Use of Hepatitis C-Positive Deceased Liver Donors in Response to the Organ Shortage in an Endemic Area.

The region of Sicily, Italy, is witnessing a chronic organ shortage. Thus, to face this critical issue, the use of marginal donors has increased over time. An example of marginal donor expansion is the use of liver donors who are positive for the hepatitis C antibody (HCV+) for HCV+ patients requiring liver transplantation (LT). In view of new advances in HCV therapy, including direct-acting agents (DAAs) to treat HCV in the post-transplant setting, our study focused on a monocentric experience in a series of consecutive LTs performed in adult patients receiving HCV+ liver donor allografts. From 2003 to 2016 at our institute we performed 10 LT using HCV+ deceased donors. In particular, the pre-LT histological examination in 1 case showed a framework of moderate steatosis (35% microvesicular and 10% macrovesicular) with micro/macrovesicular steatosis <10% in all the other cases. A fibrous framework of 1/6 according to the Ishak score in a single case, and 2/6 in 2 cases, were highlighted, while there was no fibrosis in the other 7 cases. A picture of periportal inflammation was still detected in 4 cases, with no evidence of inflammatory lesions in the remaining cases. The patient survival was 100% at 1 and 3 years, and 85.7% at 5 years post-LT. One-, three- and five-year graft survivals were 100.0%, 88.9%, and 71.4%, respectively. Only 1 patient underwent re-LT after 2 years, because of chronic rejection. Based on our experience using HCV+ deceased liver donors with a moderate degree of fibrosis, we believe that accepting marginal donors is a feasible therapeutic option when facing a liver donor shortage.

Predictive factors of downstaging of hepatocellular carcinoma beyond the Milan criteria treated with intra-arterial therapies.

PURPOSE: This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. METHODS: A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECIST criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. RESULTS: Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). CONCLUSIONS: Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.

Management of Liver Failure: From Transplantation to Cell-Based Therapy.

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed.

Transjugular intrahepatic portosystemic shunt with accidental diagnosis of persistence of the left superior vena cava.

Transjugular intrahepatic portosystemic shunt (TIPSS) is considered a valid therapeutic option for the treatment of portal hypertension and its complications. The guidelines for this procedure have already been established on the basis of the normal vascular anatomy and of various technical radiological aspects. In some few rare cases, diagnosis of a congenital vascular anomaly can be made accidentally by interventional radiologists, making the procedure of the TIPSS placement extremely difficult or in some cases technically impossible. This report describes a rare vascular malformation characterized by the absence of the right superior vena cava and persistence of the left superior vena cava in a patient with a diagnosis of advanced liver cirrhosis who needed a TIPSS placement in order to control refractory ascites.

Early graft dysfunction following adult-to-adult living-related 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, intra-operative 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 pre-transplant 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.

Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis.

PURPOSE: To assess the safety of transarterial treatments of hepatocellular carcinoma (HCC), and the statistical correlation of various patient factors with the frequency of complications, in selected patients with cirrhosis when adhering to well-standardized protocols. MATERIALS AND METHODS: Three hundred twenty consecutive patients with unresectable HCC were treated with transarterial chemoembolization, oil chemoembolization, and embolization. A total of 712 treatments were performed, with an average of 2.3 treatments for each patient. The epirubicin dose was adjusted according to defined laboratory criteria. An early complication was defined as one that occurred within 4 weeks of treatment. Complications were classified as minor and major and assessed by using clinical and laboratory data. RESULTS: Of the 712 procedures, 21 complications (2.9%) occurred in 17 of the 320 patients (5.3%). Major complications included acute liver failure (n = 1, 0.1%), variceal bleeding (n = 2, 0.3%), moderate-to-severe ascites (n = 4, 0.6%), sepsis (n = 3, 0.4%), cholecystitis (n = 1, 0.1%), and diverticulitis (n = 1, 0.1%). Minor complications were hepatic artery damage, including spontaneously resolved dissection (n = 3, 0.4%), mild encephalopathy (n = 1, 0.1%), and aspartate aminotransferase/alanine aminotransferase levels greater than 500 U/L (n = 5, 0.7%). The 30-day mortality rate was 0.003% (n = 1). Constitutional syndrome (P = .0001), Child-Pugh score (P = .0001), ascites (P = .037), and the Model for End-Stage Liver Disease score (P = .02) were found to have a statistically significant correlation with complications after univariate analysis. Child-Pugh score (P = .012) and constitutional syndrome (P = .003) were found to have a statistically significant correlation with complications after logistic regression analysis. CONCLUSIONS: Transarterial treatments can be considered safe in patients with Child class A and B cirrhosis when an adjusted dose of epirubicin is used according to body surface, severity of liver disease, and white blood cell count. Accurate patient selection and procedure-related factors may reduce the frequency of complications and help preserve liver function.

Clinical applications of hepatocyte transplantation.

The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with life-threatening 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 specific 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.