Maria Lucia Cardoso Gomes Ferraz

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

Background:u2002 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.

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

Summary.u2002 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 (Pu2003=u20030.001), platelet count (Pu2003=u20030.004) and HA (Pu2003=u20030.042) 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.

Gender influence on treatment of chronic hepatitis C genotype 1

INTRODUCTIONnAlthough 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.nnnMETHODSnA 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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnThis 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.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients mean weight was 70.6 kg, and 65% of the patients weighed less than 77 kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

Interferon (IFN)-alpha receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-alpha therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-alpha receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-alpha in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFN-alpha 2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-alpha response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcription-polymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/beta-actin-mRNA ratio (mean +/- SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 +/- 0.15; N = 5; P < 0.05) compared to non-responders (0.35 +/- 0.17; N = 12) and controls (0.30 +/- 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in non-responders during IFN-alpha therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-alpha response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

Anti-hepatitis C virus-positive blood donors: are women any different?

summary We sought to assess clinical, epidemiological, biochemical, serological and histological characteristics of anti‐hepatitis C virus (HCV)‐positive female blood donors and compare them with men. As women are frequently the minority among blood donors, studies evaluating this population usually reflect characteristics of male gender. This retrospective study included 380 blood donors with confirmed positive anti‐HCV. The mean age was 36·9u2003±u200311·3u2003years and 33·2% were women. Compared with men, female donors showed higher prevalence of prior transfusion of blood products (Pu2003=u20030·031) and lower prevalence of intravenous drug use (Pu2003=u20030·001) and alcohol abuse (Pu2003<u20030·001). Women exhibited lower medians of alanine aminotransferase (Pu2003<u20030·001) and gamma‐glutamyltransferase (Pu2003<u20030·001). They also showed higher platelet count (Pu2003<u20030·001) and prothrombin activity (Pu2003=u20030·049), and a lower frequency of antibody against core antigen of hepatitis B virus (anti‐HBc) positivity (Pu2003=u20030·032). A higher proportion of spontaneous viral clearance (Pu2003=u20030·001) and a lower frequency of viraemia (Pu2003< 0·001) were observed among women. On liver biopsy, women had lower prevalence of fibrosis stage ≥ 2. Multivariate analysis identified age (ORu2003=u20031·050, 95% CI: 1·019–1·081, Pu2003=u20030·001) and anti‐HBc positivity (ORu2003=u20032·184, 95% CI: 1·010–4·722, Pu2003=u20030·047) as independent predictors of significant fibrosis. Female blood donors presented higher prevalence of spontaneous viral clearance as well as biochemical and histological evidence of less advanced liver disease. These findings could be because of intrinsic characteristics of female gender or secondary to associated factors such as younger age or anti‐HBc positivity.

Histological evolution of hepatitis C virus infection after renal transplantation

information regarding histological progression of hepatitis C after renal transplant (RTx) is scarce.

Impact of cyclosporine‐based immunosuppressive therapy on liver histology of hepatitis C virus–infected renal transplant patients

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Impact of CD4+ T‐cell count on the performance of non‐invasive fibrosis markers in HIV–HCV patients

SIRS, We read the article by Singal et al. evaluating the impact of CD4 count on the diagnostic performance of APRI and FIB-4 models in HIV–HCV patients with interest. We performed a similar analysis in our cohort of co-infected patients, previously described in a study aimed to validate APRI and FIB-4 models. The CD4 count was available for 103 of the 111 individuals included in the original study (72%, mean age 39.9 7.7 years). Significant fibrosis (defined as METAVIR ‡ 2) was observed in 39% of all subjects (38% of patients with CD4 £ 250 and 39% of those with CD4 > 250). The area under the receiveroperating curves (ROC) for APRI and FIB-4 in the diagnosis of significant fibrosis was 0.766 0.048 and 0.796 0.047, respectively. When we evaluated the area under the ROC for APRI and FIB-4 according to CD4 counts, no differences were observed for individuals with CD4 count £250, compared with those with CD4 count >250 (APRI: 0.769 0.124 vs. 0.772 0.052, P = 0,982; FIB-4: 0.817 0.107 vs. 0.799 0.052, P = 0.888). Table 1

Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase

CONTEXT AND OBJECTIVEnThe main causes of hepatic steatosis (HS) are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90% of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT) levels.nnnDESIGN AND SETTINGnCross-sectional study in a single tertiary care center.nnnMETHODSnIndividuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded.nnnRESULTSnAmong 94 individuals included, 40% presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043), with higher body mass index (BMI) (P = 0.003), diabetes prevalence (P = 0.024), fasting glucose levels (P = 0.001) and triglycerides (P = 0.003). Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95% confidence interval, CI: 1.049-1.341; P = 0.006) and diabetes mellitus (OR = 12.721; 95% CI: 1.380-117.247; P = 0.025) were independently associated with HS.nnnCONCLUSIONSnSimple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.