117 liver transplant recipients ≥4 weeks after the second SARS-CoV-2 mRNA vaccination from 07/2021-04/2022. In case of antibody levels of <100 AU/ml, patients received a third vaccination and antibodies were re-measured. Patients with antibody levels of >100 AU/ml were defined as "responders", those with 12-100 AU/ml as "partial responders" and those with <12 AU/ml as "non-responders". RESULTS: After two vaccinations, 36/117 (31%) were responders, 42/117 (36%) were partial responders and 39/117 (33%) were non-responders. The humoral immune response improved significantly after the third vaccination, resulting in 31/55 (56%) responders among the previous partial or non-responders. A total of 26 patients developed COVID-19, of whom two had a moderate or severe course (both non-responders after three doses). DISCUSSION: One third of liver transplant recipients showed an optimal response following two vaccinations; a third dose achieved a complete antibody response in more than half of partial and non-responders. We observed only one severe course of COVID-19 and no deaths from COVID-19 in the vaccinated liver transplant recipients.

Long-term hepatitis B and liver outcomes among adults taking tenofovir-containing antiretroviral therapy for HBV/HIV coinfection in Zambia.

BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for HBV/HIV coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART (included tenofovir DF + lamivudine) initiation. On therapy, we ascertained HBV viral load (VL) non-suppression, ALT elevation, serologic end-points, progression of liver fibrosis, based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants, at ART start, median age was 34 years, 40·1% were women, median CD4 count was 191 cells/mm3, 44·2% were hepatitis B e antigen-positive, and 28·4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13·6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9·4% at 2 and 15·4% at 5 years, with higher rates among patients with low baseline HBV replication markers. DISCUSSION: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Clonality of circulating tumor cells in breast cancer brain metastasis patients.

BACKGROUND: The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. METHODS: Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). RESULTS: CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. CONCLUSION: The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment.

Frequency of Circulating Tumor Cells (CTC) in Patients with Brain Metastases: Implications as a Risk Assessment Marker in Oligo-Metastatic Disease.

Forty percent of non-small cell lung cancer (NSCLC) patients develop brain metastases, resulting in a dismal prognosis. However, patients in an oligo-metastatic brain disease setting seem to have better outcomes. Here, we investigate the possibility of using circulating tumor cells (CTCs) as biomarkers to differentiate oligo-metastatic patients for better risk assessment. Using the CellSearch® system, few CTCs were detected among NSCLC patients with brain metastases (n = 52, 12.5% ≥ two and 8.9% ≥ five CTC/7.5 mL blood) and especially oligo-metastatic brain patients (n = 34, 5.9%, and 2.9%). Still, thresholds of both ≥ two and ≥ five CTCs were independent prognostic indicators for shorter overall survival time among all of the NSCLC patients (n = 90, two CTC ≥ HR: 1.629, p = 0.024, 95% CI: 1.137⁻6.465 and five CTC ≥ HR: 2.846, p = 0.0304, CI: 1.104⁻7.339), as well as among patients with brain metastases (two CTC ≥ HR: 4.694, p = 0.004, CI: 1.650⁻13.354, and five CTC ≥ HR: 4.963, p = 0.003, CI: 1.752⁻14.061). Also, oligo-brain NSCLC metastatic patients with CTCs had a very poor prognosis (p = 0.019). Similarly, in other tumor entities, only 9.6% of patients with brain metastases (n = 52) had detectable CTCs. Our data indicate that although patients with brain metastases more seldom harbor CTCs, they are still predictive for overall survival, and CTCs might be a useful biomarker to identify oligo-metastatic NSCLC patients who might benefit from a more intense therapy.