The Combination of APRI and ALBI Facilitates Preoperative Risk Stratification for Patients Undergoing Liver Surgery After Neoadjuvant Chemotherapy

Abstract

Background: Neoadjuvant chemotherapy (NeoCTx) is performed for most patients with colorectal cancer liver metastases (CRCLM). However, chemotherapy-associated liver injury (CALI) has been associated with poor postoperative outcome. To date, however, no clinically applicable and noninvasive tool exists to assess CALI before liver resection.

Methods: Routine blood parameters were assessed in 339 patients before and after completion of NeoCTx and before surgery. The study assessed the prognostic potential of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), the albumin-bilirubin grade (ALBI), and their combinations. Furthermore, an independent multi-center validation cohort (n = 161) was included to confirm the findings concerning the prediction of postoperative outcome.

Results: Higher ALBI, APRI, and APRI + ALBI were found in patients with postoperative morbidity (P = 0.001, P = 0.064, P = 0.001, respectively), liver dysfunction (LD) (P = 0.009, P = 0.012, P < 0.001), or mortality (P = 0.037, P = 0.045, P = 0.016), and APRI + ALBI had the highest predictive potential for LD (area under the curve [AUC], 0.695). An increase in APRI + ALBI was observed during NeoCTx (P < 0.001). Patients with longer periods between NeoCTx and surgery showed a greater decrease in APRI + ALBI (P = 0.006) and a trend for decreased CALI at surgery. A cutoff for APRI + ALBI at - 2.46 before surgery was found to identify patients with CALI (P = 0.002) and patients at risk for a prolonged hospital stay (P = 0.001), intensive care (P < 0.001), morbidity (P < 0.001), LD (P < 0.001), and mortality (P = 0.021). Importantly, the study was able to confirm the predictive potential of APRI + ALBI for postoperative LD and mortality in a multicenter validation cohort.

Conclusion: Determination of APRI + ALBI before surgery enables identification of high-risk patients for liver resection. The combined score seems to dynamically reflect CALI. Thus, APRI + ALBI could be a clinically relevant tool for optimizing timing of surgery in CRCLM patients after NeoCTx.

Fig. 1

Albumin-bilirubin grade (ALBI), aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and APRI + ALBI in accordance with clinical outcome after liver resection. Levels of ALBI (a, c, e), APRI (b, d, f), and APRI + ALBI (g, h, i) are shown for patients with and without postoperative morbidity (a, b, g), for patients with and without postoperative liver dysfunction (LD) (c, d, h), and for patients with and those without postoperative mortality (e, f, i). *P < 0.05. **P < 0.005

Fig. 2

Frequencies of adverse clinical outcome for patients above and below the proposed cutoff of–2.46 for APRI + ALBI. Incidences of (a) prolonged hospitalization, (b) prolonged intensive care unit (ICU) stay, (c) liver dysfunction (LD), (d) morbidity, and (e) mortality are shown according to the proposed risk groups (APRI + ALBI^low/high). *P < 0.05. **P < 0.005. APRI, aspartate aminotransferase (AST)-to-platelet ratio index; ALBI, albumin-bilirubin grade

Fig. 3

Patients above the proposed cutoff of – 2.46 for APRI + ALBI show a higher prevalence of chemotherapy-associated liver injury (CALI). Levels of APRI + ALBI are shown for patients who were or were not treated with neoadjuvant chemotherapy (NeoCTx). Patients with (a) less hepatotoxic chemotherapy (for detailed information refer to Table S1) compared with (b) more hepatotoxic (irinotecan/oxaliplatin-based) NeoCTx, and (c) according to the type of NeoCTx. Furthermore, prevalence of (d) CALI, (e) steatosis, (f) chemotherapy-associated steatohepatitis according to nonalcoholic fatty liver disease activity score (NAS) and Brunt et al., and (g) sinusoidal obstruction syndrome (SOS) are shown for patients with high or low values of preoperative APRI + ALBI. APRI, aspartate aminotransferase (AST)-to-platelet ratio index; ALBI, albumin-bilirubin grade; LH, less hepatotoxic chemotherapeutic regimens; Iri, irinotecan; Ox, oxaliplatin. *P < 0.05. **P < 0.005

Fig. 4

APRI + ALBI is associated with chemotherapy-associated liver injury (CALI) in patients undergoing neoadjuvant chemotherapy (NeoCTx) before liver resection. (a) Time course of APRI + ALBI from before NeoCTx (preNeoCTx) to completion of NeoCTx (postNeoCTx) and the preoperative time point (preOP) are shown. (b) Furthermore, change of APRI + ALBI from postNeoCTx to preOP (ΔAPRI + ALBI) is illustrated for patients grouped according to the length of the chemotherapy-free interval before surgery. (c) For the same patient groups, prevalence of CALI, steatosis, chemotherapy-associated steatohepatitis according to nonalcoholic fatty liver disease activity score (NAS) and Brunt et al. , and sinusoidal obstruction syndrome (SOS) is shown. *P < 0.05. **P < 0.005. APRI, aspartate aminotransferase (AST)-to-platelet ratio index; ALBI, albumin-bilirubin grade

Fig. 5

Multi-institutional validation of the predictive potential of APRI + ALBI for poor postoperative outcome. Frequencies of adverse clinical outcome are given in accordance with the proposed cutoff of –2.46 for APRI + ALBI. Incidences of (a) prolonged hospitalization, (b) prolonged intensive care unit (ICU) stay, (c) liver dysfunction (LD), (d) morbidity, and (e) mortality, are shown according to the risk groups (APRI + ALBI^low/high). *P < 0.05. **P < 0.005