Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease.

There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.

Unexpectedly High Efficacy of SARS-CoV-2 BNT162b2 Vaccine in Liver versus Kidney Transplant Recipients-Is It Related to Immunosuppression Only?

The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 µg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4-6 weeks after the first dose and 4-8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.

Hepatocellular Carcinoma Is a Negative Predictor of Sustained Viral Response in Liver Transplant Recipients With Hepatitis C Treated With Direct-Acting Antivirals.

INTRODUCTION: Treatment with direct-acting antivirals (DAA) for hepatitis C (HCV) in liver transplant (LTX) recipients is very effective, but some studies showed that the treatment effectiveness might be impaired in patients with hepatocellular carcinoma (HCC). The study aimed to evaluate the predictors of DAA treatment failure in LTX recipients. METHODS: Liver biopsy was done before the treatment in 107 of the 120 patients included. All patients had an abdominal ultrasound and liver elastography performed before and after the therapy. Blood HCV polymerase chain reaction was done before; during; and at 4, 12, and 24 weeks after the treatment. RESULTS: Overall sustained viral response 24 weeks after treatment (SVR24) was 96%. There were 2 patients with HCC at the start of the DAA treatment and 3 cases of HCC recurrence during a 1-year follow-up. Treatment failure was observed in 1/115 (0.9%) patients without HCC and 4/5 (80%) with active HCC (P = .0001). Liver fibrosis and previous interferon treatment had no impact on treatment efficacy. Time to viremia elimination on treatment was shorter in the responder versus nonresponder group (28 vs 58 days, P = .03). CONCLUSIONS: HCC is a negative predictor of DAA therapy success in LTX recipients.

Modulation of the Immune System in Chronic Hepatitis C and During Antiviral Interferon-Free Therapy.

The treatment of patients with chronic hepatitis C virus (HCV) infection has changed tremendously over the past 2 years, with an increasing variety of all-oral direct-acting antiviral (DAA) treatment regimens available for different HCV genotypes and distinct clinical settings. These treatments have significantly improved safety in patients with advanced liver disease compared with interferon (IFN)-based regimens. HCV modifies the human immune system to escape immunosurveillance via several mechanisms. One of the basic mechanisms of HCV is the ability to "switch" the immune response by reducing the activity of cells responsible for the elimination of virus-infected cells. IFN-free DAA treatment regimens provide a unique opportunity to assess the effect of HCV elimination on the immune system. Abrupt changes in the immune system can in some cases be responsible for two alarming processes: viral reactivation in patients with chronic hepatitis B and recurrence of hepatocellular carcinoma in patients with previous successful cancer treatment.