Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: the multicenter VITALITY study.

BACKGROUND AND AIMS: The use of immune checkpoint inhibitors (ICI) in patients with advanced hepatocellular carcinoma (HCC) has become widespread with encouraging outcomes in the neoadjuvant setting. Safety and intention to treat (ITT) outcomes in the peri transplant setting are currently based on small and heterogenous single center reports. METHODS: This first multiregional US study (2016-2023) included 117 consecutive HCC patients assessed for LT and treated preoperatively with ICIs. Intention to treat ITT and survival analyses were conducted with evaluation of post LT rejection rates. RESULTS: In total, 86 (73.5%) patients exceeded MC and 65 (75.6%) were successfully downstaged (DS) within a median of 5.6 months. 43 (36.7%) underwent transplantation, including 18 (15.4%) within MC and 23 (19.7%) initially beyond and DS. Overall, 94% of the cohort received concurrent ICIs and locoregional therapies. No grade 4-5 adverse events occurred on the waiting list. The 3-year cumulative probability of dropout was 28% for those within MC and 48% for those beyond. Independent predictors of dropout included: being beyond MC (p<0.001), AFP doubling from baseline (p=0.014) and radiographic responses (p<0.001). The 3-year ITT survival was 71.1% (73.5% within MC vs 69.7% beyond MC, p=0.329), with 3-year post LT survival rate of 85%. Post-LT rejection occurred in 7 patients, six received their last dose of ICI less than 3 months prior to LT, resulting in one graft loss. CONCLUSIONS: The first multicenter evaluation of HCC patients receiving ICI pre-LT demonstrates favorable survival and safety outcomes, justifying continued utilization and further evaluation of this strategy in clinical practice. High tumor burden, doubling of AFP levels, and radiographic response were identified as predictors of unfavorable oncologic outcomes. IMPACT AND IMPLICATIONS: The first multicenter evaluation of pre-transplant immune-checkpoint-inhibitors in hepatocellular carcinoma to show promising intention-to-treat survival, safety and rejection rates. Immune-checkpoint-inhibitors, either alone or combined with LRT, demonstrate reliable efficacy. This preoperative strategy could be particularly beneficial for high-risk patients, including those requiring downstaging or with elevated AFP levels despite locoregional treatment. These findings fill current knowledge gaps and offer reassuring evidence for the feasibility of pre-transplant use of immune-checkpoint-inhibitors, pending results from ongoing trials.

Psychosocial predictors of return to alcohol use after liver transplant: A multicenter cohort study.

BACKGROUND: Alcohol use after liver transplant (LT) is associated with higher rates of graft loss and increased mortality; however, there are limited data evaluating predictors of return to alcohol use using biochemical markers like phosphatidylethanol (PEth). METHODS: This multicenter retrospective cohort study evaluated psychosocial predictors of return to alcohol use using PEth testing in patients transplanted for alcohol-associated liver disease (ALD). The study included 223 patients at three centers who had received a LT for ALD and had at least one PEth measurement post-LT. RESULTS: The rate of return to alcohol use was 6.9 cases per 100 person-years (26 patients total) over a median 555 days of follow-up after transplant. Younger age (HR 0.96; 95% CI 0.92-0.99, p = 0.02), mental health comorbidities (HR 2.83; 95% CI 1.25-6.39, p = 0.01), and non-Hispanic White race (HR 3.79; 95% CI 1.42-10.15, p = 0.01) were associated with return to alcohol use post-LT. There was no difference between post-LT return to alcohol use rates or short-term survival among patients with less than 6 months of sobriety prior to listing compared with those with more than 6 months. Patients with sustained alcohol use post-LT had increased odds of history of illicit substance use (OR 5.20; 95% CI 1.01-26.83, p = 0.04) but no significant difference in time from the last drink to listing (OR 1.03; 95% CI 0.18-5.80, p = 0.97). CONCLUSIONS: These findings emphasize the importance of mental health comorbidities rather than period of sobriety in predicting post-LT return to alcohol use. Furthermore, the higher risk of return to alcohol use in non-Hispanic White patients suggests a potential disparity with referral and selection of higher risk White patients.

Post-acute sequelae of COVID-19 in solid organ transplant recipients.

BACKGROUND: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. METHODS: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis. RESULTS: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. CONCLUSION: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

Psoriatic disease and non-alcoholic fatty liver disease shared pathogenesis review.

Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients.  Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.