Hepatitis: Fontaine H

Fontaine H, Petitprez K, Roudot-Thoraval F, Trinchet JC, Anonymous00285, Anonymous00286, Anonymous00287, Anonymous00288, Anonymous00289, Anonymous00290, Anonymous00291. · Unité d'Hépatologie Médicale, Hôpital Cochin, Paris, France. · Gastroenterol Clin Biol. · Pubmed #17541342 No free full text.

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Vallet-Pichard A, Fontaine H, Pol S. · Unité d'Hépatologie et U-370, Hôpital Necker, Paris. · Gastroenterol Clin Biol. · Pubmed #12483129 No free full text.

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Lebray P, Vallet-Pichard A, Michel ML, Fontaine H, Sobesky R, Bréchot C, Pol S. · Service d'Hépatologie, Hôpital Necker Enfants Malades, 75730 Paris Cédex 15, France. · J Hepatol. · Pubmed #14708695 No free full text.

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Fontaine H. · Service d'Hépatologie adulte, Hôpital Necker Enfants-Malades, 149, rue de Sèvres, 75015 Paris. · Gastroenterol Clin Biol. · Pubmed #12180314 No free full text.

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Pol S, Vallet-Pichard A, Fontaine H, Lebray P. · Unité d'Hépatologie et Inserm V-370, Hôpital Necker, Paris, France. · Semin Nephrol. · Pubmed #12118398 No free full text.

Abstract: Hepatitis C virus (HCV) infections are frequent in hemodialyzed patients and are mainly related to transfusions and nosocomial contamination. HCV-related infection may result in cirrhosis in 10% of dialysis patients and is worsened by transplantation because of the immunosuppressive therapy for prevention of graft rejection. Because there is a risk for significant liver disease and because cirrhosis contraindicates a renal transplantation, a liver biopsy should be performed early in HCV-RNA positive hemodialysis patients to evaluate histologic impact of the liver disease. A combined liver-kidney transplantation should be discussed in dialysis patients with cirrhosis. Standard alpha-interferon is the only treatment for HCV in dialysis patients because ribavirin is contraindicated by a high risk for hemolytic anemia. It leads to an overall 30% rate of sustained viral eradication. It is indicated in dialysis patients with acute hepatitis C, significant liver disease (fibrosis score > or =2), or symptomatic cryoglobulinemia, and to candidates for renal transplantation, whatever the severity of the liver disease. Indeed, alpha-interferon is contraindicated in kidney recipients given the risk for rejection. Preventive treatment for HCV is only respect for universal hygiene rules in the dialysis setting because there is no available vaccine.

Pol S, Vallet-Pichard A, Fontaine H. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, Paris, France. · J Viral Hepat. · Pubmed #11851897 No free full text.

Abstract: Interactions between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been widely studied before the introduction of highly active antiretroviral therapies (HAART). We reviewed the potential impact of HAART on hepatitis C as well as the interactions between HIV and HCV therapies. Physicians should be aware of the potential risk of: (i) symptomatic liver disease in HCV-HIV-coinfected patients at the era of triple antiretroviral therapy; (ii) potential liver deterioration paralleling immune restoration; (iii) lack of impact of triple antiretroviral therapy on HCV load; and (iv) potential drug-related hepatitis which may modify the natural history of HCV-related liver disease. Liver biopsies should be performed regularly in these patients in order to identify patients with severe liver disease who require early initiation of anti-HCV therapy under close monitoring of their immune status. Treatment is, to date, based on the combination of ribavirin and interferon with an expected sustained response rate around 25%. An important unresolved issue is to better delineate the temporal place of anti-HCV and anti-HIV antiviral therapies. At least in coinfected patients with significant liver disease, namely necro-inflammatory activity and/or fibrosis >or= 2, we believe that anti-HCV therapy is the priority since it lessens the risk of drug-induced hepatitis and of hepatitis due to immune restoration.

Fontaine H, Pol S. · Unité d'hépatologie et INSERM U370, Hôpital Necker, Paris. · Nephrologie. · Pubmed #11817211 No free full text.

Abstract: Viral hepatotropic infections may lead to diagnostic and therapeutic problems in hemodialysis patients and kidney recipients. The parenteral and community-acquired routes of contamination of hepatitis B and C viruses explain their high frequency in this population. Their impact, because the immunosuppressive treatments, is harmful with a decrease in patients and allografts survival; cirrhosis is a contra-indication for renal transplantation since associated with a bad short-term prognosis and may require a combined kidney-liver transplantation. Thus, a liver biopsy is recommended in order to evaluate the histopathological severity of the liver disease (stage and grade) and to precise if an antiviral treatment appears necessary, especially because interferon-alpha, the main treatment of hepatitis B and C infections, is contra-indicated in kidney recipients because of the risk of graft rejection. In summary, the diagnosis of viral hepatotropic infections has to be early undergone and its pathological impact has to be evaluated by a liver biopsy. The best treatment has to be prophylactic (vaccination against hepatitis B virus and the respect of universal hygiene rules for hepatitis C virus).

Pol S, Fontaine H, Vallet-Pichard A. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, 149, rue de Sèvres, 75743 Paris Cedex 15. · Gastroenterol Clin Biol. · Pubmed #11395676 No free full text.

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Fontaine H, Pol S. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, Paris, France. · Transplant Proc. · Pubmed #11377548 No free full text.

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Pol S, Zylberberg H, Fontaine H, Bréchot C. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, Paris, France. · J Hepatol. · Pubmed #10622589 No free full text.

Abstract: Little is known about treatment of hepatitis C virus (HCV) infection in "other groups" than the general population, namely patients with hematologic or renal disorders and patients with human immune deficiency (HIV) co-infection. The aim was to better define HCV therapies in these groups. We analyzed the medical literature focusing on treatment of HCV infection in other populations to suggest conclusions about indications based on tolerance and efficacy. As in the general population, the decision to treat should be based mainly on liver pathology, and to a lesser extent on virologic profiles (genotype, quantitative viremia). Hemophilia does not modify therapeutic strategies which combine interferon-alpha and ribavirin. Similar combinations should be discussed in patients with inherited hemoglobin disorders but iron overload (secondary hemochromatosis) associated with multiple transfusions may decrease the potential efficacy of interferon-alpha and chronic anemia may limit the use of ribavirin. In hemodialyzed patients, therapy by interferon-alpha is feasible with 3 MU subcutaneously after each hemodialysis three times weekly for 6-12 months. Virologic results are at least similar to those obtained in the general population with frequent pathological improvement. Combinations are not possible because ribavirin is contraindicated for pharmacokinetic reasons. In kidney recipients, interferon-alpha is deleterious and inefficient; ribavirin monotherapy has a potential interest which remains to be evaluated. In HIV co-infected patients, treatment is mandatory given the high rate of cirrhosis and the improved survival related to multiple anti-HIV therapies (which have no clear efficacy for quantitative HCV viremia). Due to the limited efficacy of interferon-alpha monotherapy, the combination of interferon-alpha and ribavirin appears to be the logical treatment. An important point is the in vitro inhibition of phosphorylation by ribavirin of HIV reverse transcriptase inhibitors which has to be analyzed in vivo before the combination can be recommended. On the basis of the results of liver biopsy, antiviral treatments may be proposed for HCV-infected patients with hematologic or renal disorders as well as for HIV co-infected patients. The choice of therapy (monotherapy or combined therapies) should be based on the clinical situation (contraindicated with chronic anemia or renal failure, for example) and its duration on the virologic factors of response as in the general population.

Fontaine H, Vallet-Pichard A, Chaix ML, Currie G, Serpaggi J, Verkarre V, Varaut A, Morales E, Nalpas B, Brosgart C, Pol S. · Liver Unit, Necker Hospital, Paris, France. · Transplantation. · Pubmed #16278590 No free full text.

Abstract: BACKGROUND: This study analyzes the biochemical, serological, and virological efficacy and the safety of adefovir dipivoxil in patients with renal disturbances. METHODS: Twelve patients with lamivudine-resistant hepatitis B virus (HBV) chronic infection were treated for a median time of 15 (3-19) months. The daily dosage was 10 mg initially and then adjusted according to renal function. RESULTS: Median (range) ALT values remained stable: 55 (13-117) and 37 (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from 8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No virologic breakthrough was observed. One of the six HBeAg-positive patients lost HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no significant clinical and biochemical adverse effects. In the 11 nonhemodialysed patients, the creatinine clearance significantly improved from 70 (30-100) to 88 (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to 0.12 (0.01-0.74) g/day (NS). CONCLUSIONS: Adefovir dipivoxil is safe for the treatment of chronic hepatitis B in patients with varying degrees of renal dysfunction and lamivudine-resistant HBV and results in biochemical and virological efficacy similar to that reported in the general population.

Mancini-Bourgine M, Fontaine H, Scott-Algara D, Pol S, Bréchot C, Michel ML. · Carcinogénèse Hépatique et Virologie Moléculaire/Institut National de la Santé et de la Recherche Médicale Unité 370, Institut Pasteur, Paris, France. · Hepatology. · Pubmed #15382173 No free full text.

Abstract: Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV-specific T-cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T-cell responsiveness. Ten patients with chronic active hepatitis B nonresponder to approved treatments for HBV infection were given 4 intramuscular injections of 1 mg of a DNA vaccine encoding HBV envelope proteins. HBV-specific T-cell responses were assessed by proliferation, ELISpot assays, and tetramer staining. Secondary end points included safety and the monitoring of HBV viraemia and serological markers. Proliferative responses to hepatitis B surface antigen were detected in two patients after DNA injections. Few HBV-specific interferon gamma-secreting T cells were detectable before immunization, but the frequency of such responses was significantly increased by 3 DNA injections. Immunization was well tolerated. Serum HBV DNA levels decreased in 5 patients after 3 vaccine injections, and complete clearance was observed in 1 patient. In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective. We demonstrate that DNA vaccination can specifically but transiently activate T-cell responses in some chronic HBV carriers who do not respond to current antiviral therapies.

Fontaine H, Chaix ML, Lagneau JL, Bréchot C, Pol S. · No affiliation provided · Lancet. · Pubmed #10892765 No free full text.

Abstract: In 45 sustained responders to interferon alfa and ribavirin, we found long-lasting elimination of hepatitis C virus RNA from serum and liver, together with histopathological improvement, suggesting complete recovery from chronic hepatitis C.

Mallet V, Dhalluin-Venier V, Roussin C, Bourliere M, Pettinelli ME, Giry C, Vallet-Pichard A, Fontaine H, Pol S. · Université Paris Descartes, Paris, France. · Aliment Pharmacol Ther. · Pubmed #19035983 No free full text.

Abstract: BACKGROUND: The Fib-4 index is a simple and inexpensive biomarker to delineate liver fibrosis in chronic hepatitis C. AIM: To assess the accuracy of the FIB-4 index in chronic hepatitis B. METHODS: We compared the FIB-4 index with 138 synchronous liver biopsies and with 372 synchronous FibroTest performed either in France or in an endemic area (Mayotte, an overseas collectivity of France). RESULTS: The FIB-4 index allowed the correct identification of patients with nil-to-moderate fibrosis with an area under the receiving operating characteristic curve of 0.81 (P < 0.001), increasing as a function of the length of the liver biopsy (up to 0.94 for liver biopsies >or=20 mm). A cut-off value <or=1.45 differentiated moderate fibrosis from severe fibrosis with a negative predictive value of 86%, a sensitivity of 71.1% and a specificity of 73.1%. Beyond 1.45, the FIB-4 index was not informative. The FIB-4 index was more precise than the AST-to-platelet ratio index and correlated with the FibroTest in 89% of the cases (kappa = 0.27, P < 0.001) to exclude severe fibrosis. CONCLUSION: The FIB-4 index is a simple, accurate and inexpensive method to exclude significant liver fibrosis in chronic hepatitis B, a major advantage in HBV-endemic developing countries.

Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. · Université Paris Descartes; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, INSERM U 567, Paris, France. · Ann Intern Med. · Pubmed #18794559 links to  free full text

Abstract: BACKGROUND: The effect of regression of cirrhosis in chronic hepatitis C is unknown. OBJECTIVE: To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy. DESIGN: A cohort of patients with cirrhosis treated between 1988 and 2001. SETTING: Hepatology unit of a tertiary care center in France. PATIENTS: 96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006. MEASUREMENTS: Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to <or=2 METAVIR units on posttherapy liver biopsy). RESULTS: The median follow-up was 118 months (interquartile range, 86 to 138 months). Eighteen patients had regression of cirrhosis. The incidence of the combined end point per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression of cirrhosis (P = 0.002, log-rank test). The transplantation-free survival rate at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression of cirrhosis (P = 0.025). LIMITATIONS: Selection of patients was retrospective; selection and survival biases may have influenced the estimates of the overall rate of regression of cirrhosis. The low number of patients who experienced regression of cirrhosis precludes analysis of factors that could predict regression of cirrhosis. CONCLUSION: Regression of cirrhosis occurs after antiviral therapy in some patients with chronic hepatitis C. Regression is associated with decreased disease-related morbidity and improved survival.

Trabut JB, Plat A, Thepot V, Fontaine H, Vallet-Pichard A, Nalpas B, Pol S. · Unité d'Hépatologie-Hôpital Cochin, 27, rue du Faubourg St Jacques, 75014 Paris, France. · Alcohol Alcohol. · Pubmed #18621800 No free full text.

Abstract: BACKGROUND: Liver biopsy indication for the evaluation of alcoholic liver disease is controversial. Our aim was to investigate the influence of the biopsy on the patients' motivation for abstinence. METHODS: We retrospectively analysed, in a population of 324 patients hospitalized for alcohol withdrawal, the impact of liver biopsy on the following clinical outcomes: rapid loss to follow-up (immediately after hospital discharge), early relapse (< 3 months) and long-lasting abstinence (> 12 months). The biopsy was performed in 136 patients who had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. RESULTS: In univariate analysis, patients who had a liver biopsy were less likely to be rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age was the only factor significantly associated with clinical outcome: older patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among patients who had a biopsy, those with severe hepatic lesions had a lower rate of rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P = 0.018) but the rate of long-term abstinence was similar in the three groups. CONCLUSION: This observational study does not support the notion that liver biopsy has a significant influence on the maintenance of alcohol abstinence in patients with alcoholic liver disease.

Sobesky R, Lebray P, Nalpas B, Vallet-Pichard A, Fontaine H, Lagneau JL, Pol S. · INSERM U785, Centre Hepato-Biliaire, Hopital Paul Brousse, Villejuif, France. · World J Gastroenterol. · Pubmed #18609710 links to  free full text

Abstract: AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions. METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score < or = 3, with 2 liver biopsies and detectable HCV-RNA were included. Markers of fibrosis progression were assessed. RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and 4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) > 25. Fibrosis progression correlated with the time interval between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression (P = 0.003). Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI > 25 and the time interval between 2 biopsies. CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI > 25.

Ghosn J, Thibault V, Delaugerre C, Fontaine H, Lortholary O, Rouzioux C, Pol S, Chaix ML. · AP-HP, EA MRT 3620, Université Paris Descartes, Department of Virology, Necker Hospital, Paris, France. · AIDS. · Pubmed #18317011 No free full text.

Abstract: We report two cases of sexually transmitted hepatitis C virus (HCV) superinfection in HIV/HCV-co-infected patients with high-risk sexual behaviour. The two patients had chronic HCV and a history of sexually transmitted infections. HCV superinfection was confirmed by phylogenetic analysis. No risk factors for HCV were found except unprotected anal sex with multiple casual male partners. HCV serology and serum HCV RNA should be examined periodically in HIV-infected men who have sex with men engaging in high-risk sexual behaviours.

Braks RE, Ganne-Carrie N, Fontaine H, Paries J, Grando-Lemaire V, Beaugrand M, Pol S, Trinchet JC. · Department of Hepatology, Hopital Jean Verdier, Bondy 93140, France. · World J Gastroenterol. · Pubmed #17948941 links to  free full text

Abstract: AIM: To assess the long-term clinical benefit of sustained virological response (SVR) in patients with hepatitis C virus (HCV) cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated. METHODS: One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment > or = 3 mo and followed > or = 30 mo were included. The occurrence of linical events [hepatocellular carcinoma (HCC), decompensation and death] was compared in SVR and non SVR patients. RESULTS: Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients (33%). During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC (24/76 vs 1/37, P = 0.01). No SVR patient died while 20/76 non-SVR did (P = 0.002), mainly in relation to HCC (45%). CONCLUSION: In patients with HCV-related cirrhosis, SVR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis.

Le Pendeven C, Cuzon G, Fontaine H, Zatla F, Schneider V, Amiel C, Khayat R, Nicolas JC, Soussan P. · Laboratoire de Virologie, Hôpital Tenon, AP-HP, Paris, France. · J Clin Virol. · Pubmed #17652016 No free full text.

This publication has no abstract.

Roulot D, Bourcier V, Grando V, Deny P, Baazia Y, Fontaine H, Bailly F, Castera L, De Ledinghen V, Marcellin P, Poupon R, Bourlière M, Zarski JP, Roudot-Thoraval F, Anonymous00237. · Service d'Hépatogastroentérologie, Hôpital Jean Verdier, Bondy, France. · J Viral Hepat. · Pubmed #17576387 No free full text.

Abstract: Hepatitis C virus genotype 4 (HCV-4) infection is progressing in Europe, where epidemiology and sustained virological response (SVR) seem to be different than in the Middle East. We analysed epidemiological features and SVR rates in a retrospective study of 1532 HCV-4-infected patients, including 1056 patients infected in France, 227 immigrants infected in Egypt and 249 in sub-Saharan Africa. SVR rates were assessed in 242 naive patients of the 1532, who received peginterferon plus ribavirin for 48 weeks. HCV subtype 4a or 4d was the most common among patients infected in France, where the predominant route of transmission was intravenous drug abuse. The 4a subtype was largely predominant (93%) among patients infected in Egypt, where transmission was mostly because of parenteral treatment for schistosomiasis. More than seven different subtypes and no predominant route of infection were found in patients infected in sub-Saharan Africa. Liver fibrosis was significantly less severe in patients infected in France and Africa than in patients infected in Egypt. SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3% and 32.4%, respectively, P < 0.05). An overall better response was observed in patients infected with the 4a subtype. In multivariate analysis, two factors were associated independently with SVR: the Egyptian origin of transmission and the absence of severe fibrosis. In conclusion, the distribution of HCV-4 subtypes varies with the geographical origin of transmission and affects the SVR following antiviral treatment.

Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S. · Université Paris-Descartes, Paris, France. · Hepatology. · Pubmed #17567829 No free full text.

Abstract: To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (kappa = 0.561, P < 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. CONCLUSION: For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.

Malmassari SL, Deng Q, Fontaine H, Houitte D, Rimlinger F, Thiers V, Maillere B, Pol S, Michel ML. · INSERM U812, Pathogenèse des Hépatites Virales B et Immunothérapie, Paris, France. · Hepatology. · Pubmed #17465004 No free full text.

Abstract: The hepatitis B X (HBx) protein is a crucial component in HBV infection in vivo and has been implicated in HCC. In this study, we aimed to detect and characterize peripheral HBx-specific T cells in chronically infected patients at the inactive carrier state of the disease. HBx-specific IFN-gamma-secreting T cells were found in 36 of 52 patients (69%), and 78% (28/36) of responding patients had T cells targeting epitopes in the carboxy-terminal part of HBx. IL-10 secretion after the stimulation of T cells with HBx-derived peptides was weak or undetectable. IFN-gamma-secreting T cells recognized a previously unknown immunodominant CD4+ T cell epitope, HBx 126-140 (EIRLKVFVLGGCRHK), in 86% (24 of 28) of patients. This peptide bound several HLA-DR molecules (HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*1301, and HLA-DRB5*0101). Its coding sequence overlaps a domain of the HBV genome encompassing the basic core promoter (BCP) region. Taking into account the selection of viral core promoter mutants during HBV infection, we found that HBV variants with BCP mutations were present in patient sera. We further demonstrated that these viral mutant sequences activated T cells specific for the immunodominant epitope only weakly, if at all. This is the first study linking BCP mutations and HBx-specific T cell responses. CONCLUSION: Wild-type and variant peptides may represent potential tools for monitoring the HBV-specific T cell responses involved in sequence evolution during disease progression. Finally, the degenerate HLA-DR binding of this promiscuous, immunodominant peptide would make it a valuable component of vaccines for protecting large and ethnically diverse patient populations.

Serpaggi J, Carnot F, Nalpas B, Canioni D, Guéchot J, Lebray P, Vallet-Pichard A, Fontaine H, Bedossa P, Pol S. · Service d'Hépatologie et INSERM U-567, Hôpital Necker Enfants-Malades, Paris, France. · Hum Pathol. · Pubmed #16997354 No free full text.

Abstract: The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/- 0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease.

Bonny C, Fontaine H, Poynard T, Hézode C, Larrey D, Marcellin P, Bourlière M, Bronowicki JP, Merle P, Zarski JP, Sapey T, Guillemard C, Ughetto S, Henquell C, Nicolas C, Roche C, Randl K, Bommelaer G, Abergel A. · Service d'Hépato-Gastroentérologie, Hôtel-Dieu, Clermont-Ferrand, France. · Aliment Pharmacol Ther. · Pubmed #16907892 No free full text.

Abstract: AIM: To assess the rate of sustained virological response in naïve hepatitis C virus-type 5 patients treated by standard interferon or pegylated-interferon [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND METHODS: A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus-5 patients treated with interferon and peg-interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus-5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus-1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098). CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5-infected patients. Sustained virological response seems better in hepatitis C virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of hepatitis C virus-2-3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus-5 patients.