Antonio Eduardo Benedito Silva

Role of γ‐glutamyl transferase activity in patients with chronic hepatitis C virus infection

Background:  Increased serum γ‐glutamyl transferase (GGT) levels are frequently observed in chronic hepatitis C virus (HCV) infection. However, the significance of this finding remains unclear. The purpose of the present paper was to assess the relationship between GGT levels and clinical, biochemical and histological features in chronic HCV‐infected carriers.

Simple blood tests as noninvasive markers of liver fibrosis in hemodialysis patients with chronic hepatitis C virus infection.

HCV infection is common among patients with end‐stage renal disease (ESRD) on hemodialysis, and it has been considered an independent risk factor for mortality in this setting. Although liver biopsy in ESRD patients with HCV infection is useful before kidney transplantation, it carries a high risk of complications. We sought to assess the diagnostic value of noninvasive markers to stage liver fibrosis in 203 ESRD HCV‐infected patients. Univariate and multivariate analysis were used to identify variables associated with significant fibrosis (METAVIR F2, F3, or F4 stages). Significant liver fibrosis was observed in 48 patients (24%). Logistic regression analysis identified AST and platelet count as independent predictors of significant fibrosis (P < 0.001 and P = 0.001, respectively). The area under the receiver operating characteristic curve of the AST to platelet ratio index (APRI) for predicting significant fibrosis was 0.801. An APRI < 0.40 accurately identified patients with fibrosis stage 0 or 1 in 93% of the cases (NPV = 93%), and all misclassified subjects were F2. A cutoff ≥ 0.95 to confirm significant fibrosis had a PPV of 66%. If biopsy indication was restricted to APRI scores in the intermediate range (≥0.40 and < 0.95), 52% of liver biopsies could have been correctly avoided. Conclusion: Stage of liver fibrosis can be reliably predicted in ESRD HCV‐infected subjects by simple and widely available blood tests such as AST levels and platelet count. These tests might obviate the requirement for a liver biopsy in a significant proportion of those patients. (HEPATOLOGY 2007.)

Efficacy and tolerance of interferon-alpha in the treatment of chronic Hepatitis C in end-stage renal disease patients on hemodialysis

Abstract: Background: Patients with end‐stage renal disease (ESRD) show a high prevalence of hepatitis C, with a negative impact on the survival on hemodialysis and after renal transplantation. We evaluated the efficacy and tolerance of interferon‐α (IFN‐α) in HCV‐infected ESRD patients on dialysis.

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co‐infection

Aim: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients.

Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study.

Background:  Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)‐infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV‐infected carriers.

Serum levels of YKL‐40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection

Summary.  Hepatitis C virus (HCV) infection is highly prevalent among end‐stage renal disease (ESRD) patients undergoing haemodialysis and it is an important cause of morbidity and mortality in this population. The aim of this study was to evaluate the diagnostic value of YKL‐40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in 185 ESRD HCV‐infected patients. Significant liver fibrosis was defined as METAVIR F2, F3 or F4 stages. Significant fibrosis was observed in 45 patients (24%). By univariate analysis, higher levels of YKL‐40, HA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma‐glutamyltransferase (GGT) as well as reduced platelet count were associated with fibrosis. However, by multivariate analysis, only AST (P = 0.001), platelet count (P = 0.004) and HA (P = 0.042) were independently associated with significant fibrosis. For the prediction of significant fibrosis, the areas under receiver operating characterictic curve (AUROC) of the regression model (0.798) was significantly higher than the AUROC of YKL‐40 (0.607) and HA (0.650). No difference was noted between the AUROC of the regression model and AST to platelet ratio index (APRI) (0.787). Values <8.38 of the regression model showed a negative predictive value of 94% and scores ≥9.6 exhibited a positive predictive value of 65%. If biopsy indication was restricted to scores in the intermediate range of the regression model, it could have been correctly avoided in 61% of the cases. In conclusion, APRI and a model based on AST, platelet count and HA showed better accuracy than YKL‐40 and HA (when used solely) for the prediction of significant fibrosis in ESRD HCV‐infected patients.

Steatosis in chronic hepatitis C : Relationship to the virus and host risk factors

Background:  Steatosis occurs frequently in hepatitis C. However, the mechanisms leading to this lesion are still unknown, and the role of steatosis in the progression of the disease remains controversial. The aim of the present paper was to determine the prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV) genotype, viral load and the presence of risk factors for steatosis, and to analyze the association between steatosis and the intensity of liver disease.

Gender influence on treatment of chronic hepatitis C genotype 1

INTRODUCTION Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. METHODS A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN alpha-2b at a dose of 1.5 microg/kg or Peg-IFN alpha-2a at a dose of 180 microg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. RESULTS Among 181 patients undergoing treatment, the mean age was 46.4 +/- 11.0 years and 46% were women. At baseline, 32% of the patients had advanced fibrosis (F3-F4 Scheuer), and 83% of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45% (female) vs 41% (male); p=0.464. CONCLUSIONS This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.

Antinuclear antibody positivity in patients with chronic hepatitis C: clinically relevant or an epiphenomenon?

Background Serum autoantibodies such as antinuclear antibody (ANA) are frequently detected in patients with chronic hepatitis C virus (HCV) infection, but its relevance is a matter of discussion. Aim To assess the association of ANA positivity with clinical and histological features, and with the outcome of antiviral therapy in patients with HCV infection. Methods Baseline samples from patients with hepatitis C treated with interferon and ribavirin were tested for ANA positivity by indirect immunofluorescence. Results The mean age was 48.3±11.1 years and 56% were men. Among 234 included patients, 22 patients (9.4%) were positive for ANA. These patients showed significantly higher median alanine aminotransferase level (3.52 vs. 2.39 x upper limit of normal, P=0.009) when compared with ANA-negative patients. Fibrosis stage and necroinflammatory grading were not influenced by ANA positivity. Sustained virological response (SVR) rates were similar between ANA-positive and ANA-negative patients (27 vs. 29%, P=0.882). Alanine aminotransferase flares (≥1.5-fold the baseline) during treatment were observed in 28 patients (12%), irrespective of the presence of ANA and without any clinical significance. Conclusion Among HCV patients, ANA positivity seems to represent an immunological epiphenomenon. It neither influences clinical, biochemical, and histological features of chronic hepatitis C nor predicts response to antiviral treatment.

Management of hepatitis C in patients with chronic kidney disease

Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus.