[Show abstract][Hide abstract] ABSTRACT: In 2011 direct-acting antivirals, including telaprevir, have been developed to achieve a better antiviral effect. It was reported that telaprevir is a substrate of P-glycoprotein (ABCB1) and cytochrome P450 3A4. The aim of this retrospective study was the evaluation of the influence of some single nucleotide polymorphisms (SNPs) of genes (ABCB1, SLC28A2/3, SLC29A1) involved in TLV and RBV transport and their correlation with plasma TLV drug exposure at 1 month of therapy. We also investigated the association of a SNP in ABCB11 gene, whose role in TLV transport was not yet shown. Twenty-nine HCV-1 patients treated with telaprevir, ribavirin and pegylated-interferon-α were retrospectively analyzed; allelic discrimination was performed by real-time PCR. Telaprevir Ctrough levels were influenced by Metavir score (P = 0.023), ABCB1 2677 G>T (P = 0.006), ABCB1 1236 C>T (P = 0.015) and ABCB11 1131 T>C (P = 0.033) SNPs. Regarding ABCB1 3435 C>T, a not statistically significant trend in telaprevir plasma concentration was observed. Metavir score (P = 0.002, OR –336; 95% CI –535;–138), ABCB1 2677 (P = 0.020, OR 497; 95% CI 86; 910), ABCB11 1131 (P = 0.002, OR 641; 95% CI 259;1023) and CNT2 -146 (P = 0.006, OR –426; 95% CI –721;–132) were able to predict telaprevir plasma levels in the regression analysis. Other SNPs showed no association. This study reveals BSEP implication in telaprevir transport and confirms the involvement and influence of P-glycoprotein on telaprevir plasma levels. To date, no similar data concerning pharmacogenetics and pharmacokinetics were published, but further studies in different and bigger cohorts are needed.
[Show abstract][Hide abstract] ABSTRACT: Abstract Background. The clinical pictures of functional gastrointestinal disorders and inflammatory diseases can be quite similar leading to inappropriate and expensive investigations. Objective. To investigate fecal calprotectin (FC) diagnostic performance in different gastrointestinal conditions. Material and methods. Stool specimens of 66 outpatients referred for colonoscopy were collected for further FC determination. Diagnostic accuracy was assessed by the area under the curve (AUC). Sensitivity (Se), specificity (Sp), positive (PPV), and negative predictive values (NPV) were calculated according to the presence of inflammation and the main final diagnosis. Results. Histological inflammation was found in 45 (68%) patients: 24 had a diagnosis of inflammatory bowel disease (IBD) while 21 reported miscellaneous conditions (5 microscopic colitis, 2 eosinophilic colitis, and 14 nonspecific chronic colitis). The diagnosis in the 21 (32%) patients without inflammation was irritable bowel syndrome (IBS). Median FC values were 268 µg/g (95% CI, 151-343) and 49 µg/g (95% CI, 23-101) in patients with and without inflammation, respectively (p = 0.0001). AUC value of FC was 0.811 (Se = 68.9%, Sp = 71.4%, PPV = 83.8%, and NPV = 56.3% with a cutoff value of 100 µg/g) for discriminating between patients with and without inflammation and 0.931 (Se = 87.5%, Sp = 90.5%, PPV = 91.3%, and NPV = 86.4% with a cutoff value of 150 µg/g) for discriminating between patients with IBS and IBD. Using the cutoff value recommended by the manufacturer (50 µg/g), we found Se =100%, Sp =52.4%, PPV =70.6%, and NPV =100% for the diagnosis of IBD. Conclusions. FC appears to be a reliable noninvasive biomarker of intestinal inflammation useful to improve the appropriateness of colonoscopy requests.
Scandinavian journal of gastroenterology. 11/2014;
[Show abstract][Hide abstract] ABSTRACT: Currently, there are several drugs approved for the treatment of chronic hepatitis B including recombinant interferons, such as Interferon--α and its pegylated formulation, and the nucleos(t)ide analogues, such as Lamivudine, Adefovir, Telbivudine, Entecavir and Tenofovir. Pegylated--Interferon is an immune--modulatory agent that works mainly by enhancing the innate immune response while nucleos(t)ide analogues are oral drugs with direct inhibition of viral replication. Each agent has its own advantages and drawbacks. Pegylated--Interferon treatment has a finite duration without induction of drug resistance but only a limited number of patients achieve a sustained virological response to therapy. On the other hand, the care with nucleos(t)ide analogues requires a long--term treatment with a potential risk of induction of drug resistance, but higher rates of viral replication suppression are achieved. Nevertheless, second generation nucleos(t)ide analogues, such as Entecavir and Tenofovir, have both high genetic barrier to resistance and potent antiviral action. This review describes the mechanisms of antiviral activity and the efficacy of viral suppression of the different available drugs for chronic hepatitis B treatment, considering the recent clinical guidelines for an optimal management of chronic HBV infection.
Minerva gastroenterologica e dietologica. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: Background and AimChronic hepatitis C (CHC) has been associated with lymphoproliferaitive disorders (LPD) such as mixed cryoglobulinemia syndrome (MCS), monoclonal gammopathy of undetermined significance (MGUS) and B-cell non-Hodgkin lymphoma (B-NHL). The aim of the present study is to assess MCS, MGUS and B-NHL prevalence in a cohort of CHC infected patients and to evaluate the association of demographic, clinical and virologic factors with the presence of LPDs.MethodsA total of 121 CHC patients with LPDs (50M, 71F; mean age 61.5 ± 11.8) and 130 CHC patients without extra-hepatic manifestations (60M, 70F; mean age 60.4 ± 9.2) were retrospectively enrolled from a cohort of 1313 CHC patients between January 2006 and December 2013. Patients with LPDs included: 25 patients with MCS (9M, 16F; mean age 60.2 ± 1.4), 55 patients with MGUS (18M, 37F; mean age 61.3 ± 12.1) and 41 patients with B-NHL (23M, 18F; mean age 62.5 ± 11.0)ResultsPatients with MCS (25/1313; 1.9%), MGUS (55/1313; 4.2%) and B-LNH (41/1313; 3.1%) did not differ in age, severity of liver disease, HCV genotype and response to antiviral therapy. Using multivariate logistic regression analysis, a positive association was found between the presence of cirrhosis and MGUS (OR=2.8924, 95%CI 1.2693-6.5909; p=0.012) and between cirrhosis and B-NHL (OR=3.9407, 95%CI 1.7226-9.0153; p=0.001), while no association with MCS diagnosis emerged.Conclusions
Despite the pathogenetic mechanism of HCV-associated LPDs is still unclear, cirrhosis is an additional risk factor for the development of lymphoproliferative disorders in patients with chronic HCV infection.
Journal of Gastroenterology and Hepatology 10/2014; · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
World journal of gastroenterology : WJG. 09/2014; 20(36):13146-52.
[Show abstract][Hide abstract] ABSTRACT: Occult hepatitis B virus infection is defined as detectable HBV-DNA in liver of HBsAg-negative individuals, with or without detectable serum HBV-DNA. In deceased liver donors, results of tissue analysis cannot be obtained prior to allocation for liver transplantation.
[Show abstract][Hide abstract] ABSTRACT: The standard-of-care for the treatment of genotype-1 chronic hepatitis C is based on the combination of direct acting antivirals, such as boceprevir and telaprevir, with ribavirin and pegylated-interferon alfa. These triple regimens give a higher response rate than dual therapy, but on the other hand show a more than 10% higher rate of anaemia. Not enough focus has been given to the interaction between telaprevir and RBV. In this work, we aimed to study and deepen this relationship by comparing ribavirin plasma and intra-erythrocytic concentrations at one month of triple and dual therapy (17 vs. 119 patients). Moreover, we determined telaprevir isomers concentrations and tested them for correlation with ribavirin concentrations and haemoglobin loss at one month of treatment. Finally, all drugs concentration data were tested for their correlation with the renal function during treatment. The comparisons of ribavirin concentration and toxicity data were repeated on a sub-group of 9 patients who had been treated 1 year before with dual therapy and then re-treated with triple therapy. The observed ribavirin plasma and intra-erythrocytic concentrations in triple therapy were significantly higher compared to dual therapy, both in whole group and sub-group comparison. Ribavirin concentrations were significantly correlated to the haemoglobin loss and telaprevir-S isomer concentrations (r(2)=0.317 Pvalue=0.023 and r(2)=0.388 Pvalue=0.008, respectively). Renal function had a significant decrease from the baseline value, but was not significantly correlated with drugs concentrations. These results highlight for the first time that, in the context of triple therapy with telaprevir, ribavirin exposure is related to the telaprevir-S isomer plasma concentration. We conclude that the addition of telaprevir to the dual therapy increases ribavirin exposure and haemoglobin loss: this effect could probably be managed through the therapeutic drug monitoring of ribavirin and telaprevir-S concentrations.
[Show abstract][Hide abstract] ABSTRACT: Recent technologic innovations allow for quantitative assessment of hepatitis B surface antigen (HBsAg) levels in serum; this has been used to monitor the course of chronic HBV hepatitis (CHB) and predict treatment response. LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest immunoassay CE approved to quantify HBsAg.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2014; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The management of patients with chronic liver disease (CLD) requires an accurate definition of the staging and grading, as the is latter related to the progression of liver fibrosis. Albeit liver biopsy (LB) is an invasive procedure with possible complications, it is currently the "gold standard" for the assessment of hepatic fibrosis. Over the past decade, several non-invasive approaches have been proposed as surrogates in the evaluation of liver fibrosis. These include serum direct and indirect markers of fibrosis linked, respectively, to fibrogenesis and hepatic function, and instrumental techniques, which measure liver stiffness, a parameter directly correlated to liver fibrosis. Although accuracy of non-invasive methods was initially investigated in chronic hepatitis C, there is now increasing literature referred to their application in other CLD. While in specific settings, there is still need for LB, non-invasive methods have an increasing and crucial role in clinical practice to monitor fibrosis progression in patients with CLD. The aim of this review is to present the current status of knowledge in this new exciting field and to highlight the key-messages useful for clinicians.
Polskie archiwum medycyny wewnȩtrznej 04/2014; 124(6):329-35. · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Annals of hepatology: official journal of the Mexican Association of Hepatology 01/2014; 13(1):91-7. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Recent technologic innovations allow for quantitative assessment of hepatitis B surface antigen (HBsAg) levels in serum; this has been used to monitor the course of chronic HBV hepatitis (CHB) and predict treatment response. LIAISON-XL Murex HBsAg Quant assay (DiaSorin, Saluggia, I) is the newest immunoassay CE approved to quantify HBsAg.
To compare LIAISON-XL performances with ARCHITECT-QT HBsAg (Abbott Diagnostics, IL, US), as reference test.
Study design: Sequential serum samples (n = 152) from 14 HBe-negative patients with CHB, the majority of them infected by HBV genotype D undergoing antiviral treatment, were retrospectively tested with both assays. The 2nd WHO Standard 00/588 for HBsAg was used as reference.
LIAISON-XL and ARCHITECT-QT correlated by r = 0.95, p < 0.0001; by Bland-Altman analysis agreement of mean difference was 0.21 ± 0.15 log10 IU/mL, 95% CI: −0.07-0.5). Performance of LIAISON-XL against the 2nd WHO standard was r = 0.998, p < 0.0001 (95% CI: 0.993-0.999) with results nearer to the expected WHO values compared to ARCHITECT-QT. Median baseline HBsAg level was similar with the two methods before antiviral treatment, throughout fluctuations of HBsAg level in treatment non-responders and during the decrease of HBsAg titer in treatment responders. Correlation between HBsAg levels and HBV DNA was statistically significant for both the two immunoassays (LIAISON-XL: r = 0.4988, 95%CI: 0.3452-0.6264, p < 0.0001; ARCHITECT-QT: r= 0.480, 95%CI: 0.3233-0.6111, p < 0.0001).
Correlation between HBsAg measurement with LIAISON-XL and ARCHITECT-QT was high. LIAISON-XL accurately quantified HBsAg in clinical samples at baseline or during antiviral therapy; it can be applied for HBsAg quantification in clinical practice and decision making in CHB.
[Show abstract][Hide abstract] ABSTRACT: Background
Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon + ribavirin therapy.
In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response. The model was then validated in 423 patients (validation cohort).
In the derivation cohort, 257 achieved rapid virological response and 818 did not, with sustained virological response rates of 80.2% and 25.4%, respectively; interleukin-28B polymorphisms, fibrosis staging, gamma-glutamyl transferase, and viral load predicted sustained virological response. Assuming a <30% sustained virological response probability for not recommending Peg-interferon + ribavirin, 100 patients (25.6%) in the validation cohort were predicted a priori to fail this regimen. Assuming a ≥80% sustained virological response probability as a threshold to continue with Peg-interferon + ribavirin, 61 patients were predicted to obtain sustained virological response, and 55 of them (90.2%) eventually did.
This model uses easily determined variables for a personalized estimate of the probability of sustained virological response with Peg-interferon + ribavirin, allowing to identify patients who may benefit from conventional therapy.