10/20/2017 Disclosures Liver Disease in Pregnancy • None UCSF Obstetrics & Gynecology Update October 19 th , 2017 Monika Sarkar, MD, MAS Division of GI/Hepatology Outline Case 1: Liver disease in pregnancy- what an OBGYN • 30 yo Asian F, G0P1 at 8 weeks gestation should know… • HBsAg screen is positive Chronic liver disease • Liver tests are normal. She is not aware of Coincidental to pregnancy having HBV. Unique to pregnancy 1
10/20/2017 What do you typically do with + HBsAg Case 2: screen? A. Order DNA level alone • 30 yo Asian F G0P1 at 18 weeks gestation 50% B. Order DNA level + liver tests • Prenatal HbsAg negative 39% • Went to ED with abdominal pain C. Order DNA level + liver tests. Refer to GI/liver if abnormal. • Liver tests elevated and told to follow-up in clinic D. Order DNA level + liver tests. • Pain resolved with maalox, but liver tests 10% unchanged on follow-up 2 weeks later Refer to GI/liver regardless of 1% results. Tbili 0.6 Order DNA level + liver tests Order DNA level alone Order DNA level + liver te... Order DNA level + liver te... WHAT DO YOU DO? AST 90 ALT 75 Alk Phos albumin 3.5 180 Liver diseases in pregnancy Expected Changes With Pregnancy • 3 main categories: Laboratory – Chronic liver disease AST, ALT No change – Diseases coincidental to pregnancy No change or Total bilirubin Elevations in transaminases, bilirubin, and INR are – Diseases unique to pregnancy Alkaline phosphatase abnormal in pregnancy and should be investigated Albumin Alpha fetoprotein INR No change *ALT of 19IU/ml is the upper limit of normal for women Bacq et al, Hepatology 1996; Prati et al, Annals of Intern Med 2002 2
10/20/2017 Liver diseases in pregnancy • 3 main categories: Chronic liver diseases For OB to consider: – Chronic liver disease • Hepatitis B – Diseases coincidental Hepatitis B in Pregnancy • Hepatitis C to pregnancy – Diseases unique to pregnancy For GI/hepatologist to consider: • Autoimmune hepatitis • Primary biliary cholangitis • Wilson’s disease • Hemachromotosis Ordering and Interpreting Impact of Immigration on US HBV and Related Labs HBV Prevalence Lab Test What It’s Assessing Immigration Numbers by Continent: 2000-2009 [1] HBsAg Active infection (chronic or acute) ~ 3.6 million Asians HBcIgM Acute infection HBcIgG Exposure (cleared or chronic infxn) HBsAb Immunity (from cleared infxn or vaccine) Immune state of active HBV that guides HBeAg/HBeAb ~ 875,000 treatment thresholds South Americans HBV DNA Level of viremia HBsAg Prevalence [2] ALT HBV disease activity (liver inflammation) ≥ 8% (high) ~ 804,000 2% to 7% (intermediate) Africans < 2% (low) 1. US Department of Homeland Security 2009. 2. Weinbaum CM, et al. MMWR Recomm Rep. 2008 3
10/20/2017 Case 1. What to order if pre-natal HBsAg screen positive iiiiiiiiiiiiiiiiiiiiiiiiiii Lab Test What It’s Assessing HBsAg Active infection (chronic or acute) HBcIgM Acute infection HBcIgG Exposure (cleared or chronic infxn) HBsAb Immunity (from cleared infxn or vaccine) Immune state of active HBV that guides HBeAg/HBeAb treatment thresholds VVVJJJJJJJJJJJJJJJ HBV DNA Level of viremia NNNNNNNN VVVJJJJJJJJJJJJJJJ Breastfeeding on antivirals is not contraindicated ALT HBV disease activity (liver inflammation) NNNNNNNN (2017 AASLD Guidelines) JJJJJ JJJJJ *False positive HBsAg uncommon in healthy patients, unless within 2-3 weeks of HBV vaccination Sarkar M & Terrault N, Hepatology 2014 Mother to Child Transmission (MTCT) HBV Treatment During Pregnancy of HBV • MTCT is reduced with passive/active immunization - Fails in 10-30% of infants of highly viremic moms Rate of • Third trimester antiviral therapy reduces MTCT to 0- Pregnancy Risk of birth maternal-to- Antiviral Resistance 3% (rare transmission via placenta) Category defects child transmission Lamivudine C 3% Telbivudine B No increased 0% risk None Tenofovir B 0% reported Tan et al. J Viral Hep 2016; Pan et al. NEJM 2016 4
10/20/2017 Which of the following are established Pregnancy & Hepatitis B risk factors for vertical transmission? A. High HBV viral load • 95% of adults clear acute HBV 56% • But 80-90% of infants with vertical transmission B. Breastfeeding 38% develop chronic HBV C. Vaginal delivery • Perinatal transmission accounts for 50% of the D. High viral load and global burden of chronic HBV breastfeeding 4% 2% • Transmission from exposure to maternal blood/ at delivery, and less commonly via placenta d g y g a n r n o e i i d l d v l e i e a e l e r e i f d f v t s t s a l V a a e n e B H r g i r B b a h V d g n H i a d a o l a l r v i h g i H Case 2. What HBV-specific tests to order if Pregnancy & Hepatitis B woman with abnormal liver tests? Lab Test What It’s Assessing • High HBV DNA levels is most important risk factor for MTCT HBsAg Active infection (chronic or acute) HBcIgM Acute infection HBcIgG Exposure (cleared or chronic infxn) • Insufficient data to advise on the mode of HBsAb Immunity (from cleared infxn or vaccine) delivery Immune state of active HBV that guides HBeAg/HBeAb treatment thresholds HBV DNA Level of viremia • Breastfeeding doesn’t increase perinatal AST, ALT HBV disease activity (liver inflammation) transmission Li et al, J Clinical Gastro 2017; AASLD Guidelines 2017; EASL Guidelines 2016 5
10/20/2017 Refer ALL HBsAg Positive Women to GI/Hepatology WHY? • To assess whether MOM’s liver needs treatment now Hepatitis C in Pregnancy • To assess whether BABY needs to be protected from vertical transmission • To discuss drug safety in pregnancy • To counsel women on natural history of HBV and liver cancer risk, need for long-term monitoring, post delivery HBV management, and family screening…this is a chronic medical condition Hepatitis C & Pregnancy Which of the following is not a risk factor for HCV vertical transmission? - Rising number of reproductive-aged women with HCV, and babies - 364% increase in HCV A. High HCV viral load receiving HCV testing infection related to 71% injection drug use among B. Breastfeeding persons aged < 30 in southeast U.S. (KY, TN, C. Prolonged rupture of WV, VA) membranes 19% - ~ 4% of pregnant 9% women in U.S. are D. Invasive fetal monitoring 1% chronically infected High HCV viral load Breastfeeding Invasive fetal monitoring Prolonged rupture of m... Hughes et al, Am J Obstet Gynecol 2017 Zibbell et al,. CDC MMWR Morb Mortal Wkly Rep 2015 Koneru et al, CDC MMWR Morb Mortal Wkly Rep 2016 6
10/20/2017 Factors Linked with Risk of MTCT- Pregnancy & Hepatitis C Mode of Delivery • Overall, pregnancy has little impact on HCV Studies Strength of Variable Summary of Findings # women Evidence activity Elective c-section vs. 4 cohort studies, Low No difference, but trends in • Mom may be slightly increased risk of gestational vaginal delivery N=2080 opposite directions in highest quality studies diabetes and premature rupture of membranes C-section vs. vaginal 11 cohort studies, Moderate No association • Vertical transmission of HCV: delivery N=2308 – Transient HCV perinatal infection in ~ 15% chronic infection in 3-5% • Increased risk of vertical transmission with HIV- HCV co-infection , high viral load, prolonged rupture of membranes >6 hrs Sookoian S et al, Ann Hepatol. 2006 Rac M et al, Obstet Gynecol Clin North Am 2014 Cottrell E et al, Ann Intern Med 2013 Kanninen et al. Hepatology. 2015 Factors Linked with Risk of MTCT Factors Linked with Risk of MTCT • Delivery related Studies Strength of Variable Summary of Findings Studies Strength of Society for Maternal and Fetal Medicine 2017 # women Evidence Variable Summary of Findings # women Evidence Elective c-section vs. 4 cohort studies, Low No difference, but trends in Invasive fetal 3 cohort studies, Insufficient Inconsistent but one good vaginal delivery N=2080 opposite directions in - HCV status should not guide mode of delivery monitoring vs none N=928 quality study OR=6.7 (95% CI highest quality studies 1.1-36) - Avoid episiotomy C-section vs. vaginal 11 cohort studies, Moderate No association Prolonged rupture of 2 cohort studies, Low Yes with >6 hrs having - Avoid prolonged rupture of membranes delivery N=2308 membranes vs. none N=245 OR=9.3 (95% CI 1.5-180) - If invasive fetal monitoring, inform women of Invasive fetal 3 cohort studies, Insufficient Inconsistent but one good monitoring vs none N=928 quality study OR=6.7 (95% CI increased HCV transmission risk 1.1-36) • Breastfeeding does not increase MTCT, though avoid if - Breastfeeding should be encouraged nipple bleeding Prolonged rupture of 2 cohort studies, Low Yes with >6 hrs having membranes vs. none N=245 OR=9.3 (95% CI 1.5-180) Rac M et al, Obstet Gynecol Clin North Am 2014 Cottrell E, Ann Intern Med 2013;158(2):109-13 Cottrell E et al, Ann Intern Med 2013 Rac M, Obstet Gynecol Clin North Am ;41(4):573-92 7
10/20/2017 Hepatitis C in Pregnancy Hepatitis C in Pregnancy • Who to screen: • Who to screen: Risk based Risk based Hughes et al, Am J Obstet Gynecol 2017 Hughes et al, Am J Obstet Gynecol 2017 Hepatitis C in Pregnancy Hepatitis C in Pregnancy • Who to screen: • Who to screen: Risk based Risk based Hughes et al, Am J Obstet Gynecol 2017 Hughes et al, Am J Obstet Gynecol 2017 8
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