Hépatite : News 2013 Dr BASTENS - CHC

Estimated Current Prevalence of HCV Infection in Europe < 0.5% < 0.5-1 % 1.1-1.5 % 1.6-2.5 % 2.6-3.5 % > 3.6 % This illustrates the estimated current prevalence of HCV infection in Europe. In Northern Europe the epidemic was mainly transmitted by IDU. With an overall prevalence between 0.1 and 1%, in these countries most prevalent infections are found among adults 30–50 years old. In Central Europe HCV prevalence is intermediate, ranging from 0.2% in the Netherlands to 1.2% in France. In Southern Europe (i.e. Spain, Italy, Greece, Southern France), the overall prevalence ranges between 2.5% and 3.5%. In these countries, an initial epidemic (occurring > 50 years ago) of iatrogenic nature led to a high infection prevalence in older people, followed, some 30 years later, by a still-ongoing IDU related epidemic which spread the infection among younger people. Indeed, using epidemiological data and molecular evolutionary methods, some research groups showed that the spread of genotype 1b in Spain and France, and that of genotype 3a in the former Soviet Union, coincided with local outbreaks of unsafe parenteral treatments. In Eastern European countries epidemiological data in the general population are limited. In a review of the epidemiology of HCV in Eastern Europe, based on published data, a high prevalence of infection (0.9% to 5%) among blood donors, health care workers (1–10%) and high-risk groups (50–92% in hemophiliacs; 13–48% in hemodialysis patients) was reported. Nosocomial transmission (in-hospital diagnostic or treatment procedures) appeared to play a major role in HCV infection (40% to 70% of prevalent cases). The reported incidence of acute hepatitis C (2.2 – 9 cases per 100,000 population) was already increasing in the mid 1990s among people aged 15 to 29, as a result of the epidemic of IDU that had already started in several Eastern European countries. Esteban J, et al. Journal of Hepatology 2008;48:148-162.

Age Distribution of Newly Diagnosed HCV Patients 1999-2001 in a US Community-Based Study, N=442 This describes the distribution of newly diagnosed HCV cases during 1999–2001 in 3 distinct US communities by age categories. A total of 2,353 patients with newly diagnosed chronic liver diseases from a total population under surveillance of approximately 1.5 million (63.92 cases/100,000 population) were reported. 442 new cases of HCV were reported. The largest percentage of these patients were in the 46 to 54 age category. Greater than 60% of new cases were in patients aged over 45. Bell B, et al. Am J Gastroenterology 2008;103:1-10.

Underlying Etiologies in Patients with Newly Diagnosed Chronic Liver Disease in a US Community-Based Study, N=1,040 (1999-2001) This illustrates the most common etiology of newly diagnosed chronic liver disease patients between 1999–2001 in a US community based study of N=1,040. Hepatitis C was reported in (670 [64%]), either alone (442 [42%]), or in combination with alcohol-related liver disease (228 [22%]). There were an additional 82 (8%) patients with alcoholic liver disease (65 [6%] definite and 17 [2%] probable), 95 (9%) with nonalcoholic fatty liver disease (45 [4%] definite and 50 [5%] probable), and 36 (3%) with hepatitis B. Bell B, et al. Am J Gastroenterology 2008;103:1-10.

Who is at Risk for HCV Infection? Current or former IVDUs, including those who injected only once many years ago. Recipients of clotting factor concentrates made before 1987. Recipients of blood transfusions or solid organ transplants before July 1992. People who received body piercing or tattoos done with non-sterile instruments. Chronic hemodialysis patients. Persons with known exposures to HCV, such as healthcare workers. Persons with HIV infection. Children born to HCV-positive mothers. This describes people at highest risk for HCV infection. Current or former IVDUs, including those who injected only once many years ago. Recipients of clotting factor concentrates made before 1987. Recipients of blood transfusions or solid organ transplants before July 1992. People who received body piercing or tattoos done with non-sterile instruments. Chronic hemodialysis patients. Persons with known exposures to HCV, such as healthcare workers. Persons with HIV infection. Children born to HCV-positive mothers. The epidemic of hepatitis C virus (HCV) infection in Europe is continuously evolving and epidemiological parameters (prevalence, incidence, disease transmission patterns and genotype distribution) have changed substantially during the last 15 years. Four main factors contribute to such changes: increased blood transfusion safety, improvement of healthcare conditions, continuous expansion of intravenous drug use and immigration to Europe from endemic areas. As a result, intravenous drug use has become the main risk factor for HCV transmission, prevalent infections have increased and genotype distribution has changed and diversified. CDC – http://www.cdc.gov/hepatitis/C/cFAQ.htm#cFAQ13. Accessed August 2008.

Natural History of HCV Infection 100% (100) HCV is asymptomatic slowly progressive disease evolving over 10 to 20 years Acute Infection 75% (75) Chronic 20% (15) Cirrhosis 25% (4) Liver failure, Liver Cancer Transplant Death Adapted from: Di Bisceglie A, Hepatology 2000;31(4) ;1014-8.

Diagnosis Hepatitis C antibody test: HCV RNA testing: if positive: previous contact with HCV is confirmed HCV RNA testing: if positive: Chronic Hepatitis C is confirmed If negative: spontaneous cure

QUI TRAITER ?? But : éliminer le virus pour empêcher la progression de la maladie vers la cirrhose et ses complications MAIS : Limites : effets secondaires et contre-indications

Pretreatment tests Genotype Viral load Laboratory tests (ALT, platelets, coagulation tests…) Fibrosis assessment: Metavir ≥ F2 => antiviral treatment Cirrhosis => HCC screening, HTP prevention

Methods of liver fibrosis assessment Liver biopsy (“ gold standard “) Blood tests (fibrosis scores) Liver stiffness (Fibroscan®)

Liver stiffness measurement Fibroscan ® 2.5 cm 4 cm 1 cm  Volume Probe LB x 100 Shear wave velocity Stiffness (kPa) Sandrin et al. Ultrasound Med Biol 2003;29:1-8

Liver stiffness and survival Fibrotest FibroScan Vergniol J, et al. Gastroenterology 2011;140:1970–9

SVR in genotype 1 HCV in 2011: boceprevir and telaprevir now both approved in Europe 100 80 60 40 20 63–79%* DAA + Peg-IFN + RBV5,6 42–54% Peg-IFN + RBV2–4 SVR rate (%) 16–28% IFN + RBV1 The HCV treatment paradigm has evolved over the last two decades As new treatments have become available, old regimens have generally become obsolete, with Peg-IFN replacing IFN and Peg-IFN/RBV combinations replacing monotherapy Changes in clinical practice have provided improved chances of success Higher SVR rates in all HCV-infected patients Shorter duration of therapy Opportunities for therapy individualization The introduction of DAAs provides further opportunities for improving treatment outcome and moving the treatment paradigm forward 2–7% IFN1 1. McHutchison JG, et al. N Engl J Med 1998;339:1485–92; 2. Fried M, et al. N Engl J Med 2002;347:975–82 3. Manns MP, et al. Lancet 2001;358:958–65; 4. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346–55 5. Telaprevir EU SmPC; 6.Boceprevir EU SmPC *Treatment-naïve patients

Telaprevir regimen in G1 HCV-infected patients: treatment-naïve without cirrhosis Stop at Week 24 if undetectable at Week 4 and 12 Telaprevir + PR Peg-IFN alfa + ribavirin Peg-IFN alfa + ribavirin if detectable at Week 4 or 12* If >1000 IU/mL at Week 4 or 12: discontinue all drugs If detectable at Week 24 or 36: discontinue PR HCV RNA: 48 Weeks 4 24 36 12 *In Phase III studies, a sensitive real-time PCR assay with a limit of quantification of 25 IU/mL and a limit of detection of 10–15 IU/mL was used to determine whether HCV RNA levels were undetectable. Detectable HCV RNA below the lower limit of assay quantification should not be used as a substitute for ‘undetectable’ for making decisions on treatment duration, as this may lead to an insufficient duration of therapy and higher relapse rates Telaprevir EU SmPC

ADVANCE: SVR rates in Telaprevir-treated Patients Compared with PR Alone 6% difference (95% CI: –12.5% to +0.6%) * * Key Point In the ADVANCE trial, the proportion of patients achieving an SVR was significantly higher in the two telaprevir treatment groups than in the control group.1 Notes Significantly higher SVR rates were observed with telaprevir versus control: 75% and 69% in the T12PR and T8PR arms versus 44% in the PR48 arm. The differences in response rates were 31% between T12PR and PR48 (95% CI: 24%–38%) and 25% between T8PR and PR (95% CI: 18%–32%). Patients in the T8PR arm achieved a slightly lower SVR rate than those in the T12PR arm. For reference, SVR rates of 63–66% were observed with boceprevir in the SPRINT-2 trial.2 References Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A. Poordad F, et al. Hepatology 2010;52(Suppl.):402A. PR48 158/361 T12PR 271/363 T8PR 250/364 n/N = *p<0.0001 vs PR48 Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A

if undetectable at Week 8 and 24 Assess for RGT criterion Boceprevir regimen in G1 HCV-infected patients: treatment naïve without cirrhosis Stop treatment at Week 28 if undetectable at Week 8 and 24 PR lead-in BOC + PR If detectable at Week 8 but undetectable at Week 24: BOC + PR* PR* Weeks 4 8 12 24 28 36 48 Assess for RGT criterion If ≥100 IU/mL discontinue all drugs If detectable discontinue all drugs HCV RNA *This regimen has only been tested in patients who have failed previous therapy who were late responders Boceprevir EU SmPC

SPRINT-2: SVR rates in Boceprevir-treated Patients Compared with PR Alone Key Point In the SPRINT-2 trial, the proportion of patients achieving an SVR was higher in the two boceprevir treatment groups than in the control group.1 Notes Higher SVR rates were observed with boceprevir versus control: 63% and 66% in the BOC RGT and BOC44/PR48 arms versus 38% in the PR arm. For reference, an SVR rate of 75% was observed with the telaprevir T12PR regimen in the ADVANCE trial.2 References Poordad F, et al. Hepatology 2010;52(Suppl.):402A. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A. PR48 137/363 BOC RGT 233/368 BOC44/PR48 242/366 n/N = Adapted from Poordad F, et al. Hepatology 2010;52(Suppl.):402A

Summary In Phase 3 trials, use of either telaprevir or boceprevir plus PR significantly improved SVR versus PR alone1–3 Telaprevir1,2 SVR: 72-75% in T12PR vs 44% in PR Treatment duration: 58-65% of patients were eligible to receive 24 weeks of a telaprevir-based regimen No lead-in required Telaprevir administered for 12 weeks Boceprevir3 SVR: 63% in BOC RGT, 66% in BOC44/PR48 arms vs 38% in PR Treatment duration: 44% of patients were eligible to receive 28 weeks of a boceprevir-based regimen Lead-in mandatory Boceprevir administered for 24 (BOC RGT) or 44 (BOC44/PR48) weeks 1. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A 2. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A 3. Poordad F, et al. Hepatology 2010;52(Suppl.):402A Note that there are inherent limitations of comparing findings from across trials

Définition des types de réponse à un précédent traitement Source: Shiffman. (2006). Chronic Hepatitis C: Treatment of Pegylated Interferon/Ribavirin Nonresponders. Current Gastroenterology Reports, Vol 8.

Taux de réponse chez les patients en retraitement (RESPOND-2/PROVIDE) ** Dans l’étude RESPOND-2, ces patients sont appelés “Prior nonresponders” (diminution du taux d’ARN du VHC d’au moins 2log UI par millilitre à la semaine 12 mais avec un taux d’ARN du VHC détectable pendant toute la durée du traitement) Remarque: Les schémas de traitement préconisés par l’EMA sont différents de ceux des études pour certains groupes de patients. Ces résultats sont donnés à titre informatif.

Prior partial responders REALIZE: SVR in Prior Relapsers, Partial Responders, and Null Responders Prior relapsers Prior partial responders Prior null responders * * * * SVR (%) * * Key Point Telaprevir plus PR was significantly superior to PR alone across all treatment-experienced populations including prior null and partial responders, and relapsers. Notes Telaprevir is the only DAA that has been evaluated in Phase 3 trials in all categories of previously treated patients, including true null responders (patients with a <2 log10 decline in HCV RNA at week 12 of previous PR therapy). In each of the prior response categories, telaprevir in combination with PR significantly improved SVR rates. In prior null responders, who were excluded from the boceprevir-based RESPOND-2 trial, telaprevir/PR led to a 6-fold increase in SVR rates versus PR alone (29–33% versus 5%). In the REALIZE trial, no significant differences in SVR rates were observed between the concurrent and delayed initiation of telaprevir with PR. Therefore, and in contrast to boceprevir, a PR lead-in will not be required with telaprevir. References Foster GR, et al. Hepatol Int 2011;5: Abstract PS02-04 PR48 16/68 LI T12/ PR48 124/141 T12/ PR48 121/145 PR48 4/27 LI T12/ PR48 26/48 T12/ PR48 29/49 PR48 2/37 LI T12/ PR48 25/75 T12/ PR48 21/72 n/N= *p<0.001 vs PR48 Foster GR, et al. Hepatol Int 2011;5(Suppl. 1):14

Safety and Tolerability with DAAs Common AEs with PR include:1–3 Fatigue, headache, nausea, pyrexia and myalgia Anemia and neutropenia Depression, irritability and insomnia Rash Additional management considerations with DAAs* Telaprevir:4–6 rash, pruritus, anemia, anorectal symptoms, nausea and diarrhea Boceprevir:7,8 anemia, dry skin, dysgeusia and rash, neutropenia Key Point Adding telaprevir or boceprevir to peginterferon/ribavirin treatment leads to some additional side effects that need to be considered when treating genotype 1 HCV patients with triple therapy. Notes Existing treatment for HCV infection (peginterferon plus ribavirin) is associated with a range of AEs, most commonly fatigue and influenza-like symptoms associated with peginterferon and anemia associated with ribavirin. The advent of DAAs is likely to somewhat change the spectrum of AEs seen with routine HCV treatment. Telaprevir treatment is associated with increased rash, pruritus, anemia, anorectal symptoms, nausea and diarrhea versus control.1–3 Boceprevir treatment is associated with increased anemia, dysgeusia (taste alteration) and neutropenia versus control.4,5 Additionally, in RESPOND-2 only, boceprevir was associated with a significantly greater frequency of dry skin and rash.5 References Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A. Foster GR, et al. Hepatol Int 2011;5: Abstract PS02-04. Poordad F, et al. N Engl J Med 2011;364:1195-206. Bacon BR, et al. N Engl J Med 2011;364:1207-17 . 1. Pegintron EMA Summary of Product Characteristics 2. Pegasys EMA Summary of Product Characteristics 3. Rebetol EMA Summary of Product Characteristics 4. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A 5. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A 6. Foster GR, et al. Hepatol Int 2011;5: Abstract PS02-04 7. Poordad F, et al. N Engl J Med 2011;364:1195-206 8. Bacon BR, et al. N Engl J Med 2011;364:1207-17 *Common AEs that occurred more frequently (p<0.05) vs PR

Boceprevir Phase 3 Studies: Summary of AEs over Course of Therapy BOC RGT BOC44/ PR48 PR SPRINT-2 (Naive)1,2 N=368 N=366 N=363 Deaths1,2 N=1 N=4 Serious AEs1 11% 12% 9% Discontinued due to AEs2 16% RESPOND-2 (Experienced)3 N=162 N=161 N=80 Deaths N=0 Serious AEs 10% 14% 5% Discontinued due to AE 8% 2% Key Point In treatment-experienced patients, serious AEs and AEs leading to treatment discontinuation were more frequent with boceprevir regimens than the PR control arm.1 In treatment-naive patients, the incidence of these events was similar across arms.2,3 Notes In both Phase 3 trials with boceprevir, the frequency of deaths was similar across study arms.1–3 In the SPRINT-2 trial in treatment-naive patients, the frequency of serious AEs and discontinuations due to AEs were also similar across arms.2,3 However, in RESPOND-2 in treatment-experienced patients, boceprevir was more frequently associated with serious AEs and AEs leading to treatment discontinuation than PR alone.1 References Bacon BR, et al. N Engl J Med 2011;364:1207-17. Poordad F, et al. N Engl J Med 2011;364:1195-206. Poordad F, et al. N Engl J Med 2011;364:1195-206 (supplementary appendix). 1. Poordad F, et al. N Engl J Med 2011;364:1195-206; 2. Poordad F, et al. N Engl J Med 2011;364:1195-206 (supplementary appendix); 3. Bacon BR, et al. N Engl J Med 2011;364:1207-17

Pooled placebo-controlled Phase 2 and 3 studies T12/PR (N=1346) Rash*during Telaprevir Treatment Period in Placebo-Controlled Phase 2 and 3 Studies Proportion (%) of patients with: Pooled placebo-controlled Phase 2 and 3 studies T12/PR (N=1346) Incidence of rash during telaprevir/placebo treatment period: Telaprevir/PR vs Placebo/PR 55 vs 33 Severity Mild (Grade 1) Moderate (Grade 2) At least Severe (Grade 3) 37 14 5 Permanent stop of telaprevir only 6 Key Point In controlled Phase 2/3 studies, the T12/PR regimen was associated with an increased incidence of rash versus placebo/PR (23% risk difference between regimens). However, the proportion of patients discontinuing telaprevir due to rash was low (6%). Notes The T12/PR regimen was associated with a greater incidence of rash versus placebo/PR (55% versus 33%). However, the majority of rash was mild or moderate and the incidence of severe (Grade 3/4) rash events (5%) was relatively low. Overall, 6% of patients permanently stopped telaprevir in controlled Phase 2/3 studies due to rash. References http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252562.pdf http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ Drugs/AntiviralDrugsAdvisoryCommittee/UCM252562.pdf *Reported within a special search category

Intéractions médicamenteuses Il faut être prudent avec Victrelis® ou Incivo en cas d’administration conjointe de médicaments dont la clairance dépend fortement du CYP3A4/5 et pour lesquels des concentrations plasmatiques élevées sont associées à des événements graves et/ou engageant le pronostic vital, tels que: Bzd : Midazolam (administré par voie orale), Triazolam Antiépileptiques : Phénytoine, Carbamazépine Bépridil Pimozide Antifongiques Hypolipémiants Inhibiteurs de la tyrosine kinase Dérivés de l’ergot de seigle Dihydroergotamine Ergonovine Ergotamine Méthylergonovine ! www.hep-druginteractions.org www.hep-druginteractions.org Source: SmPC Victrelis®

Summary and Conclusions Key Point Telaprevir- and boceprevir-based therapy have the potential to significantly improve SVR rates among HCV genotype 1-infected treatment-naive patients. However, with these increased response rates there are also additional patient management considerations. Particularly, telaprevir may lead to increases in anemia, rash and anorectal events, which are generally manageable and do not lead to discontinuation. In addition, boceprevir can increase the occurrence of anemia and dysgeusia. Notes Treatment with DAAs may result in additional patient management considerations. With telaprevir treatment, increased rash, anemia and anorectal events have been recorded.1–4 With boceprevir treatment, increased anemia and dysgeusia events may occur.5,6 Rash events with telaprevir are generally mild or moderate and can be managed using the rash management plan implemented for Phase 3 trials. Study drug interruption is generally not needed for grade 1 rash. For grade 2 rash, treatment interruption is sometimes required, in which case the telaprevir component should be removed from the regimen first. For grade 3 rash, telaprevir treatment must be stopped immediately. Rash adverse events resulted in 6% discontinuation of telaprevir, were manageable and reversible upon cessation of treatment. Anemia was observed at higher frequency in patients treated with boceprevir and telaprevir. Anemia occurred in around 30% of patients treated with telaprevir and half of patients treated with boceprevir. Patients treated in the SPRINT-1 boceprevir trial frequently received erythropoietin. However, erythropoietin was not allowed during telaprevir dosing in the PROVE trials. References 1. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A. 2. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A. 3. Foster GR, et al. Hepatol Int 2011;5: Abstract PS02-04. 4. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/ UCM252562.pdf 5. Poordad F, et al. N Engl J Med 2011;364:1195-206. 6. Bacon BR, et al. N Engl J Med 2011;364:1207-17. 1. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A; 2. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A; 3. Foster GR, et al. Hepatol Int 2011;5: Abstract PS02-04; 4. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252562.pdf; 5. Poordad F, et al. N Engl J Med 2011;364:1195-206; 6. Bacon BR, et al. N Engl J Med 2011;364:1207-17

COMMENTAIRES Nets progrès dans le taux de guérison avec les trithérapies Nécessité d’une compliance stricte du patient Nécessité d’un suivi étroit par un hépatologue expérimenté, et collaboration avec médecin traitant

The beginning of a new era in genotype 1 HCV SVR up to 79% in naïve patients SVR up to 88% in prior relapsers and 61% in partial responders Reduced treatment duration for most patients Increased management considerations (safety, resistance and drug interactions)

Elévation chronique des TGP Alcool : 40-50% des cas, TGO>TGP Stéatose : obésité, hypertriglycéridémie et/ou diabète : 30% Hépatite C : 16% Hépatite B : 2,5% Autres : -hémochromatose , auto-immun, Wilson, médicaments..

Hémochromatose ↑ fer, ferritine, et surtout coefficient saturation (45% ♀ et 50% ♂) Affect° autosomique récessive : présence des 2 gênes mutés : C282Y Quantificat° surcharge : IRM Traitement : saignées Follow up : ECHO , Bio ( risque CHC )

STEATOSE et STEATO HEPATITE Responsable de ~30% des cas d’élévation des transaminases

Histologie Stéatose : simple accumulation de graisse ds hépatocyte Stéato hépatite : idem + inflammation et nécrose, corps de Mallory, fibrose périportale, voire cirrhose

Critères diagnostiques Obésité et/ou diabète type 2 avec présence critères du syndrome métabolique Consommat° alcool < 30 g Foie hyperéchogène diffusément Hépatomégalie, hépatalgies, ↑ TGP>TGO

Critères : S Métabolique Tour de taille>102 cms chez ♂ et 88 cms chez ♀ TGL >1,5 g/l HDL Cholestérol < 0,4 g/l Glycémie a jeun > 1,1 g/l Tension artérielle > 130/85

Explorations Anamnèse ( antécédents, poids antérieur ) Examen clinique ( périmètre abdominal..) Bio : foie, paramètres métaboliques Fer : svt ↑ fer et ferritine Echo, voir IRM Difficultés ∆∆ stéatose ↔ stéato - hépatite

Biopsie hépatique Indiquée si : Age > 50 ans IMC > 28 TGP> 2N, ou TGO>TGP

Evolution « NASH » Evolut°→ cirrhose chez 10-25% cas Si cirrhose : risque complicat° habituels : Hémorragie sur varices Decompensation, insuffisance hépato cellulaire Risque carcinome

Traitement Régime et exercice physique Hypolipémiants Metformine Ursofalk Vitamine E

Bilan d’une élévation chronique des TGP Anamnèse, Examen clinique Ag HBs, Ac HBc, Ac HBs, Ac HCV Fer-Ferritine Echo foie

Médicaments AINS Antidépresseurs Tricycliques Hypolipémiants Augmentin, Furadantine, INH, Cordarone Paracetamol : ! Si alcool Furadantine Papavérine Phytothérapie

Foie et Hormones Hormonothérapie substitutive : R.A.S. Contraceptifs : ↑ faible et transitoire des TGP est fréquente au début Contraceptifs : en pratique OK si cholestase ou cytolyse < 2N Contraceptifs : stop si tumeur bénigne du foie (adénome, HNF )

Foie et Hormones Hormonothérapie substitutive : R.A.S. Contraceptifs : ↑ faible et transitoire des TGP est fréquente au début Contraceptifs : en pratique OK si cholestase ou cytolyse < 2N Contraceptifs : stop si tumeur bénigne du foie (adénome, HNF )

Conclusions : traitement HCV Evolution spectaculaire de l’efficacité des traitements Balance avantages-inconvénients du traitement : pas d’urgence à traiter, tenir compte des effets secondaires, et des contre-indications

Suivi du traitement Rôle spécialiste + médecin traitant : -Informer : durée, efficacité, effets second. -Encourager et stimuler compliance : -Ttmt incomplet ↓ chances de guérison : règle des 80% Remboursement limité à 1 ttmt

Suivi du traitement (2) Spécialiste plus généraliste : Arrêt consommation alcool et drogues : Alcool ↑ virémie et ↓ immunité Alcool ↓ efficacité traitement Méthadone OK