Hepatitis: Bedossa P

Bedossa P, Carrat F. · No affiliation provided · J Hepatol. · Pubmed #19017551 No free full text.

This publication has no abstract.

Zucman-Rossi J, Clément B, Buendia MA, Lerat H, Beers BV, Bedossa P, Taieb J, Rosenbaum J. · Inserm, U674 ; université Paris-Diderot-Paris-VII, 75010 Paris, France. · Bull Cancer. · Pubmed #19211359 No free full text.

Abstract: Hepatocellular carcinogenesis is usually the result of a muti-step process. It begins with an exposure to various risk factors; followed by the development of a chronic hepatitis and cirrhosis that is a pre-neoplastic step; and finally after the occurrence of an hepatocellular carcinoma (HCC), different molecular events control aggressiveness of the tumors. The aim of this work was to identify in the international context, forces and priorities of the fundamental and translational HCC research.

Bedossa P. · Department of Pathology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, INSERM, Paris-Diderot University, Paris, France. · Liver Int. · Pubmed #19207962 No free full text.

Abstract: Chronic viral hepatitis is a prolonged inflammatory disease of the liver that may lead to the development of fibrosis, necro-inflammation and other associated pathological features. Because fibrosis and its end-point cirrhosis are the main causes of morbidity and mortality, fibrosis assessment is considered as the most relevant information for the evaluation of the severity of the disease and as a useful indicator for prognosis and treatment decision. Because fibrosis implies morphological damage, liver biopsy has come to be the natural gold standard for staging the disease. However, the high prevalence of chronic hepatitis C in addition to the cost and constraints generated by this procedure have triggered an intensive search for alternative methods for fibrosis evaluation. In this article, the strengths and weaknesses of liver biopsy and of non-invasive markers will be reviewed and their respective roles in management of patients with chronic hepatitis C will be discussed.

Asselah T, Bièche I, Sabbagh A, Bedossa P, Moreau R, Valla D, Vidaud M, Marcellin P. · INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Paris, France. · Gut. · Pubmed #19074178 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.

Zarski JP, Doffoel M, Filoche B, Marcellin P, Samuel D, Bedossa P. · Clinique Universitaire d'Hépato-Gastroentérologie, Pôle DIGI-DUNE, Centre de recherche INSERM/UJF U823 IAPC Institut Albert Bonniot, CHU de Grenoble BP 217, 38043 Grenoble cedex, France. · Gastroenterol Clin Biol. · Pubmed #18675181 No free full text.

Abstract: The screening for the detection of hepatocellular carcinoma is based on ultrasound sonography which should be realised in patients with post-hepatitis C cirrhosis with a delay between 3 and 6 months according to the most identified risk factors, in particular age and sex male. In the case of discovery of hypoechogen nodule < or = 1cm, a follow-up is mandatory because it is usually untypical by ultrasound sonography and to propose a liver biopsy in the case of an increasing in size is shown. The ultrasound guided cutting biopsy can precise the histological characteristics of the nodule, the grade, and indicate prognostic factors. The liver biopsy is also mandatory in the case of a nodule > 2 cm and when the ultrasound sonography is not contributive, especially when the nodule is between 1 and 2 cm in size.

Zarski JP, Bedossa P, Bronowicki JP, Doffoel M, Poynard T. · Clinique Universitaire d'Hépato-Gastroentérologie, Pôle DIGI-DUNE, Unité INSERM U 548, CHU de Grenoble, Grenoble cedex 9. · Gastroenterol Clin Biol. · Pubmed #17965633 No free full text.

Abstract: Non invasive fibrosis markers, recently developed, are now an interesting alternative to liver biopsy in order to appreciate the severity of chronic hepatitis C. Serological markers, especially Fibrotest and Fibrometer, have a good diagnostic accuracy to discriminate patients with mild fibrosis to those with severe fibrosis. For intermediate stages, the discordance is very important and often justifies liver biopsy or using of several markers. Transient elastography (Fibroscan) is a new non invasive method subject to good conditions of utilisation. Diagnostic accuracy is improved by the using of all the markers, especially of Fibrotest. Transient elastography is also a promising method for assessing the severity of cirrhosis.

Asselah T, Bièche I, Paradis V, Bedossa P, Vidaud M, Marcellin P. · Service d'Hépatologie and INSERM U773, CRB3, University of Paris VII, AP-HP Hôpital Beaujon, Clichy, France. · Semin Liver Dis. · Pubmed #17295174 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The severity of disease varies widely from mild illness to cirrhosis and hepatocellular carcinoma. The progression of liver fibrosis in HCV patients determines the prognosis and, thus, the need for and urgency of therapy. In addition to viral and environmental behavioral factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of patients chronically infected with HCV. The sequencing of the human genome together with the development of high-throughput technologies has provided opportunities to distinguish discrete subsets of HCV disease and predict the disease outcome or the response to therapy. This article reviews genetic, genomic, and proteomic aspects associated with the natural history of HCV infection (i.e., viral clearance, fibrosis progression) and the response to therapy.

Bedossa P, Paradis V. · Service d'Anatomie Pathologique, CNRS FRE2443, Hôpital de Bicêtre, 78 Avenue Géneral Leclerc, 94275 Le Kremlin-Bicêtre, France. · J Pathol. · Pubmed #12845618 No free full text.

Abstract: Liver fibrosis is the hallmark of every chronic liver disease. It is also the major factor of morbidity and mortality due to the development of cirrhosis and its complications including hepatocellular carcinoma. But even at the beginning of the process of liver fibrosis and due to the strategic position of the extracellular matrix at the interface between blood flow and epithelial compartment, any quantitative or qualitative modification of extracellular matrix will rapidly affect structure and function of the liver. The development of several animal models of liver fibrosis as well as isolation and cultivation of hepatic stellate cells, the major fibrogenic cell type in the liver, led to the gathering of recent knowledge on the mechanism of liver fibrosis. Activation of hepatic stellate cells is a key event in this process and many details on this finely tuned mechanism are now available. In addition to these experimental data, experience from chronic hepatitis C now allows the development of new concepts and perspectives such as liver fibrosis regression and antifibrotic therapies.

Bedossa P, Paradis V. · Department of Pathology, Service d'anatomie pathologique, Hôpital Bicêtre, Université Paris XI, 78 rue du general Leclerc, 94725 Le Kremlin-Bicêtre, France. · Clin Liver Dis. · Pubmed #12691467 No free full text.

Abstract: In the past 20 years, the elucidation of the mechanisms responsible for liver fibrogenesis has provided many potential targets for antifibrotic treatments. Difficulty has arisen, however, from the fact that fibrogenesis is part of a general beneficial wound healing process. To be successful, an antifibrotic treatment of HCV might need to be delivered selectively to the hepatic site of fibrogenesis or targeted precisely at an HCV-specific regulatory mechanism. It is likely that in the future, besides viral eradication, another treatment goal in chronic HCV infection will be to reverse existing fibrosis, but considerable work is necessary before making this a reality.

Bedossa P. · Service d'Anatomie Pathologique, CNRS ESA8067, Hôpital de Bicêtre, Le Kremlin-Bicêtre. · Gastroenterol Clin Biol. · Pubmed #12180284 No free full text.

This publication has no abstract.

Poynard T, Ratziu V, Benmanov Y, Di Martino V, Bedossa P, Opolon P. · Service d'Hépato-Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Semin Liver Dis. · Pubmed #10895431 No free full text.

Abstract: Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression represent important surrogate end points for evaluation of the vulnerability of an individual patient and for assessment of the impact of treatment on natural history in chronic hepatitis C. Using the median fibrosis progression rate, the median expected time to cirrhosis in untreated patients is around 30 years. However, one third of patients have an expected median time to cirrhosis of less than 20 years and one third will only progress to cirrhosis in more than 50 years, if ever. Factors independently associated with fibrosis progression are duration of infection, age, male gender, consumption of alcohol, human immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis progression is useful to decide treatment. Among patients with sustained viral response, fibrosis regresses. Evaluation of fibrosis progression has permitted validation of the concept of suppressive therapy. Among patients without viral clearance, interferon alone or in combination with ribavirin significantly reduces fibrosis progression rate in comparison with progression before treatment and to control groups. There is a major need for noninvasive markers of liver fibrosis. None are clearly useful today for the diagnosis of early stages of fibrosis.

Poynard T, Ratziu V, Benhamou Y, Opolon P, Cacoub P, Bedossa P. · Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Baillieres Best Pract Res Clin Gastroenterol. · Pubmed #10890317 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are at risk of developing both hepatological and non-hepatological manifestations. HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis after more than 50 years, if ever. Several factors are associated with fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with more than 70% of HCV patients experiencing fatigue or at least one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. Several immunological abnormalities are frequently observed, including cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1% for systemic vasculitis.

Poynard T, Ratziu V, Bedossa P. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Can J Gastroenterol. · Pubmed #10888734 links to  free full text

Abstract: This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heterogeneous opinions concerning the appropriateness of liver biopsy. Appropriateness should be evaluated for different techniques such as percutaneous liver biopsy, guided or not by ultrasonography, and the types of needles, automatic or not. The present paper reviews the evaluation of liver biopsy appropriateness in the real world, the adverse events and mortality of liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease and chronic hepatitis C. The authors conclude that liver biopsy is used extensively, but its appropriateness has not been evaluated perfectly. Therefore, further evaluation of the appropriateness of liver biopsy in the practical algorithm of such diseases is needed.

Poynard T, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, Carrilho F, Schmidt W, Berg T, McGarrity T, Heathcote EJ, Gonçales F, Diago M, Craxi A, Silva M, Bedossa P, Mukhopadhyay P, Griffel L, Burroughs M, Brass C, Albrecht J, Anonymous00084. · Service d'hepatologie, Université Pierre et Marie Curie Liver Center, Hôpital La Pitié Salpêtrière, Paris, France. · Gastroenterology. · Pubmed #19208349 No free full text.

Abstract: BACKGROUND & AIMS: Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. METHODS: This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 microg/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request. RESULTS: Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (< or =600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. CONCLUSIONS: Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

Bani-Sadr F, Bedossa P, Rosenthal E, Merrien D, Perre P, Lascoux-Combe C, Cacoub P, Perronne C, Pol S, Anonymous00141. · No affiliation provided · J Acquir Immune Defic Syndr. · Pubmed #19155771 No free full text.

This publication has no abstract.

Males S, Gad RR, Esmat G, Abobakr H, Anwar M, Rekacewicz C, El Hoseiny M, Zalata K, Abdel-Hamid M, Bedossa P, Pol S, Mohamed MK, Fontanet A. · Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France. · Antivir Ther. · Pubmed #17713163 No free full text.

Abstract: OBJECTIVES: To analyse the association between serum alpha-foetoprotein (AFP) levels and sustained virological response (SVR) in treated patients. METHODS: One-hundred patients with chronic hepatitis C were treated with pegylated interferon alpha-2a plus ribavirin for 48 weeks. The primary endpoint was SVR. Linear regression analysis was performed to identify clinical, biological, and histological factors affecting baseline AFP levels. The association between pretreatment serum AFP and SVR was assessed by multivariate logistic regression analysis. RESULTS: Of 100 patients, 95 were infected with genotype 4, one with genotype 1, and four with undetermined genotype. The median serum AFP level was 4.5 ng/ml and AFP values ranged from 1.2 to 49.8 ng/ml. In multivariate analysis, higher fibrosis stage and higher steatosis score were independently associated with higher serum AFP levels. SVR rate was 61.0% (61/100), and was lower for patients with AFP levels above rather than below the median value (40.8% versus 80.4%, respectively, P < 0.001). In multivariate analysis, including adjustment for age, gender, body mass index, steatosis score, fibrosis stage, ALT level, haemoglobin level, clotting time, HCV RNA viral load, and treatment dose received, a baseline serum AFP level above the median value was associated with a lower SVR rate (OR [95% CI]=0.10 [0.03-0.42], P < 0.001). None of the seven patients with increased (above 15 ng/ml) pretreatment AFP achieved SVR. CONCLUSIONS: In this study, higher baseline serum AFP levels independently predicted a lower SVR rate among patients with chronic hepatitis C. If confirmed with genotypes other than 4, these findings would suggest adding serum AFP to the list of factors predictive of treatment response.

Poynard T, Marcellin P, Bissery A, Myers RP, Moussalli J, Degos F, Dhumeaux D, Riachi G, Bronowicki JP, Brissot P, Buffet C, Serfaty L, Naveau S, Sogni P, Beaugrand M, Gayno S, Larrey D, Samuel D, Eugene C, Pol S, Bedossa P, Daurat V, Chaumet-Riffaud P, Anonymous00216. · Service d'Hepatogastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Université Paris 6, 47-83 Boulevard de l'Hôpital, CNRS ESA 8067, 75651 Paris Cedex 13, France. · J Viral Hepat. · Pubmed #12753338 No free full text.

Abstract: Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Poynard T, Daurat V, Chevret S, Moussalli J, Degos F, Bailly F, Borotto E, Buffet C, Bartolomei-Portal I, Richardet JP, Riachi G, Calmus Y, Bréchot C, Vidaud M, Olivi M, Bedossa P, Riffaud PC, Chastang C. · Service d'Hépato Gastroentérologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · J Viral Hepat. · Pubmed #10607254 No free full text.

Abstract: The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-alpha2b (IFN-alpha2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-alpha has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.

Martinot-Peignoux M, Maylin S, Moucari R, Ripault MP, Boyer N, Cardoso AC, Giuily N, Castelnau C, Pouteau M, Stern C, Aupérin A, Bedossa P, Asselah T, Marcellin P. · INSERM, U-773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris VII, Hôpital Beaujon, Clichy, France. · Antivir Ther. · Pubmed #19578235 No free full text.

Abstract: BACKGROUND: Viral kinetics during therapy provides information on how to individualize treatment. To determine the benefit of assessing positive predictive values (PPVs) and negative predictive values (NPVs) of rapid virological responses (RVRs) and early virological responses (EVRs), on-treatment outcomes in chronic hepatitis C patients were examined. METHODS: A total of 408 patients (221 treatment-naive) treated with pegylated interferon-alpha2b and ribavirin were included. Hepatitis C virus (HCV) RNA was measured at baseline, 4 weeks and 12 weeks. RVR was defined as undetectable HCV RNA at 4 weeks and EVR as >/=2 log(10) decrease in HCV RNA at 12 weeks. The additive value of RVR on predicting sustained virological response (SVR) was assessed with receiver operating characteristic (ROC) curves. RESULTS: SVR, RVR and EVR were observed in 46%, 23% and 78% of patients, respectively. PPVs of RVR were 96%, 100% and 100% in treatment-naive patients, relapsers and non-responders, respectively. NPVs of failure to achieve EVR were 97%, 75% and 91%, in treatment-naive patients, relapsers and non-responders, respectively. At 4 weeks, patients with RVR had the highest probability to achieve SVR (odds ratio 44.98 in the entire population and 32.95 in treatment-naive patients). ROC curves showed the area under the ROC curve to be 0.758 versus 0.832 in the entire population and 0.795 versus 0.858 in treatment-naive patients at baseline versus week 4, respectively. CONCLUSIONS: RVR is a strong predictor of SVR (PPV>96%) and failure to achieve EVR is a strong predictor of non-SVR (NPV>75%), independent of patients' pretreatment status. Added to baseline characteristics, RVR increased the accuracy to predict SVR. The combination of RVR and EVR provided complementary information, and thus provides a key opportunity to individualize treatment and improve the benefit/risk ratio of therapy.

Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, Vidaud M, Valla D, Bedossa P, Marcellin P. · AP-HP, Hôpital Beaujon, Service d'Hépatologie, 100 Boulevard du Général Leclerc, 92100 Clichy, France. · J Hepatol. · Pubmed #19376603 No free full text.

Abstract: BACKGROUND/AIMS: To assess the HBsAg seroconversion rate and its impact on the long-term outcome in chronic hepatitis B patients treated with conventional interferon, and to analyze the serum HBsAg concentration prior to seroconversion. METHODS: Ninety-seven HBeAg-positive patients were retrospectively evaluated. Sustained virological response (SVR) was defined as HBeAg seroconversion and undetectable serum HBV-DNA 48 weeks after treatment discontinuation. HBsAg level was assessed at yearly intervals until seroconversion in SVRs. RESULTS: Twenty-five patients (26%) achieved SVR. By multivariate analysis, SVR was associated with low serum HBV DNA level and severe liver fibrosis. During a median follow-up of 14 years (range, 5-20 years), 28 patients (29%) developed HBsAg seroconversion including 16 SVRs (64%) and 12 non-SVRs (16%), p < 0.001. HBsAg quantification showed a major decrease (median = 46%, range = 19-100%) in the first year after interferon starting in SVR patients. Six patients developed hepatocellular carcinoma, none of them had undergone HBsAg seroconversion. Liver fibrosis improved in 70% of patients with HBsAg seroconversion compared to 30% of those without HBsAg seroconversion (p < 0.01). CONCLUSIONS: HBsAg seroconversion is achieved with a high steady rate in patients responding to interferon, and associated with excellent outcome. Prospective studies are needed to clarify the utility of on-treatment quantitative serum HBsAg in interferon-based therapy.

Halfon P, Pénaranda G, Carrat F, Bedossa P, Bourlière M, Ouzan D, Renou C, Tran A, Rosenthal E, Wartelle C, Delasalle P, Cacoub P. · Laboratoire Alphabio, Marseille, France. · Aliment Pharmacol Ther. · Pubmed #19292832 No free full text.

Abstract: BACKGROUND: Insulin resistance (IR), the major feature of the metabolic syndrome, is also common in patients with chronic HCV infection. Liver fibrosis and steatosis are known potential outcome of chronic hepatitis B or C infection. Studies have shown that HIV positive individuals co-infected with HCV have more rapid live disease progression than those with HIV alone. Few data have reported the influence of IR on steatosis and fibrosis in the context of HIV-HCV coinfection. AIM: To test the association among insulin resistance (IR), liver fibrosis and liver steatosis in HIV-HCV and HCV-infected patients. PATIENTS AND METHODS: A total of 170 HIV-HCV-infected patients matched by age, gender and genotype with 170 HCV mono-infected patients were included. Patients were considered to be IR when the homeostasis model assessment of IR >2. Significant fibrosis was considered if METAVIR >or=F2 and significant steatosis if >or=10%. RESULTS: Insulin resistance was independently associated in HCV patients with fibrosis [odds ratio (OR) = 2.04 (95% CI 1.02-4)], a body mass index (BMI) >25 kg/m(2) [OR = 3.33 (1.47-7.69)] and steatosis [OR = 3.33 (1.67-6.67)]. Fibrosis >or=F2 was associated in HCV patients with high liver activity grade (>or=A2) [OR = 8.33 (3.85-16.67)], male gender [OR = 3.03 (1.33-7.14)] and IR [OR = 2.44 (1.15-5)]. In HIV-HCV patients, >or=A2 [OR = 5.56 (1.64-20)] was associated with fibrosis. Steatosis >or=10% was associated in HCV patients with IR [OR = 3.13 (1.59-6.25) and >or=F2 (OR = 2.22 (1.15-4.17)]. In HIV-HCV, a BMI >25 kg/m(2) [OR = 3.85 (1.64-9.10)], >or=A2 [OR = 2.16 (1.02-4.55); P = 0.044] and nucleoside reverse transcriptase inhibitor [OR = 3.61 (1.19-10.96); P = 0.023] were independently associated with significant liver steatosis. CONCLUSIONS: Insulin resistance is associated with liver fibrosis and steatosis in HCV mono-infected, but not in HIV-HCV co-infected patients. Significant liver fibrosis is associated with IR independent of liver steatosis only in HCV mono-infected patients.

Moucari R, Mackiewicz V, Lada O, Ripault MP, Castelnau C, Martinot-Peignoux M, Dauvergne A, Asselah T, Boyer N, Bedossa P, Valla D, Vidaud M, Nicolas-Chanoine MH, Marcellin P. · Service d'Hépatologie, Hôpital Beaujon, Clichy, France. · Hepatology. · Pubmed #19115222 No free full text.

Abstract: Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) in 20% of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. In addition, loss of hepatitis B surface antigen (HBsAg) is achieved with a 10% yearly rate after treatment cessation in sustained responders. The aim of this study was to assess on-treatment serum HBsAg kinetics to predict SVR in HBeAg-negative patients treated with PEG-IFN. Forty-eight consecutive patients were treated with PEG-IFN (180 microg/week) for 48 weeks. Serum hepatitis B virus (HBV) DNA (COBAS TaqMan) and HBsAg (Abbott Architect HBsAg QT assay) were assessed at baseline, during treatment (weeks 12, 24, and 48), and during follow-up (weeks 72 and 96). SVR was defined as undetectable serum HBV DNA (<70 copies/mL) 24 weeks after treatment cessation. Twenty-five percent of patients achieved SVR. They were not different from those who failed treatment regarding age, sex, ethnicity, HBV genotype, baseline serum HBV DNA and HBsAg levels, or liver histology. During treatment, serum HBsAg levels decreased only in patients who developed SVR, with mean decreases of 0.8 +/- 0.5, 1.5 +/- 0.6, and 2.1 +/- 1.2 log(10) IU/mL at weeks 12, 24, and 48, respectively. A decrease of 0.5 and 1 log(10) IU/mL in serum HBsAg levels at weeks 12 and 24 of therapy, respectively, had high predictive values of SVR (negative predictive value [NPV] 90%, positive predictive value [PPV] 89% for week 12; NPV 97%, PPV 92% for week 24). HBsAg loss was observed in three patients, all with SVR. CONCLUSION: Early serum HBsAg drop has high predictive values of SVR to PEG-IFN in HBeAg-negative CHB patients. Serum quantitative HBsAg may be a useful tool to optimize the management of PEG-IFN therapy in these patients.

Asselah T, Bièche I, Laurendeau I, Martinot-Peignoux M, Paradis V, Vidaud D, Valla DC, Bedossa P, Marcellin P, Vidaud M. · Service d'Hépatologie & Institut National de la Santé et de la Recherche Médicale (INSERM) U733, CRB3, Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, France. · Hepatology. · Pubmed #18726958 No free full text.

Abstract: Gene expression technologies allow the analysis of gene networks whose expression is associated with specific pathological conditions compared with normal tissue. We hypothesized that histologically normal tissue obtained in different ways (percutaneous or surgical liver biopsies), usually used as normal controls in gene expression studies, could have different gene expression patterns. Group A comprised percutaneous liver biopsies in 14 patients with mildly elevated alanine aminotransferase in whom all causes of liver disease had been ruled out. Group B comprised 14 surgical liver biopsies of nontumoral livers. All 28 specimens were histologically normal. Real-time quantitative reverse-transcription polymerase chain reaction were used to compare the messenger RNA expression of 240 selected genes in these two groups. Expression of 26 of the 240 genes was significantly different between groups A and B; 23 genes were up-regulated in group A, while three were down-regulated in group B. The most notable changes occurred in the inflammatory response family genes. Eight genes discriminated perfectly between groups A and B: seven up-regulated genes (PAI1, THBS1, IL8, PTGS2, CXCR4, JUN, and FOS), and one down-regulated gene (IHH). In chronic hepatitis C liver samples, a lower or higher expression of a IL8 was found depending on whether the controls were obtained percutaneously or surgically. CONCLUSION: Our study demonstrates that histologically normal liver tissue obtained in two different ways (percutaneous or surgical) has different gene expression patterns emphasizing the importance of an adequate selection of histologically normal controls to prevent discordant results in gene expression studies.

Marcellin P, Ziol M, Bedossa P, Douvin C, Poupon R, de Lédinghen V, Beaugrand M. · Service d'Hépatologie and INSERM U 773, Hôpital Beaujon, AP-HP, University of Paris, Clichy, France. · Liver Int. · Pubmed #18637064 No free full text.

Abstract: BACKGROUND: The need for new non-invasive tools to assess liver fibrosis in chronic liver diseases has been largely advocated. Liver stiffness measurement (LSM) using transient elastography (FibroScan), Echosens) has been shown to be correlated to liver fibrosis in various chronic liver diseases. This study aims to assess its diagnosis accuracy in patients with chronic hepatitis B. PATIENTS AND METHODS: We prospectively enrolled 202 patients with chronic hepatitis B in a multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and Ishak liver fibrosis stages were assessed by two pathologists. RESULTS: LSM or LB was considered unreliable in 29 patients. Statistical analysis was conducted in 173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65) and Ishak fibrosis stage (0.65). The area under receiver-operating characteristic curves were 0.81 (95% confidence intervals, 0.73-0.86) for F>/=2, 0.93 (0.88-0.96) for F>/=3 and 0.93 (0.82-0.98) for F=4. Optimal LSM cut-off values were 7.2 and 11.0 kPa for F>/=2 and F=4, respectively, by maximizing the sum D of sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis accuracy. CONCLUSION: In conclusion, LSM appears to be reliable for detection of significant fibrosis or cirrhosis in HBV patients and cut-off values are only slightly different from those observed in HCV patients.

Carrat F, Bedossa P, Lunel-Fabiani F, Morand P, Pialoux G, Piroth L, Salmon-Céron D, Bani-Sadr F, Perronne C, Cacoub P, Pol S. · UPMC-Paris6, UMR-S707, INSERM, UMR-S707, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris, France. · AIDS. · Pubmed #18614875 No free full text.

Abstract: We explored the link between serum alpha-fetoprotein levels and virologic response in 383 HIV-hepatitis C virus coinfected patients. A low alpha-fetoprotein level (<5.0 ng/ml) was an independent predictor of sustained virologic response (odds ratio = 1.83; 95% confidence interval 1.05-3.20). Serum alpha-fetoprotein measurement should be integrated in the pretreatment assessment of prognostic factors of a virologic response.