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.

Background and aims Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking Methods Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis, Results Between March 1st and June 27 th 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39/204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age > 70 (HR 4.16; 95%CI 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR 0.55; 95%CI 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR 1.95; 95%CI 1.06 - 3.58) and chronic kidney disease (HR 1.97; 95%CI 1.05 - 3.67) emerged as associated with death Conclusions Twenty-five per cent of patients requiring hospitalization for Covid-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 ؋ 10 6 , 3 times a week, for 1 year) (n ‫؍‬ 30) or symptomatic treatment (n ‫؍‬ 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 ؎ 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of ␣-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P ‫؍‬ .19, log rank P ‫؍‬ .14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression (P ‫؍‬ .17), or deterioration of Child-Pugh class (P ‫؍‬ .37), performance status (P ‫؍‬ .07), or Okuda stage (P ‫؍‬ .44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival. (HEPATOLOGY 2000;31:54-58.)

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