Pharmacological Management for Prevention and Treatment of Posthepatectomy Liver Failure

Can Peri-operative Lactate Kinetics Predict Liver Failure Following Major Liver Resection?

Assessment of liver function: what are we measuring?

Summary: Introduction: Posthepatectomy liver failure (PHLF) is still a dreaded disease entity despite medical advances. The primary aim of the work was to retrospectively apply selected scoring systems used to assess the risk of PHLF to a group of patients after major liver resections operated at the authors‘ workplace. We anticipate that the latest scoring systems will provide a more accurate picture of PHLF risk. Methods: Between 2007 and 2016, 82 patients meeting the inclusion criteria (elective removal of three or more liver segments for neoplasm) were identified. Five scoring systems were applied to them, namely: “50-50” criterion, ISGLS classification, Hyder score, ALBI and Liu score. Results: Using the “50-50” criterion, none of the patients reached the diagnosis of PHLF. Applying the ISGLS scoring system, 68 patients (86%) had grade “A” and 11 had grade “B” PHLF on the 5th postoperative day. Hyder‘s score above 11 was achieved by two patients who died on the 14th and 34th postoperative day. In the ALBI score, only one patient achieved a value of more than –1.39 (–0.4), while he died on the second postoperative day. Within the Liu score, 55 patients had a predicted very serious risk of developing PHLF, while 46 patients died with an average survival of 27 months after resection. Of the five applied scoring systems, only in the case of ALBI and Liu scores was a statistically significant difference between subgroups of patients with different degrees of presence or prediction of PHLF. A marginally significant difference in the proportion of genders was also noted within the entire set, with men having a higher chance of death (OR 2.63; 95% CI 0.83–8.32). Discussion: The ALBI scoring system correlates with the literature. It has shown very good prediction in several meta-analyses of cohorts of patients after major liver resection. A significantly positive clinical factor of the use of this system is that it is based on preoperative values of laboratory blood tests and can be proposed as a stable prediction model for short-term results after liver resection. Conclusion: The presented scoring systems still represent a rather heterogeneous view of PHLF. Our work points to the ALBI score as the best scoring system. Consistent stratification of patients and treatment in high-volume centers are key pillars of prevention of PHLF. Key words: hepatectomy – liver failure – liver neoplasm – posthepatectomy liver failure – major liver resection – scoring systems

To evaluate the predictive value of portal vein pressure (PVP) after major liver resection for posthepatectomy liver failure (PLF) and 90-day mortality in patients without cirrhosis. As elevated PVP is associated with liver failure after living donor liver transplantation, we hypothesized that the outcome after major hepatectomy may be influenced by posthepatectomy PVP. All patients without severe fibrosis or cirrhosis who underwent a major liver resection (≥3 segments) with an intraoperative measurement of PVP at the end of the procedure were included. Outcome was analyzed regarding 3 most widely used definitions of PLF: "50-50" criteria, peak of serum bilirubin greater than 120 μmol/L, and grade C PLF proposed by the International Study Group of Liver Surgery (ISGLS). Receiver operating characteristic curves and logistic regression model were used to determine the optimal cutoff of PVP and independent risk factors of PLF. The study population consisted of 277 patients. Posthepatectomy PVP was gradually correlated with the PLF risk. Probability for PLF was nil when PVP was 10 mm Hg or less, ranges from 13% to 16%, depending on PLF definitions, when PVP was 20 mm Hg, and from 24% to 33% when PVP was 30 mm Hg. The optimal value of posthepatectomy PVP to predict PLF was 22 mm Hg when considering the "50-50" criteria and grade C PLF (proposed by the International Study Group of Liver Surgery). A value of 21 mm Hg best predicted PLF defined by peak of serum bilirubin greater than 120 μmol/L and 90-day mortality. At multivariate analysis, posthepatectomy PVP remained an independent predictor of PLF as well as the extent of resection, intraoperative transfusion, and the presence of diabetes. The 90-day mortality was associated with PVP greater than 21 mm Hg, older than 70 years, and intraoperative transfusion. Posthepatectomy PVP is an independent predictive factor of PLF and of 90-day mortality after major liver resection in patients without cirrhosis. Intraoperative modulation of PVP would be advisable when PVP exceeds 20 mm Hg.

Rescue liver transplantation after post-hepatectomy acute liver failure: A systematic review and pooled analysis

Posthepatectomy liver failure (PHLF) is a major cause of morbidity and mortality after major liver resection. Postoperative excessive portal pressure could cause shear stress to the small remnant liver leading to a PHLF. This study aimed to report the clinical experience of somatostatin for portal modulation in patients with severe PHLF. This retrospective study enrolled 15 patients who received somatostatin for the treatment of PHLF between 2016 and 2019. When the patients fulfilled the 50-50 criteria (serum bilirubin > 2.9 mg/dL and prothrombin time < 50%) on or before postoperative day 5, somatostatin (3.5 μg/kg/h) was administered by continuous infusion. The discontinuation criteria were as follows: serum bilirubin < 2 mg/dL and prothrombin time ≥ 50%. Prospectively collected clinical characteristics, laboratory tests, postoperative morbidity and mortality were evaluated. The study cohort consisted of 8 patients with hepatocellular carcinoma, 6 with cholangiocarcinoma, and 1 with colon cancer liver metastasis. Seven patients (46.7%) had underlying liver cirrhosis, and 14 (93.3%) underwent major hepatectomy. The median start time of somatostatin was postoperative day 1 (range, 1-19), and the median duration of administration was 9 days (2-29 days). There was no obvious side effects or hypersensitivity related to the somatostatin. The median hospital stay was 37 days (21-249 days). The 30-day and 90-day mortality were both 6.7% (1 of 15 patients). Administration of somatostatin in the early postoperative period is considered to be effective for the treatment of PHLF. Further prospective comparative clinical trials are needed to validate this finding.

Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. We aimed to assess the association between LBM and PHLF in HCC patients. PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172-0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

BackgroundThe preoperative prediction of post hepatectomy liver failure (PHLF) is essential, but there is no gold standard for the prediction at present, and the efficacy of different methods for the prediction has not been compared systematically. In this study, we aimed to compare the efficacy of preoperative two-dimensional shear wave elastography (2D-SWE), indocyanine green (ICG) clearance test and biomarkers for PHLF prediction in patients with hepatocellular carcinoma (HCC).MethodsWe retrospectively studied 215 patients with HCC, who had undergone major liver resection in our hospital. Preoperative data of each patient, including liver stiffness value (LSV) of underlying hepatic parenchyma measured by 2D-SWE, ICG retention rate at 15 min (ICG-R15) measured by ICG clearance test, albumin-bilirubin (ALBI) scores, aspartate aminotransferase–platelet ratio index (APRI), and Fibrosis-4 (FIB-4) were collected for analysis. Post hepatectomy outcomes of study patients were also recorded for assessment of PHLF. The study patients were divided into development cohort (133 patients without PHLF, and 17 patients with PHLF) and validation cohort (59 patients without PHLF, and 6 patients with PHLF) randomly.ResultsIn the development cohort, LSV, ICG-R15 and ALBI scores were significantly different between patients with and without PHLF, while no significant difference of APRI and FIB-4 scores was found. LSV had higher AUC (the area under the receiver operating characteristic curve) (AUC = 0.795) for PHLF prediction than ICG-R15 (AUC = 0.619) and ALBI scores (AUC = 0.686) (p < 0.05 for all comparisons). In the validation cohort, the cutoff value of LSV obtained from the development cohort, 10.35 kPa, revealed higher specificity (76.3%) for PHLF prediction than ICG-R15 (specificity: 66.1%) and ALBI scores (specificity: 69.5%) (p < 0.0001).ConclusionsCompared with ICG-R15, ALBI scores, APRI and FIB-4, LSV measured by 2D-SWE may demonstrate better efficacy for preoperative PHLF prediction in patients with HCC.

BackgroundThis study aimed to analyze the predictive value of Hepatobiliary scintigraphy (HBS) for posthepatectomy liver failure (PHLF) after major liver resection with a comparison to assessment of liver volume in a multicenter cohort. MethodsPatients who underwent liver resection after HBS were included from six centers. Remnant liver volume was calculated from CT images. PHLF was scored and graded according to the grade B/C ISGLS criteria. ResultsIn 547 patients PHLF incidence was 10% (56/547) and 90-day mortality rate 8% (42/547). Overall predictive value of remnant liver function was 0.66 (0.58–0.74) and similar to that of remnant volume (0.63 (0.72). For biliary tumors, a function cut-off of 2.7%/min/m2 and 30% volume cut-off resulted in a PHLF rate 12% and 13%, respectively. While an 8.5%/min (4.5%/min/m2) function cut-off resulted in 7% PHLF for those with a function above the cutoff while a 40% volume cutoff still resulted in 14% PHLF rate. In the multivariable analyses for PHLF, liver function was predictive but liver volume was not. ConclusionThe current study shows that preoperative liver function assessment using HBS is at least as predictive for PHLF as liver volume assessment, and likely has several advantages, particularly in the high-risk sub-group of biliary tumors.

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 15min (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 (> 3mg/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.

Portal flow modulation by splenic artery ligation to prevent posthepatectomy liver failure: A randomized controlled trial.

Outcome of Major Liver Resections with Routine Use of Pringle’s Maneuver: Single Team Experience from Developing HPB Unit of University Teaching Hospital

Post-hepatectomy liver failure (PHLF) is one of the most serious complications and major causes of liver resection mortality. The purpose of this study is to investigate and compare the performance of preoperative two-dimensional shear wave elastography (2D-SWE) and the indocyanine green (ICG) clearance test for the prediction of PHLF. A total of 172 consecutive patients who were undergoing major liver resection were prospectively identified. Patients were evaluated by preoperative 2D-SWE and ICG clearance test. According to the International Study Group of Liver Surgery (ISGLS) recommendations, No PHLF, PHLF A, PHLF B, and PHLF C group classifications were defined. The differences in liver stiffness value (LSV) and ICG retention rate at 15 minutes (ICGR15) among the different PHLF classifications were investigated. The performance of LSV and ICGR15 for diagnosing different classifications of PHLF was compared. PHLF occurred in 43 (25.0%) patients, and 24 (14.0%) patients were grade A, 14 (8.1%) were grade B, and 5 (2.9%) were grade C. Both LSV and ICGR15 of the PHLF C group were significantly higher than those of the No PHLF group (P=0.025, P=0.001, respectively). According to univariate and multivariate logistic regression analysis, LSV and ICGR15 were significantly related to PHLF (P=0.051, P=0.084, respectively). For diagnosis of ≥ PHLF A, ≥ PHLF B, and ≥ PHLF C, the areas under the receiver operating characteristic curve (AUCs) for 2D-SWE were 0.624 [95% confidence interval (CI): 0.536-0.712, P=0.015], 0.699 (95% CI: 0.576-0.821, P=0.005), and 0.831 (95% CI: 0.737-0.925, P=0.01), respectively. The AUCs of the ICG clearance test were 0.631 (95% CI: 0.542-0.721, P=0.01), 0.570 (95% CI: 0.436-0.704, P=0.32), and 0.717 (95% CI: 0.515-0.920, P=0.098), respectively. The AUC of LSV for the diagnosis of ≥ PHLF A was comparable to that of ICGR15 (P=0.17). The AUCs of LSV were significantly higher than those of ICGR15 for the diagnosis of ≥ PHLF B (P=0.002) and C (P=0.038). 2D-SWE demonstrates the potential to aid in the prediction of the severity of PHLF. Our findings also suggest that the performance of 2D-SWE is better than the ICG clearance test.

Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50:50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5‐7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60‐ and 90‐day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60‐ and 90‐day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial. (Hepatology Communications 2018;2:445‐454)

Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.