Clarice Neuenschwander Lins de Morais

Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus

OBJECTIVE To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-alpha and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS NAFLD was observed in 42% of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, TNF-alpha, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, gamma-GT, uric acid, TNF-alpha, insulin and HOMA-IR than subjects without NAFLD.

Cytokine profile associated with chronic and acute human schistosomiasis mansoni.

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-gamma) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-gamma when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.

Association between Schistosomiasis mansoni and hepatitis C: systematic review

OBJECTIVE: To perform a systematic review of the prevalence of the HCV/S. mansoni co-infection and associated factors in Schistosoma mansoni-infected populations. METHODS: The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies’ selection and the extraction data were based on systematic review methods. Forty fi ve studies were found, with nine being excluded in a fi rst screening. Thirteen articles were used for data extraction. RESULTS: The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defi ned methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS: Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid

Abstract Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north–eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A–F, according to the World Health Organization’s ‘Niamey protocol’. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 μg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human Schistosomiasis mansoni

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific.

Plasma myeloperoxidase levels correlate with hepatocellular carcinoma in chronic hepatitis C

Myeloperoxidase (MPO) is an enzyme responsible for generating hypochlorous acid and reactive oxidants that may lead to liver injury and cancer in hepatitis C (HCV) infection. MPO expression level is regulated by a polymorphism in the promoter region -463 of MPO gene. In the current study, MPO plasma levels and the G-463A MPO polymorphism were determined in 158 chronically HCV infected patients with and without hepatocellular carcinoma (HCC). MPO plasma levels were determined using a commercially ELISA kit. The G-463A MPO polymorphism was accessed by real time PCR using TaqMan probes. The MPO plasma levels of patients with HCV-HCC were higher in comparison to patients with chronic hepatitis or with those patients with severe fibrosis (p=0.01 and p=0.04, respectively). The MPO G-463A polymorphism was not associated with HCV outcome. These findings suggest MPO levels monitoring may be a potential biological marker to HCC screening in patients with HCV.

Increased levels of IgA antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi differentiate digestive forms of Chagas disease

In the chronic phase of Chagas disease, individuals infected by Trypanosoma cruzi may be asymptomatic or may present cardiac and/or digestive complications. Our aim here was to analyze the relationship between the presence of specific immunoglobulin A antibodies and the different chronic clinical forms of Chagas disease using two recombinant antigens of Trypanosoma cruzi, cytoplasmatic repetitive antigen and flagellar repetitive antigen. The association of this immunoglobulin isotype with the digestive and cardio-digestive forms of the disease determined by indirect enzyme-linked immunosorbent assay, strongly suggests that IgA antibodies against these recombinant antigens of T. cruzi can be used as an immunological marker of the digestive alterations caused by Chagas disease. The tests performed in this study show that it is possible to differentiate digestive forms of Chagas disease. The knowledge provided by these results may help physicians to manage early alterations in the digestive tract of patients with the indeterminate or cardiac forms of Chagas disease. Prospective studies, however, with follow-up of the patients that presenting with high levels of immunoglobulin A against cytoplasmatic repetitive antigen and flagellar repetitive antigen recombinant antigens, need to be conducted to confirm this hypothesis.

Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

BACKGROUND A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS The average age was 41 years old and 25 female patients (61%). Ten patients (24%) from 41 showed serum globulins levels raised and 21 (51%) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0.047), as well as those who showed standards D and E as compared to C (P = 0.011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.