Portal hypertension is the main driver of liver stiffness in advanced liver cirrhosis

Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8 %), minority of patients were Child-Pugh A (18/81, 22.2 %). LS showed the best correlation with HVPG (r=0.719, p<0.001), correlation of LS with CPA (r=0.441, p<0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p<0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS=2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience

BackgroundIn the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT).MethodsAll patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT.ResultsA total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47–311) after BT and 202 days (range 44–775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT.ConclusionBoth SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.

Pre-transplant Psoas Muscle Density as a Ready-to-Use and Low-cost Predictor of Patient Survival After Liver Transplant

Background: Sarcopenia, defined as low muscle mass with reduced function, is frequently encountered in cirrhotic patients and is a major predictor of adverse events, including post-liver transplant (LT) outcome. Objectives: This study assessed the impact of sarcopenia using computed tomography (CT)-based measurements on post-LT mortality and complications. Methods: From January 2008 to June 2016, 646 adult patients underwent 613 LTs at our institution. We analyzed the postoperative outcome of 287 patients who had pathologically proven cirrhosis on the explanted liver and who had performed a CT examination three months before LT. Psoas muscle density (PMD) was detected for every patient using standard instruments present in the radiological workstation and was related to postoperative survival rates and complications. Statistical analysis was carried out using the appropriate tests. Results: Postoperative mortality was 6.3%. At least one grade III-IV postoperative complication was experienced by 121 patients. Respiratory and infective complications occurred in 30 and 32 patients, respectively. Also, PMD was an independent predictor of postoperative mortality (P = 0.021), respiratory complications (P = 0.015), and infections (P = 0.010). The ROC analysis identified a PMD ≤ 43.72 HU as the best cutoff value for predicting 90-day mortality after LT. Conclusions: Psoas muscle density accurately predicted post-LT mortality and complications. Its ease and low-cost determination can allow widespread use of this parameter to improve clinical care and help with the decision to give these patients some priority on the transplant waiting list.

Liver Transplantation for Hepatic Adenomatosis: The First Case Report in Thailand and Literature Review

Hepatic adenomas are benign solid liver tumors commonly found in young females and usually asymptomatic. Hepatic adenomatosis is characterized by more than 10 adenomas in an otherwise normal liver. Bleeding and malignant transformation uncommonly occur especially in tumor larger than 5 cm and in male patients. The authors reported a case of a young female with large multiple hepatic adenomas from hepatic adenomatosis that presented with abdominal pain, large abdominal mass, weight lost, and abnormal liver function tests. She failed transarterial embolization. Surgical resection was not offered due to extent of the hepatic adenomas. She received orthotopic liver transplantation as rescue therapy. Her explanted liver showed multiple foci of hepatocellular carcinoma (HCC). Her post-operative was uneventful. The authors reported a case of liver transplantation for the treatment of unresectable hepatic adenomatosis. Keywords: Hepatic adenomatosis, Malignant transformation, Liver transplantation

Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis

Purpose. We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). Methods. This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. Results. Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603 ), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190 ), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006 ), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001 ). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001 ). Conclusion. In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

7-T MRI of explanted liver and ex-vivo pancreatic specimens: prospective study protocol of radiological-pathological correlation feasibility (the EXLIPSE project)

The study focuses on radiological-pathological correlation between imaging of ex vivo samples obtained by a 7-T scanner and histological examination. The specimens will be derived from native explanted cirrhotic livers, liver grafts excluded from donation because of severe steatosis, and primary pancreatic tumours. Magnetic resonance imaging (MRI) examinations will be performed within 24 h from liver or pancreatic lesion surgical removal. The MRI protocol will include morphological sequences, quantitative T1, T2, and fat-, water-fraction maps with Cartesian k-space acquisition, and multiparametric methods based on a transient-state “MRI fingerprinting”. Finally, the specimen will be fixed by formalin. Qualitative imaging analysis will be performed by two independent blinded radiologists to assess image consistency score. Quantitative analysis will be performed by drawing regions of interest on different tissue zones to measure T1 and T2 relaxation times as well as fat- and water-fraction. The same tissue areas will be analysed by the pathologists. This study will provide the possibility to improve our knowledge about qualitative and quantitative abdominal imaging assessment at 7 T, by correlating imaging characteristics and the corresponding histological composition of ex vivo specimens, in order to identify imaging biomarkers. Trial registration: ClinicalTrials.gov: 13646. Registered 9 July 2019—retrospectively registered