Liver and pregnancy part 2 : pregnancy in patient with underlying liver disease

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1 Liver and pregnancy part 2 : pregnancy in patient with underlying liver disease Ahmad Shavakhi.MD Associate professor Isfahan university of medical sciences

2 Pregnancy in cirrhosis Pregnancy is a rare event in patients with cirrhosis Two reason : 45 of 100,000 women in reproductive age Anovulation and amenorrhea Benjaminov FS, Heathcote J. Liver disease in pregnancy. Am J Gastroenterol 2004;99:

3 Complication for mother Esophageal variceal bleeding :18% to 32% Band ligation in 2 nd trimester, inderal Hepatic Decompensation: 24% Splenic Artery Aneurysm Rupture: 2.6% Postpartum Uterine Hemorrhage :7 to 10% SBP:rare Hepatic encephalopathy LIVER TRANSPLANTATION 14: , 2008

4 Splenic Artery Aneurysm Rupture 2.6% 20% of all ruptures occur during pregnancy 70% occurring during the third trimester maternal and fetal mortality :70%and 80% Mechanism: high flow, PHT, high estrogen Rx: splenectomy, embolization, stent Russell MA, Craigo SD. Cirrhosis and portal hypertension in pregnancy. Semin Perinatol 1998;22:

5 Fetal Outcomes Spontaneous abortion : 30% to 40% Risk of prematurity : 25% Perinatal death rate : 18%30 versus 1.08% in noncirrhotic population (old literature )

6 How to approach delivery Area of controversy Risk of variceal bleeding Repetitive Valsalva maneuver : PHT Elective caesarian section or forceps delivery under extradural analgesia Vascular surgeon should be available bleeding from abdominopelvic collaterals

7 Pregnancy : yes or no EGD and child and MELD Our experience : Do not decide alone Consent form

8 Upper endoscopy Safe during pregnancy Main risk : fetal hypoxia Sedative drugs positioning No risk of premature labor or fetal malformations

9 Chronic HBV Infection in Women Considering Starting a Family Should plans to start a family influence management decisions? Uncertainty regarding safety of antiviral medications in pregnancy Careful discussion with patient and spouse regarding benefits vs risks Indications for treatment Start now: advanced fibrosis/cirrhosis, severe flares/persistently high ALT Defer: no/mild fibrosis, normal/minimally elevated ALT

10 HBV Infection in Women Considering Starting a Family: Which Drug? FDA classification: based on in vitro and animal studies Pregnancy class B: telbivudine and tenofovir Pregnancy class C: interferon, adefovir, entecavir, and lamivudine Human data: Antiretroviral pregnancy registry: safety established for lamivudine and tenofovir, including exposure in first trimester Clinical studies of antiviral therapy to prevent perinatal transmission: safety established for lamivudine and telbivudine, mainly exposure in third trimester Antiretroviral Pregnancy Registry. December Xu WM, et al. J Viral Hepat. 2009;16: Shi Z, et al. Obstet Gynecol. 2010;116: Han GR, et al. J Hepatology. 2011;55: Pan CQ, et al. Clin Gastroenterol Hepatol. 2012;10:

11 Limitations of the Antiretroviral Pregnancy Registry Depends on voluntary reporting Information is reviewed but not verified Long-term follow-up is limited Data available for live births only No data on miscarriages or subsequent developmental delay Limited data on antivirals used for HBV monoinfection. < 100 pregnancies reported for exposure to adefovir, entecavir, or telbivudine Antiretroviral Pregnancy Registry. December 2012

12 Antiviral Therapy for Chronic HBV Infection in Women Starting a Family in Near Future Moderate-severe inflammation; advanced fibrosis/cirrhosis? Yes No Finite treatment with pegifn before pregnancy* If possible, delay therapy until completion of family Treatment failure/ pegifn not possible Success Initiate NUC

13 Considering Antiviral Therapy for Chronic HBV Infection in Women starting a Family Which nucleos(t)ide analogue? Safety to fetus, including exposure during first trimester Lamivudine, tenofovir, telbivudine Risk of drug resistance Lamivudine > telbivudine > tenofovir Preferred drug: tenofovir Established safety; potent; low risk of drug resistance Benefit vs risk discussed with patient and spouse Inform if become pregnant

14 Women Receiving Antiviral Therapy Who Desire to Breast-feed Breast-feeding : not recommended while receiving antivirals Nucleos(t)ide analogues present in breast milk Tenofovir: a prodrug with low oral bioavailability Nursing rhesus macaques administered tenofovir (n = 2): peak concentration in breast milk 2% to 4% of that in serum; HIV-infected women (n = 5): median concentration of tenofovir in breast milk 0.03% of proposed oral infant doses Existing data suggest tenofovir is safe. Van Rompay K, et al. Antimicrob Agents Chemother. 2005;49: Benaboud S, et al. Antimicrob Agents Chemother. 2011;55:1315

15 Algorithm for HBV Management in Women During Pregnancy Pregnant women with HBV infection 1st trimester: assess HBV replication and liver disease Active disease/suspected cirrhosis: consider initiating treatment with tenofovir End of 2nd trimester: quantitative HBV DNA and ALT levels HBV DNA < 106 IU/mL* HBV DNA > 106 IU/mL* Monitor; infant receives HBIG + vaccine at birth Consider initiating treatment with tenofovir, lamivudine, or telbivudine at wks Infant receives HBIG + vaccine at birth

16 Caesarian section for prevention of HBV transmission Most obstetrical algorithms do not include change in the planned mode of delivery Prolonged rupture of membranes (>6 hours) may increase the risk of transmission, so it is recommended that the second stage of labor be kept short

17 HCV infection and pregnancy Fetal outcome Low birth weight Small for gestational age need assisted ventilation low apgar scores prematurity neonatal jaundice J, Surti B, Saab S. Pregnancy and cirrhosis. Liver Transpl 2008; 14:1081.

18 HCV infection and pregnancy Effect on mother improvement in serum aminotransferase concentrations histologic progression :conflicting results

19 HCV infection and pregnancy transmission of hepatitis C from to infant 4 to 10% Risk factor : high levels of viral RNA prolonged time from rupture of membranes genotypes 1 and 3 elevated alanine aminotransferase levels coinfection with HIV Sookoian S. Effect of pregnancy on pre-existing liver disease: chronic viral hepatitis. Ann Hepatol 2006;5:

20 HCV infection and pregnancy Breast feeding : recommended Treatment : not recommended because of ribaverine Mode of delivery : like HBV infection Sookoian S. Effect of pregnancy on pre-existing liver disease: chronic viral hepatitis. Ann Hepatol 2006;5:

21 HEV infection and pregnancy 14.3% in blood donors in iran 3.8% in Isfahan.iran j microbiol 2013 Jun;5(2):172-6.

22 HEV infection and pregnancy FHF was significantly higher in pregnant women with HEV infection as supposed to other viral hepatitis (69.2% vs. 10%, p<0.001) Not differ significantly in various stages of gestation mother-to-infant transmission of 100% Still birth 0.04% and anicteric hepatitis

23 Management The literature at present is not supportive of the fact that delivery of the baby may decrease the maternal mortality Role of immune serum globulin is unknown

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