André Castro Lyra

Distribution of hepatitis B virus genotypes among patients with chronic infection

Abstract: Hepatitis B virus (HBV) can be classified into at least eight genotypes, A–H. We evaluated the distribution HBV genotypes among patients with chronic infection.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not.

Current Status of Stem Cell Therapy for Liver Diseases

Liver failure is one of the main causes of death worldwide and is a growing health problem. Since the discovery of stem cell populations capable of differentiating into specialized cell types, including hepatocytes, the possibility of their utilization in the regeneration of the damaged liver has been a focus of intense investigation. A variety of cell types were tested both in vitro and in vivo, but the definition of a more suitable cell preparation for therapeutic use in each type of liver lesions is yet to be determined. Here we review the protocols described for differentiation of stem cells into hepatocytes, the results of cell therapy in animal models of liver diseases, as well as the available data of the clinical trials in patients with advanced chronic liver disease.

Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus–infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2% were overweight, 48.1% had a high waist circumference, 85.2% had an increased body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95% CI: 1.09–6.25), elevated gamma-glutamyl transferase (γGT) (OR 2.63; 95% CI: 1.04–7.29), elevated fasting glucose (OR 8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07–7.16), hypertriglyceridemia (OR 7.91; 95% CI: 2.88–22.71), elevated waist circumference (OR 10.33; 95% CI: 3.72–30.67), overweight (OR 11.33; 95% CI: 3.97–41.07), and increased body fat percentage (OR 8.34; 95% CI: 2.94–30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63–44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33–42.34). However, metabolic syndrome risk was also high for those with blood glucose ≥5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64–76.35; OR 7.23; 95% CI: 1.86–32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus–infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight.

Molecular biology and clinical implication of hepatitis C virus

Hepatitis C virus (HCV) was first described in 1989 as the putative viral agent of non-A non-B hepatitis. It is a member of the Flaviviridae family and has been recognized as the major causative agent of chronic liver disease, including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a positive RNA virus with a genome containing approximately 9500 nucleotides. It has an open reading frame that encodes a large polyprotein of about 3000 amino acids and is characterized by extensive genetic diversity. HCV has been classified into at least 6 major genotypes with many subtypes and circulates within an infected individual as a number of closely related but distinct variants known as quasispecies. This article reviews aspects of the molecular biology of HCV and their clinical implication.

Liver histological alterations in patients with chronic hepatitis C and normal ALT levels in the city of Salvador, Northeast-Brazil

UNLABELLED Patients with chronic hepatitis C can have variable clinical progression. Hepatic histological alterations appear to be milder in asymptomatic subjects who have persistently normal ALT levels. AIMS To evaluate the severity of histological liver alterations in blood donors with normal and elevated ALT levels. METHODS We evaluated volunteer blood donors from the main blood bank of the city of Salvador-Brazil. Those who were anti-HCV positive were invited to participate in the study. Serum ALT and AST levels were measured at two time points, two months apart. Donors were divided into two groups: group I, individuals with ALT > 1.5 times the upper limit of normal in at least one time point and group II, individuals with normal or near normal ALT, at both time points RESULTS We evaluated 30,232 blood donors and 528 (1.7%) of them were anti-HCV positive. Eighty-two attended our service and HCV infection was confirmed in 66 individuals. Male gender predominated in both groups; the mean age was 36 for group I, and 33 for group II. Tattoos and intravenous illicit drug use were frequently-encountered risk factors. Liver biopsy was done in 43 subjects. Among donors with elevated ALT, two (10%) had minimum alterations, while in group II normal liver or minimum alterations were observed in six (26%) subjects. Chronic hepatitis or cirrhosis was encountered in 35 (81%) individuals: three (15%) and five (21%) subjects had chronic hepatitis without inflammatory activity, 10 (50%) and 11 (48%) had minimum to moderate activity and five (25%) and one (4.3%) had cirrhosis, in groups I and II, respectively (P was not significant). CONCLUSIONS The prevalence of anti-HCV among this population of volunteer blood donors was 1.7%, and these subjects had few liver histological alterations or chronic hepatitis and cirrhosis. Liver injury severity was significant in patients with elevated ALT, however subjects with normal levels may also present chronic hepatitis and cirrhosis.

Evidence for action of ribavirin through the hepatitis C virus RNA polymerase

Summary.  Hepatitis C virus (HCV) infections are treated with interferon α plus ribavirin, but it is unknown how ribavirin works against HCV. Ribavirin is a guanosine analogue that can be a substrate for the viral RNA polymerase. HCV is genetically variable, and this genetic variation could affect the polymerase’s use of ribavirin triphosphate. Thirteen patients infected with HCV who failed interferon α monotherapy and were retreated with interferon α plus ribavirin were identified; seven were responders and six were nonresponders to combination therapy. The consensus sequences encoding the 13 polymerases plus seven sequences from treatment‐naive controls were determined. The responder sequences were more genetically variable than the nonresponders and controls, the amino acid variations unique to responders had lower BLOSUM90 scores than variations in nonresponders and controls, and the amino acid variations correlated with response to therapy clustered around the RNA‐binding channel of the polymerase. These data imply that that the responder enzymes were probably more functionally variable than the nonresponder enzymes. Enzymatic activity was measured for 10 recombinant polymerases; RNA synthesis activity varied by over sevenfold and polymerases from two of the responders used GTP much better than UTP, but technical limitations prevented direct measurement of ribavirin triphosphate use. Because response to combination therapy in these patients was primarily due to addition of ribavirin to the treatment regimen, these data imply that genetic variation in the polymerase may have affected the efficiency of ribavirin incorporation into the viral genome and hence may have modulated ribavirin’s efficacy against HCV.

Factors Associated with Insulin Resistance in Patients with Chronic HCV Genotype 1 Infection without Obesity or Type 2 Diabetes.

Objective: To investigate the prevalence of insulin resistance (IR) and its association with clinical parameters in patients with hepatitis C virus (HCV) genotype 1 without obesity or type 2 diabetes. Methods: One hundred and twenty-seven HCV-infected patients admitted to the Nutrition and Hepatology Clinic were included. Statistical analysis was performed using the Mann-Whitney test, Fishers exact test, and Poisson regression analysis. Results: The prevalence of IR (homeostasis model assessment [HOMA]-IR ≥ 3.0) was 37.0%. The independent predictors for IR included the following: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper normal limit (odds ratio [PR] = 2.06, 95% CI, 1.16–3.66; PR = 2.32, 95% CI, 1.26–4.49, respectively); gamma glutamyl transferase (γGT) ≥ 85 U/L (PR = 2.09, 95% CI, 1.12–4.12); increased waist circumference (PR = 2.24, 95% CI, 1.25–4.17); increased waist : hip ratio (PR = 2.24, 95% CI, 1.11–5.17); increased body fat percentage (PR = 2.21, 95% CI, 1.01–5.79); overweight (PR = 2.54, 95% CI, 1.40–4.82); and metabolic syndrome (PR = 3.05, 95% CI, 1.69–5.44). High ALT levels and anthropometric parameters remained in the model of multivariate regression analysis. Conclusions: Our findings showed a significantly high prevalence of insulin resistance in nondiabetic, nonobese patients with hepatitis C genotype 1. High ALT levels and anthropometric parameters were significantly associated with IR after multivariate regression analysis. Our data show the importance of monitoring IR, weight, and body composition in patients with chronic hepatitis C. Nutritional management seems to be important in the control of comorbidities related to excess weight and the enhancement of therapeutic responses.

Application of the Vienna classification for Crohn s disease to a single center from Brazil

BACKGROUND Crohns disease is a chronic inflammatory disorder with diversity on its clinical presentation that may be observed from the varying age of onset of symptoms to the site of occurrence of the illness. There is a need for a replicable and uniform description of the disease allowing a comparison between distinct study populations. The 1998 Vienna classification characterizes patients according to three clinical aspects: age at diagnosis, location and disease behavior. AIM To describe Crohns disease in patients from a reference center of Salvador, BA, Brazil according to the Vienna classification. METHODS Between January and October of 2005, patients (n = 47) having at least one endoscopic and radiological examination of the intestine participated in this study. RESULTS Most of the participants had the diagnosis of the disease when they were younger than 40 years old (70.2%) while an ileocolic location (38.3%) and the penetrating form (46.8%) were the most prevalent clinical presentation. The restricted location of the ileum (L1) was more frequent in nonstricturing, nonpenetrating disease (B1) while the ileocolic disease (L3) was more associated with the penetrating behavior (B3). CONCLUSION In this study, differently from the first description of the Vienna classification, the large number of patients presenting a complicated stage of the disease can be attributed to the fact that it was carried out at a reference center, where many patients present with the disease at an advanced stage.

n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

BACKGROUND Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients. METHODS In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05 (two-tailed) was considered statistically significant. RESULTS Comparisons between groups showed that n-3 PUFA supplementation was more effective than the control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3 PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0) versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) μIU mL(-1) versus 10.9 (8.6-14.6) μIU mL(-1) (P = 0.001); and glycated haemoglobin 5.4% (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in interleukin-1 97.5 (0.0-199.8) pg mL(-1) versus 192.4 (102.2-266.8) pg mL(-1) (P = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL(-1) versus 185.7 (98.0-246.9) pg mL(-1) (P = 0.003). CONCLUSIONS n-3 PUFA supplementation reduces insulin resistance in genotype 1 HCV infected patients.