A case of polyserositis, chylous ascites and hepatitis induced by immune checkpoint-inhibitors

We describe a rare case of polyserositis with chylous ascites following nivolumab therapy, highlighting the challenges in recognizing and managing immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICPIs)

Comparison of three HDV-RNA quantitative commercially available tests in untreated and in myrcludex-B treated patients with hdv related chronic hepatitis in a real-life setting

As new anti-hepatitis delta (HDV) therapies are being developed, highly sensitive and reliable quantitative tests are needed. Aim of the study was to compare three commercially available HDV-RNA kits. Methods. 92 serum samples from 4 categories of patients were tested for HDV-RNA by 3 assays: RoboGene (HDV-RNA quantification 2.0, Aj-Roboscreen, Germany, LLQ 6 IU/mL), EurobioPlex (HDV qRT-PCR, Eurobio, France, 100 IU/mL) and Dia.Pro (HDV-RNA Quantitation, Dia.Pro Diagnostic Bioprobes, Italy, 50 IU/mL). Total RNA was extracted by EZ1 DSP Virus Kit (Qiagen, Hilden, Germany).</jats:p

Safety, effectiveness and t-cell activation profiles of long-term myrcludex-B treatment in two patients with hdv related compensated cirrhosis

Mycludex B (MYR) is a new promising anti-HDV therapy, but the effectiveness and safety of long-term administration in compensated cirrhotics treated in a real-life setting are presently unknown. Aim of this study was therefore to describe the effectiveness, safety and impact on HDV/HBV-specific T cell profiles in the first two European patients treated with MYR outside clinical trials. Methods. A 69-year-old female and 51-year-old male Caucasian HBeAg-negative patients with HDV related compensated cirrhosis on long-term term TDF treatment, started MYR 10 mg/day on January and May 2018 in a compassionate use program. Liver function tests, bile acids and virological markers were monitored every 4 weeks. HDV RNA was tested by RoboGene®.</jats:p

Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs)

The goal of antiviral therapy is to improve the quality of life and survival of patients with chronic hepatitis B (CHB) by halting the progression to cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC), thus preventing anticipated liver-related death. Oral administration of potent and less resistance-prone nucleot(s)ide analogues (NUCs), such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF) has become the most popular treatment strategy worldwide because of their excellent efficacy and safety profile as well as easy management confirmed in both registration trials and in clinical practice studies. Long-term administration of ETV or TDF suppresses HBV replication in >95% of patients, resulting in biochemical remission, histological improvement including the regression of cirrhosis and prevention or reversal of clinical decompensation but not the development of HCC, particularly in patients with cirrhosis. Moreover, NUCs can be administered to all patients including those with severe liver disease, the elderly and in those who do not respond, are unwilling to take or have contraindications to interferon. The need for long-term, perhaps indefinite, treatment is the main limitation of NUCs therapy with the associated costs, unknown long-term safety and the low rates of hepatitis B surface antigen (HBsAg) seroclearance, which is still the best stopping rule for NUCs-treated patients with cirrhosis

Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?

Introduction: Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg-positive or -negative patients, TAF showed similar viral suppression but was associated with significantly higher alanine aminotransferase normalization rates and more favourable renal and bone safety compared to TDF. In a 48-week TAF switch study enrolling patients treated with TDF for 96 weeks, glomerular, tubular and bone safety parameters rapidly improved while virological suppression was maintained. Expert commentary: Waiting long-term large scale clinical practice studies aimed to confirm these advantages, TAF represents an helpful treatment option for both naïve and TDF-exposed CHB patients

Vaccinations in Paediatric Solid Organ Transplant Candidates and Recipients

Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost&ndash;benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be na&iuml;ve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients