Luciana Costa Faria

Tuberculosis in liver transplant recipients: a single Brazilian center experience.

Background. Tuberculosis (TB) is an important opportunistic infection in transplant recipients worldwide. The frequency of Mycobacterium tuberculosis disease varies among different regions, but the incidence of TB in adult liver transplant (LT) recipients is largely unknown. The estimated frequency ranges from 0.7% to 2.3%, with mortality rate up to 30%. However, these data are based on individual case reports or series with small samples. In LT recipients, therapy is generally associated with significant hepatotoxicity and interactions with immunosuppressive drugs. Methods. This retrospective analysis included 319 patients who underwent LT at University Hospital, Federal University of Minas Gerais, Brazil, between September 1994 and July 2007 and survived more than 1 month. Among these, TB was diagnosed in five patients. No patients received chemoprophylaxis before or after LT. Results. All five patients were women, mean age 39.6±16.5 years. Two patients had disseminated TB, two pulmonary involvement, and one extrapulmonary disease. Cultures were positive in four patients. Overall, four patients received isoniazid, rifampin, and pyrazinamide for 6 to 12 months, with good tolerance, but one patient presented recurrence. Another patient presented raised hepatic enzymes levels after initiating therapy. All patients are alive and well. Conclusions. In this series, the TB frequency after liver transplantation was 1.57%, with no confirmed hepatotoxicity with conventional treatment and an excellent survival rate (100%).

An unusual presentation of mesenteric panniculitis.

Mesenteric panniculitis is a rare disorder characterized by a tumor-like expansion of the mesentery due to variable degrees of fat necrosis, chronic inflammation and fibrosis. Its pathophysiology remains unclear despite the description of associations with inflammatory disorders or malignancies, especially lymphomas.1 The disease remains asymptomatic in 30–50% of cases, and the most common clinical presentations are abdominal pain, palpable abdominal mass or intestinal obstruction.1,2 Most patients present a benign, slowly progressive course, and the outcome of the disease is usually favorable.1,2 Nevertheless, in about 20% of patients, mesenteric panniculitis is associated with significant morbidity and a chronic debilitating course.3 We report a case of this poorly known entity, which presented as a systemic disease with severe constitutional manifestations and rapid deterioration of the general condition of the patient, which made diagnosis difficult.

Visceral leishmaniasis in liver transplant recipients from an endemic area.

Visceral leishmaniasis (VL) is a parasitic infection generally caused by the Leishmania donovani complex, and in Brazil by Leishmania chagasi. Every year, half a million new cases are diagnosed worldwide, and five countries— Nepal, Bangladesh, Brazil, India, and Sudan—account for up to 90% of cases (1, 2). Although considered a rare disease among transplant recipients, the number of reported cases has increased over the last two decades (3). VL diagnosis should also be considered in transplant recipients from nonendemic areas, in view of increasing migration and the globalized world. We report three cases of VL in liver transplantation (LT) recipients in a single center from Brazil. Hospital records of 595 patients who underwent LT from September 1994 to December 2009 at the Federal University Hospital of Minas Gerais, Brazil, were reviewed. Three of the 595 liver transplanted patients were diagnosed with VL. Their detailed clinical characteristics are shown in Table 1. A case is defined as the presence of Leishmania amastigotes in bone marrow aspirate or specimens of other reticuloendothelial system organs in patients with symptoms consistent with VL. The typical clinical picture is characterized by fever, splenomegaly, weight loss, blood cytopenia, and hypergammaglobulinemia (2, 4). All patients presented with fatigue, pancytopenia, and hypergammaglobulinemia, and two patients had fever and splenomegaly. Diagnosis was established by the presence of Leishmania amastigotes in bone marrow aspirate (Fig. 1) in all cases. Initial therapy was amphotericin B deoxycholate, which caused nephrotoxicity in all three patients and was replaced by liposomal amphotericin B. Immunosuppression was reduced once the VL diagnosis was established, and maintained at the lowest possible level for a few months. Two patients are alive and free of disease. The other patient is alive but experienced a VL relapse; he was retreated with liposomal amphotericin B and has continued on monthly secondary prophylaxis (3 mg/kg/monthly). VL infection in transplant recipients may occur in four ways: (1) the recipient may be infected by the graft; (2) by transfusion; (3) a previously infected recipient may reactivate a latent infection; and (4) immunosuppressed patients may develop de novo infections (3, 5). Because specific antibody responses are not protective (6), suppression of the T-cell host response after organ transplantation may reactivate a latent VL infection. In the present series, it was not possible to identify the way of transmission. The rising number of transplants, including in VL-endemic regions, justifies the increasing interest in such a neglected disease. Timely diagnosis followed by prompt treatment can have an impact on the high lethality rates (3). Until now, only 10 cases of VL in LT recipients have been described, one of them by our group (7–14). Cases are probably underestimated by misdiagnosis. Given that the liver is a reticuloendothelial organ preferentially affected by the protozoan, the risk of transmission through the graft may be greater than in other transplants. Transplanted patients should benefit from lipid formulations as of the beginning of treatment, because immunosuppressive drugs are also nephrotoxic and renal dysfunction is frequent. Cure is generally defined by clinical and hematological criteria (resolution of fever, hepatosplenomegaly, and pancitopenia). Follow-up is recommended for 6 months after treatment (15, 16). Although some authors also consider negative bone marrow biopsies or aspirate cultures after treatment (17), these are invasive procedures and absence of parasites does not define resolution or exclude relapse (18). VL cure rates after amphotericin treatment in transplanted patients are approximately 80%. However, relapse may occur in up to 35% of the cases, associated to poor prognosis (13). One described patient, despite adequate treatment, presented a relapse 5 months after amphotericin discontinuation. He was then retreated and remains on secondary prophylaxis with monthly liposomal amphotericin. Some studies have shown that secondary prophylaxis may prevent a VL relapse, but they were carried out in HIV patients (18, 19). The evidence of this recommendation in transplanted patients is not yet established, but it should be considered in those who relapse. Asymptomatic infection (from donors or recipients) in the pretransplant phase could facilitate the suspicion of VL after LT in the presence of certain symptoms (19). We do not perform VL serology routinely for screening liver donors and recipients before transplant, but this is the matter of an ongoing research project. At present, if recipients or donors have a positive result, we perform a stricter follow-up with a lower threshold of suspicion for VL. In conclusion, VL is a potential infectious complication in liver transplanted patients, mainly in endemic areas, and probably remains underestimated and underdiagnosed in these patients. Prompt diagnosis and treatment are essential to reduce lethality.

Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis.

The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the hosts immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease.

SEVERE AND PROLONGED CHOLESTASIS CAUSED BY TRIMETHOPRIM-SULFAMETHOXAZOLE: A CASE REPORT

Trimethoprim-sulfamethoxazole (TMP-SMX) is a widely used antibiotic in the prophylaxis and treatment of a variety of common infections. Hepatic injuries caused by TMP-SMX are considered rare and are classified as unpredictable or idiosyncratic types of hepatotoxic reactions.1 The pattern of injury may be characterized by hepatocellular necrosis,1,2 mixed hepatocellular-cholestasis,1,3,4 or cholestasis.5–7 We describe a case of severe and prolonged cholestasis, which arose 30 days after a 5-day course of TMP-SMX treatment, and provide a review of related cases.

Whipple's disease. Report of five cases with different clinical features

Whipples disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

Laryngeal histoplasmosis in an immunocompetent patient from a non-endemic region: case report.

Histoplasma capsulatum infection involving the larynx is a rare manifestation, especially in immunocompetent individuals and a high index of suspicion is needed to establish the diagnosis correctly. We report a case of a 50‐year‐old Brazilian man who presented with progressive hoarseness and throat pain for 4 months. Laryngoscopy showed a supraglottic vegetant lesion, and the biopsies chronic granulomatous inflammation without any specific agent. A second laryngoscopy with biopsies was performed and after 17 days of incubation in specific medium, H. capsulatum was isolated. The patient was successfully treated with amphotericin B.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Impact of Model for End-Stage Liver Disease in the occurrence of infectious events and survival in a cohort of liver transplant recipients.

The Model for End-Stage Liver Disease (MELD), which predicts mortality on the waiting list before liver transplantation, has changed organ allocation criteria to prioritize severely ill patients. The aim of this study was to investigate the impact of the new criteria on the incidence of Healthcare Associated Infections (HAI) and patient survival after liver transplantation. This retrospective cohort included liver transplant recipients from 2005 to 2007. Infection notification followed the recommended criteria of the National Healthcare Safety Network (NHSN). Statistical analysis was performed using the Statistical Package for the Social Sciences. Of 142 patients, 67 (47.2%) underwent transplantation before June 2006. There were no differences between the 2 periods considering patient gender, diagnosis, age, length of hospitalization, and mean time to first infection occurrence. However, the length of intensive care unit (ICU) hospitalization (P = .006) and central venous catheter (CVC) use (P = .025) were higher in the first period of the study. Comparison of time until first systemic infection before and after changes in allocation criteria showed no significant difference (log-rank = 0.06; P = .81). There was a trend toward greater lethality during the second period of the study (P = .09). There was no difference in time to death between the 2 periods (log-rank = 0.9; P = .76). However, when comparing time to death of all patients with systemic infection versus those without this event, patients without infection showed a higher mortality rate (log-rank = 15.7; P < .001).

Evolution of patients undergoing liver transplantation due to viral hepatitiss

Objectives: to describe the evolution of patients with a diagnosis of viral hepatitis B or C undergoing liver transplantation at a reference hospital. Methods: this was a cross-sectional study conducted in the Organ Transplantation Service of the Alfa Institute of Gastroenterology, General Hospital, Federal University of Minas Gerais, from 2005 to 2007. Data were collected from medical records and service databases. Results: out of 173 patients undergoing liver transplantation, 61 had hepatitis C, nine had hepatitis B, and one developed fulminant hepatitis A. Among patients with hepatitis C, 31 were treated before the transplantation (seven with sustained virological response). Only two patients with hepatitis B were pretreated. After liver transplantation, the recurrence of hepatitis occurred in 21 patients with hepatitis C, and in none with hepatitis B. The drug treatment after liver transplant was performed in 13 out of 21 patients with recurrent hepatitis C. Discussion: in cases of cirrhosis caused by the hepatitis C virus, recurrence of infection is common after liver transplantation and indicates the need for an effective treatment. Post-transplant survival in patients infected with hepatitis B virus depends on prevention using combined prophylaxis. Conclusion: viral hepatitis accounts for a significant proportion of indications for a liver transplant. Recurrence of hepatitis C persists as a major problem in transplanted patients due to viral hepatitis. Prophylaxis of hepatitis B post-transplant recurrence is mandatory with immunoglobulin and nucleoside analogs.