B and T Cell Responses to SARS-CoV-2 Vaccination in Kidney and Liver Transplant Recipients with and without Previous COVID-19.

(1) Background: Vulnerable populations including transplant recipients are jeopardised by COVID-19. Herein, we report on B and T cell responses among liver and kidney organ recipients at our centre. (2) Methods: 23 liver and 45 kidney (14 thereof combined kidney/pancreas) transplanted patients were vaccinated with two doses of BNT162b2 followed by a booster dose of mRNA-1273 in 28 non-responders 4 months thereafter. Anti-SARS-CoV-2-Ig was measured by specific ELISA and virus neutralisation assay; T cell responses were measured by a spike protein-specific IFN-γ release assay. (3) Results: Compared to controls, B and T cell responses were weak in transplant recipients, particularly in those without prior exposure to SARS-CoV-2. Within this group, only 15% after the first and 58.3% after the second vaccination achieved seroconversion. A total of 14 out of 28 vaccination non-responders achieved a seroconversion after a third dose. Vaccination side effects were more frequent in healthy controls. The use of mycophenolate was associated with reduced anti-SARS-CoV-2-Ig production. (4) Conclusions: Our data confirm that vaccination responses are insufficient after standard vaccination in liver and kidney transplant recipients and are affected to a variable degree by specific immunosuppressants, particularly mycophenolate. Monitoring vaccination success and re-vaccinating those who are unresponsive seems prudent to achieve sufficient titres. Overall, prospective large-scale, multinational, multicentre studies or high-quality meta-analyses will be needed to generate personalised vaccination strategies in order to achieve protective immunity in high-risk, hard-to-immunize populations.

Response-guided long-term treatment of chronic hepatitis D patients with bulevirtide-results of a "real world" study.

BACKGROUND AND AIM: Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real-life data on BLV efficacy are limited. METHODS: Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV-RNA after 24 weeks were offered PEG-IFN as an add-on therapy in a response-guided manner. RESULTS: Twenty-three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV-RNA: 2.1 × 105 copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty-two completed ≥24 weeks of treatment (24-137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV-RNA undetectability, but both became HDV-RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG-IFN in eight patients induced an HDV-RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV-RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. CONCLUSION: Long-term BLV monotherapy is safe and effectively decreases HDV-RNA and ALT-even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG-IFN remains to be established. An algorithm for a response-guided BLV treatment approach is proposed.

Hepatitis D virus (HDV) prevalence in Austria is low but causes considerable morbidity due to fast progression to cirrhosis.

BACKGROUND: Hepatitis D virus (HDV) coinfection aggravates the course of hepatitis B virus (HBV). The prevalence of HDV in Austria is unknown. OBJECTIVE: This national study aimed at (i) recording the prevalence of HDV-infection in Austria and (ii) characterizing the "active" HDV cohort in Austria. METHODS: A total of 10 hepatitis treatment centers in Austria participated in this multicenter study and retrospectively collected their HDV patients between Q1/2010 and Q4/2020. Positive anti-HDV and/or HDV-RNA-polymerase chain reaction (PCR) results were retrieved from local database queries. Disease severity was assessed by individual chart review. Viremic HDV patients with clinical visits in/after Q1/2019 were considered as the "active" HDV cohort. RESULTS: A total of 347 anti-HDV positive patients were identified. In 202 (58.2%) patients, HDV-RNA-PCR test was performed, and 126/202 (62.4%) had confirmed viremia. Hepatocellular carcinoma was diagnosed in 7 (5.6%) patients, 7 (5.6%) patients underwent liver transplantation, and 11 (8.7%) patients died during follow-up. The "active" Austrian HDV cohort included 74 (58.7%) patients: Evidence for advanced chronic liver disease (ACLD, i.e., histological F3/F4 fibrosis, liver stiffness ≥10 kPa, varices, or hepatic venous pressure gradient ≥6 mmHg) was detected in 38 (51.4%) patients, including 2 (5.3%) with decompensation (ascites/hepatic encephalopathy). About 37 (50.0%) patients of the "active" HDV cohort had previously received interferon treatment. Treatment with the sodium-taurocholate cotransporting polypeptide inhibitor bulevirtide was initiated in 20 (27.0%) patients. CONCLUSION: The number of confirmed HDV viremic cases in Austria is low (<1% of HBV patients) but potentially underestimated. Testing all HBV patients will increase the diagnostic yield. More than half of viremic HDV patients had ACLD. Improved HDV testing and workup strategies will facilitate access to novel antiviral therapies.