Elevated CD4+/CD25+ T-cell frequency and function during hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIM: Factors involved in hepatitis C virus (HCV) recurrence versus acute cellular rejection are not fully understood. The aim of the present study was to investigate whether patients with recurrence after liver transplantation (OLT) showed similar CD4(+)/CD25(+) cell frequency and function as those who became chronically infected. PATIENTS AND METHODS: After written informed consent, we enrolled 20 patients (group A) who underwent OLT with HCV recurrence within 6 months. HCV-RNA and hypertransaminasemia were used to assess the reactivation of viral hepatitis. CD4(+)/CD25(+) T cells were enumerated using a flow cytometry assay, gated on CD3 cells, stained for FoxP3. After immunomagnetic sorting (Dynal, Oslo, NW), Treg suppressor activity was measured, as the ability to inhibit proliferation of autologous CD4(+)/CD25(-) T cells (anti-CD3/CD28 stimulation-1:2, 1:20 ratio). Eight patients with acute hepatitis C who evolved to a chronic infection after 6 months (group B) were used as positive controls, while 10 healthy individuals were negative controls (group C). RESULTS: We did not observe any difference in CD4(+)/CD25(+) frequency or function among group A compared with group B (CD4(+)/CD25(+) = 14% +/- 2% versus CD4(+)/CD25(+) = 16% +/- 3%), although both groups were significantly increased with respect to group A (CD4(+)/CD25(+) = 6% +/- 3%; Mann-Whitney U test, P < .01). CONCLUSION: Patients developing HCV recurrence after OLT have the same immunoregulatory network as patients with acute hepatitis C evolving to persistent infection, likely suggesting that CD4(+)/CD25(+) numbers may be a marker to predict recurrence of HCV after OLT.

Model for End-Stage Liver Disease (MELD) score system to evaluate patients with viral hepatitis on the waiting list: better than the Child-Turcotte-Pugh (CTP) system?

BACKGROUND: The Model for End-Stage Liver Disease (MELD), based on creatinine, bilirubin, and International normalized ratio (INR), has been shown to be superior to the Child-Turcotte-Pugh (CTP) score in predicting 3-month mortality among patients on the transplant waiting list due to end-stage liver disease (ESLD). An additional advantage of MELD is the possibility to add "adjustment points" for exceptional patients at risk for death because of liver disease not identified by changes in the used parameters, as occurs in the case of hepatocellular carcinoma (HCC). Although it is useful, MELD has some important limitations: There are no differences for patients with or without ascites, and for the absence of other laboratory parameters involved in the etiology of disease. In this study, we evaluated dropouts of patients on the waiting list for orthotopic liver transplantation (OLT) based upon the characteristics of these subjects before and after introduction of the MELD score. METHODS: All patients on the OLT waiting list from June 1, 2006 to June 30, 2007 were enrolled in the MELD group (A) and evaluated with CHILD and MELD score, while those listed from January 1, 2004 to May 31, 2005 were enrolled in pre-MELD group (B) to be evaluated with CHILD. In these subjects we assessed the drop out frequency and waiting time and we compared the results to assess possible differences (U Mann-Whitney Test; P<.05). RESULTS: The total number of patients included in this study was 176: 116 patients in Group A and 60 in Group B. We had a drop-out frequency of 21% with a median of 9+/-6 S.E. months in Group A, while 9% with a median of 15+/-8 months S.E. in Group B. The dropout frequencies were as follows: Group A--16 deaths (1 HCC--15 disease complications) while in Group B we had 13 drop outs, 10 exitus (4 HCC and 6 disease complications) and three exclusions for nonmedical reasons. In Group A we had a higher number of deaths due to disease complications than in group B (P<.05). Further, we had 32 OLTx in Group A and 45 in Group B. Survival rate did not show any differences between the two groups while number needed to harm was 11. CONCLUSIONS: The use of MELD score in this group of patients produced an advantage for HCC, but seemed to cutoff patients with viral hepatitis complications during the waiting time. Particularly, about one in every 11 patients may receive an harm using this score system. Other parameters should be introduced as adjustment points to make the MELD score suitable also for patients with infectious liver diseases.

Acute rejection after liver transplantation: Is there a specific immunological pattern?

The aim of the study was to assess various T-cell subsets and cytokine secretion patterns both in liver tissue and in the peripheral blood of 24 liver transplant patients to assess possible specific immunological involvement in early acute rejection episodes after liver transplantation. Particularly, we studied CD4+ CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine possible Th1-like immune responses and the immunomodulation expressed by Treg cells in acute liver rejection, respectively. As a control group we included patients transplanted without acute rejection. Early acute rejection within the first 4 weeks was proven histologically in 42% of patients. It was associated with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells was evident in patients with acute rejection (P < .001). Our data suggested that a preferential Th1-like immune mechanism operated in local fashion as characterized by a decreased presence in the liver and blood of Treg cells.

The marginal donor: a single-center experience in orthotopic liver transplantation.

The use of marginal donors has become more common worldwide due to the sharp increase in recipients with a consequent shortage of suitable organs. The definition of "marginal donor" has not been reached by all centers. We herein analyzed our single-center experience over the last 3 years in liver transplantation (OLT) to evaluate the outcomes of using a high percentage of so-called "marginal donors", according to the current classification from the National (Italian) Center of Transplantation (CNT). Among the 78 OLT performed in 77 patients from January 1, 2003 to October 31, 2005, donor livers were divided into three groups according to the CNT classification. We evaluated donor variables, cold ischemia time (CIT), warm ischemia time (WIT), MELD score, and length of hospital stay. Histologic graft steatosis was correlated with estimated steatosis by ultrasound. There were no differences among the three graft recipient groups concerning CIT, WIT, MELD score, and the length of hospital stay. Steatosis is indicated in all series as a definite variable for a higher risk of postoperative mortality. CIT is necessarily related to donor retrieval policy and organization. Donor age seemed also to be related to a possible increase in postoperative mortality, but there are significant variations in the definition of the age limit. We failed to observe a correlation between a higher mortality rate and any of the variables currently listed to define a "marginal donor." A shorter CIT seemed to positively influence the role played by the other variables identifying a "marginal liver." Finally, the use of HCV(+) or HBV(+) grafts did not lead to an increased mortality.

Living donor liver transplantation: early single-center experience.

Adult living donor liver transplantation (ALDLT) is an accepted procedure to overcome the organ shortage. The advantages of ALDLT must be balanced against the first concern of donor safety. We analyzed the results of our early experience among a series of eight ALDLT performed between April 2001 and October 2003. All patients were listed as United Network for Organ Sharing UNOS status 2b and 3. Transplant recipients consisted of four men and four women. The living donors included four sons, three daughters, and one son-in-law (ages 20 to 45 years). One donor was anti-HBc-positive and negative for hepatitis B virus-DNA by polymerase chain reaction analysis in serum and in liver tissue. GR/WR >0.8 and fatty liver <10% were considered suitable for the hepatectomy. Residual left lobe volume was at least 33%. No exogenous blood and blood products were transfused into the donors and a cell-saver device was used in all donors (blood loss 490 +/- 160 mL). All procedures were right lobe hepatectomy; in one case the middle hepatic vein was withdrawn with the right graft. The mean ischemia time was 1.5 +/- 0.5 hours. All donors survived the procedure. Median hospital stay was 8.5 +/- 2.1 days in all donors but one who had a long stay because of drug-related hepatitis. One graft was lost and one donor aborted because of preoperative overestimated volumetry. Complications were experienced by two donors (25%). Five recipients (62.5%) experienced major complications; one patient underwent retransplantation because of donor graft loss. Two biliary and two vascular complications (33.3%) occurred in three patients. No perioperative death occurred. Two patients died at 9 and 10 months after transplant because of heart and respiratory failure in the first case and tumor recurrence in the second. One-year actuarial survival is 75%. ALDLT using right lobe has gained acceptance to overcome the organ shortage. Donor selection criteria must be stringent with respect to residual donor hepatic volume, steatosis, and liver function.

[Treatment of major iatrogenic lesions of the bile ducts]. / Trattamento delle lesioni iatrogene maggiori della via biliare.

BACKGROUND: The appropriate treatment of major bile duct injuries is mandatory in order to avoid serious complications, such as bile peritonitis or secondary biliary liver cirrhosis. In the last fourty years, surgical, endoscopic or radiologic techniques of cure have been proposed, but in our opinions, the preferred option is given by Roux-en-Y choledochojejunostomy or hepaticojejunostomy. Creating an anastomosis on narrow bile duct could be difficult; in these really rare cases, the jejunal loop could be secured by a second suture to the hilar plate with satisfactory long-term results. PATIENTS AND METHODS: In the last four years, in our Institution, six patients underwent surgery for major bile duct injuries. A Roux-en-Y hepaticochojejunostomy was performed for all of them. Two patients had the jejunal loop secured to the hilar plate. RESULTS: Operative morality was nil, and long-term results at a mean follow-up of 20 months are encouraging. CONCLUSIONS: The prevention of major bile duct injuries remains the main target during cholecystectomy or surgery in the area of the hepatoduodenal ligament. In our experience, in general agreement with data from literature, bile reconstruction is best achieved by Roux-en-Y hepaticojejanostomy. In patients unsuitable for surgery, endoscopic balloon dilatation and stent positioning represent a satisfactory alternative.

[The use of prosthetic materials placed intraperitoneally in the repair of large defects of the abdominal wall, reflections on a limited case series]. / L'utilizzo dei materiali protesici in sede intraperitoneale nella riparazione dei grandi difetti di parete addominale, riflessioni in merito ad una limitata casistica.

To evaluate the best prosthetic material in direct contact with intestinal loops in the repair of large abdominal wall defects, four cases were reevaluated and an extensive review of the literature was undertake to point out the pathophysiology of prosthetic materials in abdominal wall surgery. For its intrinsic features, Gore-Tex represents the best prosthetic material to locate intraperitoneally, but the slow foreign body reaction is responsible for postoperative complications (e.g. hematoma, seroma, dehiscence). Marlex should not be used in direct contact with intestine because of the risk of multiple fistulas, very difficult to treat, while, the intense foreign body reaction rapidly integrate the mesh into the abdominal wall. To treat large abdominal wall defects are now been proposed mixed prostheses (Gore-Tex in intraperitoneal location, Marlex at the exterior) and dual mesh Gore-Tex (two textures at different microporosity on each side of the mesh). Preliminary studies have shown the safety and utility of these prostheses.