Patients and Preoperative Factors
This retrospective study was approved by the ethics committee of Kobe University Hospital (#190313). All the procedures were conducted in accordance with the principles of the Declaration of Helsinki and its later revisions. From January 2014 to December 2018, 272 consecutive patients with HCC who underwent an initial hepatectomy at Kobe University Hospital were included in the study. Demographic data were collected prior to surgery and included age, sex, performance status according to the Eastern Cooperative Oncology Group (6), body mass index, alcohol consumption, and presence of diabetes mellitus. For the evaluation of preoperative liver function, all the patients underwent several blood tests before undergoing hepatectomy, including complete blood count, total bilirubin level, albumin level, prothrombin time/international normalized ratio (PT-INR), and the retention rate of indocyanine green at 15 min (ICGR15; normal range, <10%). For the evaluation of HCC and fibrosis, abdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 99mTc-GSA scintigraphy were used.
Surgical Procedures
The patient selection criteria for hepatectomy included the extent of comorbidity, Child-Pugh status A or B, and remnant liver volume of >35% of the whole liver. The patients who underwent hepatectomy was categorized into two groups as follows: those who required a major resection (n = 77) and those who required a minor resection (n = 195). Major resection consisted of extended right hepatectomies, right hepatectomies, extended left hepatectomies, left hepatectomies, central resections, and sectionectomies. Minor resections consisted of segmentectomies or less extent of resection.
Preoperative and Intraoperative Liver Biopsies and Pathological Evaluation
Preoperative liver biopsy was performed only for the cases with poor liver function based on an ICGR15 > 10, a PT-INR > 1.15, the Child-Pugh grade, or the 99mTc-GSA scintigraphy index. For all the patients, a final diagnosis of HCC was pathologically confirmed after hepatectomy using a sample from surgically removed liver tissue. Tumor stage was assessed suing the seventh edition of the International Union Against Cancer classification. The degree of hepatic fibrosis was assessed by a pathologist using the METAVIR scoring system as follows: F0, absent; F1, portal fibrosis without septa; F2, portal fibrosis with rare septa; F3, numerous septa; and F4, cirrhosis (7). Intraoperative liver biopsy was performed for the cases with major resection and macroscopically damaged liver.
Postoperative Morbidity and Mortality
Overall morbidity was defined as the occurrence of postoperative complications during the hospital stay after hepatectomy. PHLF was diagnosed on the basis of the ISGLS definition (4). In brief, the ISGLS defines PHLF as increased INR and hyperbilirubinemia on or after postoperative day 5. PHLF is further categorized into three severity grades as follows: grade A, PHLF resulting in abnormal laboratory parameters but requiring no change in the patient’s clinical management; grade B, PHLF resulting in a deviation from the regular clinical management but manageable without invasive treatment; and grade C, PHLF resulting in a deviation from regular clinical management and requiring invasive treatment. After discharge, all the patients were followed up with laboratory tests and CT or MRI examination at the outpatient clinic every 3 to 6 months for the first 5 years and, thereafter, at least once every 12 months until death. Overall survival (OS) was defined as the interval between hepatectomy and death or the last follow-up. For the patients who survived during the analysis, the last follow-up was set as December 31, 2020. Mortality was defined as death during the hospital stay after hepatectomy.
Statistical Analyses
Continuous data were expressed as median (range). Univariate and multivariate Cox proportional hazard regression models were performed to identify independent factors. A multivariate logistic regression analysis was used to identify independent risk factors. Statistical significance was considered when the two-sided p value was <0.05. All statistical analyses were performed using the JMP version 14 software (SAS Institute, Cary, NC, USA).