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The aim of our study was to assess the incidence course, influence on liver function, diagnostic methods, prophylaxis of, and cost treatment effectiveness of CMV infection among 123 consecutive liver transplant recipients. All patients received immunoglobulin and parenterall gancyclovir as prophylaxis. CMV IgM and IgG antibodies were determined using an ELISA method. Thirty seven patients (30.0%) developed CMV infection. Main indications for primary LTX were: immune liver disease (n = 22), viral hepatitis (n = 5), and other (n = 10). CMV infection occurred between the days 5 and 416. Ten patients (27.0%) developed more than one infection (52 infections in total). Asymptomatic CMV infection was diagnosed in six cases (16.2%), CMV syndrome in 11 cases (29.7%), and hepatitis in 35 cases. All patients were treated with gancyclovir and immunoglobulin (18 cases). The intensity of infection was mild or moderate. There was no case of pneumonia or neurological disease, nor the need to use foscarnet. The correlations between the incidence of CMV infection and acute rejection, tacrolimus versus cyclosporine regimens, dual versus triple immunosupressive schemes were not statistically significant, whereas anti-IL-2R-ab antibodies markedly reduced the incidence of CMV infection (P < .05). The values of CMV IgM significantly differred before/during infection (P < .001) and before/after infection (P < .05). In conclusion, prophylaxis and antiviral treatment result in a mild or moderate intensity of CMV infection with acceptable costs. Among immunosuppressive drugs, only anti-IL-2Rab was proved to significantly reduce the incidence of CMV. [Copyright &y& Elsevier]

: BackgroundThe development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state.: MethodsThis analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration.: ResultsDuring the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels.: ConclusionsThe conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM. [Copyright &y& Elsevier]

The aim of this study was to assess the usefulness of liver grafts procured from “marginal donors.” Among 62 liver transplants in 2002, almost half were harvested from donors who were not deemed acceptable by other transplant units. The authors compared the data concerning the donor''s status with the function of the transplanted liver. The relations between individual parameters were estimated, as well as the differences between two groups of recipients: those who received a graft from the “poorer” donors versus those who received “better” grafts. Regardless of the relations between particular parameters a statistical analysis revealed that differences of liver function that were detected during the first 5 days after transplantation disappeared thereafter. [Copyright &y& Elsevier]

Primary biliary cirrhosis (PBC) is an immune-mediated disorder of unknown cause characterized by progressive destruction of intrahepatic bile ducts and the presence of antimitochondrial antibodies. There is no known cure for PBC, and treatment generally includes various combinations of ursodeoxycholic acid and immunosuppressive agents. However, in most patients with end-stage PBC, liver transplantation offers a good quality of life.Recurrent PBC after transplantation is controversial, because most patients with suspected recurrent disease are asymptomatic. Antimitochondrial antibodies frequently persist and do not correlate with disease recurrence. However, most studies support disease recurrence within the graft. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate-term patient and graft survivals are excellent, but the long-term outcome remains unknown. Many immunosuppressive agents have been studied with regard to their anti-recurrence properties; however, no standard therapy has been established for this group of patients. In this study we present two patients transplanted for PBC who displayed early recurrence of disease confirmed by liver biopsy and elevated serum AMA. Both individuals received the same immunosuppressive regimen. The data suggest that two doses of daclizumab and tacrolimus monotherapy in the early posttransplant period is insufficient to prevent recurrence of PBC. Addition of glucocorticoids may have beneficial effects in these patients. [Copyright &y& Elsevier]

Renal failure, mainly due to calcineurin inhibitor (CNI) nephrotoxicity, is the most common complication following orthotopic liver transplantation (ltx). The aim of this study was to evaluate the incidence and course of renal failure in adult ltx patients. Severe acute renal failure in early postoperative period due to impaired hemodynamics and CNI nephrotoxicity, occurred in 14 patients, 3 of whom required dialysis. The creatinine clearance after ltx showed a tendency to decrease, but there was no statistically significant difference (P > .05) in the change in serum creatinine clearance levels between patients treated with tacrolimus (TAC) versus Cyclosporine (CsA) during the first 2 years of follow-up. Fourteen patients required conversion of their regimen because of CNI nephrotoxicity namely, dose reduction (n = 7) or discontinuation of CNI therapy with the replacement by mycophenolate mofetil (MMF) (n = 5) or SRL (n = 5). Dose reduction or CNI withdrawal significantly improved the creatinine clearance (P < .05) without affecting lives graft function. No episode of acute rejection was observed after conversion. Neither conversion of CsA to TAC nor the reverse maneuver significantly influenced the serum creatinine level (P > .05). Reduction of the CNI dose or CNI discontinuation or replacement with MMF or SRL in patients with stable liver but impaired renal function is safe, resulting in a significant improvement in renal function. [Copyright &y& Elsevier]

The aim of this study was to assess the incidence of acute rejection (AR), and the efficacy of high doses of steroids during induction of immunosuppression for AR treatment. Fifty-five patients (33.5%) experienced AR episodes in our series; but, there were no deaths or retransplantations related to AR. The median time from liver transplantation to AR was 18.5 days (range, 2–351 days). In the group with the initial dose of methylprednisolone (MP) ≤0.75 g, AR occurred in 32.9% of patients; and in the group with higher dose of MP, 43.6% (P > 0.05). After 1-year observation, liver function tests were similar in both AR and non-AR groups. The only biochemical parameter that was significantly lower in the non-AR group was the aspartate aminotransferase (AST). Liver function tests determined after 1-year follow-up were not significantly different between the groups with AR treated with doses of MP lower versus higher than 1.25 g. However, liver function tests in the group treated for AR with higher doses of MP were slightly better than in the remaining subjects. Recurrence of AR occurred in 5 cases in the group with lower doses of MP (≤1.25 g), and in 2 cases in the group with higher doses of MP (>1.25 g). A relatively low dose of MP was effective to treat AR. The tendency of AR patients treated with higher dose of MP to display better liver function needs further investigation. However, AR does not seem to affect later liver function. [Copyright &y& Elsevier]

Despite the use of modern immunosuppressive drugs, acute liver rejection (AR) continues to affect up to 70% of transplant recipients. The aim of this retrospective study was to assess the incidence of acute rejection episodes in patients treated with different immunosuppressive protocols. In our series, 37.3% of patients developed a clinical episode of AR. Analysis of immunosuppression has shown that the most effective immunosuppressive protocols, with regard to prevention of AR, include: antibody anti–IL-2R (anti–IL-2R) + tacrolimus (Tac) + mycophenolate mofetil (MMF) + prednisolone (Pred); anti–IL-2R + tacrolimus (Tac) + Pred; or Tac + Pred (25% vs 28.6% vs 30.4%, respectively). The highest rate of AR (66.6%) was observed among patients with anti–IL-2R and Tac but no steroid treatment, mostly (77.7%) in the initial period after liver transplantation. There were no statistical differences in liver function tests between the group treated with a CsA-based versus a Tac-based therapy. Strong immunosuppression contributed to a relatively low incidence of clinical AR in our series. The lowest rate of AR was observed among patients treated with anti–IL-2R antibody. Tac, and Pred. Deprivation of steroids in the early phase after liver transplantation substantially increased the risk of acute rejection episodes despite the use of anti–CD25. There were no statistically significant differences in liver function tests among those treated with Tac versus CsA in the short-term follow-up. [Copyright &y& Elsevier]

End-stage liver disease associated with HCV infection has become one of the leading indications for liver transplantation and it is the most common disease recurring after liver transplantation. The aim of this retrospective study was to asses factors potentially affecting outcome in patients transplanted for HCV-related liver disease. Among 164 adult patients who underwent orthotopic liver transplantation from December 1994 to December 2002, 134 survived >2 months, including 25 with HCV-related liver disease. Mean follow-up after LTx was 24.8 months (range, 2.1–99.4). Anti-HCV was negative in all donors. The parameters considered in our analysis were: the course, outcome, and liver function tests at 1-year follow-up after HCV reinfection: the potential impact of maintenance and induction immunosuppressive regimens; and episodes of acute rejection. Deterioration of graft function because of HCV reinfection occurred in 16 patients (64%). Mean time for deterioration of liver function related to reinfection was 4.5 months (range, 0.83–23). Induction and maintenance immunosuppression did not affect outcome of HCV-infected liver transplant recipients. Aminotransferases were significantly higher among HCV-infected recipients than among the other patients in our series. There was a slight tendency for earlier recurrence of HCV hepatitis among patients treated with high-dose steroids because of acute rejection. [Copyright &y& Elsevier]

The liver is involved in many synthetic and metabolic functions. It takes part in the regulation of circulation, thermoregulation, and digestion. All liver functions are disturbed during harvesting, preservation, and transplantation. The assessment of graft function is still a matter of concern. Many methods including analysis of hepatic enzymes, ketone body ratio, and level of drug metabolites do not give complete and reliable information on graft function. Liver biopsy is still the best diagnostic tool, however, it is invasive, carrying the risk of complications. High-resolution proton spectroscopy of nuclear magnetic resonance was used for analysis of the bile sample obtained from a patient after orthotopic liver transplantation. [Copyright &y& Elsevier]

: Background: ObjectiveThis study assessed the results of liver transplantation in patients with a variety of different indications.: MethodsFrom 1989 to April 2003, 209 orthotopic liver transplantations (OLTx) were performed on 196 patients, including 178 cases. The diagnoses were: PBC (n = 34); PSC (n = 13); elective postinflammatory cirrhosis in the course of hepatitis C (n = 29); hepatitis B (n = 16); postalcoholic cirrhosis (n = 23), autoimmune cirrhosis (n = 11); Wilson''s disease (n = 6); cirrhosis of unknown etiology (n = 10); secondary biliary cirrhosis (n = 5); Budd–Chiari syndrome (n = 6); and benign liver neoplasms (n = 7).: ResultsThe 3-year survival rate in the group of patients transplanted electively was 74.1%. In other groups it was: PBC, 91.4%; PSC, 69.2%; hepatitis C, 69.6%; hepatitis B, 55.5%; postalcoholic cirrhosis, 80%; autoimmune cirrhosis, 81.8%; Wilson''s disease, 57.1%; secondary biliary cirrhosis, 40%; Budd–Chiari syndrome, 66.6%; hemochromatosis, 100%; benign neoplasms of the liver, 87.5%; and liver cysts, 100%.: ConclusionsResults of liver transplantation were closely related to the urgency of the procedure. Better results were achieved in patients operated upon routinely compared with in those operated upon emergently (74.1% vs 50%). The best results of liver transplantation were achieved in patients transplanted on a routine basis with a diagnosis of PBC (91.4%), autoimmunologic cirrhosis (81.1%), postalcoholic cirrhosis (80%), or hemochoromatosis (100%). Patients with liver insufficiency due to hepatitis B and Wilson''s disease have an increased risk of graft destruction, and the rate of survival in these patients is significantly lower than in other patients. [Copyright &y& Elsevier]

The authors present an analysis of early and remote liver transplantation outcomes related to the presence of emergent indications among 196 of the 209 operations performed from 1989 to April 2003; namely 178 elective and 18 emergent transplantations. Perioperative mortality was 15%. The survival rate during the first 12 months was 79.8% and within 3 years 73.5% among patients operated on an elective basis (UNOS 3 and 2B). In contrast, patients with acute liver failure (UNOS 1 and 2A) showed rates of 45%, 50%, and 47%, respectively. Liver transplant outcomes depend primarily on the urgency of an operation. Longterm results are much better among patients operated on electively. Liver transplantation in patients with acute hepatic insufficiency is burdened with a high 45% mortality. [Copyright &y& Elsevier]

: IntroductionBiliary tract complications, which occur in 5.8% to 24.5% of adult liver transplant recipients, remain one of the most common problems following transplantation. The aim of this study was to evaluate these problems and analyze methods of treatment.: Material and methodsFrom 1989 to 2003, 36 (18.7%) among 193 patients who underwent orthotopic liver transplantations in our center developed biliary complications. Biliary strictures that developed in 18 cases (9.3%) were the most common complications. Clinical manifestations of strictures developed at 2 to 24 months after transplantation. Bile leaks occurred in 10 patients (5.2%), and were diagnosed in along the T-tube 4 cases and was not accompanied by any clinical manifestation. Bile leak to the peritoneum after T-tube removal occurred in 2 patients (1.1%). Solitary gallstone formation in one case (0.5%) was removed with the use of ECPW. One patient required retransplantation within 3 months after transplantation, because of the most severe complication—ischemic necrosis of biliary tract.: ResultsUneventful recovery was achieved in 34 patients in the analyzed group (94.4%). There was no case of recurrence during outpatient follow up. Two patients died in late follow-up of unrelated causes: namely, gastrointestinal bleeding due to a duodenal ulcer and multi-organ failure (MOF) due to a third severe episode of acute liver transplant rejection.: ConclusionsBiliary complications remain an important problem in liver transplantation. Endoscopic and radiologic management are effective in the majority of cases. Surgical intervention is obligatory in selected cases. [Copyright &y& Elsevier]