albi

Prof. Raoul Poupon

UPMC Univ Paris 06, UMRS_893, CdR Saint-Antoine, F-75012, Paris, France
INSERM, UMRS_893, CdR Saint-Antoine, F-75012, Paris, France
AP-HP, Hôpital Saint-Antoine, Service d’Hépatologie & Centre de Référence des Maladies Inflammatoires des Voies Biliaires, F-75012, Paris, France

Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that affects mainly the biliary cells lining the small bile ducts of the liver. As many other autoimmune disorders PBC occurs mostly women. Its peak incidence occurs in the fifth decade of life, and it is uncommon in persons under 25 years of age. From a clinical standpoint PBC is defined empirically as a syndrome characterized by chronic cholestasis and autoantibodies directed mainly against the E2 subunits of pyruvate dehydrogenase complex of mitochondria. Histologically the typical lesion is the so-called non-suppurative destructive cholangitis (NSDC) often associated with ductopenia and inflammation extending beyond the portal tracts into the surrounding parenchyma. Spreading of the inflammatory process into the lobule is associated with hepatocellular destruction and manifested either under the form of lymphocytic piecemeal necrosis or biliary piecemeal necrosis. As the result of hepatocellular death the limiting plates are progressively replaced by newly formed connective tissue making fibrous septa linking adjacent portal tracts and leading eventually to cirrhosis. The severity of this pathological process and its rate of progression are highly variable from one patient to another.

There are 3 major forms of the disease. The typical form is represented by the slowly progressive decline of patent small bile ducts and progressive parallel increase in liver fibrosis leading to biliary cirrhosis over a period of 10 to 20 years. A second form that affects about 15 to 20 % of the patients is characterized by the fluctuating or persistent presence of the features of autoimmune hepatitis (1). These patients have a more severe course with early development of liver fibrosis and liver failure. A third form that affects 5 to 10% of the patients is represented by the so-called premature ductopenic variant (2). Its hallmark is a very rapid onset of ductopenia and severe cholestasis progressing very quickly towards cirrhosis in less than 5 years.

Diagnosis and evaluation of the patient with PBC

The diagnosis of PBC is generally easy. The diagnosis is based on the 3 following criteria: a) abnormal biochemical tests with preferential elevation of serum alkaline phosphatase and gammaglutamyltranspeptidase activities) ; presence of antimitochondrial antibodies with M2 (AMA) specificity as confirmed by ELISA or immunoblotting; c) evidence of NSDC at histology.

Criteria a and b or c are sufficient for the diagnosis considering the high specificity of anti-M2 antibody and NSDC. Patients with AMA and normal biochemical tests are at risk of developing true PBC. Patients with biochemical evidence of cholestasis but AMA negative may have PBC if portal inflammation and ductopenia are demonstrated at liver biopsy. The diagnosis is further supported in this setting if antinuclear antibodies against GP 210, Nucleoporin 62, sp100 giving nuclear-rim or nuclear –dot pattern are present. In some patients AMA appear during the follow-up of these patients. NSDC is highly suggestive of PBC but is not pathognomonic since it may be present in patients with autoimmune hepatitis, primary slerosing cholangitis, lymphoma and viral hepatitis C and E.

The evaluation of the patient is of considerable importance for the prognosis and treatment.

Mucosal infections especially recurrent urinary infections and cigarette smoking are two main risk factors of PBC (3, 4). Infections should be treated or prevented; passive or active smoking should be avoided.

About 30% of the patients exhibit simultaneous or consecutive other autoimmune diseases, the most frequent being autoimmune hepatitis, CREST syndrome and/ or sleroderma and thyroiditis. Sicca symptoms are sought by direct questioning. They include xerostomia but also dental caries, gum infection and tracheobronchitis. Celiac disease is not so frequent but should be recognized because of the beneficial effect of the gluten free diet.

First-degree relatives of patients with PBC are at high risk of PBC or other autoimmune diseases. The patients and their relatives should be informed and evaluated for these conditions.
While the pathogenesis of fatigue and pruritus is still unknown and their treatment empirical these two symptoms should be carefully analyzed and if possible quantified.

Next the attention should focus on the severity or potential severity of the disease.

Is there evidence of cirrhosis? Asymptomatic cirrhosis is probable if splenomegaly is disclosed, if prothrombin index is lower than 80%, if serum albumin is lower than 38 g/L, if serum bilirubin is more than 2 mg/dl, if the platelet count is les than 150000/microl. In these patients eosophageal varices should be evaluated and treated if of large size. The cirrhotic patients are at risk of developing hepatocellular carcinoma and as such need to be regularly investigated by imaging techniques.

Is there evidence of indices of severity and predictors of poor response to ursodeoxycholic acid (UDCA) therapy apart cirrhosis? Fatigue and pruritus are in most cases not related to the severity of PBC and does not have major prognostic value. Serum bilirubin level is the best predictor of prognosis and of long-term response to UDCA treament. Patients even with mild elevation (more than 1mg/dl ) are at risk of developing extensive fibrosis or cirrhosis in the next ten years. Patients with high serum bilirubin level (more than 3mg/l), high serum alkaline phosphatase activity and cholesterol have usually severe
ductopenia at presentation (the premature ductopenic variant of PBC) and will not respond to any medical therapy. These patients should be informed that liver transplantation is the only therapeutic alternative.

Is there evidence of features of autoimmune hepatitis ? Patients with both the criteria of PBC and autoimmune hepatitis need to be given both UDCA and glucocorticoids. High levels of serum bilirubin together with high ALTand IgG as well the presence of antiactine and anti SLA antibodies is very suggestive of this condition. HLA DR3 and DR4 could be another marker of this PBC variant.

Liver biopsy is mandatory to fully evaluate the prognosis and to establish the best medical treatment. Given the risk of sampling error at least 10 portal tracts should be available. The individual lesions have to be graded. We used the Metavir score to assess both fibrosis and interface hepatitis (under the form of lymphocytic piecemeal necrosis). Presence and extent of the NSDC should be noted. Ductopenia should be quantified. However, in case of heavy portal inflammation this quantification may be difficult even with the use of cytokeratin histochemical staining. The presence and extent of biliary piece meal necrosis i.e, the mixture of ductular proliferation, macrophages, polymorphonuclears and fibroplasia should be assessed. Nodular regenerative hyperplasia, sometimes present may indicate portal vascular damage by inflammatory cells. Presence of numerous fibrous septa, loss of more than 50% of the interlobular bile ducts, moderate to severe lymphocytic or biliary piecemeal necrosis are indices of severe prognosis (5, 6).

Because the prognosis of PBC is far better than 2 or 3 decades ago two associated conditions deserve particular attention. Hypercholesterolemia with increased LDL cholesterol is observed in about 20% of the patients. Accordingly the risk of cardiovascular disease should be evaluated and medical therapy possibly proposed. Osteoporosis and osteopenia might be more frequent in PBC women than in a control population although this remains controversial. Nevertheless metabolic bone disease should be assessed and prevented in particular in those at risk of receiving glucocorticoids.

Specific therapy for PBC

All PBC patients with abnormal liver biochemistry should be considered for specific therapy.

UDCA, at the dose of 13 to 15mg/Kg/day, is currently considered the mainstay of therapy for PBC. Randomized, double-blinded, placebo-control trials have consistently shown that UDCA improves parameters of liver biochemistry including serum bilirubin, the major prognostic marker in PBC. UDCA delays the progression of fibrosis and of histological stage (7-10). A combined analysis of three randomized-controlled trials including 548 patients with PBC showed improved survival free of liver transplantation in patients with moderate to severe disease treated with UDCA at doses of 13 to 15 mg/kg/day for up to 4 years (11). Long-term observational studies from France, Spain and the Netherlands (6, 12-14) have shown that UDCA therapy provides a better survival than that predicted by the Mayo model. The survival rate of UDCA treated patients in stage 1 and 2 is similar to that in a control population (6). Some metaanalysis (but not all) including short-term trials with low doses of UDCA (less than 12mg/Kg/day) have questioned the efficacy of UDCA. However on the basis of all available data, it is currently recommended to treat PBC with UDCA using doses of at least 13 mg/kg/day and to start early. UDCA could be taken in divided doses or as a single dose. I recommend one dose in the morning, the other in the evening, and both at meals. In some active patients the compliance seems better with a single dose. Because UDCA is an acid it could produce in some patients gastric discomfort, burning sensation and symptomatic reflux. These symptoms are easily managed with proton pump inhibitors or by ingesting the bile acid at the end of meals.

Overall UDCA is extremely safe. The majority of the patients note a weight gain (2 Kg, on average). This weight gain may be more significant in the patients who have stopped smoking. In patients with pruritus and frank cholestasis, UDCA may increase pruritus if given at the dose of 13-15 mg/Kg/day. In these patients I recommend to start UDCA therapy at a low dose (200-4OO) mg/day and to progressively increase the daily dosage over a period of 4 to 8 weeks.

The aim of UDCA therapy is to provide the normalisation of the serum bilirubin, alkaline phosphatase and ALT or AST levels at the end of the first year of therapy. In many patients this could not be achieved. We define the optimal response to UDCA when serum bilirubin is less than 1mg/dl and AST less than two times the upper limit of normal, and alkaline phosphatase less than 3 times the upper limit of normal at the end of the first year of therapy. Indeed the patients with these criteria have a normal life expectancy without liver transplantation (15). Others (13) have observed that patients with a decline of serum alkaline phosphatase of more 50% achieved an excellent long-term prognosis. In a small subset of patients the daily dose of 13-15 mg is not sufficient to achieve the best biochemical response. In the patients who do respond adequately we measure by LC-MS the blood and biliary enrichment in UDCA. In those with a low percentage of UDCA (less than 40%) a trial with daily doses up to 20mg/Kg/day is proposed to achieve a better response.

About 40% of our patients have a suboptimal response to UDCA. These patients need an adjuvant therapy.

Adjuvant therapies

Patients with features of autoimmune hepatitis, severe interface hepatitis, abnormal serum bilirubin level or suboptimal response to UDCA -as defined above- deserve trials with adjuvant therapies. Currently glucocorticoids (prednisone or budesonide) and methothrexate could be considered for these patients.

The rationale for the use of glucocorticoids is based on the following arguments. Glucocorticoids and specificically budesonide have been shown to provide benefit in patients treated by UDCA (16-18). Combination of both affords better biochemical response and better histological response in terms of inflammation and fibrosis. Budesonide is given at 6 to 9 mg/day in non-cirrhotic patients. The drug is contraindicated in patients with cirrhosis. Preliminary studies in our patients indicate that patients with a suboptimal response to UDCA benefit from the combination of UDCA and glucocorticoids (prednisone or budesonide) in terms of survival without liver transplantation.

Methotrexate improved biochemical test results and liver histological findings when it was added to UDCA in patients who had an incomplete response to UDCA (19). However other studies found no efficacy of methotrexate was used alone or in combination with UDCA. In a 10-year study, survival was the same in patients taking methotrexate and UDCA as in those taking colchicine and UDCA and survival was similar to that predicted by the Mayo model. However, one third of the patients had few signs of PBC after 10 years of treatment (20). No patient who was in the precirhotic stage at baseline showed progression to cirrhosis. Methotrexate may cause interstitial pneumonitis similar to that seen in rheumatoid arthritis.

Several drugs, colchicine, bezafibrate, ciclosporine, chlorambucil, penicillamine azathioprine, mycophenolate mophetil, malotilate, thalidomide have been evaluated in PBC. Many of them are either ineffective or toxic. None of them have been shown to be effective in UDCA treated patients at risk of development of cirrhosis or liver failure as defined above.

Orthopic liver transplantation

Liver transplantation has greatly improved survival in patients with PBC. It is the only effective treatment for those with decompensated cirrhosis or liver failure. The patients who present with the features of the premature ductopenic variant of PBC do not respond to any medical therapy and despite the absence of any decompensation draws a major benefit from liver transplantation. PBC recurs in about 25% of patients at 5 years. Recurrence is more frequent in patients without a glucocorticoid and ciclosporin regimen. The beneficial long-term effect of UDCA in this setting remains unknown.

Treatment of symptoms and complications

Pruritus

The first line therapy is rifampicin at the daily dose of 300-600 mg/day in patients receiving UDCA. However the drug may induce hepatitis in some cases. Second line therapies include glucocorticoids, cholestyramine, and opioids antagonists. Plasmapheresis or biliary drainage may be successful when other treaments fail. In very rare patients resistant pruritus may be an indication for liver transplantation

Fatigue

Fatigue is a frequent complaint in PBC. The symptom is unrelated to the severity of the disease. Whether it is a specific symptom or not remains unknown. Fatigue has a major impact on the quality of life of PBC patients. It is associated with cognitive and emotional dysfunction, depression, sensory and autonomic abnormalities (21, 22). It is also associated with excessive day-time somnolence (23). Modafinil, a drug approved for the treament of narcolepsy have been reported in open studies to provide significant benefit in PBC patients with fatigue (24, 25). The drug used at a dose up to 400 mg /day seems well tolerated and in our experience very effective in those with excessive fatigue and day-time somnolence.
Hypercholesterolemia
UDCA induces an average 15-20 % falls in total and LDL cholesterol at one year of therapy. Statins and ezetimibe are safe and effective in those who still have increased LDL cholesterol.

Portal hypertension

A minority of patients with PBC develop presinusoidal portal hypertension before becoming cirrhotic. The management of portal hypertension in patients with PBC should be as for all cirrhotic patients. Severe portal hypertension even without any other sign of decompensation is a good indication of liver transplantation. Liver transplantation should be preferred to TIPS.

Osteopenia and osteoporosis.

Current treatments for osteopenia and osteoporosis that affect up to 30% of PBC patients included physical activity, calcium and vitamin D supplementation in order to achieve at least 30 ng/ml of serum 25OH D3, biphosphonates or estrogens supplementation.

References

1.    Poupon R. Autoimmune overlapping syndromes. Clin Liver Dis 2003;7:865-878.
2.    Vleggaar FP, van Buuren HR, Zondervan PE, ten Kate FJ, Hop WC. Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant. Gut 2001;49:276-281.
3.    Gershwin ME, Selmi C, Worman HJ, Gold EB, Watnik M, Utts J, Lindor KD, et al. Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients. Hepatology 2005;42:1194-1202.
4.    Zein CO, Beatty K, Post AB, Logan L, Debanne S, McCullough AJ. Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: A cross validated retrospective assessment. Hepatology 2006;44:1564-1571.
5.    Corpechot C, Carrat F, Poupon R, Poupon RE. Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients. Gastroenterology 2002;122:652-658.
6.    Corpechot C, Carrat F, Bahr A, Chretien Y, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology 2005;128:297-303.
7.    Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 2000;32:1196-1199.
8.    Pares A, Caballeria L, Rodes J, Bruguera M, Rodrigo L, Garcia-Plaza A, Berenguer J, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol 2000;32:561-566.
9.    Angulo P, Batts KP, Therneau TM, Jorgensen RA, Dickson ER, Lindor KD. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis. Hepatology 1999;29:644-647.
10.    Poupon RE, Lindor KD, Pares A, Chazouilleres O, Poupon R, Heathcote EJ. Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis. J Hepatol 2003;39:12-16.
11.    Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997;113:884-890.
12.    Poupon RE, Bonnand AM, Chretien Y, Poupon R. Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group. Hepatology 1999;29:1668-1671.
13.    Pares A, Caballeria L, Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology 2006;130:715-720.
14.    ter Borg PC, Schalm SW, Hansen BE, van Buuren HR. Prognosis of ursodeoxycholic Acid-treated patients with primary biliary cirrhosis. Results of a 10-yr cohort study involving 297 patients. Am J Gastroenterol 2006;101:2044-2050.
15.    Corpechot C, Abenaboli L, Rabahi N, Chrétien Y, Johanet C, Chazouilleres O, Poupon R. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 2008;in press.
16.    Leuschner M, Guldutuna S, You T, Hubner K, Bhatti S, Leuschner U. Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis. J Hepatol 1996;25:49-57.
17.    Leuschner M, Maier KP, Schlichting J, Strahl S, Herrmann G, Dahm HH, Ackermann H, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 1999;117:918-925.
18.    Rautiainen H, Karkkainen P, Karvonen AL, Nurmi H, Pikkarainen P, Nuutinen H, Farkkila M. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 2005;41:747-752.
19.    Kaplan MM, Schmid C, Provenzale D, Sharma A, Dickstein G, McKusick A. A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Gastroenterology 1999;117:1173-1180.
20.    Kaplan MM, Cheng S, Price LL, Bonis PA. A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results. Hepatology 2004;39:915-923.
21.    Jacoby A, Rannard A, Buck D, Bhala N, Newton JL, James OF, Jones DE. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut 2005;54:1622-1629.
22.    Poupon RE, Chretien Y, Chazouilleres O, Poupon R, Chwalow J. Quality of life in patients with primary biliary cirrhosis. Hepatology 2004;40:489-494.
23.    Newton JL, Gibson GJ, Tomlinson M, Wilton K, Jones D. Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence. Hepatology 2006;44:91-98.
24.    Kaplan MM, Bonis PA. Modafinil for the treatment of fatigue in primary biliary cirrhosis. Ann Intern Med 2005;143:546-547.
25.    Jones DE, Newton JL. An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis. Aliment Pharmacol Ther 2007;25:471-476.

Notre Assemblée Générale statutaire s’est bien déroulée et a donné lieu à un nombre record de présents et votants ( 134 votants).

Tous les points de l’ordre du jour ont été adoptés.

Notre Réunion Annuelle d’Informations s’est tenue le même jour à la suite de notre Assemblée Générale: elle a rassemblé 70 personnes. Avec la participation notamment des spécialistes du Centre de Référence des Maladies Inflammatoires du Foie et des Voies Biliaires sous la direction du Professeur Raoul Poupon.

Après une introduction à la journée et une présentation de l’ordre du jour par Madame Angela Leburgue, présidente d’ALBI, celle-ci a passé la parole aux intervenants .

Philippe Durand, responsable de la communication d’ALBI et webmestre de notre site, a fait un bref rappel de l’historique de l’association ainsi que de la fréquentation de notre site a et a pu faire des démonstrations des nouveautés qui y sont implantées depuis quelques mois; celles-ci évoluent désormais très fréquemment en fonction de l’actualité grâce à la technique employée qui s’apparente à la technique de “blog”.

Les conférenciers du Centre de Référence ont présenté les nouvelles pistes de recherche :

C’est notamment ainsi que Mademoiselle Audrey Coilly, médecin interne au service d’hépatologie de l’Hôpital Saint Antoine, dans le cadre d’un mastère en Biologie, nous a parlé de l’étude qu’elle a réalisée, et pour laquelle ALBI lui a octroyé une bourse de recherche : son étude a permis de démontrer des différences dans des groupes de gènes chez des patients atteints de CBP par rapport à un groupe témoin de personnes saines. L’étude n’est pas terminée mais en phase finale.

Monsieur Nicolas Chignard, Maître de conférence à L’Université Pierre et Marie Curie de Paris, a montré les résultats d’une recherche démontrant comment agit l’acide ursodésoxycholique au coeur des cellules hépatiques afin de les protéger des agressions .

Le Docteur Christophe Corpechot a commenté l’étude menée en France sur les facteurs de risques environnementaux concernant le développement de la cirrhose biliaire primitive, étude menée grâce à la participation des adhérents d’ALBI, et le soutien des sociétés AXCAN et IPSOS.

Les conférenciers ont également fait le point sur l’évolution des pratiques clinique basées sur les connaissances actualisées concernant la cirrhose biliaire primitive (CBP), par le Professeur Poupon, la cholangite sclérosante primitive (CSP), par le Professeur Chazouillères, et l’hépatite auto-immune (HAI) par le Docteur Christophe Corpechot.

Madame Paulette Morin, présidente de l’Association Française du syndrome de Marfan et porte-parole de l’Alliance Maladies Rares a ensuite évoqué le plan Maladie Rares et les droits des malades atteints de maladie rares eu égard à différents aspects (ALD, prêts bancaires, aménagement de travail , etc..).

Enfin Madame Annie Mollet, Trésorière de l’Association, a informé les participants de la liste des services d’Hépatologie des Hôpitaux que le Centre de Références des Maladies Inflammatoires du Foie et des Voies Biliaires avait proposé au Ministère de la Santé afin qu’ils soient nommés Centre de Compétences concernant les maladies qui sont l’objet de notre association. La nomination officielle de ces centres devrait intervenir d’ici juin prochain.

Comme d’habitude , un dialogue s’est instauré entre les conférenciers et les participants à cette réunion, dans une atmosphère conviviale, tant durant les cycles de conférences que durant le déjeuner, réunissant conférenciers et participants.

Tous les adhérents recevront le compte rendu de l’assemblée générale et un résumé écrit de la réunion d’information; ce dernier demande un très gros travail de compilation de la vidéo de la réunion, de sa transcription en un résumé compréhensible et aussi complet que possible en s’assurant qu’il ne comporte pas d’erreur scientifique, et de validation scientifique par les conférenciers.

Aussi la parution du compte rendu de la réunion d’information ne sera sans doute pas disponible avant de très nombreuses semaines.

Chers amis adhérents;Vous avez tous reçu la convocation à notre assemblée générale ordinaire et notre invitation à participer à la journée d’informations médicales qui auront lieu au même endroit le 16 février 2008.Pour les retardaires , il est encore temps- mais c’est très urgent-  d’envoyer votre bulletin d’inscription accompagné d’un chèque du montant de votre participation aux frais d’organisation de la journée d’informations médicales.Merci d’agir au plus vite: les inscriptions seront définitivement closes le 11 février à 18 heures. Pour ceux qui ne seront pas présents ce jour là, n’oubliez pas , si vous ne l’avez encore fait,  de nous faire parvenir soit votre bulletin de vote par correspondance, soit votre mandat donnant pouvoir à un autre adhérent de voter pour vous.D’avance MERCI!Pour information: avec les données en notre possession arrétées au  07/02/2008, nous attendons 70 personnes présentes à la journée d’informations médicales.Le nombre de votants à l’assemblée générale devrait atteindre quant à lui  140 votants ( en incluant pouvoirs et votes par correspondance).  

Cirrhose Biliaire Primitive

CBP : une fausse réputation de bénignité
Prince M, Chetwynd A, Newman W, Metcalf JV, James OFW.
Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis : follow-up for up to 28 years
Gastroenterology 2002; 123 :1044-1051

CBP et carcinome hépatocellulaire : une complicationnon exceptionnelle
Caballeria L, Pares A, Castells A, Gines A, Bru C, Rodes J.
Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis
Am J Gastroenterol 2001; 96 :1160-1163

Overlap syndrome : est-ce plus grave ?
Joshi S, Cauch-Dudek K, Wanless I, Lindor K, Jorgensen R, Batts K, HeathcoteEJ.
Primary biliary cirrhosis with additional features of autoimmune hepatitis : response to therapy with ursodeoxycholic acidHepatology 2002; 35 :409-413Chazouillères O, Poupon R.
Ursodeoxycholic acid and primary biliary cirrhosis with additional features of autoimmune hepatitis
Hepatology 2002; 36 :1026-1027

L’AUDC freine la progression de la fibrose hépatiqueau cours de la CBP
Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R.
The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis
Hepatology 2000; 32 :1196-1199.

CBP et pronostic histologique: incidence et facteursprédictifsde développement de la cirrhose sous AUDC
Corpechot C, Carrat F, Poupon R, Poupon RE.
Primary biliary cirrhosis : incidence and predictive factors of cirrhosis development in ursodiol-treated patients
Gastroenterology 2002; 122 :652-658.

Acide ursodésoxycholique : la polémique (meta-analyseou analyse combinée des données individuelles ?)
Goulis J, Leandro G, Burroughs A.
Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis : a meta-analysisLancet 1999; 354 :1053-1060Lindor K, Poupon R, Poupon RE, Heathcote EJ, Therneau T.
Ursodeoxycholic acid for primary biliary cirrhosis
Lancet 2000; 355 :657-658

CBP et corticoïdes : une question de timing?
Leuschner M, Maier KP, Schlichting J, Strahl S, Herrmann G, Dahm HH,Ackermann H, Happ J, Leuschner U.
Oral budesonide and ursodeoxycholic acid treatment of primary biliary cirrhosis : results of a prospective bouble-blind trial.
Gastroenterology 1999; 117 :918-925

Angulo P, Jorgensen RA, Keach JC, Dickson ER, Smith C, Lindor K.
Oral budesonide in the treatment of patients with primary biliary cirrhosis with suboptimal response to ursodeoxycholic acid
Hepatology 2000; 31 :318-323

CBP et transplantation : 20 ans de recul
Liermann Garcia RF, Garcia CE, McMaster P, Neuberger J.
Transplantation for primary biliary cirrhosis : retrospective analysis of 400 patients in a single center
Hepatology 2001; 33 :22-27

Depuis 1999, lors d’un bilan de santé, mes taux des transaminases étaient plus élevés que la normale. Le médecin avait demandé à l’époque de faire une analyse pour voir si j’avais de l’hépatite. Le résultat étant négatif, il paraissait rassuré. Comme cela se reproduisait à chaque fois, il a jugé plus sûr que j’aille voir un gastro-entérologue. Après discussion et au regard des analyses, cela n’a pas paru inquiétant à ses yeux. Ainsi, plusieurs années ce sont passées jusqu’à ce que je sois allée voir un autre gastro-entérologue qui, immédiatement, a demandé des analyses complémentaires. Et, en arrivant du bureau j’avais déjà un message du laboratoire ainsi que les résultats de mon examen. Quelle n’a pas été ma surprise de voir un taux d’anticorps antimitochondrie (AMA) très élevé. Immédiatement je suis allée voir sur internet la signification de ces anticorps : marqueur d’une maladie chronique du foie, la cirrhose biliaire primitive (CBP).

Même si j’ai appris à apprécier la bonne cuisine française ainsi que les vins d’excellente qualité depuis mon arrivée en France, je ne pensais pas pouvoir justifier d’une cirrhose. En lisant sur Internet, j’ai pu comprendre que cirrhose dans la CBP n’avait rien à voir avec l’alcool. Mais le pronostic était pour le moins désespéré. En regardant les textes disponibles à l’époque et la façon dont la description de la maladie était faite, il devait me rester au maximum de 3 à 5 ans de vie. Ou, dans le meilleur des cas, la greffe de foie.

Mon gastro-entérologue m’a prescrit l’acide ursodésoxycholique. Je me suis accrochée à ce traitement en ayant l’impression de subir le destin. Mais quoi faire de mes centaines des questions sans réponses, de l’impression de me trouver seule avec cette maladie avec un nom honteux, dont personne ne connaissait la cause et dont on n’avait pas de traitement curatif ? Où trouver quelqu’un pour me rassurer ?

Heureusement je comptais sur l’appui constant et chaleureux de mon mari qui m’a permis de continuer à me battre sans sombrer dans une quasi dépression qui m’avais gangée. Mais malgré tout il ne pouvait pas m’apporter les réponses à mes questions.
Après des semaines d’angoisse j’ai trouvé un article, toujours sur internet, sur le premier professeur à avoir fait des publications sur l’utilisation de ce médicament pour le traitement de la CBP. Ce professeur se trouvait en France (Prof. Poupon). J’ai pris rendez-vous avec lui et j’ai vu en face de moi une personne pouvant répondre à mes questions et surtout capable de me rassurer. C’est ce que je cherchais. C’était le début de la sortie de mon état de découragement.
Après cela, j’ai pu commencer à penser aux autres qui, comme moi, atteints de cette maladie, se sentaient seuls et sans réponses. Après avoir suivi à distance le travail merveilleux fait aux USA, UK et Canada par les associations de patients, l’idée de faire de même en France m’a paru indispensable. Je n’étais pas la seule à avoir songé. D’autres avaient déjà eu cette idée restée latente. Comme en physique ou en économie, il a ainsi fallu qu’une masse critique suffisante d’énergies et de volontés soit atteinte pour passer de l’idée à la réalisation.

C’est donc ainsi que naquit ALBI….

Et nous voila maintenant sur Internet en essayant de communiquer cette énergie de solidarité, afin d’aider les personnes souffrant de cette maladie ainsi que leur entourage. Le corps médical et scientifique a également besoin de notre support pour mieux se battre contre cette maladie afin de mieux aider les patients.

Les laboratoires pharmaceutiques sont également de notre côté dans cette lutte. Notamment dans le cas de la molécule l’acide ursodésoxycholique, qui est la seule actuellement disponible pour ralentir la progression de cette maladie, le nombre de malades étant faible, la rentabilité pour eux n’est pas comparable à des maladies plus répandues.
Il nous reste à chercher l’adhésion des pouvoir publics à notre cause et à capter l’attention de sponsors afin de poursuivre notre but : améliorer le cadre de vie des personnes atteintes de la CBP ainsi que d’autres maladies biliaires inflammatoires en général (comme la cholangite sclérosante, par exemple) et aider les équipes de recherche à trouver la cause et la guérison de ces maladies.