Clinical applications of hepatocyte transplantation

The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with lifethreatening liver diseases dying while on the waiting list. The use of cell transplantation for liver disease is an attempt to correct metabolic defects, or to support liver function as a bridge to liver transplantation and, as such, has raised a number of expectations. Most of the available studies briefly reported here focus on adult hepatocyte transplantation (HT), and the results are neither reproducible nor comparable, because the means of infusion, amount of injected cells and clinical variability differ among the studies. To better understand the specif ic role of HT in the management of end-stage liver disease, it is important that controlled studies, designed on the principles of evidence-based medicine, be done in order to guarantee the reproducibility of results.

Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma

AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:69%,69%,52%,68%,50% and,13% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads may improve the effect on tumor necrosis.

Early graft dysfunction following adult-to-adult livingrelated liver transplantation:Predictive factors and outcomes

AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is characterized by EGD when the graft-to-recipient body weight ratio(GRBWR)is below 0.8%.However, patients transplanted with GRBWR above 0.8%can develop dysfunction of the graft.In 73 recipients of LRLT(GRBWR>0.8%),we identified 10 patients who developed EGD.The main measures of outcomes analyzed were overall mortality,number of re-transplants and length of stay in days(LOS).Furthermore we analyzed other clinical pre-transplant variables,intraoperative parameters and post transplant data.RESULTS:A trend in favor of the non-EGD group(3-mo actuarial survival 98%vs 88%,P=0.09;3-mo graft mortality 4.7%vs 20%,P=0.07)was observed as well as shorter LOS(13 d vs 41.5 d;P=0.001)and smaller requirement of peri-operative Units of Plasma (4 vs 14;P=0.036).Univariate analysis of pre- transplant variables identified platelet count,serum bilirubin,INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P=0.025,OR:1.175)and pretransplant platelet count(P=0.043,OR:0.956)were independently associated with EGD. CONCLUSION:EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.

Predictive factors of tumor response to trans-catheter treatment in cirrhotic patients with hepatocellular carcinoma:A multivariate analysis of pre-treatment findings

AIM: To elucidate the pre-treatment clinical and imaging findings affecting the tumor response to the transcatheter treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Two hundred cirrhotic patients with HCC received a total of 425 transcatheter treatments. The tumor response was evaluated by helical CT and a massive necrosis (MN) was def ined as a necrosis > 90%. Twenty-f ive clinical and imaging variables were analyzed: uninodular/multinodular HCC, unilobar/bilobar, tumor capsula, hypervascular lesion, portal vein thrombosis, portal hypertension, ascites, platelets count, aspartate transaminases/alanine transaminases (AST/ALT), alfa- fetoprotein (AFP) > 100, AFP > 400, serum creatinine, virus hepatitis C (VHC) cirrhosis, performance status, age, Okuda stage, Child-Pugg stage, sex, CLIP (Cancer of the Liver Italian Program) score, serum bilirubin, constitutional syndrome, serum albumine, prothrombin activity, BCLC (Barcelona Clinic Liver Cancer) stage. Prognostic factors of response were subjected to univariate analysis and thereafter, when significant, to the multivariate analyses. RESULTS: On imaging analysis, complete response wasobtained in 60 (30%) patients, necrosis > 90% in 38 (19%) patients, necrosis > 50% in 44 (22%) patients, and necrosis < 50% in 58 (29%) patients. Ninety-eight (49%) of the 200 patients were considered to have a MN. In univariate analysis, significant variables (P < 0.01) were: uninodular tumor, unilobar, tumor size 2-6 cm, CLIP score < 2, absence of constitutional syndrome, and BCLC stage < 2. In a multivariate analysis, the variables reaching statistical signifi cance were: presence of tumor capsule (P < 0.0001), tumor size 2-6 cm (P < 0.03), CLIP score < 2 (P < 0.006), and absence of constitutional syndrome (P < 0.03). Kaplan-Mayer cumulative survival at 12 mo was 80% at 24 mo was 56%. MN was associated with a longer survival (P < 0.0001). CONCLUSION: MN after transcatheter treatment is more common in the presence of tumor capsule, maximum diameter of the main lesion between 2 and 6 cm, CLIP score < 2 and absence of constitutional syndrome. The ability to predict which patients will respond to transcatheter treatment may be useful in the clinical decision-making process, and in stratifying the randomization of patients in clinical trials.

Protective benefit of minimally invasive liver surgery for hepatocellular carcinoma prior to transplant

Aim:The purpose of this study is to assess the benefit of laparoscopic liver resection(LLR)for hepatocellular carcinoma(HCC)given recurrence and future need for liver transplantation(LT).Methods:Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione(IRCCS-ISMETT)from 2003-2021.A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process.A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR.Results:From 2012 to 2020,ISMETT’s mean annual LLR rate was 45%.Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits.Compared to open surgery or LT,LLR is protective against the risk of de-listing,post-transplant patient death,tumor recurrence,adhesions,and bleeding in a cirrhotic patient.Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR(P=0.658).Conclusion:Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC,particularly since treatment is not always curative.LLR can be considered a bridge therapy for transplantation,ensuring less crowding of waiting lists,a desirable condition in areas of donor storage.