BACKGROUND: Post-hepatectomy liver failure (PHLF) is a common consequence of radical partial hepatectomy in hepatocellular carcinoma (HCC).
OBJECTIVE: To investigate the relationship between preoperative antiviral therapy and PHLF, as well as assess the potential efficacy of hepatitis B virus (HBV) DNA level in predicting PHLF.
METHODS: A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy. Receiver operating characteristic (ROC) analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses. Logistic regression analyses were performed to assess the independent risk factors of PHLF. The increase in the area under the ROC curve, categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to quantify the efficacy of HBV DNA level for predicting PHLF. The P < 0.05 was considered statistically significant.
RESULTS: Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF (P < 0.05). HBV DNA level with an optimal cutoff value of 269 IU/mL (P < 0.001) was an independent risk factor of PHLF. All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve, categorical NRI, and IDI, particularly for the fibrosis-4 model, with values of 0.729 (95%CI: 0.705-0.754), 1.382 (95%CI: 1.341-1.423), and 0.112 (95%CI: 0.110-0.114), respectively. All the above findings were statistically significant.
CONCLUSIONS: In summary, preoperative antiviral treatment can reduce the incidence of PHLF, whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF.
OBJECTIVE: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma.
METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF.
RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF.
CONCLUSIONS: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH.
BACKGROUND: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC.
METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram.
RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR.
CONCLUSIONS: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Background: The association between surgical approach and post-hepatectomy liver failure (PHLF) in cirrhotic patients is poorly understood. We hypothesize that patients will have similar rates of liver failure regardless of whether they undergo minimally invasive liver resection (MILR) or open liver resection (OLR) in major liver resections. In contrast, there will be lower rates of PHLF in patients undergoing minor hepatectomy via the MILR approach.Methods: Propensity score matching was used to analyze regression by matching the MILR to the OLR cohort. Patient demographics from the American College of Surgeons National Surgical Quality Improvement Program, including race, age, gender, and ethnicity, were matched. Chronic obstructive pulmonary disease, congestive heart failure, smoking, hypertension, diabetes, renal failure, dyspnea, dialysis dependence, body mass index, and American Society of Anesthesiologists (ASA) classification (>ASA III) were among the preoperative patient characteristics subject to matching. PHLF (Grade A vs B. vs C) was our primary outcome measure.Results: A total of 2129 cirrhotic patients were included in the study. In the minor hepatectomy group, patients undergoing an OLR were more likely to get discharged to a facility (7.0% vs 4.4%; P = .03), had greater hospital length of stay (5 vs 3 days; P = .02), and had a greater need for invasive postoperative interventions (10.7% vs 4.6%; P < .01). They were also noted to have higher rates of organ space superficial surgical infections (SSIs) (7.3% vs 3.7%; P = .003), Clostridium difficile infection (.9% vs .1%; P = .05), renal insufficiency (2.1% vs .1%; P < .01), unplanned intubations (3.1% vs 1.4%; P = .03), and Grade C liver failure (2.3% vs .9%; P = .03).Conclusion: A higher incidence of PHLF grade C was found in patients undergoing OLR in the minor hepatectomy group. Therefore, in cirrhotic patients who can tolerate minimally invasive approaches, MILR should be offered to prevent postoperative complications as part of their optimization plan.

Surgical resection stands as the preeminent therapeutic approach for both primary hepatocellular carcinoma and metastatic liver malignancies. Its efficacy is contingent upon the attainment of a comprehensive excision while ensuring a sufficient future liver remnant (FLR). However, post-hepatectomy liver failure (PHLF) remains a significant challenge, particularly in patients with preexisting liver disease. The present study aims to investigate the predictive value of the preoperative indocyanine green retention test at 15 min (ICG-R15) in identifying patients at risk of PHLF following major liver resection. This retrospective review focused on patients who underwent the ICG-R15 test before major liver resection between August 2021 and January 2023. All patients underwent standard preoperative evaluation and staging. Patients with primary or metastatic liver cancer planned for major resection and undergoing ICG-R15 were included in the study. Patients with elevated serum bilirubin (> 3 mg/dl) and those not undergoing liver resection or minor liver resection (< 3 segments) were excluded from the study. PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria. Follow-up was performed to identify 90-day morbidity. Using univariate and multivariate logistic regression analyses, we confirmed independent risk parameters that predicted postoperative major complications and severe PHLF. The study included 72 patients who underwent preoperative ICG-R15 testing prior to major liver resection. PHLF occurred in 28 patients (38.9%), with 24 patients (33.3%) classified as severity score B and 3 patients (4.16%) had severity score C. Univariate analysis revealed future liver remnant (FLR), ICG-R15, and blood transfusion as predictors of PHLF. Multivariate analysis confirmed FLR (p = 0.019) and ICG-R15 (p = 0.032) as significant predictors. Receiver operating characteristic curve analysis yielded an area under the curve of 0.642 for ICG-R15 in predicting PHLF. An optimal cut-point of 7.5 was determined. Our study highlights the importance of preoperative risk assessment of liver function evaluation using the ICG-R15 test, to predict the risk of PHLF following liver resection. Implementing appropriate interventions, especially in patients with borderline FLR, can improve surgical outcomes and enhance patient safety. Further research and prospective studies are essential to refine risk prediction models and improve rates of PHLF after liver resections.

Background: Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC. Methods: We retrospectively collected data from 972 patients with HCC who had undergone initial curative liver resection between February 2000 and December 2020 at our hospital. Multivariate logistic regression analysis using a restricted cubic spline was performed to evaluate the effect of 7s collagen on the incidence of PHLF. A nomogram was developed based on 7s collagen. Results: PHLF grades B or C were identified in 104 patients (11%): 98 (10%) and 6 (1%) PHLF grades B and C, respectively. Multivariate logistic regression analysis revealed that the preoperative serum level of 7s collagen was significantly associated with a proportional increase in the risk of PHLF, which was confirmed in both laparoscopic and open liver resections. A nomogram was developed based on 7s collagen, with a concordance index of 0.768. The inclusion of 7s collagen values in the predictive model increased the predictive accuracy. Conclusion: The findings highlight the efficacy of the serum level of 7s collagen as a predictive factor for PHLF. Our novel nomogram using 7s collagen may be useful for predicting the risk of PHLF.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

Post-hepatectomy liver failure (PHLF) is a potentially life-threatening complication following liver resection. Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease, which increases the risk of PHLF. This study aimed to investigate the ability of the combination of liver function and fibrosis markers (ALBI score and FIB-4 index) to predict PHLF in patients with HCC. Patients who underwent hepatectomy for HCC between August 2012 and September 2022 were considered for inclusion. Multivariable logistic regression analysis was used to identify factors associated with PHLF, and ALBI score and FIB-4 index were combined based on their regression coefficients. The performance of the combined ALBI-FIB4 score in predicting PHLF and postoperative mortality was compared with Child-Pugh score, MELD score, ALBI score, and FIB-4 index. A total of 215 patients were enrolled in this study. PHLF occurred in 35 patients (16.3%). The incidence of severe PHLF (grade B and grade C PHLF) was 9.3%. Postoperative 90-d mortality was 2.8%. ALBI score, FIB-4 index, prothrombin time, and extent of liver resection were identified as independent factors for predicting PHLF. The AUC of the ALBI-FIB4 score in predicting PHLF was 0.783(95%CI: 0.694-0.872), higher than other models. The ALBI-FIB4 score could divide patients into two risk groups based on a cut-off value of - 1.82. High-risk patients had a high incidence of PHLF of 39.1%, while PHLF just occurred in 6.6% of low-risk patients. Similarly, the AUCs of the ALBI-FIB4 score in predicting severe PHLF and postoperative 90-d mortality were also higher than other models. Preoperative ALBI-FIB4 score showed good performance in predicting PHLF and postoperative mortality in patients undergoing hepatectomy for HCC, superior to the currently commonly used liver function and fibrosis scoring systems.

Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis. All these events were ameliorated by hepatic transfusion of human bone marrow-derived MSCs. Treatment attenuated platelet and macrophage recruitment to the liver, both major sources of THBS1. By mitigating THBS1, MSCs muted surgery-induced tissue deterioration and dysfunction, and thus supported post-hepatectomy regeneration. After liver surgery, patients displayed increased tissue THBS1, which is associated with functional impairment and may indicate a higher risk of post-surgery complications. Since liver dysfunction involving THBS1 improves with MSC treatment in various animal models, it seems feasible to also modulate THBS1 in humans to impede post-surgery acute liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF.
METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF.
RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792).
CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.