Fernanda Fernandes Souza

Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: a case report.

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

Liver transplantation: expectation with MELD score for liver allocation in Brazil

Liver transplantation represents the most effective therapy for patients suffering from chronic end-stage liver disease. Until very recently, in Brazil, liver allocation was based on the Child-Turcotte-Pugh score and the waiting list followed a chronological criterion. In February 2002 the Model for End-stage Liver Disease (MELD) score was adopted for the allocation of donor livers in the US. After that change, an increased number of patients with more severe liver disease was observed, although there was no difference in 1-year patient and graft survival. A reduction in waiting-list mortality was also observed. In Brazil, the MELD score was adopted on May 31st, 2006. Good results are expected regarding the new criterion for allocation.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45 (51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded.

IL‐18, TNF, and IFN‐γ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury

This study evaluated the association of polymorphisms in the IL‐18 (−607C/A and −137C/G), IFNγ (+874 A/T), and TNF (−238 A/G and −308 A/G) genes with susceptibility to HBV infection and severity of liver injury. A total of 259 chronic HBV‐infected patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy individuals were studied. Four Single Nucleotide Polymorphisms (SNPs) were amplified by Polymerase Chain Reaction (PCR). Liver biopsy was performed in 212 HBV‐infected patients and classified according to severity of liver fibrosis (scores 0–4) and necroinflammatory activity (HAI scores 0–18). TNF‐308*A allele (P < 0.001; OR = 2.16) and TNF −308 AA genotype (P = 0.026; OR = 5.43) were associated with susceptibility to HBV infection. An association was found between severe liver fibrosis when compared to mild fibrosis and the following polymorphisms: Alleles IL‐18 ‐137*G (P = 0.004; OR = 3.45), TNF −308*A (P < 0.001; OR = 3.39), and IFNγ +874*T (P = 0.029; OR = 1.85) and IL‐18 −137 GG genotype (P = 0.009; OR = 3.70). No significant association was found between IL‐18 (−607 A/C) polymorphism and severity of liver fibrosis. Alleles IL‐18 −137*G (P = 0.028; OR = 2.64) and TNF‐308*A (P = 0.002; OR = 3.06) and IL‐18 −137 GG genotype (P = 0.011; OR = 4.20) were associated with severe necroinflammatory activity (HAI>12) when compared to mild necroinflammatory activity (HAI 1–8). The results suggest that IL‐18 −137C/G, TNF‐308 G/A and IFNγ +874 A/T SNPs were associated to more severe liver injury in chronic HBV infection. TNF −308*A allele and TNF −308 AA genotype could play a role in the susceptibility to HBV infection. J. Med. Virol. 87:1689–1696, 2015.

Doação de órgãos para transplantes no Brasil: o que está faltando? O que pode ser feito?

The fundamental problem in the modern practice of organ transplantation is the striking disparity between the number of patients potentially treatable with the donation of viable grafts and the same impressive organ shortage, particularly in our country. What is missing in order to solve this problem is a way to solve it effectively? We must make the whole transplant process effective, bringing hope to many sick people waiting possible curative therapy, the replacement of an organ for terminal illnesses. The transplant is an effective therapeutic indication in irreversible kidney, heart, liver, lungs and pancreas diseases. The patients in terminal states of renal function and endocrine pancreas have therapeutic alternative to transplantation, dialysis and administration of exogenous insulin, respectively. In terminal states of the heart, liver or lung have the sole option to replace the diseased organ. As a cause of bankruptcy are very common diseases in our population such as diabetes, hypertension, alcoholic liver disease and viral hepatitis1,3,5. Given this scenario it is observed in Brazil, on one hand, the large number of patients waiting for a transplant, and other, donations and recovery of organs below the needs of large waiting list. Additionally, it is important to emphasize that the effectiveness of organ transplantation is directly related to the donation process and in our country, in cases of liver transplantation, almost totally dependent on the deceased organs donor . It is noteworthy that by the end of third quarter of 2010, 1059 of liver transplants performed in Brazil, only 7% were living donors4. It appears, therefore, crucial to deceased donor liver transplantation in adults as for children, by the shortage of deceased donors with low age, live donors appears as the best alternative option3. In Brazil, two types of solid organ transplants were better developed: kidney and liver. After a difficult initial phase 60s and 80s with the establishment and standardization of surgical techniques, new immunosuppressive drugs, clinical management of learning and adaptation of logistics throughout the transplant process, in 90s the rate of growth of these two modes did well. Others was also evolved as the heart, pancreas, kidney, pancreas, lungs and intestine3,4. Brazil, with its continental size and presenting external causes as the main predictor of mortality in young adults2 during the 2000s showed no increase in the number of transplants, particularly kidney (18.2 per million population pmp in 2005 to 24.4 pmp in 2010) and liver (5.2 pmp in 2005 to 7.4 pmp in 2010). Currently, with the country population of 190 million people and possessing high potential transplant recipients, more than half the states do not do transplants in general, particularly the liver. They are states of the Midwest, Northern and most of the Northeast4. Interestingly, transplant groups were installed in our country following the same route of colonization, from east to west-central. Nevertheless, the states of the federation who do, their implementation is not distributed equally and there is great heterogeneity of numbers of procedures per million people. This is due to the absence of national policy with regard to both the donation of organs as well as encouraging the formation of transplantation teams, which most often are formed by individual effort of persons. The state of Sao Paulo holds more than half of liver transplants done in the country (17.8 pmp), while Brazil as a whole, reached the 2010 mark of 7.4 pmp, ranging from 2.4 (Bahia ) to 17.8 pmp (Sao Paulo); additionally, various federal states do not perform the procedure. The state of São Paulo reached levels very similar to the vast majority of U.S. states (U.S. is 17.9 pmp). Spain, with well-organized political organ donation and transplantation, achieved more than 35 liver transplants pmp, per year, above the national brazilian average1,3,4. In a country the size of Brazil, this small increase in the number is due to limiting factors, such as donation not approved by family and bad conditions of maintenance of the donor in hospital. When analyzing separately the state of Sao Paulo, the number of potential donors is 63

Preoperative variables associated with transfusion requirements in orthotopic liver transplantation

BACKGROUND Patients with end-stage chronic liver disease (CLD) and submitted to orthotopic liver transplantation (OLT) usually require blood transfusion during the procedure or in the post-operative period due to hemorrhage. Risk factors for transfusion need are not fully known. This study aimed to identify the factors associated with blood components requirements. METHODS In this retrospective study a total of 166 consecutive patients submitted to OLT with the piggyback technique, between 2001 and 2011, were evaluated for number of blood components transfused during surgical procedure and the four subsequent days (total of 5 days). We evaluated the association between the number of units transfused and clinical variables, such as: Child-Turcotte-Pugh (CTP) and MELD scores, hemoglobin concentration (Hb), INR, serum creatinine, bilirubin and albumin concentrations, and total, hypothermic and normothermic time of graft ischemia. RESULTS 152 (91.6%) Patients were transfused (median of 24 units of blood components). Risk factors for higher blood transfusion requirements were CTP, INR, Hb and total time of graft ischemia. The group with CTP-A score received less blood components than CTP-B/C (11.5 vs 27; P=0.002). The group with Hb<10 required a higher number of blood units (34.5 vs 23; P=0.003). The group with INR<1.5 received less blood units (20.5 vs 31; P=0.012). The group transplanted with a graft exposed to less than the median of 555 min of ischemia received less transfusion (21 vs 27; P=0.03). MELD score and the other factors were not associated with blood requirements. CONCLUSION These results demonstrate that CTP, but not MELD score, hemoglobin concentration, INR, and total time of graft ischemia are preoperative variables associated with blood requirements during OLT and in the subsequent days.

The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C.

Background Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. Aim To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. Methods Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. Results Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. Conclusion The H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits.

The HLA-G 14-base pair deletion allele and the deletion/deletion genotype are associated with persistent HBe antigenemia in chronic hepatis B infection

BACKGROUND AND AIMS HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection. METHODS We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers. RESULTS The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele (P=0.0460; OR=1.26; 95%CI=1.01-1.45) and of the deletion/deletion genotype (P=0.0356; OR=2.08; 95%CI=1.05-4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients. CONCLUSIONS Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.

Liver transplantation at a university hospital, faculty of the medicine of Ribeirão Preto, University of São Paulo: results for the first 60 recipients.

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

Analysis of 83 consecutive liver transplants performed at a tertiary care reference hospital in the interior of the state of Sao Paulo

PURPOSE To analyze pre-, intra- and immediate postoperative parameters of patients submitted to liver transplantation. METHODS Eighty-three consecutive orthotopic liver transplants performed from January 2009 to July 2011 were analyzed. The patients were divided into 2 groups: A, survivors (MELD between 9 and 60) and B, non-survivors (MELD between 14 and 40), with 30.6% of group A patients being CHILD C, 51℅ CHILD B and 18,4℅ CHILD A. In group B, 32.1℅ of the patients were CHILD C, 42,9℅ CHILD B, and 25℅ CHILD A. All orthotopic liver transplantations were performed using the piggyback technique without a portacaval shunt. Systemic arterial pressure and serum ALT and AST levels were determined preoperatively and 5, 60 and 1440 minutes after arterial graft revascularization. Serum ALT and AST profiles were evaluated for seven days after surgery. RESULTS Systemic arterial blood pressure levels, time of hot and hypothermic ischemia and time of graft implant were statistically similar for the two groups (p>0.05). Serum levels (U/L) of ALT and AST at the 5, 60 and 1440 minute time points after arterial revascularization of the graft were also similar for the two groups studied, as also were the serum ALT and AST profiles. CONCLUSIONS No statistically significant difference in any of the parameters studied was detected between the two groups. Under the conditions of the present study and on the basis of the parameters evaluated, no direct relation was detected between the intraoperative period and the type of patient outcome in the two groups studied.