TUGAS SISTEM REPRODUKSI

PENATALAKSANAAN TBC DAN HEPATITIS PADA IBU HAMIL

Reinildis Hildegardis Uruk Hane 1008012032

PROGRAM STUDI PENDIDIKAN DOKTER FAKULTAS KEDOKTERAN UNIVERSITAS NUSA CENDANA KUPANG 2012

PENATALAKSANAAN TBC PADA IBU HAMIL

Kehamilan Pada prinsipnya pengobatan TB pada kehamilan tidak berbeda dengan pengobatan TB pada umumnya. Menurut WHO, hampir semua OAT aman untuk kehamilan,kecuali streptomisin. Streptomisin tidak dapat dipakai pada kehamilan karena bersifatpermanent ototoxic dan dapat menembus barier placenta. Keadaan ini dapatmengakibatkan terjadinya gangguan pendengaran dan keseimbangan yang menetap pada bayi yang akan dilahirkan. Perlu dijelaskan kepada ibu hamil bahwa keberhasilan pengobatannya sangat penting artinya supaya proses kelahiran dapat berjalan lancar dan bayi yang akan dilahirkan terhindar dari kemungkinan tertular TB. Rationale for treatment during pregnancy Untreated TB causes more serious complications to the mother and fetus than the ATT related adverse effects. Treatment is important to prevent transmission to fetus/infant and improves pregnancy outcomes. TB may worsen in the mother if left untreated. TB may spread to her contacts ATT and adverse effect in pregnancy First line drugs Isoniazid Higher risk of hepatitis in pregnancy. The dose of pyridoxine may be increased to 50mg/day to avoid neurotoxicity in fetus and mother. Isoniazid is considered as relatively safe drug that has been used extensively in pregnancy. Can cause neonatal seizures if pyridoxine is not given. Rifampicin Can be used safely in pregnancy. Ethambutol Animal studies showed teratogenicity. Has been used in pregnancy and so far no fetal organ malformations have been reported. Can cause retrobulbar neuritis if used after birth in neonate Pyrazinamide Animals studies are limited. If pyrazinamide is used the ATT regimen is for 6 months. If it is not used the treatment needs to be continued for 9 months. Widely used in pregnancy and so far no significant adverse effect noted. Streptomycin Should not be used in pregnancy as it causes vestibular damage in fetus. Children born to mothers treated with streptomycin have hearing impairment and deafness. Second line drugs The information regarding the adverse effects of second line drugs in pregnancy is limited. Amikacin, Kanamycin and Capreomycin - have the theoretical adverse effect of ototoxicity similar to streptomycin. Ethionamide - known to be teratogenic and can also cause premature labour Aminoglycosides - cause both nephrotoxicity and ototoxicity Quinolones cause developmental anomalies of bones

Rifabutin - known to cause congenital defects in animal studies Rifapentine - can cause bleeding in pregnancy Limited data is available for cycloserine, PAS, thiacetazone, clofazimine, clarithromycin Clarithromycin is associated with adverse fetal outcomes Clofazimine can result in bronze discoloration of infant skin. Treatment Active Tuberculosis The treatment is similar to the non-pregnant state except streptomycin should not be used. Treatment should be commenced as soon as the diagnosis if made to reduce the perinatal complications related to TB. Isoniazid, Rifampicin, ethambutol and pyrazinamide have been used widely and does not cause significant adverse complications in pregnancy related outcomes. Since the risk of pyrazinamide is unknown, some suggest a regimen of Isoniazid, Rifampicin, ethambutol for 2 months followed by 7 months of isoniazid and rifampicin. Pyrazinamide if used is helpful in rapid sputum conversion. Latent Tuberculosis Latent tuberculosis during pregnancy can be treated with isoniazid. Since the risk of hepatitis due to isoniazid is increased during pregnancy, some experts suggest that treatment for latent TB can be withheld till the pregnancy is over and then treatment can begin. The usefulness of treating latent TB in high endemic countries is not clear. But if the mother is co-infected with HIV infection, the risk of latent TB becoming active TB is high and it such instances the latent TB should be treated. MDR-TB Multi drug resistance is resistance to the first line drugs Rifampicin and Isoniazid. MDR-TB is difficult to treat in pregnancy as many of the second line drugs are less effective but more toxic. Individualized treatment regimens (ITR) are used for patient with MDR-TB. Information regarding the teratogenicity of these drugs is not fully studied. But several case reports have suggested successful treatment for MDR-TB during pregnancy. All MDR-TB patients of child bearing age should be counseled regarding possible adverse effects of second line drugs on fetus and if possible to plan pregnancy after the completion of therapy. Some experts suggest delaying the treatment till the second trimester as the maximum risk of teratogenicity occurs in the first trimester. Although withholding the treatment in the first trimester resulted in less toxic exposure, higher rates of TB related complications were noted. TB with HIV in pregnant women All pregnant females with TB should be screened for HIV and vice versa. Active tuberculosis may result in placental inflammation and can facilitate the intrauterine transmission of HIV from

the mother to child. Hence increased mother to child transmission of HIV is noted if the mother is suffering from active tuberculosis. HIV positive pregnant female with tuberculosis depending on the clinical situation should be treated with both ATT and HAART. But combining both regimens is complex and possibly lead to drug-drug interactions and increased toxicities. Rifampicin interacts with protease inhibitors and the drug levels can decrease to ineffective range. But HAART is essential to reduce the vertical transmission of HIV. Individualized treatement should be formulated based on the clinical situation of the patient. Pyrazinamide should be used as it benefits outweigh unknown adverse effects in HIV positive pregnant women. Treatment of neonate Neonatal tuberculosis is difficult to diagnose. The neonate can acquire TB through transplacental route, aspiration or ingestion of amniotic fluid/cervicovaginal secretions. Transmission can also occur during breast feeding, from a common household contact eg. Father and airborne transmission from mother in postnatal period. The child should be examined for perinatal tuberculosis. Investigations done are gastric aspirate, nasopharngeal aspirate for smear and culture of AFB. The infant disease is predominantly smear negative but culture positive. Chest radiography should be taken. Other specimens like lymph node biopsy, urine, tracheal aspirate can also be used. The placenta can also be examined for tuberculous lesions. Mantoux is not useful due to immunological immaturity. The utility of newer tests based on interferon gamma release assays have not be fully studied for use in neonatal population. If the mother has active tuberculosis, then the infant should be given isoniazid prophylaxis (5 mg/kg) with pyridoxine supplementation for 6 months or isoniazid plus rifampicin for 3 months. If TB is detected, multi drug regimen of ATT should be given. Ethambutol should be avoided in infants as it may cause retrobulbar neuritis. BCG vaccination should be given to the infant as it protects against disseminated TB and TB meningitis. The infant should be monitored for a period of 1 to 2 years with repeat TST and chest x ray if needed. Breast feeding Ideally the mother and the neonate should be separated till the sputum conversion but it is not practically feasible in developing countries. Hence breast feeding can be continued, the only contraindication being tuberculous breast abscess. The ATT drug levels are lower in the breast milk and do not harm the infant. Compliance to therapy Non-compliance to medications can be high in pregnancy due to parental concerns about adverse effects of drugs on the fetus, toxicity and side effects like nausea. The patient should be counselled and involved in decision to treat and explained the rationale for drug treatment during pregnancy.

Infertility Improved fertility outcome are seen in women with genital tuberculosis when treated with the anti-TB drugs. Rifampicin and Contraception The rifampicin can interact with the oral contraceptive medication and make them ineffective. Hence patients on rifampicin should be advised alternative methods of contraception. Contraindications The following antituberculosis drugs are contraindicated in pregnant women:

Streptomycin Kanamycin Amikacin Capreomycin Fluoroquinolones

Women who are being treated for drug-resistant TB should receive counseling concerning the risk to the fetus because of the known and unknown risks of second-line antituberculosis drugs.

Sumber : Keputusan Menteri Kesehatan Republik Indonesia Nomor 364/Menkes/Sk/V/2009 Tentangpedoman Penanggulangan Tuberkulosis (Tb) Menteri Kesehatan Republik Indonesia http://emedicinelive.com/medical-news/12-obstetrics/155-management-of-tuberculosis-duringpregnancy http://www.cdc.gov/tb/publications/factsheets/specpop/pregnancy.htm

PENATALAKSANAAN HEPATITIS PADA IBU HAMIL Artikel Indonesia

Pengelolaan Pengelolaan secara konservatif adalah terapi pilihan untuk penderita hepatitis virus pada kehamilan.1 2 8 11 12 Pengobatan infeksi hepatitis virus pada kehamilan tidak berbeda dengan wanita tidak hamil. Penderita harus tirah baring di rumah sakit sampai gejala ikterus hilang dan bilirubin serum menjadi normal, makanan yang diberikan menzandung kaya kalori dan protein. Obat obat hepatotoksik harus dihindari, termasuk alkohol dan obat obat yang diekskresi dan dikonjungasi di hati. Obat-obat yang hepatotoksik antara lain adalah klorpromasin, derivat fenotiasin, eritromisin estolat, PAS, halotan, klorpropamid, thiourasil, dan nitrofurantoin.1 Bila diduga akan terjadi perdarahan pasca persalinan karena defisiensi faktor pembekuan darah, perlil diberikan vitamin K dan transfusi plasma. Keseimbangan cairan dan elektrolit harus diperhatikan. 1 3 4 8 11 12 Apabila terdapat tanpa-tanda menjurus ke arah hepatitis fulminan, diit penderita harus diganti dengan rendah atau tanpa protein; tindakan sterilisasi usus perlu dilakukan untuk mencegah timbulnya amoniak yang berlebihan.10 Beberapa penelitian terakhir menunjukkan bahwa pemakaian kortikosteroid pada hepatitis fulminan tidak bermanfaat sama sekali.12 Hepatitis virus pada kehamilan bukan merupakan indikasi untuk tindakan terminasi kehamilan, dan tindakan anestesi serta pembedahan akan menambah morbiditas dan mortalitas penderita.1 3 4
9 11

Tidak ada pengobatan khusus untuk penyakit hepatitis virus, yang perlu dilakukan ialah pada ibu hamil yang HBsAg positif bayinya perlu dilindungi dengan segera sesudah lahir sedapat mungkin dalam waktu dua jam bayi diberi suntikan HBSIG dan langsung divaksinasi dengan vaksin hepatitis B . Pemberian HBIG hanya pada ibu yang selain HBsAg pasitif, HBe nya juga positif. Vaksin ini diulangi lagi sampai 3 kali dengan interval satu bulan atau sesuai dengan skema vaksin yang digunakan. Selain itu pada kasus seperti ini para dokter dan tenaga medis harus diberi vaksin juga. Pengelolaan secara konservatif adalah terapi pilihan untuk penderita hepatitis virus dalam kehamilan. Prinsipnya ialah suportif dan pemantauan gejala penyakit. Pada awal periode simptomatik dianjurkan : 1. Tirah baring

pada periode akut dan keadaan lemah diharuskan cukup istirahat. Istirahat mutlak tidak terbukti dapat mempercepat penyembuhan. Kecuali pada mereka dengan umur tua dan keadaan umum yang buruk 2. Diet

Tidak ada larangan spesifik terhadap makanan tertentu bagi penderita penyakit hepatitis. Sebaiknya semua makanan yang dikonsumsi pasien mengandung cukup kalori dan protein. Satusatunya yang dilarang adalah makanan maupun minuman beralkohol. jika pasien mual, tidak nafsu makan atau muntah muntah, sebaiknya diberikan infus. Jika sudah tidak mual lagi, diberikan makanan yang cukup kalori (30 35 kalori / kg BB) dengan protein cukup (1 g / kg BB). Pemberian lemak seharusnya tidak perlu dibatasi. Dulu ada kecenderungan untuk membatasi lemak, karena disamakan dengna kandung empedu. 3. Medikamentosa : a. Interferon adalah protein alami yang disintesis oleh sel-sel sistem imun tubuh sebagai respon terhadap adanya virus, bakteri, parasit, atau sel kanker. Ada tiga jenis interferon yang memiliki efek antivirus yaitu : interferon alfa, interferon beta interferon gamma.

Efek antivirus yang paling baik diberikan oleh interferon alfa. Interferon alfa bekerja hampir pada setiap tahapan replikasi virus dalam sel inang. Interferon alfa digunakan untuk melawan virus hepatitis B dan virus hepatitis C. Interferon diberikan melalui suntikan. Efek samping interferon timbul beberapa jam setelah injeksi diberikan. Efek samping dari pemberian interferon diantaranya adalah : rasa seperti gejala flu demam mengigil nyeri kepala nyeri otot dan sendi.

Setelah beberapa jam, gejala dari efek samping tersebut mereda dan hilang. Efek samping jangka panjang yang dapat timbul adalah gangguan pembentukan sel darah yaitu menurunnya jumlah sel granulosit (granulositopenia) dan menurunnya jumlah trombosit (trombositopenia), mengantuk bahkan rasa bingung. b. Lamivudin : Lamivudin adalah antivirus jenis nukleotida yang menghambat enzim reverse transcriptase yang dibutuhkan dalam pembentukan DNA. Lamivudin diberikan pada penderita hepatitis B kronis dengan replikasi virus aktif dan peradangan hati. Pemberian lamivudin dapat

meredakan peradangan hati, menormalkan kadar enzim ALT dan mengurangi jumlah virus hepatitis B pada penderita. Terapi lamivudin untuk jangka panjang menunjukkan menurunnya resiko fibrosis, sirosis dan kanker hati. Namun lamivudin memiliki kelemahan yang cukup vital yaitu dapat menimbulkan resistensi virus. Efek samping yang mungkin muncul dari pemberian lamivudin antara lain: rasa lemah mudah lelah gangguan saluran pencernaan mual, muntah nyeri otot nyeri sendi sakit kepala demam, serta kemerahan.

Efek samping yang berbahya lainnya adalah radang pankreas, meningkatnya kadar asam laktat, dan pembesaran hati. Namun umumnya efek samping tersebut dapat ditolerir oleh pasien. Terapi lamivudin ini tidak boleh diberikan pada ibu hamil.. c. Adepovir dipivoksil : Adepovir dipivoksil berfungsi sebagai penghenti proses penggandaan untai DNA (DNA chain terminator), meningkatkan jumlah sel yang berperan dalam sistem imun (sel NK) dan merangsang produksi interferon dalam tubuh. Kelebihan adepovir dipivoksil dibandingkan dengan lamivudin adalah jarang menimbulkan resistensi virus. Efek samping yang ditimbulkan adepovir dipivoksil antara lain: nyeri pada otot punggung persendian dan kepala.

Selain itu terdapat juga gangguan pada saluran pencernaan seperti mual atau diare, gejala flu, radang tenggorokan, batuk dan peningkatan kadar alanin aminotransfrase. Gangguan fungsi ginjal juga dapat terjadi pada dosis berlebih.

d. Entecavir : Entecavir berfungsi untuk menghambat enzim polymerase yang dibutuhkan dalam sintesis DNA virus. Kelebihan entecavir adalah jarang menimbulkan resistensi virus setelah terapi jangka panjang. Sedangkan efek samping yang dapat ditimbulkannya adalah : nyeri kepala pusing mengantuk diare mual nyeri pada ulu hati dan insomnia

e. Telbivudin : Telbivudin adalah jenis antivirus yang relatif baru. Terapi telbivudin diberikan pada pasien hepatitis B dengan replikasi virus dan peradangan hati yang aktif. Telbivudin berfungsi menghambat enzim DNA polymerase yang membantu proses pencetakan material genetic (DNA) virus saat bereplikasi. Meski belum didukung data yang cukup bahwa telbivudin aman bagi ibu hamil, sebaiknya terapi telbivudin tidak diberikan pada ibu hamil mupun menyusui. Efek samping dari terapi telbivudin antara lain : mudah lelah sakit kepala pusing batuk diare mual nyeri otot, dan rasa malas.

Vitamin K dapat diberikan pada kasus dengan kecenderungan pendarahan. Bila pasien dalam keadaan prekoma atau koma, penagannn seperti pada koma hepatik.

Artikel Luar Negeri

Hepatitis A
Clinical management Antibiotics are of no value in the treatment of HAV infection, and antiviral agents, as well as corticosteroids, have no effect in the management of the acute disease.[3] The administration of immunoglobulins may improve the clinical manifestations of the disease if given within 2 weeks of infection, but this treatment is of no help in the acute phase of hepatitis A.[3] Thus, medical therapy can only be supportive and is aimed at maintaining comfort and adequate nutritional balance. Complete recovery without therapy is generally the rule.[3] There are no specific dietary recommendations other than avoiding alcohol or any other hepatotoxic substances.[3, 1] Hospitalization is reserved for patients with evidence of severe disease with coagulopathy, encephalopathy, or severe malaise and asthenia. Most patients can be managed outpatient with rest and avoidance of abdominal trauma. The degree of activity is usually limited by the severity of the asthenia and malaise. Patients with fulminant hepatic necrosis may require liver transplantation. It is difficult to ascertain which patient will require a liver transplant, as many patients with advanced liver necrosis may recover completely from the disease.[1] Hepatitis B Clinical management Most individuals with HBV infection who acquire the disease during adulthood have self-limited disease and do not require treatment. During pregnancy, viral hepatitis is associated with the lowest risk of obstetric complications when compared with other potential hepatic complications, such as acute fatty liver of pregnancy, severe preeclampsia, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). In most cases, no special treatment is required during the acute phase. Bed rest is not mandatory. Drug resistance mutations are one of the biggest concerns among individuals who are chronically infected with active HBV disease. Current therapeutic options use single or combined antivirals such as lamivudine, adefovir, and entecavir and less often include immunomodulatory drugs such as interferon (IFN). Treatment with antivirals is recommended for patients with HBV DNA levels persistently greater than 10,000 copies/mL.[35] Although antivirals are not labeled as teratogens, information is limited on human exposure during pregnancy.[36]

Hepatitis C Clinical management The CDC does not recommend testing all pregnant women for HCV infection, only those who are at high risk, and care during pregnancy is not modified by HCV infection.[16] The objectives for treatment of chronic hepatitis are to reduce inflammation; prevent progression to fibrosis, cirrhosis, and hepatocellular carcinoma through the eradication of the virus; decrease infectivity; and control the spread of the disease.[42] In August 2012, the Centers for Disease Control and Prevention (CDC) expanded their existing, risk-based testing guidelines to recommend a 1-time blood test for hepatitis C virus (HCV) infection in baby boomersthe generation born between 1945 and 1965, who account for approximately three fourths of all chronic HCV infections in the United Stateswithout prior ascertainment of HCV risk (seeRecommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 19451965).[89] One-time HCV testing in this population could identify nearly 808,600 additional people with chronic infection. All individuals identified with HCV should be screened and/or managed for alcohol abuse, followed by referral to preventative and/or treatment services, as appropriate. Spontaneous resolution occurs in one third of infected persons.[40] Medical treatment is unlikely to have a significant impact on disease, as most infected individuals remain undiagnosed and have limited resources and access to care.[40]Antibiotics are of no value in the treatment of the infection, and antiviral agents, as well as corticosteroids, have no effect in the management of the acute disease. Currently the best indicator of effective treatment is a sustained viral suppression, defined by the absence of detectable HCV RNA in the serum as shown by a qualitative HCV RNA assay with lower limit of detection of 50 IU/mL or less by 24 weeks after the end of treatment.[41] PEG-IFN and ribavirin, liver transplantation The most widely used form of treatment is a combination of pegylated interferon (PEG-IFN) and ribavirin in cases of chronic HCV infection. The use of pegylated interferon leads to a suppression of viral replication in more than 50% of cases[90] ; however, its use in pregnancy is contraindicated owing to conflicting reports of decreased birth weight and increased fetal loss.[91, 92] The US Food and Drug Administration (FDA) labels ribavirin as category X, although reports exist of its use during pregnancy without adverse outcomes.[92] Transplantation is an option for patients with cirrhosis and end-stage liver disease. Despite transplantation, the donor liver almost always becomes infected, and the risk of progression to cirrhosis reappears.[93] Genotype and treatment Genotype determinations influence treatment decisions,[44] and once identified, the genotype doesn't need retested again as it doesn't change during the course of infection.[44] Patients with genotype 2 or 3 have a 2- to 3-fold likelihood of responding to therapy with alpha-interferon or a

combination of alpha-interferon and ribavirin[44] (treatment duration, 24 wk) relative to patients with genotype 1 (treatment duration 48 wk).[44, 94]

Hepatitis D Clinical management No antiviral therapy is effective against acute or chronic HDV infection. Long-term alphainterferon (IFNa) and pegylated alpha-interferon (PEG-IFNa) have been shown to induce remission of the disease with decreased viral replication. Use of acyclovir, ribavirin, lamivudine and other nucleoside analogues are ineffective against the virus. Immunosuppressive agents are also ineffective. Among patients who underwent liver transplantation for end-stage liver disease, 5-year survival is more than 80%.[101, 109]

Hepatitis E Clinical management No hyperimmune hepatitis E immunoglobulin is available for preexposure or postexposure prophylaxis, and no known therapy is available to alter the course of the disease. Therapy is directed at providing supportive care.

Hepatitis G Clinical management and prevention Medical care for HGV is supportive in symptomatic patients. In general, most patients remain asymptomatic and do not require specific treatment.[145] HGV is a parenterally transmitted infection. Cases of acute posttransfusion hepatitis have been documented with increased aminotransferase levels, positive HGV RNA, and absence of markers of viral hepatitis. Pooled blood products are a common source of infection.[128] Evidence for sexual transmission is based on the high detection rates among prostitutes and individuals with multiple sex partners.[146] The vertical transmission of HGV has been demonstrated in several different populations.[73, 147, 148, 149] Transmission may occur intrapartum or postnatally. Intrapartum transmission at the time of delivery appears to be substantiated by a significant decrease in risk of transmission when comparing cesarean to vaginal delivery.[149] Although perinatal transmission does occur, evidence suggests that it does not cause clinical disease in newborns. Given the high transmission rate, lack of consistent clinical or pathologic changes associated with infection, and lack of specific therapy, screening for HGV infection in the pregnant population is not justified.

Sumber : http://www.budilukmanto.org/index.php/seputar-hepatitis/96-hepatitis http://nandhieb.blogspot.com/2012/06/ibu-hamil-dengan-hepatitis.html http://emedicine.medscape.com/article/1562368-overview#aw2aab6b3 http://emedicine.medscape.com/article/1562368-overview#aw2aab6b4 http://emedicine.medscape.com/article/1562368-overview#aw2aab6b5 http://emedicine.medscape.com/article/1562368-overview#aw2aab6b6 http://emedicine.medscape.com/article/1562368-overview#aw2aab6b7 http://emedicine.medscape.com/article/1562368-overview#aw2aab6b8