The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope ؊0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope ؊0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT. (HEPATOLOGY 2002;35: 680-687.) C irrhosis caused by hepatitis C virus (HCV) infection is the main indication of liver transplantation (LT) in most transplant programs. Infection of the liver graft after transplantation is almost universal and persistent infection leading to chronic hepatitis, cirrhosis, and graft failure is common. 1,2 In our geographic area, 30% of patients undergoing LT for HCV-related liver disease are already cirrhotic 5 years after transplantation. 3 Regretfully, prophylaxis of HCV infection of the graft is not feasible because no specific anti-HCV immune globulin is available. In addition, antiviral treatment in patients on waiting lists for LT appears to be poorly effective and may cause severe adverse effects. 4,5 Currently, treatment of hepatitis C infection after LT seems the most feasible strategy to eradicate HCV. 6-8 Treatment of HCV infection after LT can be initiated before liver damage occurs or once liver disease is already established. Treatment in the early phase of LT seems a reasonable approach because eradication of HCV would prevent liver damage. 9-11 However, there are only a few studies analyzing the efficacy of antiviral therapy in the early posttransplantation period. Interferon monotherapy is not effective in achieving sustained virologic response in ...

Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov ( NCT04860739 ), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

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The 2-year probability of presenting SR was significantly higher in LDLT compared to CLT (45% vs. 22%, P ‫؍‬ .019). By univariate analysis LDLT (P ‫؍‬ .019) and an ALT higher than 80 IU/L 3 months after LT (P ‫؍‬ .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular necroinflammatory score >1 (P < .01), LDLT (P < .01), and biliary complications (P ‫؍‬ .046) were associated with SR. However, the only variables independently associated with SR were LDLT (odds ratio [OR], ‫؍‬ 2.8; 95% CI,1.19-6.6; P ‫؍‬ .024) and a lobular necroinflammatory score >1 (OR, 3.1; 95% CI, 1.2-8; P ‫؍‬ .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single-center experience, they should be considered in the decision-making process of transplant programs, since severe HCV recurrence may ultimately compromise graft and patient survival. (HEPATOLOGY 2004; 40:699 -707.)

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Despite its medical and legal implications, there are no prospective studies analyzing the incidence and mechanisms involved in the nosocomial transmission of hepatitis C virus (HCV) in liver units. This study prospectively investigates the nosocomial transmission of HCV in the liver unit of a tertiary care center from August 2000 to October 2002. The median prevalence of HCV infection among hospitalized patients was 50%. Anti-HCVnegative patients admitted to the liver unit during the study period were prospectively followed, and serum markers of HCV infection were repeated 6 months after discharge.

ObjectivesDrug interactions, poor adherence to medication and high-risk sexual behaviour may occur in individuals with HIV using recreational drugs. Thus, we aimed to assess the prevalence of recreational drugs use and to explore its clinical impact in HIV patients on treatment.MethodsObservational, cross sectional, study conducted in a 700 bed university hospital, Barcelona, Spain. A total of 208 adults living with HIV on treatment were included. A questionnaire was administered by clinical pharmacists, including evaluation of sociodemographic variables, past 12-month drug consumption, adherence to antiretrovirals (Simplified Medication Adherence Questionnaire) and high-risk sexual behaviour (condomless sex/multiple partners). Additional data were obtained from clinical records. Recreational drug-antiretroviral interactions were checked in reference databases. Prevalence was calculated for 5% precision and 95% CI. Crude and adjusted binary logistic regressions were performed to identify associations between recreational drug use and adherence problems, and between recreational drug use and high-risk sexual behaviour.ResultsFrom the overall sample, 92 participants (44.2%) consumed recreational drugs over the past 1 year. Of these, 44 (48.8%) had used different types of recreational drugs in this period. We detected 11 recreational substances, including sildenafil and nitrites. The most consumed drugs were: cannabis (68.5%), cocaine (45.5%), nitrites (31.5%), sildenafil (28.3) and ecstasy (19.6%). Relevant interactions occurred in 46 (50%) of the individuals consuming drugs. Recreational drug consumption was found to be related to adherence problems with antiretrovirals (OR: 2.51 (95% CI 1.32 to 4.77) p=0.005) and high-risk sexual behaviour (OR: 2.81 (95% CI 1.47 to 5.39) p=0.002).ConclusionsRecreational drugs are frequently used by HIV patients on treatment. Classical drugs and new substances consumed in sexual context are usual. Recreational drug consumption interferes with several clinical outcomes, including potentially relevant interactions between drugs and antiretrovirals, adherence problems and high-risk sexual behaviour. Thus, there is the urgent need of implementing patient-centred care involving recreational drug consumption.

Liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is the main indication for liver transplantation (LT).There is little information on HCV genetic evolution following transplantation. The aim of this study was to carefully assess early evolution of HCV quasispecies in a cohort of 18 liver transplant recipients followed prospectively. Quasispecies analysis was performed by sequence analysis of the hypervariable region 1 (HVR1) before transplantation and at day 4 and week 4 following LT. A predominant variant was present in 12 (67%) of the 18 patients before transplantation and the same variant was propagated and remained predominant after LT in 6 (50%) of these patients. In the remaining individuals, there were major changes in the quasispecies composition, mostly occurring during the first days after LT. There was a progressive decrease in the nonsynonymous (dN)/synonymous (dS) ratios from baseline (1.2) to day 4 (.6) (P ‫؍‬ .08) and to week 4 after LT (.3) (P ‫؍‬ .015). Similarly, genetic distance (GD) declined from baseline (.1) to day 4 (.03) (P ‫؍‬ .07) and to week 4 (.04) (P ‫؍‬ .04). We did not find any differences in HCV genetic evolution between patients with mild (n ‫؍‬ 10) or severe (n ‫؍‬ 8) disease recurrence. In conclusion, during the first days following transplantation, HCV quasispecies becomes more homogenous, even after major changes in its composition. Importantly, these changes persist and even increase during the 1st month after transplantation. The "bottleneck" effect caused by the implantation of a new graft and the lack of selective pressure due to the strong immunosuppression most likely explain this particular pattern of genetic evolution. (Liver Transpl 2004;10:1131-1139.) L iver cirrhosis caused by chronic hepatitis C virus (HCV) infection is the main indication for liver transplantation (LT). HCV infects the liver graft in almost all HCV-infected patients following transplantation and causes a persistent infection that leads to chronic hepatitis and cirrhosis in a significant proportion of patients. 1 -3 HCV replication is associated with a high rate of nucleotide mutations, which explains that in infected individuals, HCV circulates as a mixture of closely related but distinct genomes (quasispecies). 4,5 The quasispecies nature of HCV has been implicated in viral persistence, and, indeed, genetic evolution of the virus might permit HCV to escape the host immune surveillance. 6 LT is a unique opportunity to study HCV genetic evolution, since a circulating viral quasispecies that is in dynamic equilibrium, requires a quick adaptation to a situation derived from the removal of the main source of virus production (the liver) and the implantation of an uninfected graft. To propagate, circulating virions need to attach and enter into hepatocytes, the first step of the HCV life cycle. These events will most likely result in the selection of certain viral variants and, therefore, in significant changes in the quasispecies composition. It is obvious that studying genetic e...