non invasive methods for the assessment of hepatic fibrosis transient elastography hyaluronic acid 13c aminopyrine breath test and cytokeratin 18 fragment

Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage. Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test ( 13 C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score. Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve. Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4. Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution

IL28Bpolymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients

AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response. METHODS: A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response. RESULTS: Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G*)/rs1297860(**) in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis. CONCLUSION: Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness

Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

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Non-invasive methods for the assessment of hepatic fibrosis: transient elastography, hyaluronic acid, 13C-aminopyrine breath test and cytokeratin 18 fragment

Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage.Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test (13C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score.Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve.Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4.Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution

Evaluation of polyomavirus BK reactivation in lupus patients who underwent kidney transplantation

Background. A pathogenic role for polyomavirus BK in systemic lupus erythematosus (SLE) has been proposed, however no study evaluated the occurrence of BK replication in renal transplant recipients according to the underlying disease leading to transplantation and its potential impact. Methods. The occurrence of BK reactivation was serially evaluated in 468 renal transplant recipients, including 11 patients with SLE as underlying disease (overall, 2370 serum and 2370 urine specimens; 65 from SLE patients). Results. Considering the overall occurrence of viral reactivation (viremia and/or viruria), 26/65 (40%) specimens were positive in four SLE patients (36.3%) versus 331/2143 (15.4%) in 130/227 (57.3%) non-SLE patients. A patient transplanted for class III lupus nephritis evidenced sustained BK viremia and viruria (with viremia values potentially indicative of polyomavirus-associated nephropathy) in the absence of clinical features of renal dysfunction or recurrence of lupus nephritis. Conclusions. Further studies on larger populations and for a longer follow-up should be required to evaluate the impact of BKV reactivation in renal transplant patients with SLE as underlying disease, as well as the potential therapeutic implications

Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN), possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens): in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0%) and 12 (2.0%) specimens from 40 (11.0%) and 11 (10.4%) patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2%) and 58 (9.8%) specimens from 67 (18.5%) and 27 (25.5%) patients, being the difference of incidence highly significant (p &lt;0.0001) for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation

Anticorpi non-organo-specifici e infezione da BKV in una popolazione di trapiantati renali

Following primary infection, the polyomavirus BK remains latent in the urinary tract e peripheral blood cells. Reactivation may occur spontaneously in healthy subjects and in immunocompromised conditions. BKV reactivation may determine urinary shedding of infected urothelial cells, hemorrhagic cystitis (particularly in bone marrow transplant recipients), and nephropathy in kidney graft recipients. Moreover, a possible role for BKV in the pathogenesis of systemic lupus erythematosus (SLE) has been hypothesised. SLE is characterised by production of autoantibodies, in particular anti-double stranded (ds)-DNA antibodies. The induction of anti-dsDNA antibodies by BKV has been described in experimental animals and during naturally acquired infection in man. Therefore, it has been proposed that the BKV large T-antigen-chromatin complex may function as a hapten-carrier model with subsequent production of anti-dsDNA antibodies.Aim of this study was to evaluate the relation between BKV and autoimmunity in renal transplant recipients by determining the prevalence of non-organ-specific antibodies (NOSA) by indirect immunofluorescence on serum samples obtained from 95 renal transplant recipients during post-transplantation follow-up. BKV infection was evaluated by competitive-quantitative PCR. NOSA were present in 25/95 patients: 18 ANA and 6 SMA, one patient both ANA and SMA. BKV-DNA was positive in 16/95 patients: 3 NOSA-positive and 13 negative. BKV-DNA was negative in 79/95 patients: 22 NOSApositive and 57 negative. The prevalence of NOSA did not differ between BKV-DNA positive and negative patients. It does not seem to exist a relation between BKV and NOSA in renal transplant recipients