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Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure.

Background The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR). Objective The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy. Method We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques. Results The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin–bilirubin [APRI+ALBI] score), concurrent utilization of 99m Tc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization). Conclusion There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.

The Model for End-Stage Liver Disease (MELD) uses bilirubin, the international normalized ratio for prothrombin time, and creatinine to estimate the risk of death in patients waiting for liver transplantation. This analysis of about 14,000 registrants on the waiting list showed that the addition of the serum sodium concentration to the MELD score improves prognostic accuracy and may reduce mortality among patients on the waiting list who have low MELD scores and serum sodium levels. This analysis of registrants on the waiting list for liver transplantation showed that the addition of the serum sodium concentration to the Model for End-Stage Liver Disease (MELD) score improves prognostic accuracy and may reduce mortality among patients on the waiting list who have low MELD scores and serum sodium levels. The allocation of grafts for liver transplantation from deceased donors in the United States is based on medical urgency, which is estimated according to the Model for End-Stage Liver Disease (MELD) score. The MELD score is based on the results of three readily available, objective, and reproducible laboratory tests: the total serum bilirubin concentration, the international normalized ratio (INR) for the prothrombin time, and the serum creatinine concentration. 1 – 4 In the United States, the MELD score has been used in determining priorities for organ allocation in liver transplantation since 2002. In addition to the MELD score, the serum sodium concentration . . .

Background Post-hepatectomy liver failure (PHLF) is associated with high mortality following liver resection. There have been limited studies evaluating predictors of PHLF and clinically significant PHLF in non-cirrhotic patients. Methods This was a retrospective cohort study using the National Surgical Quality Improvement Program database (NSQIP) to evaluate 8,093 non-cirrhotic patients undergoing hepatectomy from 2014 to 2018. Primary endpoints were PHLF and clinically significant PHLF (PHLF grade B or C). Results Among all patients, 4.74% ( n  = 383) developed PHLF and 2.5% clinically significant PHLF ( n  = 203). The overall 30-day mortality was 1.35% ( n  = 109), 11.5% ( n  = 44) in patients with PHLF, and 19.2% in those with clinically significant PHLF. Factors associated with PHLF were: metastatic liver disease (OR = 1.84, CI = 1.14–2.98), trisectionectomy (OR = 3.71, CI = 2.59–5.32), right total lobectomy (OR = 4.17, CI = 3.06–5.68), transfusions (OR = 1.99, CI = 1.52–2.62), organ/space SSI (OR = 2.84, CI = 2.02–3.98), post-operative pneumonia (OR = 2.43, CI = 1.57–3.76), sepsis (OR = 2.27, CI = 1.47–3.51), and septic shock (OR = 5.67, CI = 3.43–9.36). Patients who developed PHLF or clinically significant PHLF had 2–threefold increased risk of perioperative mortality. Post-hepatectomy renal failure (OR = 8.47, CI = 3.96–18.1), older age (OR = 1.04, CI = 1.014–1.063), male sex (OR = 1.83, CI = 1.07–3.14), sepsis (OR = 2.96, CI = 1.22–7.2), and septic shock (OR = 3.92, CI = 1.61–9.58) were independently associated with 30-mortality in patients with clinically significant PHLF. Conclusion PHLF in non-cirrhotic patients increased the risk of perioperative mortality and is associated with the extent of hepatectomy and infectious complications. Careful evaluation of the liver remnant, antibiotic prophylaxis, nutritional assessment, and timely management of post-operative infections could decrease major morbidity and mortality following hepatectomy.

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients.

BackgroundThe study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC).Methods152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient’s body surface area (BSA, m2).ResultsPHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035).ConclusionThese results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.

Acute-on-chronic liver failure (ACLF) is a critical condition that arises in the context of advanced liver disease, marked by rapid liver function deterioration and associated multi-organ failure. This syndrome is associated with a major short-term mortality risk, requiring aggressive and specialized clinical care. Despite ongoing efforts, effective therapeutic options for ACLF are lacking, with liver transplantation (LT) considered the only life-saving intervention, yielding acceptable outcomes in carefully selected patients. However, the place of LT for ACLF remains a matter of debate, given the high prevalence of the syndrome, the sickness of liver transplant candidates, the persistent shortage of available liver grafts, and the increasing number of indications to LT. This review aims to provide a comprehensive analysis of the role of LT in ACLF, evaluating current evidence on patient selection, optimal timing for transplantation, and ongoing debates surrounding this practice, specifically the rationale for prioritizing graft allocation for this indication. Furthermore, we will explore global management strategies for ACLF, focusing on bridging patients to LT and improving survival outcomes. Through this review, we seek to enhance understanding of the evolving role of LT in ACLF and offer insights into future directions for clinical practice and research in this critical area.

Purpose Our objective was to investigate the impact of albumin-bilirubin (ALBI) score at the time of post-hepatectomy hepatocellular carcinoma (HCC) recurrence on survival after recurrence (SAR). We further explored the perioperative factors associated with the ALBI score at recurrence. Methods Patients who underwent primary hepatectomy for HCC between 2007 and 2018 and developed recurrence were included in the study. Cox regression models were used to assess the association between the ALBI score at recurrence and SAR. Linear regression models were used to explore factors associated with ALBI score at recurrence. Results Of the 233 patients analyzed, 158 developed recurrence within the Milan criteria (RWM) and 76 developed recurrence beyond the Milan criteria (RBM). Multivariable cox regression analysis demonstrated that higher ALBI scores at recurrence were associated with poorer SAR in both RWM and RBM groups (hazard ratios 4.5, 5.0; 95% confidence intervals 2.3–8.8, 2.2–11.6, respectively). In addition, multivariable linear regression analysis revealed that higher ALBI scores at hepatectomy and post-hepatectomy liver failure (PHLF) ≥ grade B were associated with higher ALBI scores at recurrence (β = 0.21, 0.11; 95% confidence intervals 0.15–0.26, 0.06–0.17, respectively). Conclusions The ALBI score at recurrence was a significant prognostic factor for SAR, and the ALBI scores at hepatectomy and PHLF ≥ Grade B were independently associated with the ALBI score at recurrence. Prevention of PHLF and consequent preservation of liver function at recurrence may be paramount to achieving better survival after HCC recurrence.

Background Post-hepatectomy liver failure (PHLF) represents the major source of mortality after liver resection (LR) in hepatocellular carcinoma (HCC) patients. Child-Pugh (CP) score 5 is always considered to indicate a normal liver function but represents a heterogeneous population with a considerable number suffering from PHLF. The present study aimed to access the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) to predict PHLF in HCC patients with a CP score of 5. Methods From August 2018 to May 2021, 146 HCC patients with a CP score of 5 who underwent LR were reviewed. The patients were randomly divided into training ( n  = 97) and validation ( n  = 49) groups. Logistic analyses were conducted for the risk factors and a linear model was built to predict the development of PHLF. The discrimination and calibration were assessed in the training and validation cohorts by the areas under the receiver operating characteristic curve (AUC). Results Analyses revealed that the minimum of LS (Emin) higher than 8.05 ( p  = 0.006, OR = 4.59) and future liver remnant / estimated total liver volume (FLR/eTLV) ( p  < 0.001, OR < 0.01) were independent predictors of PHLF in HCC patients with CP score 5, and the AUC calculated by the model based on them for differentiation of PHLF in the training and validation group was 0.78 and 0.76, respectively. Conclusion LS was associated with the development of PHLF. A model combining Emin and FLR/eTLV showed proper ability in predicting PHLF in HCC patients with a CP score of 5.

Mucosal-associated invariant T (MAIT) cells exert multifaceted effects such as anti-microbial activity, tissue repair, and pro-fibrotic effects across various disease settings. Nonetheless, their role in liver injury and hemostasis remains debated. Here, we report a significant depletion and functional dysregulation of MAIT cells, which is associated with disease severity and accumulated bile acids in HBV-infected patients with varying degree of liver injury. Liver transplantation facilitates a gradual recovery of recipient-originated MAIT cells. Transcriptome analysis reveals enhanced MAIT cell activation, while TCR mining demonstrates clonotype overlap between circulating and hepatic MAIT cells during significant liver injury. TCR-activated MAIT cells from transplant recipients display higher protective capacity but reduced pathological potential than those from liver failure patients. Compromised recovery of MAIT cells is linked to post-transplantation complications, whereas prompt recovery predicates favorable clinical outcome. These findings underscore the intricate interplay between MAIT cells and the hepatic environment, highlighting MAIT cells as potential therapeutic targets and sensitive predictors for clinical outcome in individuals experiencing liver failure and post liver transplantation. The role of mucosal-associated invariant T (MAIT) cells in liver injury is elusive. Here the authors identify that MAIT cells frequency and TCR activation are associated with degree of liver injury and prognosis of liver transplantation.