Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation

Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.

Assessment of Liver Function for Evaluation of Short- and Long-Term Outcomes in Type B Aortic Dissection Patients Undergoing Thoracic Endovascular Aortic Repair

Background and Aims: Patients with decreased liver function suffer from poor outcomes when undergoing procedures. We aimed to explore the impact of liver fibrosis identified by aspartate transaminase-to-platelet ratio index (APRI) and poor liver functional reserve assessed by a model of end-stage liver disease (MELD) and albumin–bilirubin(ALBI) score on the prognosis of patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR).Methods: A retrospective analysis of a prospectively maintained database from 2010 to 2017 was performed. APRI > 0.5 was used to identify those with significant liver fibrosis. Logistic and Cox regression analyses were performed to investigate the association between liver fibrosis, MELD, and ALBI with adverse events.Results: TEVAR was performed on 812 TBAD patients including 35 with liver fibrosis and 777 without. Twenty-four (3.0%) patients deceased during hospitalization and 69 (8.8%) patients died after a median 48.2 months follow-up. Multivariable analysis revealed that liver fibrosis, MELD, and ALBI were independently associated with in-hospital [fibrosis: odds ratio (OR) 23.73, 95% confidence interval (CI) 8.89–63.33, P < 0.001; MELD: OR 1.08, 95% CI 1.03–1.14, P = 0.003; ALBI: OR 4.45; 95% CI 1.56–12.67, P = 0.005] and follow-up mortality [fibrosis: hazard ratio (HR) 4.69, 95% CI 1.93–11.42, P = 0.001; MELD: HR 1.07, 95% CI 1.04–1.10, P < 0.001; ALBI: HR 2.88, 95% CI 1.53–5.43, P = 0.001]. The association was further corroborated by a subgroup analysis.Conclusion: Liver fibrosis and poor liver functional reserve could significantly increase the morbidity and mortality after TEVAR. APRI, MELD, and ALBI should be calculated and routinely used for preoperative risk stratification. Strict preoperative preparation and elaborate postoperative care are necessary to improve these patients' prognosis.

Plasma pentosidine levels are associated with prevalent fractures in patients with chronic liver disease

Aim Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD). Methods This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels. Results Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels. Conclusions Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.

Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma

A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.

Design of Liver Functional Reserve Estimation Technique Based on Optical Densitometry

This work is aimed at creating a modified invasive technique for assessing the liver’s functional reserves. A study of the degree of hepatodepression is carried out by measuring the plasma elimination of indocyanine green using the method of optical densitometry. This paper presents test results for an aqueous solution and an albumin solution, as well as the results of measurements of plasma elimination of indocyanine green for patients with liver disease. Perfecting the proposed method will make an important scientific contribution to modern diagnostic medicine. Diagnosing the stages in the progression of the disease and its developing complications can make it possible to rapidly correct the patient’s treatment algorithm, achieving positive outcomes in medical practice.