Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 ± 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.

Liver transplantation for neotropical polycystic echinococcosis caused by Echinococcus vogeli: a case report

Neotropical polycystic echinococcosis (NPE) is a parasitic disease caused by cestodes of Echinococcus vogeli. This parasite grows most commonly in the liver, where it produces multiples cysts that cause hepatic and vessel necrosis, infects the biliary ducts, and disseminates into the peritoneal cavity, spreading to other abdominal and thoracic organs. In cases of disseminated disease in the liver and involvement of biliary ducts or portal system, liver transplantation may be a favorable option. We present a report of the first case of liver transplantation for the treatment of advanced liver NPE caused by E. vogeli.

Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation

PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8%) presented a good response. The response rate for the different indications was: (1) acute cellular + sepsis - 0/1 case; (2) recurrent acute cellular - 1/1 case; (3) OKT3-resistant acute cellular - 2/2 cases; (4) steroid-resistant acute cellular + active viral infection - 3/3 cases; (5) chronic rejection - 8/11 cases (72.7% response rate). The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.

Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.

Epidemiology of fungal infections in liver transplant recipients: a six-year study of a large Brazilian liver transplantation centre

Liver transplant seems to be an effective option to prolong survival in patients with end-stage liver disease, although it still can be followed by serious complications. Invasive fungal infections (ifi) are related to high rates of morbidity and mortality. The epidemiology of fungal infections in Brazilian liver transplant recipients is unknown. The aim of this observational and retrospective study was to determine the incidence and epidemiology of fungal infections in all patients who underwent liver transplantation at Albert Einstein Israeli Hospital between 2002-2007. A total of 596 liver transplants were performed in 540 patients. Overall, 77 fungal infections occurred in 68 (13%) patients. Among the 77 fungal infections, there were 40 IFI that occurred in 37 patients (7%). Candida and Aspergillus species were the most common etiologic agents. Candida species accounted for 82% of all fungal infections and for 67% of all IFI, while Aspergillus species accounted for 9% of all fungal infections and for 17% of all IFI. Non-albicans Candida species were the predominant Candida isolates. Invasive aspergillosis tended to occur earlier in the post-transplant period. These findings can contribute to improve antifungal prophylaxis and therapy practices in Brazilian centres.

Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

The use of the Family Management Style Framework to evaluate the family management of liver transplantation in adolescence

Objective: To understand the family management experience of liver transplantation during adolescence based on the Family Management Style Framework(FMSF). Method: This is a case study that used the FMSF as theoretical framework and the hybrid model of thematic analysis as methodological reference. The case presented is from an adolescent’s family that lives in Salvador, Bahia. The data were collected through interviews with the mother and the patient charts analysis. Results: The results shows that the family defines the transplantation as threatening and there are divergence between mother and daughter related to the teen’s capabilities perception. Facing those discrepancies, the family assumes a protective posture by believing that the teen cannot take care of herself alone. The perceived consequences reflect how much the uncertainty permeates the family environment. Conclusion: It is concluded that the use of a model to evaluate the management can help professionals to direct and plan specific interventions.



Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation.Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and prolactin (PRL) of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD).Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p < 0.05), whereas E2 and PRL normalized (p < 0.05). The MELD score did not influence changes in FSH, PRL and LH, however, the more severe the cirrhosis was, the more significant was the normalization of E2 (p = 0.01).Conclusion: Patients with cirrhosis and male hypogonadism have inappropriately normal levels of FSH and LH, associated with an increase in E2 and LRP. After liver transplantation, FSH and LH increased, while E2 and PRL returned to normal. Changes in E2 levels were most pronounced in patients with MELD > 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

Is liver transplantation associated with decreased bone mass in climacteric women?

PURPOSE: To evaluate whether climacteric women undergoing liver transplantation had higher prevalence of decreased bone mass than those without any liver disease. METHODS: A cross-sectional study with 48 women receiving follow-up care at a university hospital in Southeastern Brazil, from February 4th 2009 to January 5th 2011, was conducted. Of these women, 24 were 35 years or older and had undergone liver transplantation at least one year before study entry. The remaining 24 women had no liver disease and their ages and menstrual patterns were similar to those of transplanted patients. Laboratorial tests (follicle-stimulating hormone and estradiol) and bone density measurements of the lumbar spine and femur (equipment Hologic, Discovery WI) were performed. Statistical analysis was carried out by Fisher's exact test, simple Odds Ratio (OR), and multiple logistic regression. RESULTS: Mean age of the women included in the study was 52.8 (±10.7) years-old, 27.1% were premenopausal and 72.9% were peri/postmenopausal. Approximately 14.6% of these women exhibited osteoporosis and 35.4% had low bone mass. The following items were associated with decreased bone mass: being postmenopausal (OR=71.4; 95%CI 3.8 - 1,339.7; p<0.0001), current age over 49 years-old (OR=11.4; 95%CI 2.9 - 44.0; p=0.0002), and serum estradiol levels lower than 44.5 pg/mL (OR=18.3; 95%CI 3.4 - 97.0; p<0.0001). Having a history of liver transplantation was not associated with decreased bone mass (OR=1.4; 95%CI 0.4 - 4.3; p=0.56). CONCLUSION: Liver transplantation was not associated with decreased bone mass in this group of climacteric women.

Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

Detection of human cytomegalovirus DNA in various blood components after liver transplantation

The quantification of human cytomegalovirus (HCMV DNA) by real-time PCR is currently a primary option for laboratory diagnosis of HCMV infection. However, the optimal sample material remains controversial due to the use of different PCR assays. To explore the best blood component for HCMV DNA surveillance after liver transplantation, whole blood (WB), serum (SE), and plasma (PL) specimens were collected simultaneously from targeted patients and examined for HCMV DNA using one commercially available assay. The HCMV DNA-positive rate with WB (16.67%) was higher than that with either SE or PL (8.33%, both P<0.01). Quantitative DNA levels in WB were of greater magnitude than those in SE (WB-SE mean log-transformed difference, 0.99; 95%CI=0.74-1.25; P<0.0001) and PL (WB-PL mean log-transformed difference, 1.37; 95%CI=1.07-1.66; P<0.0001). Dynamic monitoring revealed that HCMV DNA in WB was positive sooner and had higher values for a longer period of time during therapy. With earlier positive detection, higher sensitivity, and yield of greater viral loads, WB compared favorably to SE or PL and hence is recommended as the superior material for HCMV DNA surveillance after liver transplantation. In addition, infant recipients require more intensive monitoring and prophylactic care because of their higher susceptibility to primary HCMV infection.

Successful domino liver transplantation in maple syrup urine disease using a related living donor

Maple syrup urine disease (MSUD) is an autosomal recessive disease associated with high levels of branched-chain amino acids. Children with MSUD can present severe neurological damage, but liver transplantation (LT) allows the patient to resume a normal diet and avoid further neurological damage. The use of living related donors has been controversial because parents are obligatory heterozygotes. We report a case of a 2-year-old child with MSUD who underwent a living donor LT. The donor was the patient's mother, and his liver was then used as a domino graft. The postoperative course was uneventful in all three subjects. DNA analysis performed after the transplantation (sequencing of the coding regions of BCKDHA, BCKDHB, andDBT genes) showed that the MSUD patient was heterozygous for a pathogenic mutation in the BCKDHB gene. This mutation was not found in his mother, who is an obligatory carrier for MSUD according to the family history and, as expected, presented both normal clinical phenotype and levels of branched-chain amino acids. In conclusion, our data suggest that the use of a related donor in LT for MSUD was effective, and the liver of the MSUD patient was successfully used in domino transplantation. Routine donor genotyping may not be feasible, because the test is not widely available, and, most importantly, the disease is associated with both the presence of allelic and locus heterogeneity. Further studies with this population of patients are required to expand the use of related donors in MSUD.

Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3% of leukocytes and 0% of serum. human herpesvirus-7 was detected in sera of 48.2% of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.