HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR >= F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 +/- 0.081 (0.909, when adjusted by DANA). Values < 4.0 of TX-3 showed a NPV of 97% and scores > 9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 +/- 0.053 vs 0.762 +/- 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.

Objective. Hepatitis C is highly prevalent among kidney transplant (KT) recipients. In this population, the natural history of hepatitis C virus (HCV) infection and its proper management remains controversial. The invasiveness of the procedure and the interpretation variability of liver biopsy limit its use in these patients. We sought to evaluate the performance of YKL-40 and HA as markers of liver fibrosis in KT patients with HCV infection. Material and methods. This cross-sectional study included HCV infected KT individuals. Univariate analysis was used to identify variables associated with significant fibrosis (METAVIR >= F2). The diagnostic values of the YKL-40 and HA were compared using receiver operating characteristic (ROC) curves. Results. Eighty-five patients were included (60% males, mean age 44.9 +/- 9.4 years). Significant fibrosis was observed in 14 patients (17%). When compared to F0/F1 individuals, patients with significant fibrosis were older, showed a higher time since transplantation, and higher prevalence of diabetes. No difference was observed in YKL-40 levels between the groups. Significantly higher levels of HA were noted in METAVIR >= F2 subjects (108 vs. 37 ng/ml, p = 0.002). The AUROCs of YKL-40 and HA for predicting significant fibrosis were 0.615 and 0.765, respectively (p = 0.144). Levels of YKL-40 < 105 ng/ml and of HA < 27 ng/ml showed a NPV of 36% and 96%, respectively. YKL-40 >= 418 ng/ml and HA >= 120 ng/ml exhibited a PPV of 31% and 39%, respectively. Conclusions. Increased serum levels of HA but not of YKL-40 were associated with more advanced stages of liver fibrosis in KT HCV-infected patients.

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.

Primary hepatic carcinosarcoma is a rare malignant hepatic tumor containing both carcinomatous and sarcomatous elements. A 40-year-old man referred to our liver transplant team because of hepatic cirrhosis was on the waiting list, having undergone all liver tests, ultrasonography, and with normal serum alpha fetoprotein markers every 6 months to search for a tumor. He underwent a liver transplantation without complication. The pathologic findings of the original liver indicated carcinosarcoma. We have reviewed the literature on this subject.

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.

05D. Viral Hepatitis' (d) Hepatitis B Clinical Except therapyS169 them were concomitantly anti-HBs-positive (>10 IU/1).These pts were compared with a control group of 123 newly HBsAg-positive diagnosed pts.HBsAg-encoding region was amplified then directly sequenced with in-house protocols.Results: The 14 HBsAg+/HBsAb+ pts had a median age of 60 years (range, 25 87), 8 were male.Mean titers of HBsAb were 41 IU/1 (15 189).In 4/12 (33%) cases, HBsAb were <10 IU/1 with another diagnosis assay (Vidas BioM6rieux).HBsAg and HBsAb both persisted >2 months in 6/8 pts.Immunosuppression concerned 9/14 (64%) pts (kidney transplant (n 4), AIDS (2), prolonged corticotherapy (1), chemotherapy (1), myelodysplasia (1)).Prothrombin time <80% was observed in three pts suggesting advanced fibrosis.Two other pts were scored F3 (Metavir).HBV DNA was <500 copies/ml in 4/14 (29%) pts and >5 logl0 in 8 pts (57%).HBV pol sequences were obtained from 12/14 (86%) pts (41% in the control group; p 0.004).HBV genotypes were D for 7 pts (58%).Non-A genotypes were significantly more frequent vs control (91% vs 51%, p=0.043).HBsAg major hydrophilic region (MHR) showed 31 mutation in HBV from 12 pts (mean 4 vs 1 for controls).Twentytwo positions harbored mutations; T125MA, P127T/L, G145R (33% of sequences each) were the most frequent.Mutations at positions 125, 144, 165 and the G145R were significantly more frequent in HBsAg+/HBsAb+ pts vs controls (p <0.05).In one patient with high HBV-DNA levels, HBsAg (carrying P120L, P142L, D144E and G145R) was not detected using another diagnosis assay (Vidas BioM6rieux).Conclusions: HBsAb co-existence was not rare in HBsAg-positive pts in our cohort, and was associated with immunosuppression, HBV replication, non-A HBV genotypes, and a high frequency of HBsAg mutations.In these pts, HBsAg detection assays might fail to diagnose HBV chronic infection.

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-alpha (IFN-alpha) in HCV-infected ESRD patients on dialysis. Methods: Forty-six HCV-RNA-positive ESRD patients were studied. IFN-alpha regimen consisted of 3 million units three times a week for 12 months, and the patients were followed up for 6 months. End-of-treatment, and sustained biochemical and virological responses were evaluated and tolerance was assessed monthly. Results: A sustained virological response (SVR) was observed in 10/46 patients (22%) and in 10/29 who completed the treatment (34%). Alanine aminotransferase was elevated in 63% of the patients at the beginning of the study and returned to normal levels within the first month in all patients with SVR. Treatment was discontinued because of side effects in 11/46 patients (24%) and six patients (13%) were lost to follow-up. Conclusions: IFN-alpha monotherapy for hepatitis C in dialysis patients shows a high frequency of adverse effects. However, the SVR is high (34%) in patients who complete treatment, emphasizing the importance of careful selection and close follow-up in order to minimize and control possible side effects.

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.

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

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.

OBJECTIVE:The aim of our study was to evaluate the role of magnetic resonance cholangiography (MRC) in the diagnosis of biliary tract complications (BC) after orthotopic liver transplantation (OLT).MATERIALS AND METHODS:Among 21 OLT patients who underwent routine follow-up MRC using a breath-hold T2-weighted turbo spin-echo sequence with half-Fourier acquisition (HASTE), 5 had an elevated serum alkaline phosphatase level. Diagnostic confirmation was obtained with endoscopic retrograde cholangiography (ERC) (n = 11), surgery (n = 3), or clinical and laboratory follow-up of at least 1 year (n = 8).RESULTS:In 13 patients, no abnormality of the biliary tract was detected using MRC. In 8 patients, anastomotic strictures were diagnosed, 7 of which were confirmed at surgery or using ERC. One patient with normal findings at MRC and abnormal liver function test results was found to have a stricture at ERC. All patients with normal MRC and liver function tests had 1 year of uneventful follow-up and were considered true-negative cases. We found that MRC had 87.5% sensitivity, 92.3% specificity, 87.5% positive predictive value, 92.3% negative predictive value, and 90.4% accuracy for the diagnosis of BC.CONCLUSION:MRC is a valuable examination to detect BC after OLT. It provides useful information for planning interventional procedures.