Chronic infection with the hepatitis C virus (HCV) is estimated to affect 58 million people worldwide and around 700,000 individuals in Brazil. Various non-invasive markers of hepatic fibrosis have been proposed, such as transient hepatic elastography (THE) using FibroScan®. However, the reliability of the performance, by operators in the training phase is undetermined, which hinders its applicability in clinical practice. Objectives: The present study aimed to evaluate the impact of training an inexperienced operator to perform the examinations using FibroScan® in patients with chronic hepatitis C. Specifically, the frequency of unreliable results throughout the training was assessed. Methods: This is a cross-sectional study with retrospective data collection including compensated chronic hepatitis C patients who underwent the examinations using FibroScan® between March 2014 and December 2016, performed by two researchers. Included patients were divided into two groups based on the operator's experience in the examination: the Experienced Examiner (EE) group and the Examiner in Training (ET) group, with the latter divided into two phases: phase 1, consisting of the first 100 examinations, and phase 2, comprising subsequent examinations. For the reliability analysis, parameters such as success rate (SR), interquartile range (IQR) to median (Md) ratio (IQR/Md), and reliability criteria of Castéra, et al. and Boursier, et al. were used. Results: Between March 2014 and December 2016, 771 adult HCV-infected individuals were evaluated and divided into EE group (n = 161), ET phase 1 (n = 100), and ET phase 2 (n = 158), showing similar demographic, clinical, and laboratory characteristics. SR and IQR/Md ratios were similar among EE, ET phase 1, and ET phase 2 groups. The proportion of reliable results was comparable in all three groups, using Castéra, et al. reliability criteria (92.5%, 92.0%, and 97.5%, respectively) and Boursier, et al. criteria (96.9%, 95.0%, and 98.1%, respectively). Conclusion: A short training period (up to 100 examinations) seems to be sufficient for them to have good clinical applicability in the hands of an operator with initial experience in the method.

BACKGROUND:The progression of fibrosis in the early stages of chronic hepatitis C virus is variable, and the ideal interval to perform a new biopsy in untreated patients is still unknown.AIMS:We evaluated the histologic progression of patients with untreated hepatitis C virus with two liver biopsies and correlated disease progression with demographic, epidemiologic, biochemical, and histologic variables.PATIENTS AND METHODS:Untreated hepatitis C virus-infected patients with two liver biopsies at a minimum interval of 1 year were studied. Gender, age, parenteral risk factors, duration of infection, alcohol intake, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and histologic findings were analyzed.RESULTS:Fifty-five patients were included. The first biopsy showed low grades of fibrosis and periportal necroinflammatory activity in 93%. A second biopsy was performed after 39 +/- 14 months; 40% of patients showed a progression of fibrosis and/or periportal necroinflammation. Comparison between groups with and without histologic worsening revealed no differences in demographic, epidemiologic, biochemical, or histologic data.CONCLUSIONS:Histologic worsening occurred in 40% of untreated patients after 3.2 years. No factor could be established at the first biopsy to predict which patients are at risk of progression. Thus, histologic reassessment between 3 and 5 years seems to be the only approach to document disease progression and establish treatment indication.

Introduction: Renal transplant (RTx) patients with hepatitis C frequently show normal levels of alanine aminotransferase (ALT) and the significance of ALT in this group has not been established.Aim: To determine the value of ALT as a marker of histologic hepatic damage in RTx patients with hepatitis C virus (HCV) infection.Materials and methods: HCV-RNA-positive RTx patients with a liver biopsy were analyzed regarding staging and the grading of periportal and lobular necroinflammatory activity. Spearman's correlation coefficient was used to determine the correlation between ALT and histologic variables. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) of ALT in the detection of septal fibrosis and interface hepatitis, and/or confluent necrosis were calculated.Results: Fifty-three patients (32 men, 60%), with a mean age of 42 +/- 10 yr and time since transplant of 5 +/- 4 yr were included. Only 27 (51%) patients showed elevated ALT levels, which were associated with septal fibrosis (p = 0.001), interface hepatitis (p < 0.001) and confluent necrosis (p = 0.05). A correlation was observed between ALT and staging (r = 0.50, p < 0.001), periportal necroinflammatory activity (r = 0.59, p < 0.001) and lobular necroinflammatory activity (r = 0.50, p < 0.001). The sensitivity, specificity, PPV and NPV of ALT were 92, 61, 41 and 96%, respectively, for the detection of septal fibrosis, and 87, 77, 74 and 88% for the detection of interface hepatitis and/or confluent necrosis.Conclusion: ALT is a good marker of histologic hepatic lesion in HCV-infected RTx patients and, therefore, liver biopsy can be avoided in patients with persistently normal ALT.

Introduction. Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection results in more severe forms of liver disease in nonuremic patients; however, the impact of HCV coinfection is not clearly known in end-stage renal disease (ESRD) patients with HBV infection. We sought to determine the impact of HCV coinfection in UBV-infected ESRD patients.Patients and Methods. The HBsAg-positive ESRD patients evaluated between March 1999 and May 2003 were divided into two groups: group B, HBV infection alone, and group BC, HBV-HCV coinfection (anti-HCV-positive). Both groups were compared regarding epidemiological, laboratory, and histological findings. A liver biopsy was obtained in cases with evidence of viral replication and/or elevated alanine aminotransferase.Results. One hundred patients (73% men) with mean age of 42 +/- 11 years (55 patients in group B and 45 in group BC) were studied. Comparison between groups showed a difference in time on hemodialysis and duration of infection, which were higher in group BC (P < .001 and P = .001, respectively) and in history of blood transfusion, which was also more frequent in group BC (P = .04). Liver biopsies, obtained from 15 patients in group B and 28 patients in group BC, showed no difference in frequency of septal fibrosis (60% in group B vs 48% in group BC, P = .46) or interface hepatitis (73% vs 71%, P = .99).Conclusions. HBV-HCV coinfection was related to a longer time on hemodialysis, longer duration of infection, and history of blood transfusion. Contrary to nonuremic patients, HCV coinfection was not associated with more severe forms of liver disease in ESRD patients.

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.Methods: Patients presenting with anti-HCV and HCV-RNA were included. Hepatic iron concentration was determined in liver tissue by atomic absorption spectrophotometry. The association between HIC and age, gender, risk factor of transmission, duration of infection, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, iron and serum ferritin, transferrin saturation, HCV-RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann-Whitney test and a multiple linear regression model.Results: Ninety-six patients (58% male) with a mean age of 44 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 28%, 27% and 12.5% of patients, respectively. Stainable iron was detected in few patients (15.6%). Higher grades of stainable iron (2 and 3) were observed in only 7%. The HIC (>30 mmol/g dry weight) was elevated in five patients (5%). Neither grading nor staging were related to HIC. Higher HIC were observed in male patients (P <0.001), in patients with elevated serum ferritin (P = 0.001) and in patients with stainable iron (grades 2 and 3. P = 0.001). Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC (P = 0.003).Conclusions: Iron overload in chronically HCV-infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC. (C) 2004 Blackwell Publishing Asia Pty Ltd.

The behavior of hepatitis C in states of immunodeficiency is poorly understood and it is still unclear whether the characteristics of hepatitis C virus (HCV) infection in renal transplant patients differ from those observed in immunocompetent subjects. The aim of this study was to compare the biochemical and histologic characteristics of chronic HCV infection between renal transplant and immunocompetent patients. Forty-one HCV-RNA-positive renal transplant patients and 41 immunocompetent controls matched for gender, age at infection and time of infection were included in the study. The groups were compared regarding laboratory and histologic variables. Renal transplant patients showed lower alanine aminotransferase (ALT) levels (p = 0.005) and higher levels of gamma-glutamyltransferase (p = 0.003), alkaline phosphatase (p < 0.001), and direct bilirubin (p < 0.001) when compared with controls. Histologic analysis revealed less intense portal (p < 0.001) and periportal (p = 0.046) inflammatory infiltrate in renal transplant patients but a larger proportion of cases with confluent necrosis (p = 0.043). No difference in the presence of septal fibrosis, hepatic steatosis, bile duct injury and siderosis was observed. However, there was a difference in the presence of lymphoid aggregates, which were less frequent in the renal transplant group (p < 0.001). In conclusion, the characteristics of hepatitis C in renal transplant patients differ from that observed in immunocompetent patients. In renal transplant patients, HCV infection is biochemically characterized by lower ALT levels and higher frequency of cholestasis. Regarding histology, despite lower frequency of lymphoid aggregates and less intense portal/periportal inflammatory infiltrate, a greater lobular damage was observed. The impact of these differences on the progression of fibrosis remains to be established.

Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney transplant recipients are scarce. There is little information concerning natural immunity acquired after acute HAV infection. In most renal transplant recipients, anti-HAV antibodies are not detectable after vaccination; it is reasonable to suppose that immunosuppressive therapy interferes with the immunity. The objective of this study was to evaluate, in an endemic area, the prevalence of anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in 40 HCV-positive renal transplant recipients. This group showed a 90% prevalence of previous HAV infection. These findings suggest that in an endemic area, the prevalence of previous HAV infection is high, even among immunosuppressed patients. HAV antibodies acquired after natural infection are detectable even after the onset of immunosuppressive therapy. These data should be considered when renal transplant recipients are considered for HAV vaccination. Prevaccination screening of renal transplant recipients must follow the same guidelines as those for immunocompetent subjects.

Background: Increased serum gamma-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.Methods: Patients with a liver biopsy presenting anti-HCV and HCV-RNA were evaluated. Age, gender, risk factors of transmission, serum alanine aminotransferase (ALT), GGT and alkaline phosphatase (ALP) levels and histological features were assessed in all. Data were analyzed statistically by the chi(2) test and multivariate logistic regression analysis.Results: Among 201 patients studied, elevated GGT levels and bile duct damage were observed in 48% and 35% of them, respectively. No association was seen between GGT level and bile duct damage or between GGT level and hepatic steatosis. Inititally, age >40 years (P=0.007), elevated ALT (P=0.01), grading of inflammatory activity (P=0.004) and staging of fibrosis (P<0.001) were found to be associated with elevated GGT levels. After multivariate regression analysis, histology grading 3 and 4 inflammation activity (P=0.01) and staging 3 and 4 fibrosis (P=0.01) remained independently associated with elevated GGT level.Conclusions: A significant number of patients with chronic HCV infection had elevated serum GGT levels. Furthermore, this enzyme seemed to be useful as an indirect marker of more advanced liver disease in chronic hepatitis C. (C) 2004 Blackwell Publishing Asia Pty Ltd.

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.

The objectives of the present study were to assess the in vitro-induced anti-hepatitis C virus (HCV) antibody production (IVIAP) in relation to the clinical, biochemical, virologic and histologic variables of patients with HCV infection. The study included 57 patients (60% males) with HCV infection (anti-HCV and HCV-RNA positive). Alanine aminotransferase (ALT) was elevated in 89% of the patients. Mean viral load was 542,241 copies/ml and histology of the liver showed chronic hepatitis in 27/52 (52%) and cirrhosis in 11/52 (21%) patients. IVIAP levels were determined by immunoenzymatic assay at median absorbance of 0.781 at 450 nm. IVIAP was negative in 14% of the patients. When groups with IVIAP levels above and below the median were compared, high IVIAP levels were associated with the male sex, elevated ALT levels and more advanced disease stage. After logistic regression analysis, advanced histologic damage to the liver remained as the only independent variable associated with elevated IVIAP levels. Using a receiver operator characteristic curve, the best cut-off level for IVIAP was established (= 1.540), with 71% sensitivity and 94% specificity for the detection of more advanced disease stages (grades 3 and 4). These findings are consistent with the participation of immunological mechanisms in the genesis of the hepatic lesions induced by HCV and indicate that the IVIAP test may be useful as a noninvasive marker of liver damage either alone or in combination with other markers.

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95%) sera from patients in the study group and negative in 38 of the 39 (97%) sera from those in the control group, showing an accuracy of 96%. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.

Problem: HCV infection, alone or in combination with other factors, may be responsible for clonal B-cell expansion underlying systemic manifestations of mixed cryoglobulinemia (MC), and may explain the appearance of a malignant NHL in some subjects. Methods: We reported two cases of primary splenic B-cell NHL associated with HCV infection, without any evidence of MC preceding lymphoproliferative disease. Both patients were male, 44 and 40 year-old, respectively, at the time of malignancy diagnosis. Results: They went to a diagnostic splenectomy and were treated with classic chemotherapy schedules. During treatment, they had flare-up aminotransferases. Conclusion: We, as other authors, suggested that HCV infection must be searched in all patients with isolated splenic lymphoma, even in the absence of MC, and that patients with chronic HCV infection should be frequently monitored for the development of splenic NHL.

In order to determine the significance of anti-hepatitis C virus (anti-HCV) antibodies in blood donors, 46 consecutive asymptomatic individuals were recruited at the blood bank of Hospital São Paulo, São Paulo, Brazil. They were submitted to an interview to collect epidemiological data and to clinical examination and blood samples were obtained for biochemical, serological and virological analysis. All patients were followed for a minimum period of six months and those with abnormal mean alanine aminotransferase (ALT) levels were submitted to a liver biopsy after giving informed consent. Hepatitis C virus RNA (HCVRNA) was detected by the polymerase chain reaction (PCR) in 22/47 (47.8%) patients and this finding was associated with parenteral risk factors (P = 0.03) and ethanol abuse (P = 0.03). HCVRNA positivity was also associated with abnormal levels of ALT (P < 0.001) and gamma-glutamyl transpeptidase (gamma-GT) (P = 0.01). Abnormal ALT levels were good marker of viremia, with 86.4% sensitivity and 79.2% specificity. Twenty-three patients with elevated mean ALT levels were submitted to a liver biopsy and histopathological changes were observed in 17 of them (73.9%). HCVRNA positivity was associated with severe forms of hepatic disease (chronic hepatitis and cirrhosis). These results indicate the need for a judicious evaluation of all anti-HCV-positive blood donors, including clinical examination, biochemical tests and liver histology when ALT is persistently elevated.

The hepatitis B virus (HBV) can be transmitted in the dialysis setting through blood transfusions and environmental surfaces. Transfusion related hepatitis C virus (HCV) infection is very well known, but only recently the environmental transmission of this virus was postulated, In order to study the prevalence, mechanisms of transmission, and the ALT patterns of HBV and HCV infections in hemodialysis and CAPD patients before the implementation of HBV vaccination and HCV screening in the blood bank, we conducted a study from January 1987 to January 1990, Sera from 185 hemodialysis and 124 CAPD patients were stored in this period and later analyzed for HBsAg, anti-HBc, anti-HBs, and anti-HCV (second generation ELISA). The prevalence of any HBV marker was 55.7% (103/185) for hemodialysis patients and 31.5% (39/124) for CAPD patients (hemodialysis vs. CAPD, p < 0.001). The prevalence of positive anti-HCV was 35.1% (65/185) for hemodialysis and 33.9% (42/124) for CAPD patients (not significant). There was a significant association between HBV markers positivity and anti-HCV positivity. The multivariate analysis of risk factors revealed an association of the positivity of each virus with the duration of renal replacement therapy (RRT), number of previous blood transfusions, and past history of hemodialysis treatment. Thus, besides the transfusion-related transmission, hemodialysis environmental transmission may also occur for both viruses. The findings of a high prevalence of both viruses and evidence for environmental transmission in the dialysis setting are of major importance for the planning of future preventive measures.

Hepatitis B virus (HBV) serum markers (HBsAg, anti-HBs, anti-HBc) and antihepatitis C antibody (anti-HCV) were prospectively followed in haemodialysis and CAPD patients. From January 1987 to January 1990, 185 patients on haemodialysis and 124 on CAPD were analysed. Among patients susceptible to HBV (69 on haemodialysis and 70 on CAPD), there were 17 HBsAg seroconversions on haemodialysis (0.19/patient-year) and 1 on CAPD (0.01/patient-year). A Cox proportional hazards model showed that haemodialysis treatment was the only risk factor significantly associated with HBV infection, thus suggesting transmission through the environment. Regarding hepatitis C, 83 anti-HCV-negative patients on haemodialysis and 46 on CAPD were followed. There were 18 seroconversions on haemodialysis (0.15/patient-year) and two seroconversions on CAPD (0.03/patient-year). Haemodialysis treatment was also the only risk factor significantly associated with a higher risk of HCV infection. The hazard ratio for HCV infection in haemodialysis patients was 5.7 compared to CAPD patients. Nevertheless, for one patient on CAPD treatment transfusions were the only possible source of HCV infection. In conclusion, both viruses were transmitted mainly through the haemodialysis environment, but the role of transfusions could not be excluded.