evaluation of intradermal hepatitis b vaccine after imiquimod's application, in cirrhotics who did not respond to the usual vaccine regimen

Conditions: Cirrhosis, Liver; Vaccination Failure; HBV; Vaccine Reaction

Summary: in a population of cirrhotics patients who did not responde to an anti-hbv vaccination according to the recommended vaccination, the goal is to : describe the proportion of patients with hbs antibody levels greater than 10mui/ml at 1 month of the last injection of vaccine ; with a m0-m1-m6 vaccine regimen using 3 vaccines strategies : * after simple intramuscular vaccine (im) ( control group ) * after simple intradermal vaccine * after imiquimod's application followed by intradermal vaccine administration the main hypothesis of this study is : imiquimod acts as an immunity booster, so the combination of imiquimod with an intra-dermal injection of the anti-hbv vaccine allows better acquisition of post-vaccination immunization.

this study will be in a population of cirrhotic patients who have already received a hbv vaccination with a conventional regimen and who have not responded (characterized by a level of antibody hbs \< 10ui/ml at the end of the vaccine regimen). in current recommendations, up to 3 additional injections of hbv vaccine should be injected to obtain an antibody level\> 10 miu / ml. in this study, the investigator will describe the proportion of patients with hbs antibody levels greater than 10mui/ml at 1 month of the last injection of vaccine ; with a m0-m1-m6 vaccine regimen using 3 vaccines strategies : * after simple intramuscular vaccine (im) ( control group ) * after simple intradermal vaccine * after imiquimod's application followed by intradermal vaccine administration

Eligibility criteria:
inclusion criteria: * adults (\> 18 years old) * cirrhotic patient, all etiologies except related to chronic hbv infection. * cirrhotic patient who did not respond to a 1st conventional hepatitis b vaccination regimen administered intramuscularly (ac anti hbs \< 10 mui/ml) * person affiliated to a social security plan * person who received complete information about the organization of the research and who signed informed consent exclusion criteria: * patients with contraindication to the use of an intramuscular vaccine : patients on anticoagulants; hemophiliac patients, patients with severe hemostasis disorder (objectified by tp \< 30%; and/or a thombopenia with platelets \< 30g/l) * patients with end-stage chronic kidney failure defined by dfg \<15ml/min/1.73m2 _ hemodialysised patients * patients with a skin condition that does not allow vaccination (intradermal or intra-muscle): skin sores on both arms: ulcers/abrasions/bubbles ; without healthy skin intervals. * femme of childbearing age who does not have an effective method of contraception for the duration of the study. effective contraceptive methods are defined as combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral, intravaginal, transdermal); or progestin-only hormonal contraception combined with ovulation inhibition (oral, injectable, implantable); or intrauterine device (iud); or intrauterine hormone delivery system (ius); or bilateral tubal occlusion; or a vasectomized partner; or sexual abstinence; permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. menopause is defined as the absence of menstruation for at least 12 months. according to ctfg recommendations related to contraception and pregnancy testing in clinical trials; version 1.1 of 21/09/2020. * personne referred to sections l. 1121-5, l. 1121-7 and l1121-8 of the public health code. pregnant, parturient or breastfeeding mother minor (unassecipated) an adult subject to a legal protection measure (tutelage, curate, safeguarding of justice) adult person undying to express consent * persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care under sections l. 3212-1 and l. 32131. * vaccination during the 4 weeks (28 days) prior to the first vaccination in the trial * previous vaccination with another investigational vaccine * subjects who have received immunoglobulins, blood or blood derivatives within the last 3 months. * known or suspected congenital or acquired immunodeficiency; immunosuppressive therapy within the last 6 months, such as cancer chemotherapy or radiotherapy; long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the last 3 months). * acute respiratory infection or severe acute febrile illness (temperature ≥ 38.0°c), or a systemic reaction that may be of significant risk with vaccination in the month prior to inclusion.