Methyldopa által indukált akut reaktív hepatitis terhességben, a máj gyógyszer-metabolizáló képességének alakulása@@@Acute reactive hepatitis in pregnancy

Az alfa-methyldopa altalanosan hasznalt antihipertenziv medikacio a terhesseg alatt. A sympathoadrenerg rendszert csokkentő methyldopat evtizedek ota elsőkent valasztott gyogyszerkent alkalmazzak a terhesseg indukalta hypertoniaban. A reaktiv hepatitis nem gyakori, de ismert sulyos mellekhatasa az alfa-methyldopanak. A nem terhes nőknel 2,5–10%-ra becsulik a manifesztalodott hepatotoxicitast. A 35 eves gravida terhessegi hypertoniaja a 21. gestatios heten alakult ki, amely miatt oralis methyldopa-, azaz centralis hatasu alfa-adrenerg-gatlo terapiaban reszesult. A gestatio 23. heteben akut hepatitis kepe manifesztalodott. A hepatitis etiologiajanak differencialdiagnosztikajaban a methyldopa koroki szerepe felmerult, a hepatitis viralis es autoimmun eredete kizarhato volt. Ultrahangvizsgalattal magzati elteres nem volt lathato. A beteg gyogyszer-metabolizalo kepessegenek alakulasara vizsgalat tortent a verből, CYP-fenotipizalas, genexpresszio alapjan, amely meresekkel a szervezet (a maj) aktualis gyogyszer-metabolizalo kepesseget minősitettuk. A methyldopat elhagytuk es nifedipinre valtottunk. Mivel a nifedipin metabolizmusaban elsődlegesen a CYP3A4 enzim vesz reszt, a betegnel alkalmazott nifedipindozist a CYP3A4 genexpresszio mertekehez igazitottuk. Redukalt dozis (30 mg/nap) mellett ertuk el a megfelelő vernyomascsokkenest. Az anamnezis klinikai kep, kemiai laboratoriumi vizsgalatok es a gyogyszer-metabolizalo kepessegenek vizsgalata az alfa-methyldopa indukalta hepatitis diagnozisat megerősitettek. Az alfa-methyldopa hepatotoxicitasat terhessegben előszor 1969-ben Elkington kozolte. Napjainkban Aust es Coli valtozatlanul case-studyjukban javasoltak a szerumaminotranszferaz- (ALT-) szint ellenőrzeset az alfa-methyldopa-terapia bevezetesekor es a terhesseg alatt. Esetunk alatamasztja a monitorozas szuksegesseget. | Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy. Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice since decades. The reactive hepatitis is not frequent, but known serious side effect of alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity is 2.5–10%. In our case, gestation hypertension developed at the 21st gestation week of a 35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker therapy was introduced. On the 23rd gestation week acute hepatitis developed. During differential diagnosis of hepatitis, the etiology of methyldopa was taken into account. Viral and autoimmune origin was rolled out. No fetal aberration was found during ultrasound examination. The function of drug metabolizing function from blood was measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4 gene expression. With the reduced nifedipine therapy (30mg daily), blood pressure was successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was based on anamnesis, clinical picture and the results of chemical and radiological examination and confirmed by the level of drug-metabolizing capacity. The gestation hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in pregnancy in their case report. Our case report confirms that monitoring of serum aminotransferase level is still valuable when treating a pregnant woman with alpha-methyldopa.