Cristiane Alves Villela-Nogueira

Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus.

Background/Aims: Diabetic patients have an increased prevalence and severity of non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence and the factors associated with the presence of ultrasonographic NAFLD in type‐2 diabetic individuals.

Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates

BackgroundHepatitis B virus (HBV) isolates have been classified in eight genotypes, A to H, which exhibit distinct geographical distributions. Genotypes A, D and F are predominant in Brazil, a country formed by a miscegenated population, where the proportion of individuals from Caucasian, Amerindian and African origins varies by region. Genotype F, which is the most divergent, is considered indigenous to the Americas. A systematic molecular characterization of HBV isolates from different parts of the world would be invaluable in establishing HBV evolutionary origins and dispersion patterns. A large-scale study is needed to map the region-by-region distribution of the HBV genotypes in Brazil.ResultsGenotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive blood donors showed that at least two of the three genotypes, A, D, and F, co-circulate in each of the five geographic regions of Brazil. No other genotypes were identified. Overall, genotype A was most prevalent (48.5%), and most of these isolates were classified as subgenotype A1 (138/153; 90.2%). Genotype D was the most common genotype in the South (84.2%) and Central (47.6%) regions. The prevalence of genotype F was low (13%) countrywide. Nucleotide sequencing of the S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a great majority (28/32; 87.5%) belonged to subgenotype F2, cluster II. The deduced serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine-to-isoleucine substitution at position 127.ConclusionThe presence of genotypes A, D and F, and the absence of other genotypes in a large cohort of HBV infected individuals may reflect the ethnic origins of the Brazilian population. The high prevalence of isolates from subgenotype A1 (of African origin) indicates that the African influx during the colonial slavery period had a major impact on the circulation of HBV genotype A currently found in Brazil. Although most genotype F isolates belonged to cluster II, the presence of some isolates belonging to clusters I (subgroup Ib) and IV suggests the existence of two or more founder viral populations of genotype F in Brazil.

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM.

Acute kidney injury network criteria as a predictor of hospital mortality in cirrhotic patients with ascites.

Background: Acute kidney injury (AKI) is frequent in cirrhotic patients but its best definition is unclear. Recently, the Acute Kidney Injury Network (AKIN) proposed criteria to define AKI. The aims of this study were to apply AKIN criteria to cirrhotic patients with ascites and to evaluate its association to hospital mortality. Study: In this retrospective study, cirrhotic patients with ascites admitted to a university hospital in Brazil between November 2003 and December 2007 were included. AKIN criteria were applied in the first 48 hours of hospitalization, considering 2 values of creatinine in this period. Association of AKI at admission and hospital mortality was analyzed. Results: Of the 198 patients in the study, 91 (46%) presented AKI at hospital admission. Overall hospital mortality was 40.4%. Patients without AKI had a hospital mortality rate of 29.9%, whereas the same rate for patients with this complication was 52.7% (odds ratio=2.6; 95% confidence interval, 1.5-4.7; P=0.001). In a logistic regression analysis, 4 variables were independently associated to hospital mortality: infection, hepatic encephalopathy, Child score, and AKI. A receiver operating characteristic curve analysis revealed that the variation in creatinine proposed by AKIN had the best combination of sensitivity and specificity in relation to hospital mortality. Conclusions: In cirrhotic patients with ascites, prevalence of AKI at hospital admission is high. Patients with renal dysfunction defined by AKIN have significant higher hospital mortality. AKIN criteria are useful in cirrhotic patients with ascites, as it identifies earlier patients with worse prognosis.

Gamma-glutamyl transferase (GGT) as an independent predictive factor of sustained virologic response in patients with hepatitis C treated with interferon-alpha and ribavirin.

Background: Recently, gamma-glutamyl transferase (GGT) has been investigated as a predictive factor for therapy response in hepatitis C patients, but so far its value in pretreatment screening has not been established. Therefore, this study aimed at evaluating GGT as an independent predictive factor for the response to treatment with interferon-α and ribavirin in hepatitis C virus (HCV)-infected patients. Methods: Naive chronic hepatitis C patients undergoing a 6-month follow-up after interferon-alpha and ribavirin therapy had their sustained virologic response (SVR) analyzed according to age, sex, body mass index, GGT levels, genotype, and liver histology by use of a multivariate logistic regression model. Results: Of the 211 patients studied with a mean age of 48 ± 10 years, 125 (59%) were males. Overweight was detected in 47% of patients. Genotype 1 was detected in 141 (75%) of the 187 patients tested. Cirrhosis was present in 67 (32%). A high pretreatment GGT level was observed in 134 (63%). SVR was obtained in 84 (40%) patients. In the final logistic regression model, the variables independently associated with SVR were GGT (P < 0.001), genotype (P < 0.001), and liver histology (P < 0.001). Conclusion: A normal GGT level is an independent predictive factor for SVR in HCV-infected patients and should be considered for pretreatment screening.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Simultaneous detection of hepatitis c virus antigen and antibodies in dried blood spots

BACKGROUND Enzyme immunoassays (EIA) designed to detect hepatitis C virus (HCV) core antigen and anti-HCV antibodies (HCV AgAb) simultaneously can improve the early detection of HCV infection when molecular diagnostic methods are not widely available. OBJECTIVES To evaluate the suitability of dried blood spot (DBS) samples for detecting HCV AgAb using commercial EIAs. STUDY DESIGN Paired serum and DBS samples were assayed using two commercial EIAs for HCV AgAb (Monolisa™ HCV AgAb ULTRA and Murex HCV AgAb). Manufacturers recommendations were followed for sera while sample volume, incubation time and cut-off (CO) determination were evaluated for the DBS samples. The values of sensitivity, specificity, inter-rater agreement, detection limit, assay precision and stability of DBS samples at different conditions (22-26°C, 2-8°C and -20°C) were determined. RESULTS It was necessary to increase the DBS sample volume fourfold compared to the sera samples to approximate the DBS Optical Density (OD) values to the sera OD values. Using ROC curve to recalculate CO values for the DBS samples, sensitivity was 97.5% for both EIAs, while the specificity was 99.71% for Monolisa™ HCV AgAb ULTRA and 95.95% for Murex HCV AgAb. Accurate testing results were obtained with DBS samples for 60 days at all conditions evaluated; storage at -20°C resulted in low OD variation. Both EIAs demonstrated the same limit of detection among DBS samples [estimated viral load of 3.1 International Units per millilitre (IU/mL)] and low OD value variability in repetitivity and reproducibility studies. CONCLUSION DBS samples can be used for the detection of HCV AgAb by EIA as they present comparable performance characteristics and excellent stability among various storage conditions.

Is the Rapid Virologic Response a Positive Predictive Factor of Sustained Virologic Response in all Pretreatment Status Genotype 1 Hepatitis C Patients Treated With Peginterferon-α2b and Ribavirin?

Introduction Currently it is not yet defined if the rapid virologic response (RVR) can predict a sustained virologic response (SVR) in relapsers and nonresponders. Objective To evaluate treatment-RVR as a predictive factor of SVR in genotype 1 hepatitis C treatment naive, relapsers, and nonresponder patients treated with pegylated interferon-alpha (PEG-IFN-α2b) and ribavirin. Methods One hundred sixty-seven genotype 1 hepatitis C patients who were treated with PEG-IFN-α2b and ribavirin and had SVR assessed were included. Hepatitis C virus RNA analysis at the fourth week of treatment was performed in all patients. The exclusion criteria were hepatitis B virus and/or HIV co-infection. A comparative analysis was performed between the groups with and without RVR and a logistic regression model was applied. Results One hundred sixty-seven patients were analyzed, 103 (62%) were naives, 22 (13%) relapsers, and 42 (25%) nonresponders. The SVR rates were 44% in naives, 68% in relapsers, and 12% in nonresponders. RVR was attained in 51/167 (31%) patients and in this group the SVR was higher than in those without RVR (75% vs. 23%; P<0.001). This difference was also observed in all subgroups: naives (71% vs. 29%; P=0.001), relapsers (92% vs. 40%; P=0.02), and nonresponders (50% vs. 8%; P=0.06). A stepwise logistic regression model identified RVR and absence of cirrhosis as the factors independently associated to SVR. Conclusions RVR and absence of cirrhosis are the strongest predictive factors of SVR in HCV genotype 1 patients. Assessment of RVR is very useful in all pretreatment status patients in predicting SVR and provides information for individualizing therapy.

Performance of rapid hepatitis C virus antibody assays among high- and low-risk populations

BACKGROUND Rapid tests for the detection of antibodies to hepatitis C virus (anti-HCV) can facilitate access to diagnosis. OBJECTIVES This study aimed to evaluate the performance of rapid tests for anti-HCV detection in the sera, whole blood, and oral fluid samples from individuals with different endemicity profiles and risk behaviors. STUDY DESIGN Three groups donated biological samples that were tested using three anti-HCV rapid tests (WAMA, Bioeasy and OraSure): (I) suspected cases of hepatitis C, (II) individuals who were living in remote areas in Brazil and (III) crack users and beauty professionals. Reproducibility, repeatability and cross-reactivity to other infectious agents (dengue, HIV, malaria, and syphilis) were also evaluated. RESULTS In group I, specificities varied from 93.75% to 100% and sensitivities varied from 76.03% to 93.84% according to the EIA results. When anti-HCV/HCV RNA-reactive sera samples were considered true-positive HCV cases, the sensitivities and specificities varied from 86.3% to 99.09% and 93.75% to 100%, respectively. In group II, the OraSure rapid test presented the best performance. In group III, the Bioeasy assay performed best using saliva and whole blood and the OraSure assay performed best using oral fluid samples. The reproducibility and repeatability of the WAMA and Bioeasy tests were excellent. The level of concordance between the HCV EIAs and the rapid tests using samples that were reactive for other infectious agents varied from 82.35% to 100% for the WAMA assay and 94.11% to 100% for the Bioeasy assay. CONCLUSION All of the rapid tests could be used to identify active HCV infection among individuals with different endemicity profiles and risk behaviors.

Identification of novel recombinants of hepatitis B virus genotypes F and G in human immunodeficiency virus-positive patients from Argentina and Brazil

Hepatitis B virus (HBV) genotype G (HBV/G) infection is almost always detected along with a co-infecting HBV strain that can supply HBeAg, typically HBV/A2. In this study we describe, in two human immunodeficiency virus (HIV)-positive patients from Argentina and Brazil, the first report of HBV/G infection in Argentina and co-circulation of HBV/G, HBV/F and G/F recombinants in the American continent. HBV isolates carrying the 36 bp insertion of HBV/G were the most prevalent in both patients, with >99 % of colonies hybridizing to a probe specific for this insertion. Phylogenetic analyses of full-length genomes and precore/core fragments revealed that F4 and F1b were the co-infecting subgenotypes in the Brazilian and Argentinian patients, respectively. Bootscanning analysis provided evidence of recombination in several clones from both patients, with recombination breakpoints located mainly at the precore/core region. These data should encourage further investigations on the clinical implications of HBV/G recombinants in HBV/HIV co-infected patients.