Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence.

INTRODUCTION: We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. MATERIALS AND METHODS: We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. RESULTS: Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. CONCLUSION: Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.

Long-term oncological results of percutaneous radiofrequency ablation for intrahepatic cholangiocarcinoma.

INTRODUCTION: The effectiveness of percutaneous radiofrequency ablation (RFA) in intrahepatic cholangiocarcinomas (iCCA) remains insufficiently studied. METHODS: We conducted a retrospective study including patients with histologically proven iCCA within Milan criteria treated by percutaneous RFA from 2000 to 2022. The primary outcome was overall survival in treatment-naive patients and secondary outcomes included ablation completeness, adverse events, local and distant recurrence. A total of 494 patients with hepatocellular carcinoma (HCC) on cirrhosis treated by RFA were included as a comparison group. Oncological events were analysed using Kaplan-Meier, log-rank and univariate/multivariate Cox models. RESULTS: The main population included 71 patients, mostly cirrhotic (80%) with solitary tumours (66%) of a median size of 24 mm. Local recurrence was 45% at 5 years, lower in multibipolar versus monopolar RFA (22% vs. 55%, p = .007). In treatment-naive patients (n = 45), median overall and recurrence-free survivals were 26 and 11 months, respectively. Tumour size (p = .01) and Child-Pugh B (p = .001) were associated with death. The rate of distant recurrence was 59% at 5 years significantly lower for single tumours of less than 2 (p = .002) or 3 cm (p = .02). In cirrhotic patients naïve of previous treatment (n = 40), overall survival was shorter than in HCC (26 vs 68 months, p < .0001), with more local recurrences (p < .0001). Among distant recurrences, 50% were extrahepatic metastases compared to 12% in HCC (p < .001). CONCLUSION: Multibipolar RFA provides better results in terms of tumour recurrence than monopolar RFA and could be used to treat small iCCA (<3 cm). Adjuvant chemotherapy should be discussed due to the frequent extra-hepatic metastasis at recurrence.

Baveno VI and VII criteria are not suitable for screening for large varices or clinically significant portal hypertension in patients with hepatocellular carcinoma.

BACKGROUND: Baveno VI and VII criteria are used in patients with cirrhosis to rule out large size oesophageal varices (EV) and rule in/out clinically significant portal hypertension (CSPH). AIM: To evaluate their diagnostic performance in these patients. METHODS: We retrospectively included all patients with Child-Pugh A cirrhosis and HCC who had endoscopy, liver stiffness measurement (LSM) and platelet count within 6 months. They were classified according to the BCLC stage. Favourable Baveno VI criteria were defined by LSM < 20 kPa and platelets > 150 G/L (to rule out large EV), favourable Baveno VII criteria if LSM ≤ 15 kPa and platelets ≥ 150 G/L (to rule out CSPH, which was defined by a HVPG ≥ 10 mm Hg. RESULTS: We included 185 patients; 46% were BCLC-0/A, 28% BCLC-B and 26% BCLC-C. EV were present in 44% (23% large), and HVPG ≥ 10 mm Hg in 42% (mean 8 mm Hg). In patients with favourable Baveno VI criteria, 8% of the whole cohort (Se 93%, NPV 92%), 11% of BCLC-0-A (Se 89%, NPV 89%) and 10.0% of BCLC-C patients (Se 91%, NPV 90%) had large EV. Among patients with HVPG < 10 mm Hg, 6% had large EV and 17% small. CSPH was present in 23% of patients with favourable Baveno VII criteria among the whole cohort, and in 25% of those with BCLC-0/A. The specificity of LSM ≥ 25 kPa to rule in CSPH was 48%. CONCLUSIONS: Favourable Baveno VI criteria are not appropriate to rule out the presence of high-risk EV, or Baveno VII criteria to rule CSPH in/out in patients with HCC.

Baseline ALBI score and early variation of serum AFP predicts outcomes in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND: The combination of atezolizumab and bevacizumab (AtezoBev) is the current first-line treatment for patients with hepatocellular carcinoma (HCC). Our aim was to evaluate the prognostic role of alpha-foetoprotein (AFP) early response and its combination with albumin-bilirubin (ALBI) in these patients. METHODS: Patients with HCC under AtezoBev with AFP > 20 ng/ml were included in three centres. The optimal threshold of AFP variation after 3 weeks of treatment was identified for overall survival (OS) and radiological response (RR) using RECIST 1.1 and mRECIST and its ability to predict progression-free survival (PFS) and OS was tested using univariate and multivariate analysis in derivation and validation cohorts. RESULTS: Seventy-five patients with AFP values >20 ng/ml were included. Fifty-eight patients were male with a median age of 63.5 years; 73% had cirrhosis and HCC stage was classified as BCLC B (18.7%) or C (81.3%). In the derivation cohort (n = 38), a decline in AFP ≥ 20% at 3 weeks (AFP early response) was associated with RR using mRECIST criteria (OR: 13.09 95% CI: 1.44-19.34 p = .02), PFS (HR: 0.42; 95% CI: 0.19-0.93, p = .03) and OS (HR: 0.35; 95% CI: 0.15-0.83, p = .01). AFP early response was confirmed as predictor of RR (p = .02 for mRECIST) and OS (p = .03) in the validation cohort (n= 37). In the whole cohort, the combination of ALBI and AFP early response was significantly associated with OS (p = .046) and PFS (p = .012) with a poor prognosis in patients belonging to the ALBI2-AFP non-responders class. CONCLUSION: AFP early response at 3 weeks predicts oncological outcomes in HCC patients treated with AtezoBev and combination with ALBI grade refines prognostic discrimination.

Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation.

BACKGROUND AND AIMS: The natural history of hepatocellular adenomas (HCAs) remains to be better described, especially in nonresected patients. We aim to identify the predictive factors of HCA evolution after estrogen-based contraception discontinuation. APPROACH AND RESULTS: We retrospectively included patients with a histological diagnosis of HCA from three centers. Clinical, radiological, and pathological data were collected to identify predictive factors of radiological evolution per Response Evaluation Criteria in Solid Tumors, version 1.1, and occurrence of complications (bleeding, malignant transformation). We built a score using variables that modulate estrogen levels: body mass index and duration of estrogen-based contraception. An external cohort was used to validate this score. 183 patients were included in the cohort, including 161 women (89%) using estrogen-based contraception for a median of 12 years. Thirty percent of patients had at least one HNF1A -inactivated HCA, 45.5% at least one inflammatory HCA, and 11% at least one HCA with activation of ß-catenin (bHCA). Twenty-one symptomatic bleedings (11%) and eleven malignant transformations (6%) occurred. Ages < 37 years old ( p = 0.004) and HCA > 5 cm at imaging were independently associated with symptomatic bleeding ( p = 0.003), whereas a bHCA was associated with malignant transformation ( p < 0.001). After a median follow-up of 5 years, radiological regression was observed in 31%, stabilization in 47%, and progression in 22% of patients. Weight loss was associated with regression ( p < 0.0001) and weight gain with progression ( p = 0.02). The estrogen exposure score predicted radiological regression (odds ratio, 2.33; confidence interval 95%, 1.29-4.19; p = 0.005) with a linear relationship between the rate of estrogen exposure and the probability of regression. This result was confirmed in an external cohort of 72 female patients ( p = 0.003). CONCLUSION: Weight variation is strongly associated with radiological evolution after oral contraception discontinuation. A score of estrogen exposure, easily assessable in clinical practice at diagnosis, predicts regression of HCA.