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Aim: Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C virus (HCV) infection and constitutes the main burden of this disease. The molecular mechanisms underlying the development of HCC are multiple and might involve certain microRNA (miR). As discordant results have been reported concerning the detection of expression of miR‐152 and miR‐122 in HCC, our aim was to measure the levels of both miRs in serum and liver samples. Methods: We analyzed miR‐152 and miR‐122 expression by reverse transcription–quantitative polymerase chain reaction in a serum cohort from 14 HCV‐infected patients who developed HCC, 20 HCV+ patients without HCC, and 19 control patients. We also studied miR‐152 and miR‐122 in an independent tissue cohort from 11 normal livers, and from paired HCC and non‐tumor adjacent livers of 11 HCV‐infected patients and 12 non‐infected patients. Results: In serum samples, higher levels of miR‐122 were found in non‐HCC HCV+ compared to HCC HCV+ and control groups, whereas miR‐152 was detectable in a lower range in HCC HCV+ compared to non‐HCC HCV+ and control groups. We found higher signals for miR‐122 and miR‐152 in non‐tumor liver and HCC tissues compared to control tissues. Hepatocellular carcinoma etiology had no detectable influence on miR‐122 expression, whereas miR‐152 was increased in HCV+ tissue samples. Conclusions: Detection of low values of circulating miR‐152 is a potentially interesting marker of hepatocarcinogenesis in HCV+ patients, in contrast to miR‐122, which varies according to hepatocyte damage. [ABSTRACT FROM AUTHOR]

Aim Discordance between pre- LT imaging and explanted liver findings have been reported after liver transplantation ( LT) for hepatocellular carcinoma ( HCC), suggesting the need of reassessing the risk of HCC recurrence post- LT. Our aims were to compare pre- LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. Methods Staging according to pre- LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. Results Pre- LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the 'Up to seven' (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the 'Up to seven' model was superior to the Decaens model ( P=.034), which was superior to the Chan model ( P=.0041) but not to the Iwatsuki model ( P=.17). Conclusion Pre- LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based 'Up to seven' and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT. [ABSTRACT FROM AUTHOR]

To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal ablation during the waiting phase. The DS involves postponing LT until recurrence. The purpose of this study was to evaluate the DS to make sure that it did not hamper pre- and post-LT outcomes. Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to six groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. Kaplan-Meier estimates of the 18-month risk of dropout for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post-LT survival rates were compared. Median waiting-time in the DS group was 910 days. Pre-LT dropout probability was significantly lower in the DS group compared to other groups (13% vs. 19%, p = 0.0043) and significantly higher in the T1 group (25.4%, p = 0.05). Post-LT HCC recurrence rate in the multiple nodules group was significantly higher (19.6%, p = 0.019), while 5-year post-LT survival did not differ among groups and was 74% in the DS group (p = 0.22). The DELTA-HCC study shows that DS does not negatively impact either pre- nor post-LT patient outcomes, and has the potential to allow for redistribution of organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpectedly high risk of dropout in T1 patients seems related to the MELD-based offering rules underserving this subgroup. To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy was adopted in France in 2015. It involves postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA-HCC study was conducted to evaluate this nationwide strategy. It shows in a European LT program that delayed strategy does not negatively impact pre- nor post-LT patient outcomes and is relevant to up to 20% of LT candidates; thus, it could potentially enable the redistribution of organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpectedly high risk of dropout in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup. [Display omitted] • Patients with single curatively treated HCC account for 20% of LT candidates. • In these patients, LT can be safely delayed without hampering pre/post-LT outcomes. • This strategy has the potential to redirect spared organs to patients in urgent need. • The DELTA-HCC study supports extension of a delayed strategy to other LT programs. [ABSTRACT FROM AUTHOR]

There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR). This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality. A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915). Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program. [ABSTRACT FROM AUTHOR]

• Liver adenomatosis is a rare and heterogeneous disease. • If all adenomas are steatotic, a germline HNF1A mutation should be searched for. • Risks are malignant transformation (3%) and tumor bleeding (15%, mostly inaugural). • In familial steatotic liver adenomatosis, bleeding risk exists even in small adenomas. • Patients with liver adenomatosis should have a specific follow-up annually, with MRI and biological tests. Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. Forty patients (36 female) were included with a median follow-up of 10.6 (1.9–26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9–55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A -mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up. [ABSTRACT FROM AUTHOR]