Partial Splenic Embolization for the Treatment of Hypersplenism in Liver Transplanted Patients with Hepatitis C Virus Recurrence before peg-Interferon Plus Ribavirin

Reinfection of the graft follows liver transplantation (LT) patients with HCV, with an accelerated course of the disease due to immunosuppressive treatment (1). Progression to cirrhosis is increased, more than 20% of patients present severe graft damage at 5 years post-LT (2), and the rate of death and allograft failure is increased when compared with other indications (3). The lack of an efficient strategy to prevent graft reinfection and the aggressive course of HCV after LT indicate the need for an effective antiviral therapy able to preserve the viability of the graft. Recent data on the use of peg-IFN plus ribavirin (RBV) after LT are encouraging, with rates of sustained virological response (SVR) over 30%, improved graft function, and a beneficial effect on the histological disease progression (4). Therapy, however, is limited by the high rate of peg-IFN and/or RBV-related hematological toxicity leading to dose reductions and/or administration of hematopoietic growth factors, such as erythropoietin (EPO), or granulocyte-colonies stimulating factor (G-CSF) (5). To date, severe thrombocytopenia remains as an absolute contraindication for HCV therapy. Partial splenic embolization (PSE) seems to be an effective alternative to surgical splenectomy for the treatment of hematologic disorders in cirrhotic patients with hypersplenism, especially against thrombocytopenia (6), and improves liver functions (7). We aimed to evaluate the safety and effectiveness of PSE before peg-IFN/RBV in three liver recipients with HCV recurrence and hypersplenism. After pneumococcal vaccination, PSE was performed under intravenous antibiotic, sedative, and antiemetic therapy. A femoral artery approach was used for superselective distal catheterization of the splenic artery, with injection of polyvinyl-alcohol particles (355 to 500 μ) suspended in a solution of penicillin, gentamicin, and non-ionic iodine contrast, to obtain an splenic infarction ratio between 50% and 80%. Contrast-enhanced abdominal CT scan and Doppler ultrasound studies were performed before PSE and during follow-up, to assess the presence of complications. At a mean of 12 weeks after PSE all patients started weight-adjusted RBV plus peg-IFN-α-2b and were assessed in a monthly basis, including clinical assessment, complete blood and biochemistry analyses, and qualitative and quantitative HCV-RNA tests. Table 1 summarizes baseline features and treatment outcome. All subjects reported mild “postembolization syndrome”, including fever, left hypocondriac pain, and nausea, successfully managed with intravenous non-steroidal anti-inflammatory drugs and/or morphine. PSE led to significant increases in blood cell counts in all patients. During follow-up (mean 78 weeks) there were no cases of hepatic decompensation. The on-treatment follow-up time of patient 3 is too short to be presented. Patient 1 discontinued therapy at week 24 due to HCV-RNA persistence. Anemia led to RBV dose reduction between weeks 13 and 24, but peg-IFN dose was not reduced; moreover, it was increased from 80 to 100 μg after week 8. In patient 2 a pretreatment liver biopsy showed active inflammation and portal-central bridging fibrous septa. He also developed a “de novo” hepatitis B virus (HBV) superinfection, with serum markers of active replication: HBVs and HVB e positive antigens, and HBV-DNA levels over 3× 106 copies/mL. He started lamivudine (100 mg/day), peg-IFN-α-2b (120 μgr/week), and RBV (10.25 mg/kg/day). HCV-RNA reached undetectable levels by week 24, followed by viral breakthrough at week 36. Due to biochemical response, and acceptable clinical and hematological tolerance, it was decided to maintain long-term triple therapy. After 72 weeks he obtained serum HBV-DNA clearance, seroconversion to positive HBVe and HBVs antibodies, and a second liver biopsy showed HCV-related inactive chronic hepatitis and negative immunohistochemical assays for HBVc and HBVs antigens. To date he has completed 89 weeks of therapy, with no peg-IFN/RBV dose modifications. None of the patients completing therapy needed EPO or G-CSF, and there was no evidence of chronic graft rejection.TABLE 1: Baseline features and treatment outcomes after PSE and HCV therapyThis is the first report on the usefulness of PSE before peg-IFN/RBV in LT patients with HCV recurrence who otherwise would have never been considered for therapy. Hemoglobin, leukocyte, and especially platelet counts increased rapidly after PSE and remained high enough to allow the initiation and, more importantly, completion of therapy with no peg-IFN dose modifications. The mean infarction area was high (85%), and the extent of embolization seems critical in the long-term efficacy of PSE. The increase in platelet counts depends also in large part on restoration of the plasma thrombopoietin level, the key hematopoietic factor governing thrombocyte production (8). Combined therapy did not lead to non-manageable hematological toxicity, and although IFN use in LT patients may increase the risk of cellular rejection (9), none of our patients developed chronic graft rejection. Even though they did not obtain SVR, prolonged therapy in patient 2 slowed down hepatic inflammation and fibrosis progression, suggesting a beneficial effect of long-term IFN therapy on graft function and survival. In conclusion, PSE might be useful in LT patients with HCV recurrence and hypersplenism before peg-IFN plus RBV. These results should be confirmed in further prospective studies including a higher number of patients and longer follow-up periods. Rafael Bárcena Luis Gil-Grande Javier Moreno José R Foruny Elena Otón Miguel García Services of Liver-Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain Javier Blázquez Juan Sánchez Services of Interventionist Vascular Radiology, Hospital Ramón y Cajal, Madrid, Spain Ana Moreno Services of Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain Alberto Moreno Services of Pathology, Hospital Ramón y Cajal, Madrid, Spain