Vitreous amyloidosis in two sisters as the indication of transthyretin-related familial form of systemic amyloidosis among liver transplantation candidates.

Vitreous amyloidosis, a rare condition characteristic of the familial form of systemic amyloidosis with polyneuropathy, is caused by a mutation in the transthyretin (TTR) gene. Herein we have presented 2 sisters with involvement of the vitreous body, which prompted a subsequent diagnosis of the TTR-related, familial form of systemic amyloidosis. Due to the progressive character of the disease and poor prognosis, the patients have been considered for liver transplantation, which at present is the only treatment option for this disease.

Prevalence and predictors of acute renal injury in liver transplant recipients.

Renal failure is a major factor impacting liver transplant outcomes. Renal functional impairment predicts decreased survival, leading to increased morbidity and mortality. The aim of this study was to estimate the incidence, risk factors, and resolution of acute kidney injury (AKI) among liver transplant recipients during the operative hospital stay. We analyzed data from 99 orthotopic liver transplantations (OLT) performed at our center in 2008. Posttransplantation occurrence of AKI was defined as an increase in serum creatinine (SCr) concentration of 0.3 mg/dL or more, namely, 1.5-fold from baseline. AKI was observed among 31.31% of liver transplant recipients (n = 31). The mean increase in SCr was 2.49 +/- 0.78-fold from baseline. The mean posttransplant SCr level was 2.59 +/- 0.92 mg/dL. Renal replacement therapy was introduced to 16.12% (n = 5) liver recipients developing AKI. Among them, 2 subjects (6.45%) died. The mean SCr level at the time of discharge from the hospital was 1.17 +/- 0.57 mg/dL among the AKI group compared with 0.77 +/- 0.32 mg/dL among the group without AKI. Pretransplant renal impairment expressed by an elevated SCr concentration (relative risk [RR] = 1.25; P = .0386) and treatment with exogenous vasoconstrictors during the operation (RR = 2.27; P = .016) were identified as risk factors for developing AKI after liver transplantation.

Influence of oral hygiene habits on prosthetic stomatitis complicated by mucosal infection after organ transplantation.

Organ transplant patients suffer impaired immunologic defense mechanisms, including antimucosal defenses. The presence of prosthetic appliances within the oral cavity constitutes an additional factor promoting the development of infections. The aim of this study was to evaluate hygiene habits in relation to prosthetic appliances and one's own teeth practiced by patients after organ transplantation. The study was conducted for prophylaxis of stomatitis complicated by mucosal infection. The research group was composed of patients using prosthetic appliances and undergoing immunosuppressive therapy after kidney or liver transplantation. The control group included healthy wearers of prosthetic appliances. In the course of the initial interview, particular attention was devoted to hygienic habits in relation to the oral cavity and prosthetic appliances, the duration of their use, and the appearance of subjective symptoms. The following examinations concerned the oral mucosal membrane; mouth corners and hygienic condition of prosthetic appliances. Additionally, microbiological examinations were performed by taking a direct swab from the oral mucosa and the surface of dentures. The results of this study showed a greater frequency of prosthetic stomatitis complicated by mucosal infections among patients after organ transplantation, even though these patients exhibited better hygienic standards of the oral cavity and prosthetic appliances.

Successful reversal of acute vascular rejection and cyclosporine-associated nephrotoxicity in renal allograft with combined sirolimus and mycophenolate mofetil as immunotherapy.

Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.

Candida-associated denture stomatitis in patients after immunosuppression therapy.

Patients who undergo kidney or liver transplantation receive long-lasting immunosuppressive therapy. The resultant unfavorable symptoms result from immune deficiency and the side effects of the medications. The aim of this study was to establish the frequency and intensity of denture stomatitis and oral candidiasis among denture-wearing patients who were treated with immunosuppressive drugs. The study was performed in the group of denture wearers with a transplanted kidney or liver who had been treated with immunosuppressive medications. The control group included healthy people wearing dentures. We made physical and clinical examinations in both groups. The history covered nonobjective symptoms in the oral cavity, hygienic habits in the mouth, and the time span during which the dentures had been used. We also evaluated the conditions of the oral mucosal membrane, angular cheilitis, as well as denture stabilization. In both groups mycological investigations were performed by inoculating a direct swab from the oral mucosa and the denture surface on Soborauda agar. The results of our study suggest that patients with immunosuppression were more frequently subject to Candida albicans infections and stomatitis.

Posttransplant lymphoproliferative disorder: morphological picture and diagnostic difficulties.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of both solid organ and bone marrow transplantation. It includes a wide spectrum of proliferative changes ranging from reactive hyperplasia, borderline lesions to malignant lymphomas. PTLD develops in 1% to 10% of transplant recipients. We present 10 cases of PTLD. Five developed after renal, four after liver, and one after heart transplantation. Among the early lesions, we diagnosed two reactive plasmacytic hyperplasias; one infectious mononucleosis-like PTLD; one polymorphic lesion; and one "mixed" case of plasmacytic hyperplasia in one tonsil with a polymorphic PTLD in the second one. Among the lymphomas, we observed three diffuse large B-cell lymphoma (DLBCL); one mantle lymphoma; and one Hodgkin lymphoma-like PTLD. The morphological pictures of six PTLD cases were typical and posed no diagnostic problems. In the one case of plasmacytic hyperplasia, the lymph node morphology was atypical with atrophy of lymphoid components accompanying plasma cell proliferation. Contrary to a good prognosis of early, reactive PTLD, this patient experienced a rapid course and succumbed to sepsis. The most difficult case was a rare Hodgkin lymphoma-like PTLD, which was diagnosed only by a bone marrow biopsy. Because of its noncharacteristic immunophenotype, it was primarily diagnosed as an anaplastic lymphoma of the T-cell type. After additional immunohistochemical studies (BOB and OCT2), we established the final diagnosis of Hodgkin lymphoma-like PTLD. Due to the increasing number of organ transplantations, doctors of various specialties may encounter PTLD.

Safety and efficacy of hormonal therapy in menopausal kidney-allograft recipients.

AIM: A higher risk of premature menopause and osteoporosis has been observed in female kidney-allograft recipients, providing particular indications for hormonal therapy. We have summarized our 10-year-experience with hormonal therapy in menopausal kidney transplant recipients. MATERIALS AND METHODS: From 1995 to 2004, hormonal therapy was administered to 54 kidney transplant recipients. At onset of therapy the ages of the women ranged from 31 to 52 years, and the period from transplantation from 3 months to 13 years. The mean time on therapy was 4.2 years. All patients received transdermal estradiol (E(2)) in combination with oral progestin. RESULTS: Total regression of climacteric symptoms was reported in 75% of patients. After 3 months of the therapy follicle stimulating hormone (FSH) and E(2) levels normalized: FSH from 129 +/- 30.1 IU/L to 38.3 +/- 26.1 IU/L and E(2) from 18.5 +/- 5.8 pg/mL to 98.6 +/- 33.2 pg/mL. No significant change was noted in serum creatinine. Eleven patients developed abnormal uterine bleeding but none had premalignant or malignant lesions of the uterus on endometrial curettage. No incidence of breast cancer was noted during mean treatment period of 5.2 years. Seventeen patients discontinued therapy for medical indications: one for profound thrombophlebitis and 16 for significant deterioration of liver function. Twelve women made their own decision to discontinue therapy. CONCLUSION: Hormonal replacement therapy was effective with no negative impact either on graft function or sex organs among kidney transplant recipients. Liver parameter monitoring seemed to be essential for safe continuation of treatment.

Pathomorphological features of acute rejection in patients after orthotopic liver transplantation: own experience.

INTRODUCTION: Acute hepatic allograft rejection remains an important problem following liver transplantation. Liver biopsy specimens show a combination of characteristic changes, first observed by Snover as a diagnostic triad: portal inflammation, bile duct damage, and central or portal vein endothelial inflammation (endothelitis or endothelialitis). The aim of this study was to describe our histopathological assessment of liver transplants. MATERIALS AND METHODS: In the period between September 2000 and June 2004, we evaluated 150 liver biopsy specimens from 105 liver recipients. RESULTS: Acute rejection was diagnosed in 26.6% of liver biopsies taken from 31.4% patients who demonstrated clinical symptoms of liver damage. In 90% of cases the rejection was described as minimal or mild, and in 10% as moderate. There was no episode of severe acute rejection. Only four biopsies (10%) showed nothing but Snover triad changes. In 9 (22.5%) cases only acute rejection was diagnosed; the remaining showed in addition to acute rejection the possibility of other concomitant pathologies: viral infection in 15 cases (37.5%), biliary flow obstruction in 11 cases (28.5%), functional cholestasis in two cases (5%), and ischemic complications in three cases (7.5%). CONCLUSIONS: Histologically confirmed acute rejection episodes were diagnosed in 14.9% liver recipients. Liver biopsy specimens, aside from Snover triad features, often showed other unspecific morphological changes. Differentiation of acute rejection from other accompanying diseases is sometimes difficult, requiring precise clinical data and pathologist experience.

Morphologic features of hepatitis C recurrence in patients after orthotopic liver transplantation-preliminary analysis of our case observations.

INTRODUCTION: Hepatitis C virus (HCV) recurrence is almost universal in patients after liver transplantation. The diagnosis of reinfection is more difficult than that of a primary process, as shown by our pathomorphologic analysis of cases of HCV recurrence. MATERIAL: During 5.5 years, 240 liver biopsies included 54 obtained from liver transplant recipients with primary HCV infections, among whom 26 (56.5%) had clinical signs and symptoms of hepatitis. Nineteen patients from this population underwent 30 liver biopsies. In addition, seven biopsies were performed in five patients without clinical signs of reinfection. RESULTS: In 44.2% of patients with HCV recurrence and 15% without reinfection, the intensity of the primary process in the native livers was assessed as high. Reinfection was found in all patients with liver carcinoma and 67% with hepatocyte dysplasia. Histologic signs of infection were estimated as minimal (n = 4), mild (n = 19), or moderate (n = 4). In five patients with reinfections and one without recurrence, histologic manifestations of acute rejection were also observed. In conclusion, HCV was the indication for liver transplantation in 22.4% cases. Clinical manifestation of recurrence was found in 56.5% of the patients, who tended to be older than those without disease recurrence. Upon microscopy, lobular lesions predominated over the portal changes. Factors predisposing to HCV recurrence were coexistence of other liver disorders, a high intensity of the inflammatory process, hepatocyte dysplasia, and/or hepatocellular carcinoma in the native liver and acute rejection episodes.

Recurrence of primary sclerosing cholangitis in patients after liver transplantation.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. There are several specific problems related to the posttransplantation period in these patients. The aim of this study was to analyze a single center experience with 17 orthotopic liver transplantations (OLT) due to PSC. PATIENTS AND METHODS: Seventeen patients were included (10 men, 7 women). Actuarial patient and graft survival rates and the incidence of recurrent sclerosing cholangitis were determined at 1, 5, and 7 years. RESULTS: Fifteen patients received single grafts, whereas two patients required retransplants. Patients received either cyclosporine (n = 7) or tacrolimus (n = 10) based immunosuppression. The 1-, 5-, and 7-year patient survival rates were 80%, 60%, and 60%, respectively, whereas the graft survival rates were 88%, 65%, and 65%, respectively. Two patients had cholangiocarcinomas (CCA) diagnosed during OLT; both recurred within 6 months and had a fatal outcome. Two patients (12%) developed recurrent sclerosing cholangitis, as assessed by liver histology and imaging of biliary tree. CONCLUSIONS: Liver transplantation provides good patient and graft survival rates in cases affected with PSC. CCA is associated with poor recipient survival. Recurrent PSC occurs in approximately 12% of cases but does not significantly affect patient survival.

Outcome of four high-risk pregnancies in female liver transplant recipients on tacrolimus immunosuppression.

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.

Pemphigoid-like ocular lesions in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

We present two patients who developed keratitis sicca and pemphigoid-like symptoms following allogeneic bone marrow transplantation (BMT). The diagnosis of ocular graft-versus-host disease (GvHD) was considerably delayed in both. They were admitted to the reference ophthalmology and posttransplant care departments years after allogeneic BMT, when skin biopsy revealed changes typical for chronic GvHD. In both cases either systemic or local immunosuppressive treatment led to improvement of the clinical condition but did not significantly change patients' quality of life.

Autoimmune hepatitis in transplanted liver.

Liver transplantation is recognized as the appropriate treatment for end-stage liver disease. Four patients undergoing liver transplantation for classical end-stage liver disease developed de novo autoimmune hepatitis (AIH) in the graft. Recurrence of AIH after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in one other patient. Markedly elevated serum transaminases were observed, together with an elevated serum IgG and/or globulin fraction and histological feature typical of AIH on liver biopsy.

Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient.

We describe the case of successful delivery in a 21-year-old woman who became pregnant 3 years after liver transplantation and who received sirolimus during the first 6 weeks of gestation. Sirolimus was discontinued when ultrasonography revealed a pregnancy, she was switched to tacrolimus and prednisone was continued. The course of pregnancy was uneventful; there were no signs or symptoms of graft rejection. Due to fetal intrauterine threatening asphyxia the pregnancy was concluded by cesarean section in the 39th gestational week, delivering a healthy, 2950 g, Apgar 10, female infant.

Posttransplantation diabetus mellitus under calcineurin inhibitor.

BACKGROUND: The 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. METHODS: This 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. RESULTS: During 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. CONCLUSIONS: The 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.

Biochemical assessment of the early liver graft function in relation to selected donor parameters.

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.

Comparison of the results of liver transplantation for elective versus urgent indications.

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.

Results of liver transplantation according to indications for orthotopic liver transplantation.

OBJECTIVE: This study assessed the results of liver transplantation in patients with a variety of different indications. METHODS: From 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). RESULTS: The 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%. CONCLUSIONS: Results 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.

The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation.

The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the outcomes of liver transplantation. Thirty-four patients died (mortality rate, 16%) and 1-year survival rate, 64%. Mortality rates varied during different periods of observation due to increasing experience of the transplantation team. The causes of mortality were assessed for a series of 34 patients: it was 75% at the beginning of transplantation procedures while recent deaths have not recently exceeded 10% of cases.

Liver transplantation in hepatitis C virus-related cirrhosis.

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.