Liver transplant for patients outside Milan criteria

Abstract

Hepatocellular carcinoma (HCC) is one of the most indication to Liver Transplantation (LT). Milan criteria are worldwide accepted as the gold standard for LT indication for HCC. Nevertheless, expanded criteria are often used to transplant patient outside Milan. We described the most important proposed criteria outside Milan criteria. From the University of California San Francisco, to the Toronto criteria. From East to Western, and for living donor liver transplantation. In order to achieve similar results the downstaging strategy is more frequently used and for patients with locally advanced HCC. Carefully selected patients beyond the traditional criteria for transplantation may achieve excellent LT outcomes through a planned, multidisciplinary approach to treatment.

The role of preoperative albumin‐bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma

“…Apart from that, our results seem to indicate that the application of ALBI score could also improve a conservative Milan‐based LT policy. Multiple studies have shown that, even when strictly following the Milan guidelines, there remains an oncological risk of about 20%, which seems to be critical in times of severe donor organ shortage . In our MC In cohort, we noticed extremely low HCC recurrence rates in grade 1 (4%) and grade 2 patients (8.6%), while being above 50% in grade 3 recipients (55.5%), which has to be critically assessed in light of other LT indications providing much better survival probabilities.…”

“…More likely, ALBI score might be a surrogate marker for a cirrhosis‐associated milieu of inflammation and immune dysfunction, which in turn is discussed to promote tumor invasiveness and spread the circulating HCC cells . In fact, we identified grade 3 as an independent predictor of MVI (Table ), which is considered as the most important risk factor for poor ouctome . A higher surgical risk profile could be an additional proinflammatory trigger of inferior oncological outcome in grade 3 patients.…”

“…Consequently, the MC has been implemented as a worldwide benchmark for clinical and administrative management of the model of end‐stage liver disease (MELD) score‐based organ allocation . In recent years it became however clear that tumor size features as being implemented in standard and expanded morphologic HCC criteria sets, such as the University of California San Francisco and the Up‐to‐seven (UT7) criteria, do not provide sufficient discriminative capacity for selecting appropriate liver transplant candidates . Discrepancies between radiographic and histopathologic tumor staging limited their clinical applicability .…”

“…Discrepancies between radiographic and histopathologic tumor staging limited their clinical applicability . In addition, characteristics of tumor aggressiveness, such as microvascular tumor invasion (MVI) and poor differentiation rather than macromorphologic tumor load were shown to determine the posttransplant outcome . Since these intrinsic tumor factors may reliably be assessed only post‐LT on explant liver pathology, clinical surrogates of unfavorable tumor behavior like increasing serum α‐fetoprotein (AFP) levels and nonresponse to neoadjuvant locoregional tumor therapies have been considered for an optimized oncological risk stratification …”

Should selection criteria for HCC be the same (or different) between LDLT and DDLT?

“…Going further, it did not seem logical to restrict the indications only to size and number of nodules without considering the biological behavior of the tumor. Alpha-fetoprotein (AFP) level was included in a couple of studies, with different cutoff values -less than 400 ng/mL, or less than 1000 ng/mL -and were associated with tumor number or diameter [12] . Shimamura et al [10] included AFP levels to select patients for LDLT, calling the 5-5-500 criteria (tumor size ≤ 5 cm diameter, ≤ 5 nodules, AFP ≤ 500 ng/mL), and achieved a 5-year recurrence-free survival of 90%.…”