Teresa Cristina Abreu Ferrari

Hepatocellular Carcinoma Is Associated With an Increased Risk of Hepatitis B Virus Recurrence After Liver Transplantation

BACKGROUND & AIMS Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is significantly reduced by prophylaxis with hyperimmune antibody to hepatitis B surface antigen (anti-HBs) globulins (HBIG) and antiviral drugs. The role of hepatocellular carcinoma (HCC) in HBV recurrence remains unclear. We investigated the association between HCC pre-OLT and HBV recurrence post-OLT. METHODS We studied 99 hepatitis B surface antigen-positive patients who underwent OLT for cirrhosis. The median follow-up period was 43 months. All patients received HBIG, and 51 also received lamivudine and/or adefovir. Of these 99 patients, 31 had HCC before OLT. Total HBV DNA and covalently closed circular (ccc)-DNA were measured in tumor and nontumor tissues from the explanted livers of 16 of these 31 HCC patients and, also, in a context of tumor recurrence, in 3 patients who developed HBV/HCC recurrence. RESULTS Fourteen patients (14.1%) developed HBV recurrence within a median period of 15 months post-OLT. HCC at OLT, a pre-OLT HBV DNA viral load > or = 100,000 copies/mL, and HBIG monoprophylaxis were independently associated with HBV recurrence post-OLT. Eleven out of the 31 patients with HCC at OLT presented with HBV recurrence and 3 out of the 68 patients without HCC had HBV recurrence (P < .0001). HBV recurrence was more frequent in patients who developed HCC recurrence (7/8 patients, 87.5%) than in those who did not (4/23 patients, 17.4%) (P < .0001). In the 16 explanted livers, cccDNA was detectable in HCC cells in 11 and in nontumor cells in 12. cccDNA was detected in a context of HCC recurrence in 2 of the 3 patients tested who developed HBV/HCC recurrence. CONCLUSIONS The associations of HCC pre-OLT, and HCC recurrence with HBV recurrence post-OLT, and the detection of HBV DNA and cccDNA in HCC suggest that HBV replication in tumor cells may contribute to HBV recurrence post-OLT.

Neuroschistosomiasis: clinical symptoms and pathogenesis

Neuroschistosomiasis, referring to schistosomal involvement of the CNS, when symptomatic, is a severe disorder in which prognosis depends largely on early diagnosis and treatment. It is an underdiagnosed disorder, but has been increasingly reported in populations in endemic areas and in tourists. CNS involvement can occur at any time during schistosomal infection. Both the brain and the spinal cord can be affected. Schistosoma mansoni and Schistosoma haematobium usually cause myelopathy, whereas Schistosoma japonicum usually causes encephalic disease. There are substantial differences in the pathogenesis, clinical presentation, and outcome of the neurological disorder, depending on the phase and clinical form of schistosomiasis in which it occurs.

Involvement of central nervous system in the schistosomiasis

The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR) present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resources available for treating NS. The outcome is variable and is better in cerebral disease.

Spinal cord schistosomiasis: a prospective study of 63 cases emphasizing clinical and therapeutic aspects

A prospective study was conducted on 63 patients with schistosomal myeloradiculopathy admitted to a university hospital in Brazil. They were evaluated according to a protocol and treated with corticosteroid and praziquantel. The disease, in general, presented as a lower cord syndrome of acute progression characterized by motor, sensory and autonomic dysfunctions. The severity of the clinical picture was different among the patients, but the symptoms were quite constant. Cerebrospinal fluid examination showed an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. The most frequent alterations detected by imaging methods were enlargement of the medullary cone and of the roots of the cauda equina. Schistosome egg counts suggested a low parasite burden in 71.6% of the cases. Outcome was favorable in 38 (60.3%) patients and improvement usually started within the first 48 h after commencing on corticoid and was faster during the early period of treatment.

The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO) contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.

Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period: prognostic factors and in-hospital outcome.

OBJECTIVES To describe the epidemiological, clinical, and laboratory profile of infective endocarditis (IE) at a Brazilian tertiary care center, and to identify the predictors of in-hospital mortality. METHODS Data from 62 patients who fulfilled the modified Dukes criteria for IE during a seven-year period were gathered prospectively. The Cox proportional hazards model was used to identify predictive factors for death. RESULTS The mean age of patients was 45 years, and 39 patients (63%) were male. The median time from admission to diagnosis was 15 days. Rheumatic heart disease was the predominant underlying heart condition (39%), followed by valvular prosthesis (31%). Neurological complications were observed in 12 patients (19%). Echocardiography demonstrated one or more vegetations in 84% of cases. The infective agent was identified in 65% of cases, and the most frequent causative agents were staphylococci (48%), followed by streptococci (20%). The median duration of hospitalization was 39 days. Surgery was performed during the acute phase of the IE in 53% of cases. The overall in-hospital mortality was 31%. On multivariate analysis, vegetation length >13mm remained the only independent predictor of in-hospital mortality (hazard ratio 1.05 per millimeter, 95% confidence interval 1.003-1.110, p=0.038). CONCLUSIONS IE remains a severe disease affecting the young population in Brazil, and rheumatic heart disease continues to be the most common underlying heart condition. Large vegetation size, assessed early in the course of IE by transesophageal echocardiography, along with the clinical and microbiological features, may predict in-hospital death.

Serodiagnosis of Helicobacter pylori infection by Cobas Core ELISA in adults from Minas Gerais, Brazil

We evaluated the accuracy of a 2nd generation ELISA to detect Helicobacter pylori infection in adults from a developing country in view of variations in sensitivity and specificity reported for different populations. We studied 97 non-consecutive patients who underwent endoscopy for evaluation of dispeptic symptoms. The presence of H. pylori was determined in antral biopsy specimens by culture, by the preformed urease test and in carbolfuchsin-stained smears. Patients were considered to be H. pylori positive if at least two of the three tests presented a positive result or if the culture was positive, and negative if the three tests were negative. Sixty-five adults (31 with peptic ulcer) were H. pylori positive and 32 adults were H. pylori negative. Antibodies were detected by Cobas Core anti-H. pylori EIA in 62 of 65 H. pylori-positive adults and in none of the negative adults. The sensitivity, specificity and positive and negative predictive values of the test were 95.4, 100, 100 and 91.4%, respectively. The Cobas Core anti-H. pylori EIA presented high sensitivity and specificity when employed for a population in Brazil, permitting the use of the test both to confirm the clinical diagnosis and to perform epidemiologic surveys.

The value of an enzyme-linked immunosorbent assay for the diagnosis of schistosomiasis mansoni myeloradiculopathy

The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of neuroschistosomiasis has not been fully elucidated; the condition is essentially diagnosed on the basis of circumstantial evidence, which may lead to an erroneous diagnosis, especially in highly endemic areas. We therefore carried out a prospective case-control study in which we compared the concentrations of immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR) with those observed in a control group consisting of 41 patients with epidemiological and serological evidence of exposure to schistosomes, and with other neurological disorders that result in mild to moderate impairment of the blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent assay. The sensitivity, specificity and positive and negative predictive values were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A value below 0.1 micrograms/mL practically excluded the possibility of SMMR (post-test probability < 5%), a value above 1.4 micrograms/mL practically confirmed the diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5 microgram/mL had no diagnostic value (post-test probability approximately 45%), and values of 0.6 to 1.4 micrograms/mL were useful in some situations (post-test probability approximately 70%). We conclude that the estimation of anti-SEA IgG in the CSF is useful for the diagnosis of SMMR.

Clinical value of anti-live Leishmania (Viannia) braziliensis immunoglobulin G subclasses, detected by flow cytometry, for diagnosing active localized cutaneous leishmaniasis

objective To evaluate the clinical value of flow cytometry anti‐live promastigate antibody (FC‐ALPA), for diagnosing active cutaneous leishmaniasis.

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditions that include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.