Multimodal Percutaneous Thermal Ablation of Small Hepatocellular Carcinoma: Predictive Factors of Recurrence and Survival in Western Patients

International audienceBackground: To identify the predictive factors of recurrence and survival in an unselected population of Western patients who underwent multimodal percutaneous thermal ablation (PTA) for small Hepatocellular Carcinomas (HCCs).Methods: January 2015–June 2019: data on multimodal PTA for 100 ng/mL (OR = 3.027, p = 0.037) and tumor size (OR = 1.06, p = 0.001) independently predicted IDR. Multinodular HCC (HR = 2.67, p 100 ng/mL (HR = 2.767, p = 0.014) independently predicted time-to-IDR. RFS was independently predicted by multinodular HCC (HR = 2.144, p = 0.001), treatment naivety (HR = 0.546, p = 0.004) and AFP > 100 ng/mL (HR = 2.437, p = 0.013). The American Society of Anesthesiologists (ASA) score > 2 (HR = 4.273, p = 0.011), AFP (HR = 1.002, p < 0.001), multinodular HCC (HR = 3.939, p = 0.003) and steatotic HCC (HR = 1.81 × 10-16, p < 0.001) independently predicted OS.Conclusions: IDR was associated with tumor aggressiveness, suggesting a metastatic mechanism. Besides AFP association with LTP, IDR, RFS and OS, treatment-naïve patients had longer RFS, and multi-nodularity was associated with shorter RFS and OS. Steatotic HCC, identified on pre-treatment MRI, independently predicted longer OS, and needs to be further explore

Tacrolimus and the Risk of Solid Cancers After Liver Transplant: A Dose Effect Relationship

International audienceAlthough increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single-center study was conducted between 1995 and 2008 and is based on 247 tacrolimus-treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93-15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57-2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard

Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort

Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer therapy. Liver toxicity occurs in up to 25% of patients treated with ICIs. The aim of our study was to describe the different clinical patterns of ICI-induced hepatitis and to assess their outcome. Methods: We conducted a retrospective observational study of patients with checkpoint inhibitor-induced liver injury (CHILI) discussed in multidisciplinary meetings between December 2018 and March 2022 in three French centres specialised in ICI toxicity management (Montpellier, Toulouse, Lyon). The hepatitis clinical pattern was analysed by the ratio of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (R value = (ALT/ULN)/(ALP/ULN)) for characterisation as cholestatic (R − 5), or mixed (2 − 3 according to the Common Terminology Criteria for Adverse Events system) was significantly associated with the hepatocellular hepatitis (p <0.05). No cases of severe acute hepatitis were reported. Liver biopsy was performed in 41.9% of patients: granulomatous lesions, endothelitis, or lymphocytic cholangitis were described. Biliary stenosis occurred in eight patients (6.8%) and was significantly more frequent in the cholestatic clinical pattern (p < 0.001). Steroids alone were mainly administered to patients with a hepatocellular clinical pattern (26.5%), and ursodeoxycholic acid was more frequently used in the cholestatic pattern (19.7%) than in the hepatocellular or mixed clinical pattern (p <0.001). Seventeen patients improved without any treatment. Among the 51 patients (43.6%) rechallenged with ICIs, 12 (23.5%) developed CHILI recurrence. Conclusions: This large cohort indicates the different clinical patterns of ICI-induced liver injury and highlights that the cholestatic and hepatocellular patterns are the most frequent with different outcomes. Impact and Implications: ICIs can induce hepatitis. In this retrospective series, we report 117 cases of ICI-induced hepatitis, mostly grades 3 and 4. We find a similar distribution of the different patterns of hepatitis. ICI could be resumed without systematic recurrence of hepatitis