Risk stratification prior to major hepatectomy

Post-hepatectomy liver failure (PHLF) is an uncommon but potentially life-threatening complication after major hepatic resection. Although mild cases of PHLF are self-limiting, clinically significant PHLF [International Study Group of Liver Surgery (ISGLS) grades B or C] may be associated with multi-organ failure and sepsis and carries a high mortality. There is no proven treatment for PHLF, and its management is essentially supportive, including timely diagnosis and treatment of septic or vascular complications and organ support for associated renal, respiratory or cardiovascular failure. In the absence of any evidence-based interventions that may improve PHLF outcomes, liver surgeons have focussed on preoperative risk assessment and development of risk mitigation strategies. The dominant risk factors for PHLF are extent of resection and background liver function, which have been incorporated into several risk scores (1,2). Patients who undergo resection or four or more segments (i.e., right hemihepatectomy or extended left/right hemihepatectomy) or those with underlying liver disease (e.g., fibrosis, cirrhosis or chemotherapy-associated liver disease) are at particular risk of PHLF.

Wang and colleagues (1) have analysed an international cohort of over 2,000 patients from 12 centres to develop and validate risk scores that predict both clinically significant PHLF (grades B/C) and complications [Clavien Complication Index (CCI) >40] after major hepatectomy. This study has several important strengths. The dataset is comprehensive and has included data only from patients undergoing major hepatectomy. The multi-institutional nature of this analysis improves the generalizability of the results to other centres. Moreover, the risk scores have been validated and are available to access online. Both risk scores may be calculated using preoperative data alone or combined with intraoperative data if available. The risk scores developed by Wang and colleagues have potential clinical application and may provide useful information to aid patient selection and counselling prior to major hepatectomy.

The study by Wang and colleagues has several limitations that should be highlighted. Similar to other retrospective studies in this field, the authors have relied on crude surrogate measures of both liver remnant volume (number of liver segments) and function (laboratory indices), acknowledging the lack of data on computed tomography (CT) volumetric analysis and functional assessment in their cohort. The volume of individual liver segments varies significantly between patients, and there is a clear relationship between predicted future liver remnant volume (FLRV) and PHLF (3). Patients with an FLRV <30% are at significant risk of PHLF and should undergo preoperative future liver remnant (FLR) modulation (3). All patients undergoing major hepatectomy should be risk assessed, and CT volumetric assessment should be performed in all high-risk patients (3,4). In addition to volumetric analysis, there is a growing interest in functional liver assessment using single-photon emission CT (SPECT)-CT, indocyanine green (ICG) clearance or functional magnetic resonance imaging (5-7). In a recent study of 99^m technetium-mebrofinate SPECT-CT prior to major hepatectomy (6), there was a significant discrepancy between anatomical and functional distributions, and the remnant liver function strongly predicted PHLF (area under the receiver operating characteristic curve: 0.83) (6).

Although the risk score by Wang and colleagues allows accurate quantification of PHLF risk prior to major hepatectomy, their study does not provide any guidance on which patients should undergo FLR modulation. Given that clinically significant PHLF has no specific treatment and is associated with a high mortality risk, what level of PHLF risk would the authors consider to be unacceptably high? At present, liver surgeons have limited options to reduce the risk of PHLF. Preoperatively, high-risk patients may undergo portal or dual hepatic/portal vein embolization to induce hypertrophy of the FLR. However, this strategy may lead to delayed surgery, with potential risk of disease progression. Parenchymal preserving hepatectomy techniques (e.g., combined resection/ablation, R1-vascular resection or hepatic vein resection/reconstruction) are accepted alternatives to major hepatectomy for patients with multifocal colorectal liver metastases, and avoid the risks associated with major hepatectomy without any negative impact on long-term cancer-related outcomes (8,9). Patients with perihilar cholangiocarcinoma are a special group of patients who generally require extended hepatectomy in addition to biliary and/or vascular resections and are at very high risk of postoperative complications and PHLF. Although the study by Wang and colleagues included some patients with cholangiocarcinoma (14.7% of the entire cohort), the risk score was not specifically developed to risk assess this subgroup.

In summary, the study by Wang and colleagues has made a significant contribution to the available literature on risk stratification prior to major hepatectomy. The validated risk scores allow accurate quantification of an individual patient’s risk of PHLF and overall complications and will aid preoperative counselling and patient selection. Future studies on risk assessment should ideally incorporate data from both volumetric analysis and functional liver imaging to identify high-risk patients in whom preoperative modulation of the FLR may reduce the risk.

Acknowledgments

Funding: This work was funded by Cancer Research UK (CRUK) (to D.C.O.B.).

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-473/coif). The authors have no conflicts of interest to declare.

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