Liver transplant patients General population Severe COVID-19 Highlights The incidence of coronavirus disease 2019 (COVID-19) is higher in liver transplant patients. Mortality rates are lower than those observed in the matched general population. Immunosuppression withdrawal may not be justified. Mycophenolate may increase the risk of severe COVID-19 in a dosedependent manner.

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Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm (“very early”) in which results after LT can be acceptable. Twenty‐nine patients comprised the study group, eight of whom had a “very early” iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the “very early” iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1‐, 3‐ and 5‐year actuarial survival of those in the “very early” iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5‐year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

AimsTo study the effect of CYP2C8*3 , the most common CYP2C8 variant allele on the disposition of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles. MethodsThree hundred and fifty-five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)-ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes. ResultsThe allele frequency of CYP2C8 * 3 (0.17) was found to be higher than that reported for other Caucasian populations ( P = 0.0001). The frequencies of CYP2C9 * 2 and CYP2C9 * 3 were 0.19 (0.16-0.21) and 0.10 (0.08-0.12), respectively. An association between CYP2C8 * 3 and CYP2C9 * 2 alleles was observed, occurring together at a frequency 2.4-fold higher than expected for a random association of alleles ( P = 0.0001). The presence of the CYP2C8 * 3 allele was found to influence the pharmacokinetics of (R)-ibuprofen in a gene-dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half-life (95% confidence intervals) for individuals with genotypes CYP2C8 * 1/ * 1 , CYP2C8 * 1/ * 3 and CYP2C8 * 3/ * 3 , was 2.0 h (1.8-2.2), 4.2 h (1.9-6.5; P < 0.05) and 9.0 h (7.8-10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8 * 3 alleles was also observed for the area under the concentration-time curve ( P < 0.025), and drug clearance ( P < 0.03). ConclusionPolymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8 * 3 allele. The presence of the latter caused a significant effect on the disposition of (R)-ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates.