ALBI score combined with FIB-4 index to predict post-hepatectomy liver failure in patients with hepatocellular carcinoma.

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.

Validation of diagnoses of liver disorders in users of systemic azole antifungal medication in Sweden.

BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%). CONCLUSION: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Comparing the accuracy of prediction models to detect clinically relevant post-hepatectomy liver failure early after major hepatectomy.

BACKGROUND: Arterial lactate measurements were recently suggested as an early predictor of clinically relevant post-hepatectomy liver failure (PHLF). This needed to be evaluated in the subgroup of major hepatectomies only. METHOD: This observational cohort study included consecutive elective major hepatectomies at Karolinska University Hospital from 2010 to 2018. Clinical risk factors for PHLF, perioperative arterial lactate measurements and routine lab values were included in uni- and multivariable regression analysis. Receiver operating characteristics and risk cut-offs were calculated. RESULTS: In total, 649 patients constituted the study cohort, of which 92 developed PHLF grade B/C according to the International Study Group of Liver Surgery (ISGLS). Lactate reached significantly higher intra- and postoperative levels in PHLF grades B and C compared to grade A or no liver failure (all P < 0.002). Lactate on postoperative day (POD) 1 was superior to earlier measurement time points in predicting PHLF B/C (AUC 0.75), but was outperformed by both clinical risk factors (AUC 0.81, P = 0.031) and bilirubin POD1 (AUC 0.83, P = 0.013). A multivariable logistic regression model including clinical risk factors and bilirubin POD1 had the highest AUC of 0.87 (P = 0.006), with 56.6% sensitivity and 94.7% specificity for PHLF grade B/C (cut-off ≥0.32). The model identified 46.7% of patients with 90-day mortality and had an equally good discriminatory potential for mortality as the established ISGLS criteria for PHLF grade B/C but could be applied already on POD1. CONCLUSION: The potential of lactate to predict PHLF following major hepatectomy was inferior to a prediction model consisting of clinical risk factors and bilirubin on first post-operative day.

Adult-onset Still's Disease Diagnosed during Puerperium with Liver Dysfunction in Pregnancy and Liver Failure of the Infant.

Most cases of liver dysfunction in pregnancy are pregnancy-related, but the onset of systemic autoimmune diseases is also differentiated. A 24-year-old woman presented with liver dysfunction at 28 weeks' gestation with suspected autoimmune hepatitis and started taking ursodeoxycholic acid. She gave birth prematurely at 35 weeks' gestation, and the infant presented with pancytopenia and liver failure but survived because of liver transplantation. Since the patient had major symptoms during the puerperium, she was diagnosed with adult-onset Still's disease. When encountering a patient with liver dysfunction during pregnancy, we should also consider the onset of autoimmune diseases.

Predicting symptomatic post-hepatectomy liver failure in patients with hepatocellular carcinoma: development and validation of a preoperative nomogram.

OBJECTIVE: To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. RESULTS: A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5 kPa, Child-Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer-Lemeshow goodness-of-fit test, p = 0.641, p = 0.06, and p = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. CONCLUSION: An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. CLINICAL RELEVANCE STATEMENT: A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in 'how much remnant is enough in liver resection'. KEY POINTS: • An elevated liver stiffness with the best cutoff value of 9.5 kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child-Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

Liver failure as the initial presentation in cancer of unknown primary: a case report.

BACKGROUND: Liver failure is severe hepatic cellular damage caused by multiple factors that leads to clinical manifestations. Hepatic infiltration by malignancy is rarely reported as a cause of liver failure. CASE PRESENTATION: A 51-year-old male patient was admitted to the Wuhan Union Hospital complaining of bloating and jaundice. He had been diagnosed with polymyositis ten prior and was taking oral glucocorticoids. Physical examination revealed seroperitoneum and icteric sclera; laboratory tests revealed liver dysfunction, a coagulopathy, and negative results for the common causes of liver failure. Moreover, an ascitic tap and bone marrow aspirate and trephine confirmed a metastatic, poorly differentiated adenocarcinoma. These findings indicate that malignant infiltration is the most likely cause of liver failure. Regrettably, the patient refused complete liver and lymph node biopsies and was discharged on day 31. CONCLUSION: Clinicians should consider the possibility of malignant infiltration when approaching a case of liver failure with prodromal symptoms or imaging abnormalities, especially in patients with autoimmune diseases, such as polymyositis.

Clinical application of preoperative shear wave dispersion for prediction of post liver failure in patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: The aim in this study was to determine the efficacy of shear wave dispersion (SWD) technique for the prediction of post hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma after hepatectomy and develop an SWD based risk prediction model. METHODS & MATERIALS: We prospectively enrolled 205 consecutive patients who were scheduled to undergo hepatectomy for hepatocellular carcinoma (HCC), pre-operative SWD examination, laboratory data and some other clinicopathological tests were collected. The risk factors of PHLF were identified according to univariate and multivariate analysis, a predictive model was established based on logistic regression analyses. RESULTS: SWD examination was successfully performed in 205 patients. PHLF occurred in 51 patients (24.9%), including 37/11/3 patients with Grade A/B/C, respectively. There was a high correlation between SWD value of liver and liver fibrosis stage (r = 0.873, p < 0.05). Patients with PHLF has a higher median SWD value of liver than patients without PHLF [17.4 vs 14.7 (m/s)/kHz, p < 0.05]. The SWD value of liver, total bilirubin (TB), international normalized ratio of prothrombin time (INR) and splenomegaly were significantly related to PHLF based on the multivariate analysis. A new prediction model (PM) for PHLF was established (PM = -12.918 + 0.183× SWD + 6.668× INR +0.100×TB+1.240×splenomegaly). The optimal cutoff value of SWD for predicting PHLF was 16.7 (m/s)/kHz. The area under the curve (AUC) of the PM for PHLF was 0.833, which was higher than that of SWD, INR, Forns, FIB4, APRI (p < 0.005, respectively). CONCLUSION: SWD is a promising and reliable method for PHLF prediction in patients with HCC who were undergoing hepatectomy. Compared with SWD, Forns, APRI and FIB-4, PM demonstrate better efficacy for preoperative PHLF prediction.

Clinical determinants of hospital mortality in liver failure: a comprehensive analysis of 62,717 patients.

BACKGROUND: Liver failure (LF) is characterised by a loss of the synthetic and metabolic liver function and is associated with a high mortality. Large-scale data on recent developments and hospital mortality of LF in Germany are missing. A systematic analysis and careful interpretation of these datasets could help to optimise outcomes of LF. METHODS: We used standardised hospital discharge data of the Federal Statistical Office to evaluate current trends, hospital mortality and factors associated with an unfavourable course of LF in Germany between 2010 and 2019. RESULTS: A total of 62,717 hospitalised LF cases were identified. Annual LF frequency decreased from 6716 (2010) to 5855 (2019) cases and was higher among males (60.51%). Hospital mortality was 38.08% and significantly declined over the observation period. Mortality significantly correlated with patients' age and was highest among individuals with (sub)acute LF (47.5%). Multivariate regression analyses revealed pulmonary (ORARDS: 2.76, ORmechanical ventilation: 6.46) and renal complications (ORacute kidney failure: 2.04, ORhepatorenal syndrome: 2.92) and sepsis (OR: 1.92) as factors for increased mortality. Liver transplantation reduced mortality in patients with (sub)acute LF. Hospital mortality significantly decreased with the annual LF case volume and ranged from 47.46% to 29.87% in low- or high-case-volume hospitals, respectively. CONCLUSIONS: Although incidence rates and hospital mortality of LF in Germany have constantly decreased, hospital mortality has remained at a very high level. We identified a number of variables associated with increased mortality that could help to improve framework conditions for the treatment of LF in the future.

Post-hepatectomy liver failure: A timeline centered review.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. DATA SOURCES: This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black's checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. RESULTS: This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. CONCLUSIONS: Remnant liver volume manipulation is the most consistent preventive measure against PHLF.

Risk Stratification of Patients with Marginal Hepatic Functional Reserve Using the Remnant Hepatocyte Uptake Index in Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for Safe Liver Surgery.

BACKGROUND: This study aimed to explore the efficacy of gadoxetic acid-enhanced (Gd-EOB) magnetic resonance imaging (MRI) in surgical risk estimation among patients with marginal hepatic function estimated by indocyanine green (ICG) clearance test. METHODS: This analysis focused on 120 patients with marginal hepatic functional reserve (ICG clearance rate of future liver remnant [ICG-Krem] < 0.10). Preoperative Gd-EOB MRI was retrospectively reviewed, and the remnant hepatocyte uptake index (rHUI) was calculated for quantitative measurement of liver function. The predictive power of rHUI for posthepatectomy liver failure was compared with several clinical measures used in current risk estimation before hepatectomy. RESULTS: Receiver operating curve analysis showed that rHUI had the best predictive power for posthepatectomy liver failure among the tested variables (ICG-R15, ICG-Krem, albumin + bilirubin score, and albumin + ICG-R15 score). Cross-validation showed that a threshold of 925 could be the best cut-off value for estimating the postoperative risk of liver failure with sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 0.689, 0.884, 5.94, and 0.352, respectively. CONCLUSION: rHUI could be a sensitive substitute measure for posthepatectomy liver failure risk estimation among patients with marginal hepatic functional reserve.

Impact of the Intermittent Pringle Maneuver for Predicting Post-hepatectomy Liver Failure: A Cohort Study of 597 Consecutive Patients.

BACKGROUND: Intermittent Pringle maneuver (PM) is widely performed to reduce blood loss during hepatectomy; however, its impact on clinically relevant post-hepatectomy liver failure (PHLF) remains controversial. This study aimed to assess the impact of PM on PHLF and explore whether PM provides additional value for predicting PHLF. METHODS: Consecutive patients, who underwent hepatectomy without biliary and/or vascular reconstruction between 2011 and 2018 in a single institution, were retrospectively analyzed. The main outcome was PHLF grades B/C as defined by the International Study Group of Liver Surgery. A multivariable logistic regression model of variables significantly associated with PHLF was established. The model's predictive ability was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 597 patients, PHLF occurred in 42 (7.0%). PM was applied in 421 patients (70.5%) and was associated with the development of PHLF (PM vs. no-PM: 9.7 vs. 0.6%, P < 0.001). After the propensity score matching, patients with PM experienced significantly increased rates of PHLF (P = 0.010). Rem-ALPlat index (including future liver remnant, preoperative albumin level, and platelet count; P < 0.001), the number of PMs (P = 0.032), and blood loss (P = 0.007) were identified as significant predictors of PHLF. The model's AUROC combined with the intraoperative variables was higher than that of the preoperative model alone (0.877 vs. 0.789, P = 0.004). CONCLUSIONS: PM was involved in the occurrence of clinically relevant PHLF. Further, intraoperative factors including PM may provide additional value to predict PHLF and may facilitate early post-hepatectomy intervention.

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

OBJECTIVE: To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. SUMMARY OF BACKGROUND DATA: PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. METHODS: Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. RESULTS: Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. CONCLUSIONS: In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

[The development of portal hypertension and liver failure on the background of long-term intake of vitamin A in a young woman. Case report].

The use of over-the-Counter (OTC) pharmaceuticals is a common phenomenon in today's society. We present a case of liver injury associated with long-term OTC use of vitamin A. The young patient took daily up to 15 capsules of a combined preparation for 2 years containing retinol palmitate 55 mg (100,000 IU) + Alpha-Tocopherol acetate 100 mg, the content of vitamin A in which significantly exceeded the recommended daily dose. Gradually, the patient noted the appearance of arthralgia, skin itching, hyperemia of the palms and feet, exfoliation of the skin on the soles, profuse hair loss, cracks in the corners of the mouth and in the area of the earlobes. Patient's condition worsened with the development of signs of liver cirrhosis in the form of portal hypertension (ascites, splenomegaly) and a decrease in the protein-synthetic function of the organ. Chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, alcoholic liver disease were exclude. Liver biopsy showed characteristic signs of hypervitaminosis A without fibrosis. A complete regression of symptoms was observe within 8 months after discontinuation of the drug. A toxicity can lead to serious liver injury and should be considere in the differential diagnosis of chronic liver disease. Vitamin A should only be prescribe for medical reasons, for a limited period of time, and under close medical supervision.

Preoperative indocyanine green (ICG) clearance test: Can we really trust it to predict post hepatectomy liver failure? A systematic review of the literature and meta-analysis of diagnostic test accuracy.

INTRODUCTION: Post hepatectomy liver failure (PHFL) still represents a potentially fatal complication after major liver resection. Indocyanine green (ICG) clearance test represents one of the most widely adopted examinations in the preoperative workup. Despite a copious body of evidence which has been published on this topic, the role of ICG in predicting PHLF is still a matter of debate. METHODS: A systematic review of the literature was conducted according to PRISMA-DTA guidelines. The primary outcome was the assessment of diagnostic performance of ICG in predicting PHLF. The secondary outcome was the mean ICGR15 and ICGPDR in patients experiencing PHLF. RESULTS: Seventeen studies, for a total of 4852 patients, were deemed eligible. Sensitivity ranged from 25% to 83%; Specificity ranged from 66.1% to 93.8%. ICG clearance test pooled AUC was 0.673 (95% CI: 0.632-0.713). The weighted mean ICGR15 was 11 (95%CI: 8.3-13.7). The weighted mean ICGPDR was 16.5 (95%CI: 13.3-19.8). High risk of bias was detected in all examined domains. CONCLUSIONS: Preoperative ICG clearance test alone may not represent a reliable method to predict post hepatectomy liver failure. Its diagnostic significance should be framed within multiparametric models involving clinical and imaging features.