Dario Lorenzin

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co‐localized inside the thrombus.

Comparison of de novo tumours after liver transplantation with incidence rates from Italian cancer registries

AIM The purpose of this study is to describe de novo post-liver transplant malignancies and compare their frequency with incidence rates from Italian cancer registries. PATIENTS AND METHODS Four hundred and seventeen patients subjected to liver transplantation, from 1991 to 2005, surviving for at least 30 days and without a previous diagnosis of cancer (including hepatocellular carcinoma), were evaluated for the development of de novo malignancies excluding non-melanoma skin cancers. RESULTS During a total follow-up time of 2856 person-years, 43 de novo malignancies were diagnosed in 43 liver transplantation recipients (10.3%). The most common cancers were non-Hodgkin lymphoma (9 cases), cancer of the head and neck (8 cases), Kaposis sarcoma (6 cases) and esophageal carcinoma (5 cases). The 1, 3, 5 and 10 years estimated survival rates were 69%, 57%, 53% and 42%. Patients with de novo cancers had a lower 10-year survival rate than patients without cancers (58% versus 76%, p=0.005). The risk of cancer after liver transplantation was nearly 3-fold higher than that of the general population of the same age and sex (95% CI: 1.9-3.6). De novo tumour sites or types with significantly elevated SIR included Kaposis sarcoma (SIR=144), non-Hodgkin lymphoma (SIR=13.8), esophagus (SIR=23.4), head and neck cancers (SIR=7) and cervix uteri (SIR=30.7). CONCLUSIONS Tumours after liver transplantation are associated with lower long-term survival, confirming that cancer is a major cause of late mortality in liver transplantation.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention‐to‐treat basis. Forty‐eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient’s survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6–10 months after listing to reduce the dropouts for reasons of tumor progression.

STEATOSIS OF THE HEPATIC GRAFT AS A RISK FACTOR FOR POST-TRANSPLANT BILIARY COMPLICATIONS

Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Currò G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post‐transplant biliary complications.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01128.x.
© 2009 John Wiley & Sons A/S.

De Novo Tumors Are a Major Cause of Late Mortality After Orthotopic Liver Transplantation

The purpose of this study was to describe de novo post-orthotopic liver transplantation (OLT) malignancies for comparison with incidence rates in Italian cancer registries. Three hundred thirteen OLT patients engrafted from 1991 to 2006 and surviving 12 months without a previous diagnosis of cancer were evaluated for the development of de novo malignancies excluding nonmelanoma skin cancers. During a total follow-up time of 1753 PYs, 40 (12.8%) de novo malignancies were diagnosed in 40 recipients. The most common cancers were non-Hodgkin lymphoma (NHL; 20%), cancer of the head and neck (17%), Kaposi sarcoma (KS; 17%), and esophageal tumors (12%). The 1-, 3-, 5-, and 10-year estimated survival rates were 70%, 56%, 48%, and 39%. Patients with de novo cancers showed a lower 10-years survival rate (P = .0047) than patients without (39% vs 75%). The risk of cancer after OLT was 3-fold higher than that of the general population of the same age and gender (95% confidence interval [CI], 2.0-4.3). De novo tumor sites or types with significantly elevated standardized incidence ratios (SIRs) included KS (SIRs = 212), NHL (SIRs = 13.7), oesophagus (SIRs = 18.7), melanoma (SIRs = 10.1), and head and neck cancers (SIRs = 4.6). Tumors after OLT were associated with lower long-term survival, confirming that cancer is a major cause of late mortality.

Cardiovascular risk factors and immunosuppressive regimen after liver transplantation.

Cardiovascular and metabolic diseases represent important long-term complications after liver transplantation (LT), impairing long-term and disease-free survivals. A few mechanisms underlie the development of those complications, but the role of immunosuppressive drugs is major. Although several patients develop temporary metabolic diseases, which normalize after a short postoperative period and do not need long-term drug therapy, the incidences of de novo long-lasting arterial hypertension, hyperlipidemia, and diabetes mellitus are high during the first year after LT. The aim of this retrospective study was to evaluate new-onset arterial hypertension, hyperlipidemia, or diabetes among 100 LT patients at a single institution. We used chi-square statistical analysis to compare incidences during tacrolimus versus cyclosporine therapy. Hypertension did not seem to be more strongly related to tacrolimus than to cyclosporine, nor did diabetes, whereas there was a difference for the development of hyperlipidemia.

Graft Loss Due to Percutaneous Sclerotherapy of a Lymphocele Using Acetic Acid After Renal Transplantation

Development of lymphoceles after renal transplantation is a well-described complication that occurs in up to 40% of recipients. The gold standard approach for the treatment of symptomatic cases is not well defined yet. Management options include simple aspiration, marsupialization by a laparotomy or laparoscopy, and percutaneous sclerotherapy using different chemical agents. Those approaches can be associated, and they depend on type, dimension, and localization of the lymphocele. Percutaneous sclerotherapy is considered to be less invasive than the surgical approach; it can be used safely and effectively, with low morbidity, in huge, rapidly accumulating lymphoceles. Moreover, this approach is highly successful, and the complication rate is acceptable; the major drawback is a recurrence rate close to 20%. We herewith report a renal transplant case in which the patient developed a symptomatic lymphocele that was initially treated by ultrasound-guided percutaneous sclerotherapy with ethanol and thereafter using acetic acid for early recurrence. A few hours after injection of acetic acid in the lymphatic cavity, the patient started to complain of acute pain localized to the renal graft and fever. An ultrasound of the abdomen revealed thrombosis of the renal vein and artery. The patient was immediately taken to the operating room, where the diagnosis of vascular thrombosis was confirmed and the graft was urgently explanted. In conclusion, we strongly suggest avoiding the use of acetic acid as a slerosating agent for the percutaneous treatment of post-renal transplant lymphocele because, based on our experience, it could be complicated by vascular thrombosis of the kidney, ending in graft loss.

Long-Term Outcomes of Orthotopic Liver Transplantation in Human Immunodeficiency Virus–Infected Patients and Comparison With Human Immunodeficiency Virus–Negative Cases

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n=27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger (P=.013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups (P=.92). No differences were observed for donor age (P=.72) or time on the waiting list (P=.56). The median follow-up was 26 (range, 1-64) and 27 months (range, 1-48) for HIV and non-HIV recipients, respectively (P=.85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% (P=.95), and 92%, 87%, and 87% versus 95%, 88%, and 88% (P=.59) for HIV and non-HIV cases, respectively. HIV/HCV-coinfected patients were younger, namely 47 (range, 40-53) versus 52 years (range, 37-68; P=.003), and displayed lower MELD scores at transplantation compared with HCV-mono-infected patients 10 (range, 7-19) versus 17 (range, 8-30) (P=.008). For HIV/HCV-coinfected and HCV-mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% (P=.99) and 93%, 84%, and 84% versus 100%, 70%, and 60% (P=.64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.

Safety of Conversion From Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Nonadherence to immunosuppressive regimens among solid organ transplantation to range has been estimated from 15% to 55%. This problem has been identified as a leading cause of preventable graft loss. Tacrolimus once daily Advagraf has been developed to provide a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily tacrolimus (Prograf) to Advagraf in 36 stable liver transplant recipients. The tacrolimus whole blood trough level at T0 was 6.7 +/- 2.9 ng/mL with a daily dose of 3.7 +/- 1.8 mg. The mean tacrolimus blood trough levels at T1 (7 days) and T2 (14 days) were 5.8 +/- 2.5 and 5.8 +/- 1.8 ng/mL with mean daily doses of 3.9 +/- 1.9 and 4.1 +/- 1.8 mg, respectively. There was no significant difference between T0, T1, and T2, either for tacrolimus blood trough levels or for tacrolimus daily dosages. Liver and renal function tests remained stable; no episodes of acute rejection were encountered after the conversion. A switching policy using a dose ratio of 1:1 from twice-daily tacrolimus to once-daily prolonged-release tacrolimus was safely applied to stable liver transplant recipients.

Graft vessel wall pathology in a case of hepatic artery pseudo-aneurysm in a liver transplant recipient.

Pseudo-aneurysms (PAs) of the hepatic artery are rare complications of liver transplantation, which are characterized by a high mortality rate. The majority occur within the first 2 months after orthotopic liver transplantation. They become clinically manifest with sudden hypotension, gastrointestinal bleeding, and abnormal liver function test results. Early diagnosis and treatment are essential to prevent life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction, but a feasible treatment option involves an angiographic approach with the positioning of a stent or transarterial coil embolization followed by revascularization. We report a case of posttransplantation hepatic artery PA (HA-PA) with bleeding into the duodenum, diagnosed using abdominal computed tomography (CT). Arterial kinking prevented a covered stent graft from being inserted successfully using X-ray angiography, so the patient underwent emergency surgery in an attempt to exclude the PA and revascularize the organ via an aorto-hepatic bypass with an iliac vascular graft obtained from the donor. The surgical procedure failed due to progressive macroscopic dissection of the HA wall up to the bifurcation. The patient underwent retransplantation but died 25 days later due to multiple-organ failure. Histopathology of the first liver graft confirmed arterial graft dissection and pathological changes in the donor HA wall.