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1.
Rev Med Interne ; 44(10): 555-560, 2023 Oct.
Article in French | MEDLINE | ID: mdl-37597973

ABSTRACT

Chronic elevation of transaminases is recurring issue in primary care. This article aims to be practical. It offers a quick reminder of epidemiology, pathophysiology, concept of normal values of transaminases, main causes (alcohol, fatty liver disease, viral hepatitis) and first-line assessment. Then, we will go further in less frequent causes, extra-hepatic causes and additional tests. We will precise what is the role of general practitioner in this care pathway and when to address patient to specialist.

2.
Aliment Pharmacol Ther ; 47(12): 1682-1689, 2018 06.
Article in English | MEDLINE | ID: mdl-29665081

ABSTRACT

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.


Subject(s)
Hepatitis C/drug therapy , Kidney/pathology , Liver Transplantation/methods , Sofosbuvir/administration & dosage , Aged , Cohort Studies , Creatinine/blood , Female , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Humans , Longitudinal Studies , Middle Aged , Prospective Studies , Recurrence , Renal Insufficiency, Chronic/epidemiology , Ribavirin/administration & dosage , Sofosbuvir/adverse effects
3.
Aliment Pharmacol Ther ; 47(7): 989-1000, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29446106

ABSTRACT

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.


Subject(s)
Elasticity Imaging Techniques/methods , Liver Cirrhosis/diagnosis , Liver/diagnostic imaging , Adult , Biopsy , Elasticity , Female , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Cirrhosis/physiopathology , Liver Function Tests/methods , Liver Function Tests/standards , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , Retrospective Studies , Sensitivity and Specificity
4.
Aliment Pharmacol Ther ; 46(11-12): 1054-1060, 2017 12.
Article in English | MEDLINE | ID: mdl-28994127

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C/epidemiology , Liver Cirrhosis/epidemiology , Adult , Aged , Cohort Studies , Coinfection/virology , Female , Hepatitis B/pathology , Hepatitis C/pathology , Hepatitis C Antibodies , Humans , Liver Cirrhosis/pathology , Male , Middle Aged
5.
Aliment Pharmacol Ther ; 46(6): 617-627, 2017 09.
Article in English | MEDLINE | ID: mdl-28752524

ABSTRACT

BACKGROUND: The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. AIM: To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. METHODS: We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. RESULTS: LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. CONCLUSION: The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD.


Subject(s)
Liver Cirrhosis/diagnosis , Non-alcoholic Fatty Liver Disease/diagnosis , Adult , Aged , Algorithms , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , Sensitivity and Specificity
6.
Aliment Pharmacol Ther ; 45(7): 991-1003, 2017 04.
Article in English | MEDLINE | ID: mdl-28164327

ABSTRACT

BACKGROUND: In chronic hepatitis C, the European Association for the Study of the Liver and the Asociacion Latinoamericana para el Estudio del Higado recommend performing transient elastography plus a blood test to diagnose significant fibrosis; test concordance confirms the diagnosis. AIM: To validate this rule and improve it by combining a blood test, FibroMeter (virus second generation, Echosens, Paris, France) and transient elastography (constitutive tests) into a single combined test, as suggested by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. METHODS: A total of 1199 patients were included in an exploratory set (HCV, n = 679) or in two validation sets (HCV ± HIV, HBV, n = 520). Accuracy was mainly evaluated by correct diagnosis rate for severe fibrosis (pathological Metavir F ≥ 3, primary outcome) by classical test scores or a fibrosis classification, reflecting Metavir staging, as a function of test concordance. RESULTS: Score accuracy: there were no significant differences between the blood test (75.7%), elastography (79.1%) and the combined test (79.4%) (P = 0.066); the score accuracy of each test was significantly (P < 0.001) decreased in discordant vs. concordant tests. Classification accuracy: combined test accuracy (91.7%) was significantly (P < 0.001) increased vs. the blood test (84.1%) and elastography (88.2%); accuracy of each constitutive test was significantly (P < 0.001) decreased in discordant vs. concordant tests but not with combined test: 89.0 vs. 92.7% (P = 0.118). Multivariate analysis for accuracy showed an interaction between concordance and fibrosis level: in the 1% of patients with full classification discordance and severe fibrosis, non-invasive tests were unreliable. The advantage of combined test classification was confirmed in the validation sets. CONCLUSIONS: The concordance recommendation is validated. A combined test, expressed in classification instead of score, improves this rule and validates the recommendation of a combined test, avoiding 99% of biopsies, and offering precise staging.


Subject(s)
Hepatitis C, Chronic/diagnosis , Liver Cirrhosis/diagnosis , Adult , Aged , Elasticity Imaging Techniques , Female , Hematologic Tests , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/diagnostic imaging , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/diagnostic imaging , Male , Middle Aged
7.
Int J Impot Res ; 28(2): 68-73, 2016.
Article in English | MEDLINE | ID: mdl-26865102

ABSTRACT

Chronic hepatitis C (CHC) patients often have altered quality of life. Few data are available about sexual impairment (SI) in CHC. From 2011 to 2013, we included consecutive CHC outpatients. Exclusion criteria were: antiviral therapy, co-infection, age <18 or >75, transplantation, alcohol consumption, Eastern Cooperative Oncology Group >1. Non-CHC subjects were healthy blood donors. Sexual questionnaires for men and women were adapted from the International Index of Erectile Function and Female Sexual Function Index, respectively, and concerned the past 30 days. Two hundred eighty-one patients were compared with 1086 blood donors. SI was more frequent in CHC patients. Men with CHC had worse desire, confidence, erections, climax and satisfaction (P<0.001). Women with CHC had worse desire, arousal, climax, satisfaction, lubrication and comfort (P<0.001). In multivariate analysis, factors associated with SI in men were CHC (odds ratio (OR)=4.45, 95% confidence interval (CI) 2.46-8.06), age (OR=1.06, 95% CI 1.03-1.09), no intercourse (OR=8.74, 95% CI 4.65-16.04) and unemployment (OR=2.14, 95% CI 1.16-3.95). Factors associated with a worse global sexual life in women were CHC (OR=7.96, 95% CI 4.07-15.58) and no intercourse (OR=21.39, 95% CI 11.03-41.48). The study results were corroborated by propensity score-matching analysis. Sexual life is impaired in men and women with CHC. In clinical practice, sexual quality of life should be evaluated and treated.


Subject(s)
Hepatitis C, Chronic/psychology , Sexuality/psychology , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Female , Hepatitis C, Chronic/physiopathology , Humans , Male , Middle Aged , Propensity Score , Quality of Life , Sexuality/physiology
8.
J Viral Hepat ; 22(12): 1002-10, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26216230

ABSTRACT

Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.


Subject(s)
Algorithms , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Oligopeptides/therapeutic use , Proline/analogs & derivatives , Antiviral Agents/therapeutic use , Drug Therapy, Combination , Female , Hepacivirus/drug effects , Humans , Interferon-alpha/therapeutic use , Liver Cirrhosis/virology , Male , Middle Aged , Models, Theoretical , Polyethylene Glycols/therapeutic use , Proline/therapeutic use , Random Allocation , Ribavirin/therapeutic use , Treatment Outcome , Viral Load/drug effects
9.
Transpl Infect Dis ; 15(6): E211-5, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24103101

ABSTRACT

Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis in immunocompromised patients. Some glomerular diseases were found to be associated with this infection. We report the first case, to our knowledge, of a kidney transplant recipient who developed an HEV infection and de novo membranous nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed upon positive polymerase chain reaction on plasma and stool samples, and renal allograft biopsy revealed de novo MN. Typical causes of MN were definitively excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount a sustained viral response that was rapidly followed by complete remission of the nephrotic syndrome. The chronology of the onset and remission of both diseases is highly suggestive of a causal relationship between hepatitis E and MN.


Subject(s)
Glomerulonephritis, Membranous/virology , Hepatitis E/complications , Kidney Transplantation , Hepatitis E/drug therapy , Humans , Male , Middle Aged
11.
Aliment Pharmacol Ther ; 37(10): 979-88, 2013 May.
Article in English | MEDLINE | ID: mdl-23557139

ABSTRACT

BACKGROUND: Liver stiffness and non-invasive tests predict overall survival in chronic hepatitis C. However, in patients chronically infected with hepatitis B virus (HBV), only the association between liver stiffness and the risk of hepatocellular carcinoma has been published. AIM: To evaluate the 5-year prognostic value of liver stiffness, non-invasive tests of liver fibrosis, and liver biopsy, to predict overall survival in chronic hepatitis B. METHODS: In a consecutive cohort, we prospectively assessed fibrosis, with liver stiffness, FibroTest, APRI, FIB-4 and liver biopsy (if indicated). We examined death and liver transplantation during a 5-year follow-up, and factors associated with overall survival. RESULTS: A total of 600 patients (men 64%, mean age 42 years, inactive carriers 36%) with chronic hepatitis B were included. At 5 years, 25 patients were dead (13 liver-related deaths) and four patients had liver transplantation. Overall survival was 94.1% and survival without liver-related death 96.3%. No liver-related death was observed in inactive carriers. Survival was significantly decreased in patients diagnosed with severe fibrosis, whatever the non-invasive method used (P < 0.0001), or liver biopsy (P = 0.02). Patients' prognosis decreased as liver stiffness and FibroTest increased. In multivariate analysis, FibroTest and liver stiffness had the highest hazard ratio with survival. The association persisted after adjustment on age, necro-inflammatory histological activity presumed by ActiTest and treatment. CONCLUSIONS: Liver stiffness measurement or FibroTest can predict survival in chronic HBV infection. Thus, these tools may help physicians to early assess prognosis and discuss specific treatments, such as liver transplantation.


Subject(s)
Elasticity Imaging Techniques , Hepatitis B, Chronic/mortality , Liver Cirrhosis/diagnosis , Liver/pathology , Adult , Biomarkers , Biopsy , DNA, Viral/analysis , Female , Hepatitis B Antigens/immunology , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/immunology , Humans , Liver Function Tests , Liver Transplantation , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Survival Rate , Time Factors
12.
J Viral Hepat ; 19(4): 244-53, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22404722

ABSTRACT

A novel controlled attenuation parameter (CAP) has been developed for Fibroscan(®) to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan(®) and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S(0) : steatosis in <10% of hepatocytes, S(1) : 11-33%, S(2) : 34-66% and S(3) : 67-100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross-validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10(-15) ) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75-0.84) for S ≥ S(1) , 0.86 (0.81-0.92) for S ≥ S(2) and 0.88 (0.73-1) S = S(3) . CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan(®) , in patients with CHC.


Subject(s)
Clinical Laboratory Techniques/methods , Fatty Liver/diagnosis , Fatty Liver/pathology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/pathology , Adult , Biopsy , Elasticity Imaging Techniques , Female , Humans , Liver/pathology , Male , Middle Aged , ROC Curve , Severity of Illness Index
13.
Aliment Pharmacol Ther ; 34(4): 462-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21671970

ABSTRACT

BACKGROUND: Faecal calprotectin is a reliable tool for predicting Crohn's disease (CD) relapse in patients with sustained remission. Prediction of relapse with faecal calprotectin has been less studied in patients with severe CD treated with anti-TNF. AIM: To identify an association between faecal calprotectin concentration and CD clinical relapse in patients achieving remission with infliximab (IFX). METHODS: From February 2007 to October 2008, consecutive patients with refractory luminal CD were prospectively included when they received three IFX infusions (5mg/kg at weeks 0, 2 and 6) followed by maintenance with an immunomodulator alone. Faecal calprotectin and C-reactive protein (CRP) were measured at entry and at week 14 (w14). RESULTS: Sixty-five patients (43W; median age: 30.4years) were included, and 50 (77%) were in clinical remission off steroids at w14; twenty-three of fifty (46%) experienced CD clinical relapse during the first year of follow-up. Median faecal calprotectin level at w14 was similar in patients with and without CD clinical relapse (200 and 150µg/g respectively). When considering two suggested faecal calprotectin cut-offs to predict CD relapse, sensitivities and specificities were 61% and 48% for 130µg/g, respectively, and 43% and 57% for 250µg/g. Neither faecal calprotectin nor CRP at baseline and at w14 could predict relapse even when CD location subgroup analysis was considered. CONCLUSION: In patients responding to an infliximab induction regimen, faecal calprotectin measurement at w14 cannot predict Crohn's disease clinical relapse at 1year.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Crohn Disease/diagnosis , Feces/chemistry , Gastrointestinal Agents/therapeutic use , Leukocyte L1 Antigen Complex/metabolism , Tumor Necrosis Factor-alpha/therapeutic use , Adolescent , Adult , Aged , Biomarkers/metabolism , Crohn Disease/drug therapy , Crohn Disease/metabolism , Female , Follow-Up Studies , Humans , Infliximab , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Recurrence , Regression Analysis , Time Factors , Young Adult
14.
Aliment Pharmacol Ther ; 33(4): 455-65, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21235598

ABSTRACT

BACKGROUND: Non invasive methods for fibrosis evaluation remain to be validated longitudinally in hepatitis B. AIM: To evaluate longitudinally transient elastography (TE) and biomarkers for liver fibrosis assessment and follow-up of hepatitis B virus (HBV) inactive carriers. METHODS: Three hundred and twenty-nine consecutive HBeAg-negative HBV patients (201 inactive carriers) who underwent TE, Fibrotest and aspartate to platelet ratio index (APRI) the same day were studied. RESULTS: TE (median 4.8 vs. 6.8 kPa, P < 0.0001), Fibrotest (0.16 vs. 0.35, P < 0.0001) and APRI values (0.28 vs. 0.43, P < 0.0001) were significantly lower in inactive carriers than in the remaining patients whereas they did not differ among inactive carriers according to HBV DNA levels. In 82 inactive carriers with repeated examinations, although differences were observed among individual patients, TE values did not differ significantly over time (median intra-patient changes at end of follow-up relative to baseline: -0.2 kPa, P = 0.12). Conversely, significant fluctuations were observed for Fibrotest (+0.03, P = 0.012) and APRI (-0.01, P < 0.05). Eleven inactive carriers (5.5%) had initial elevated TE values (>7.2 kPa) confirmed during follow-up in two with significant fibrosis (F2 and F3) on liver biopsy. CONCLUSION: Non-invasive tools, particularly TE, could be useful, in addition to HBV DNA and transaminase levels, for follow-up of HBV inactive carriers as well as better selection of patients who require a liver biopsy.


Subject(s)
Biomarkers/blood , Elasticity Imaging Techniques/methods , Hepatitis B/complications , Liver Cirrhosis/diagnosis , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Carrier State , Cross-Sectional Studies , Female , Hepatitis B/diagnostic imaging , Hepatitis B virus , Humans , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/physiopathology , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Severity of Illness Index , Statistics as Topic
15.
Aliment Pharmacol Ther ; 33(6): 714-21, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21235604

ABSTRACT

BACKGROUND: Mucosal healing has become a new therapeutic goal in Crohn's disease and can be achieved with azathioprine (AZA) or biologics. Methotrexate (MTX) is an effective drug for both the induction and maintenance of remission in Crohn's disease. However, mucosal healing with MTX has been poorly investigated. AIM: To assess the mucosal healing rate in patients with Crohn's disease with clinical response to MTX as compared with AZA or infliximab (IFX). METHODS: From October 2007 to May 2009, consecutive patients with Crohn's disease were prospectively enrolled into a single-centre study when they met the following criteria: previous identification of mucosal ulcerations with ileo-colonoscopy, clinical remission within at least 3 months with MTX, AZA or IFX monotherapy, usual indication for colonoscopy in Crohn's disease (dysplasia/cancer screening, suspected stenosis) excluding assessment for mucosal healing. Mucosal healing was defined as absence of mucosal ulceration in all segments. RESULTS: Fifty-one patients with Crohn's disease (38 female; median age: 42 years) were included: 18 receiving MTX, 18 AZA and 15 IFX. Mucosal healing was achieved in 2/18 (11%) with MTX, in 9/18 (50%) with AZA (P =0.011 vs. MTX) and in 9/15 (60%) with IFX (P=0.008 vs. MTX). CONCLUSION: In patients with Crohn's disease in sustained clinical remission, mucosal healing is less frequently achieved with MTX as compared with AZA or IFX.


Subject(s)
Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Azathioprine/therapeutic use , Colonoscopy , Crohn Disease/physiopathology , Epidemiologic Methods , Female , Humans , Infliximab , Intestinal Mucosa/physiopathology , Male , Middle Aged , Treatment Outcome , Wound Healing/drug effects , Young Adult
16.
Gastroenterol Clin Biol ; 34(6-7): 388-96, 2010.
Article in English | MEDLINE | ID: mdl-20580175

ABSTRACT

BACKGROUND: ActiTest (AT) is a biomarker of liver necro-inflammatory histological activity validated in patients with chronic hepatitis C (HCV). AIM: The aim was to assess the accuracy of AT in comparison with alanine aminotransferase (ALT) the standard of care. METHODS: Methods used an integrated database of individual data and the new recommended Obuchowski measures. An updated "classical" meta-analysis of AT validation studies was also performed. The main end points were the area under the ROC curves (AUROCs) for the diagnosis of each histological activity grade defined using METAVIR scoring system. To avoid repeated tests and the spectrum effect of activity grades prevalence, the comparison of AT and ALT accuracies used the Obuchowski method. RESULTS: For the individual analysis, a total of 1250 patients were included and for the meta-analysis six studies (2017 patients) were included. The overall accuracy of AT for the diagnosis of any activity grade (Obuchowski measure=0.850) was significantly higher than the accuracy of ALT (Obuchowski measure=0.837; P=0.009). The updated standard meta-analysis confirmed the accuracy of AT (p<0.0001) both in independent AUROC=0.79 (95% CI, 0.73-0.85) and in non independent studies AUROC=0.74 (95% CI, 0.67-0.81). CONCLUSIONS: The accuracy of AT for grading the necro-inflammatory activity of patients with HCV was significantly higher than ALT serum activity alone, the standard biomarker.


Subject(s)
Alanine Transaminase/blood , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/pathology , ROC Curve , Adult , Biomarkers/blood , Biopsy , Blood Chemical Analysis , Female , Humans , Liver/pathology , Male , Middle Aged
17.
Aliment Pharmacol Ther ; 30(5): 487-94, 2009 Sep 01.
Article in English | MEDLINE | ID: mdl-19523176

ABSTRACT

BACKGROUND: The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated. AIM: To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin. PATIENTS AND METHODS: Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment. RESULTS: At week 4, a strong correlation was found between HCV-RNA and C(min) of ribavirin plasma level (r = -0.376, P = 0.002) and AUC(0-->12h) of ribavirin plasma level (r = -0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and C(min) of ribavirin plasma level (r = -0.384, P < 0.0001) and AUC(0-->12h) of ribavirin plasma level (r = -0.257, P = 0.002). In genotype 1 patients, AUC(0-->12h) ribavirin and C(min) were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12. CONCLUSION: C(min) of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/isolation & purification , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adolescent , Adult , Aged , Female , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/pharmacokinetics , Male , Middle Aged , Polyethylene Glycols/pharmacokinetics , Prospective Studies , Recombinant Proteins , Ribavirin/pharmacokinetics , Viral Load , Young Adult
18.
J Viral Hepat ; 16(11): 790-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19413693

ABSTRACT

Liver fibrosis progress slowly in patients with chronic hepatitis C and persistently normal alanine aminotransferase (PNALT) compared to subjects with elevated aminotransferases. Differences in liver fibrosis according to human immunodeficiency virus (HIV) status in this population have not been examined. All patients with serum hepatitis C virus (HCV)-RNA and PNALT who underwent liver fibrosis assessment using elastometry since 2004 at three different European hospitals were evaluated. Patients previously treated with interferon were excluded. PNALT was defined as ALT below the upper limit of normality in at least three consecutive determinations within the last 12 months. Fibrosis stage was defined as mild (Metavir F0-F1) if stiffness < or =7.1 kPa; moderate (F2) if 7.2-9.4 kPa; severe (F3) if 9.5-14 kPa, and cirrhosis (F4) if >14 kPa. A total of 449 HIV-negative and 133 HIV-positive patients were evaluated. HIV-negative patients were older (mean age 51.8 vs 43.5 years) and more frequently females (63%vs 37%) than the HIV counterparts. Mean serum HCV-RNA was similar in both the groups (5.9 vs 5.8 log IU/mL). Overall, 78.8% of the HIV patients were on HAART and their mean CD4 count was 525 (+/-278) cells/microL. In HIV-negatives, liver fibrosis was mild in 84.6%; moderate in 8.7%, severe in 3.3% and cirrhosis was found in 3.3%. In HIV patients, these figures were 70.7%, 18.8%, 6%, and 4.5%, respectively. In the multivariate logistic regression analysis, older age (odds ratio or OR: 1.04; 95% confidence interval or CI: 1.02-1.07; P < 0.001) and being HIV+ (OR: 2.6; 95% CI: 1.21-5.85; P < 0.01) were associated with severe liver fibrosis or cirrhosis (F3-F4). Thus, severe liver fibrosis and cirrhosis are seen in 6.6% of the HCV-monoinfected and in 10.5% of HCV-HIV co-infected patients with PNALT. Some degree of liver fibrosis that justifies treatment is seen in 15% of the HCV-monoinfected but doubles to nearly 30% in HIV-HCV co-infected patients with PNALT.


Subject(s)
Alanine Transaminase/blood , HIV Infections/complications , Hepatitis C, Chronic/complications , Liver Cirrhosis/etiology , Adult , Aged , Antiretroviral Therapy, Highly Active , Elasticity Imaging Techniques , Female , Genotype , HIV Infections/drug therapy , HIV Infections/virology , HIV Seronegativity , HIV-1/genetics , HIV-1/isolation & purification , Hepacivirus/classification , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis B Surface Antigens/blood , Hepatitis C, Chronic/virology , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Logistic Models , Male , Middle Aged , RNA, Viral/blood
19.
Aliment Pharmacol Ther ; 29(12): 1240-8, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19416134

ABSTRACT

BACKGROUND: In Crohn's disease (CD) patients naïve to immunomodulators primary responding to infliximab (IFX) induction, maintenance with scheduled IFX or with immunomodulators is possible. The benefit of additional IFX infusions after failure of maintenance with immunomodulators is not known. AIM: To assess the efficacy and factors associated with efficacy of postponed IFX retreatment. METHODS: All CD primary responders to an IFX induction regimen in maintenance with immunomodulators were retrospectively included when they received at least one additional IFX infusion after week 14. Efficacy was defined as clinical response at week 4 and absence of intolerance leading to discontinuation. RESULTS: Sixty-one patients were retreated with IFX with a 38-week median time from induction. Efficacy was achieved in 80% patients. Twelve patients had no clinical benefit: seven acute hypersensitivity reactions and five loss of response. By multivariate analysis, the only factor associated with no efficacy was a median time >50 weeks from induction to retreatment (odds ratio = 7.38; 95%CI: 1.38-39.59; P = 0.02). CONCLUSION: Postponed retreatment with IFX in CD primary responders should be administered within 50 weeks after induction, for better efficacy and tolerance.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Crohn Disease/therapy , Gastrointestinal Agents/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Infliximab , Middle Aged , Multivariate Analysis , Reference Values , Retreatment , Time Factors , Treatment Outcome , Young Adult
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