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Original Investigation |

Hierarchic Interaction of Factors Associated With Liver Decompensation After Resection for Hepatocellular Carcinoma

Davide Citterio, MD1; Antonio Facciorusso, MD2; Carlo Sposito, MD1; Roberta Rota, MD1; Sherrie Bhoori, MD1; Vincenzo Mazzaferro, MD, PhD1
[+] Author Affiliations
1Hepatology and Liver Transplantation Unit, Department of Surgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy
2Division of Gastroenterology, Department of Medical Sciences, University of Foggia, Azienda Ospedaliera Universitaria Ospedali Riuniti, Foggia, Italy
JAMA Surg. 2016;151(9):846-853. doi:10.1001/jamasurg.2016.1121.
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Importance  Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) in well-compensated liver cirrhosis. Postoperative liver decompensation (LD) is the most representative and least predictable cause of morbidity and mortality.

Objectives  To determine the hierarchy and interaction of factors associated with the risk for LD and to define applicable risk classes among surgical candidates.

Design, Setting, and Participants  This retrospective review collected data from 543 patients with chronic liver disease who underwent hepatic resection for HCC from January 1, 2000, through December 31, 2013, in a tertiary comprehensive cancer center. Final follow-up was completed on January 31, 2015, and data were assessed from February 1 to 28, 2015.

Major Outcomes and Measures  Preoperative prognostic factors and risk stratification for postoperative LD. Multivariate logistic regression was performed, and the independent risk factors for LD were included in a recursive partitioning analysis model. Results were validated by means of 10-fold cross-validation.

Results  The analysis included 543 patients, of whom 411 (75.7%) were male, 132 (24.3%) were female, and the median age was 68 (interquartile range, 62-73) years. An independent association with LD was found for major hepatectomy (odds ratio [OR], 2.41; 95% CI, 1.17-4.30; P = .01), portal hypertension (OR, 2.20; 95% CI, 1.13-4.30; P = .01), and Model for End-Stage Liver Disease (MELD) score greater than 9 (OR, 2.26; 95% CI, 1.10-4.58; P = .02). Recursive partitioning analysis confirmed portal hypertension as the most important factor (OR, 2.99; 95% CI, 1.93-4.62; P < .001), followed by extension of hepatectomy with (OR, 2.76; 95% CI, 1.85-4.77; P = .03) and without (OR, 2.98; 95% CI, 1.97-4.52; P < .001) portal hypertension, and MELD score (OR, 1.79; 95% CI, 1.23-2.13; P < .001). Low-risk patients (LD rate, 4.9% [11 of 226]) without portal hypertension underwent minor resection with a MELD score of 9 or less; intermediate-risk patients (LD rate, 28.6% [85 of 297]) had no portal hypertension and underwent major resections or, in case of minor resections, had portal hypertension or a MELD score greater than 9; and high-risk patients (LD rate, 60.0% [12 of 20]) underwent major resection with portal hypertension. Risk-class progression paralleled median length of stay (7, 8, and 11 days, respectively; P < .001) and liver-related mortality (4.4% [10 of 226], 9.0% [27 of 297], and 25.0% [5 of 20], respectively; P = .001). A 10-fold cross-validation of the model resulted in a C index of 0.78 (95% CI, 0.74-0.82) and an overall error rate of 0.06.

Conclusions and Relevance  The risk for postoperative LD after resection for HCC in chronic liver disease is associated with preoperative hierarchic interaction of portal hypertension, planned extension of hepatectomy, and the MELD score.

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Figure 1.
Different Weight of Preoperative Variables Associated With Postoperative Liver Decompensation (LD) According to the Random-Forest Model

Permutation-based decreased accuracy associated with postresection LD is depicted among 543 patients undergoing liver resections for hepatocellular carcinoma. Higher values indicate variables that weight more in association with LD. ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; ICG-R15, indocyanine green retention test at 15 minutes; and MELD, Model for End-Stage Liver Disease.

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Figure 2.
Recursive Partitioning Classification Tree of Hierarchic Interaction of Prognostic Factors for Postoperative Liver Decompensation (LD)

The tree representation (A) corresponds to a rectangular recursive partition of the feature space among the 3 main variables associated with postsurgical LD (B) in the 543 patients undergoing liver resection for hepatocellular carcinoma. The terminal nodes categorized the study sample into 3 prognostic groups according to LD rate (P < .001). The 3 groups differed also in terms of liver-related mortality during the study period and median length of stay. Major hepatectomy indicates removal of at least 3 liver segments; minor hepatectomy, less than 3 segments. LOS indicates length of stay; MELD, Model for End-Stage Liver Disease. The MELD score ranges from 6 to 40, with higher scores indicating worse liver function and increased risk for mortality.

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