1 / 73

Management of liver diseases in pregnancy

Management of liver diseases in pregnancy. Moderator-Prof. Anoop Saraya Candidate-Dr. Moka Praneeth. Contents. Pregnancy – physiologic changes Hepatitis-E Hepatitis-B Acute liver failure Cirrhosis & Portal hypertension ICP HG HELLP syndrome AFLP.

david-harvey
Download Presentation

Management of liver diseases in pregnancy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Management of liver diseases in pregnancy Moderator-Prof. AnoopSaraya Candidate-Dr. MokaPraneeth

  2. Contents • Pregnancy – physiologic changes • Hepatitis-E • Hepatitis-B • Acute liver failure • Cirrhosis & Portal hypertension • ICP • HG • HELLP syndrome • AFLP

  3. Physiological changes in liver tests during normal pregnancy

  4. Liver diseases in pregnancy coincidental with pregnancy Only in the setting of pregnancy Chronic liver diseases e.g.: cholestatic liver disease, autoimmune hepatitis, Wilson disease, viral hepatitis, etc… not associated with preeclampsia Preeclampsia- associated The preeclampsia itself • Hyperemesis • gravidarum HELLP-syndrome • Intrahepatic cholestasis • of pregnancy AFLP

  5. Hepatitis E virus infection and fulminant hepatic failure during pregnancy • 50 pregnant and 50 non-pregnant women with FHF and 150 pregnant healthy females without liver disease as controls were recruited for the study. • Serologically (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV positivity rate was found in pregnant FHF patients compared to non-pregnant women (serologically 15/50; 30%; RT-PCR 7/50; 14%). Jilani N et al. J GastroenterolHepatol. 2007

  6. Hepatitis E virus infection and fulminant hepatic failure during pregnancy • CD4 counts were lower (P < 0.05), while CD8 counts were higher (P < 0.05), and their ratio (CD4/CD8) in HEV positive pregnant FHF patients was significantly lower (P < 0.01) when compared to that of HEV negative pregnant FHF women or controls. • Levels of estrogen, progesterone and beta-HCG were also found to be higher (P < 0.001) in HEV positive pregnant FHF patients when compared to HEV negative patients or controls. • HEV infected pregnant FHF patients had a significantly higher mortality rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women (P < 0.001

  7. Immunological alterations in pregnant women with acute hepatitis E. • Pregnant women with HEV had generalized immune suppression characterized by decrease in lymphocyte response to phytohemagglutinin(PHA) with a predominant Th2 bias as compared to non pregnant women with hepatitis E and normal healthy controls. • Neither normal healthy pregnant women nor nonpregnant HEV infected women demonstrated decreased response to PHA. Pal R et al. J GastroenterolHepatol. 2005

  8. Pathogenesis of Hepatitis-E in pregnancy

  9. Probable hypotheses for the variable pathogenesis of HEV

  10. Termination of pregnancy in HEV-ALF? Banait VS et al. Indian J Gastroenterol 2007

  11. Treatment algorithm for an HBV-infected woman who is already on antiviral therapy and presents with an unexpected pregnancy

  12. Impact of pregnancy on chronic HBV • No worsening of liver disease in majority • Overall increase in HBV DNA levels during pregnancy • Median ALT levels decreased during pregnancy • Increase in ALT (3 x lowest ALT) within 6 months after delivery • Case reports of postpartum hepatic exacerbations Terrault et al. Semin Liver Dis. 2007 Soderstrom et al. Scand J Infect Dis 2003 Borg et al. J viral Hep 2008 Rasheed et al. Int J GynaecolObstet 2013

  13. 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 DF • Pregnancy class C: interferon, adefovir, entecavir, and lamivudine • Human data: • Antiretroviral pregnancy registry: safety established for lamivudine and tenofovir, including exposure in first trimester[1] • Clinical studies of antiviral therapy to prevent perinatal transmission: safety established for lamivudine and telbivudine, mainly exposure in third trimester[2-5] 1. Antiretroviral Pregnancy Registry. December 2012. 2. Xu WM, et al. J Viral Hepat. 2009;16:94-103. 3. Shi Z, et al. Obstet Gynecol. 2010;116:147-159. 4. Han GR, et al. J Hepatology. 2011;55:1215-1221. 5. Pan CQ, et al. Clin Gastroenterol Hepatol. 2012;10:520-526.

  14. Incidence of Birth Defects With in Utero Exposure to HBV Nucleos(t)ide Analogues • Data derived from Antiretroviral Pregnancy Registry, 1/1989 - 7/2012[6] • International, voluntary, prospective, exposure-registration cohort • Data on exposure in HBV-monoinfected mothers began in 1/2003 • Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance program administered by CDC[6,7] • Overall birth defects: 2.72% (95% CI: 2.68-2.76) 6. Antiretroviral Pregnancy Registry. December 2012. 7. Correa A, et al. Birth Defects Res A Clin Mol Teratol. 2007;79:65-186.

  15. Prevention of Perinatal HBV Transmission • Cornerstone: HBIG + HBV vaccine • HBIG + first dose vaccine within 12 hrs of birth, different sites • Efficacy: ~ 95% • Reasons for failure • Delay in administration of HBIG and first dose of vaccine • Failure to complete vaccine series/Poor quality vaccine • Mother HBeAg positive and/or high HBV DNA • In utero infection • HBsAg mutation/Escape mutants • Immunocompromised host 1. Lok AS, et al. Hepatology. 2009;50:661-662. 2. Mast EE, et al. MMWR Recomm Rep. 2005;54(RR-16):1-31.

  16. Meta-analysis of Lamivudine to Interrupt Perinatal Transmission of HBV Risk Ratio (95% CI)* 100 1 0.1 0.01 10 Favors Lamivudine Favors Control Risk Ratio (95% CI)* *Risk ratio calculated using the Mantel-Haenszel random-effects model. 1 0.1 100 0.01 10 Favors Lamivudine Favors Control 17. Han L, et al. World J Gastroenterol. 2011;17:4321-4333.

  17. Algorithm for HBV Management in Women During Pregnancy Pregnant women with HBV infection Active disease/suspected cirrhosis: consider initiating treatment with tenofovir 1st trimester: assess HBV replication and liver disease End of 2nd trimester: quantitative HBV DNA and ALT levels HBV DNA < 106 IU/mL* HBV DNA > 106 IU/mL* Consider initiating treatment with tenofovir, lamivudine, or telbivudine at 28-32 wks† Monitor;infant receives HBIG + vaccine at birth Infant receives HBIG + vaccine at birth *The cut-off level of maternal HBV DNA level for initiation of therapy is unclear, and HBV DNA from 6-8 log10 IU/mL can be considered for therapy based on physician and patient preference. †Tenofovir is preferred if treatment is expected to be > 12 weeks or if treatment is expected to continue while breastfeeding.

  18. Pregnant Women With High HBV DNA and Not Initially on Antiviral Therapy • When to stop antiviral after delivery? • To prevent perinatal transmission: immediately, especially if mother plans to breast-feed, or up to 3 mospostdelivery • To treat liver disease: continue until therapeutic endpoint • What is the risk of posttreatment flare? • Seemingly rare, but mild ALT elevation common; also seen in postpartum period for women not receiving antiviral • Decompensation not reported in clinical trials; likelihood low because most pregnant women have early-stage liver disease • Important to closely monitor ALT after antiviral therapy is discontinued (eg, 1, 3, and 6 mosposttreatment) 19. Ter Borg MJ, et al. J Viral Hepat. 2008;15:37-41.

  19. Cesarean vs Vaginal delivery in CHB- a meta-analysis • Infant serum Anti-HBs postivity at birth (RR= 1.24, 95% CI 0.89-1.74, p = 0.2) or at 6-7 months (RR= 0.98, 95% CI0.86-1.11, p = 0.73) was not significantly different • The incidence of infant CHB infection may have been higher in the vaginal delivery group (R=2.2, 95% CI 1.02-4.74, P = 0.04) Xu et al. Dig Dis Sci. 2014

  20. Acute HBV in pregnancy Transmission rates: • 10% in early pregnancy • 60% at or near time of delivery

  21. Prophylaxis of vertical transmission

  22. ALF in pregnancy • 1015 consecutive patients of ALF in reproductive age group, admitted in AIIMS from January 1986 to December 2006 • 249 (38.5%) were pregnant females • The mortality rate of pregnant women and girls (53.8%) was similar to nonpregnantwomen and girls (57.2%), and men and boys (57.9%); P = 0.572. Bhatia V, Acharya SK et al. Hepatology 2008

  23. ALF in pregnancy • A significantly higher proportion of ALF was attributable to HEV among pregnant women (59.4%), as compared with nonpregnantwomen (30.4%), and men (23.1%) (p < 0.001) • The outcome of HEV-related ALF was independent of the sex and pregnancy status of the patients (P = 0.103).

  24. ALF in pregnancy • Mortality in HEV-ALF and non-HEV-ALF patients in pregnant women and girls was 51% (74/145) and 54.7% (52/95)(P > 0.1), respectively. • The outcome of pregnant ALF patients was also unrelated to the trimester of pregnancy. • The mortality of non-HEV-related ALF among the pregnant women and girls (54.7%), age-matched nonpregnant women and girls (61.7%), and men and boys (62.8%) were also similar (P > 0.1). Bhatia V, Acharya SK et al. Hepatology 2008

  25. Induction of delivery in ALF with IUD • Increased risk of peripartum hemorrhage due to associated coagulopathy 1 • rFVIIa is a useful adjunct to standard management in postpartum hemorrhage secondary to acute liver failure of pregnancy-related liver disorders.1 • When a dead fetus has been in utero for 3-4 weeks, fibrinogen levels may drop, leading to a coagulopathy.2 • Does a dead (< 2 weeks) fetus lead to sepsis? • Should we routinely remove the dead fetus in pregnant women with ALF with IUD? Goel a et al. Indian J Gastroenterol. 2013 Jul Tempfer CB et al. J Womens Health (Larchmt). Apr 2009

  26. CLD- pregnancy • Preexisting varices : • 78% GI bleeding during pregnancy • T2/T3 as maternal blood volume maximally expanded and fetus causes ↑ compression of IVC collateral vasculature • Mortality rate of 18% to 50%. • Most patients with CLD infertile due to hypothalamic- pituitary dysfunction. Russell MA et al. Semin Perinatol 1998;22:156-165. • MATERNAL RISKS: • Variceal Bleeding ( 18-32 %) • Hepatic Decompensation(24%) • Hepatic Encephalopathy • PPH ( 7-10%) • Rupture of splenicA aneurysms(2.6%) FETAL RISKS : • ↑ risk of abortions (30-40%) • ↑ risk of prematurity / IUGR (25%) • Perinatal death (18%) Hay et al. Hepatology 2008

  27. Treatment of variceal bleeding • Endoscopic variceal band ligation • Superior to sclerotherapy – no chemicals instilled into blood stream. -Expert opinion • Octreotide (B) • Safety in pg not determined • Could cause arterolar vasospasm • Decreased placental perfusion and increased risk of placental abruption as well as • HTN, MI, peripheral ischemia • Endoscopy • Safe when done with caution

  28. Pregnancy and cirrhosis • Review of data from 1984 – 2009 • Kings College Hospital • 62 pregnancies in 29 women • Median MELD was 7 (range 6 – 17) • Median CPS was 5 ( range 5-8) • Live birth rate was 58% • Median gestational age 36 w Westbrook RH et al ClinGastroHep 2011;9: 694-9

  29. Pregnancy and cirrhosis • Maternal complications occurred in 10% • Ascites • Encephaolpathy • Variceal hemorrhage • Associated with MELD > 10 • MELD predicted which patients were to have liver related complications • AUC 0.8 • 83% sensitivity and 83% specificity • No one with MELD <6 had any liver related complications Westbrook RH et al ClinGastroHep 2011;9: 694-9

  30. Cesarean vs vaginal delivery in CLD • Experts use elective cesarean section or forceps delivery under extradural analgesia to decrease the risk of variceal rupture (no RCTs are available)1, 2 • If a prophylactic cesarean section is performed, a vascular surgeon should be available as bleeding from pelvic or abdominal wall collaterals may occur3 BenjaminovFS, Heathcote J. Am J Gastroenterol2004 Heriot JA et al. Br J Anes1996 Misra S, Sanyal AJ. Clin Liver Dis 1999

  31. Intrahepatic Cholestasis of Pregnancy (ICP) • Incidence 0.1% - 1% of pregnancies, 20% among twins, 7.5% of pregnancies (AIIMS) • Recurrence rate of 50-70% in subsequent pregnancies • Pruritus (initially in soles & palms, only at night, and later continuously progressing to trunk and face) develops in late 2nd and 3rdtrimester

  32. ICP • Jaundice (usually mild- bilirubin < 5 mg/dL) develops 2 weeks later, plateaus and remains constant until delivery • Pruritus worsens with the onset of jaundice • Symptoms usually abate within 2 days of delivery.

  33. ICP-lab investigations • The most specific and sensitive marker of ICP is total serum bile acid (BA) levels > 10 µmol/L • Chenodeoxycholic acid and cholic acid ↑ sed 10 times N( > 11µmol/L), ↑ cholic acid % ( > 42 %), ↓ glycine/ taurine bile acid ratio (<1) • ALT, AST- mild to 10-25 fold increase, SAP- increased upto 4 fold • GGT-mildly elevated in 30%, more likely in those with genetic component • Glutathione s- transferase α - new marker being investigated

  34. MATERNAL RISKS FETAL RISKS • Prematurity: ↑ iatrogenic prematurity ( 7- 25 % ) vs ( 4- 12 %) . • Passage Of Meconium : • preterm than in term (25% vs 12%) • preterm controls (18% vs 3%). • mc if BA > 40 umol/l vs 20 • Risk ↑ linearly ( 19.7% ↑ for each • 10 umol/l ↑ BA conc.) . • Intrapartum Fetal Distress • Kenyon et al.. BJOG 2002; 109 • Higher Caesarean Rates (10 – 36 %) → ↑ RDS & TTN • Stillbirth: (1.5 %) to that of general • population (0.5%). • RCOG 2011 • Deposition of bile acids in the skin → pruritus → dermatitis artefacta. • Hepatic impairment → prolonged prothrombin time → post partum hemorrhage RCOG 2011 Arrese. Annals of Hepatology 2006; 5 (3): 216-218 • IUD seems to be due to – • acute anoxia (placental chorionic vein • spasm , umbilical vein spasm) • umbilical vein constriction • fetal cardiac arrest ( infiltration of fetal • cardiomyocytes by bile salts) • Kenyon et al. BJOG 2002 • Gorelik et al. BJOG 2006

  35. T. UDCA 15 mg/kg/d (or > 1 g/day) (– drug of choice) reduces pruritus, ↓ total serum bile acids, ALT values and bilirubin levels, improves cholic/CDCA ratio • Other agents with limited benefit: Phenobarbital 100 mg OD, Hydroxyzine, SAME 1600 mg OD, Cholestyramine- takes 2 weeks to work, Aluminium containing antacids, Dexamethasone 12 mg QID for 7 days

  36. at

  37. Hyperemesis gravidarum

  38. Investigations for HG • Urinalysis for ketones & specific gravity • Serum electrolytes: Na, K, Cl • LFTs- Elevated transaminases (50-65%) upto 200 IU/L, SAP upto 2 times, serum bilirubin upto 4 mg/dL- makes it a liver disease? • Serum amylase & lipase upto 5 times • TSH, FT4, Urine culture, Hct, screening for HAV, HBV, HCV • Obstetric & abdominal USG

  39. Management of HG • i.v. fluids (NS, RL) over 2-3 hours • Thiamine/vitamin B1 • Enteral/Parenteral nutrition • Separating solids & liquids, Eating small frequent meals of bland foods, Avoiding fatty foods (eg: Potato chips) • Avoid drinking cold/sweet beverages • Eliminate pills with iron; give high protein snacks

  40. COMPLICATIONS Maternal complications Fetal complications No increased risk of congenital malformations . Growth restriction. Wernicke’s encephalopathy is associated with a 40% incidence of fetal death. • Hypokalemia - lethargy, skeletal muscle weakness and cardiac arrhythmias • Hyponatremia and CPM. • Vitamin B6/B12 def • Malnutrition. • Mallory-Weiss oesophageal tears. • Wernicke’s encephalopathy. • Venous thromboembolism . • Psychological morbidity. NICE 2010

  41. HELLP Syndrome • 1 in 1000 , 10-20 % of severe preeclampsia / eclampsia • Most common in white, multiparous and older women

  42. Clinical Presentation SYMPTOMS

  43. Clinical Presentation signs

  44. Laboratory Diagnostic Criteria for HELLP syndrome Haemolysis Abnormal peripheral smear : spherocytes, schistocytes, triangular cells and burr cells Total Bilirubin level > 1.2 mg/dL Lactate dehydrogenase level > 600U/L Elevated liver function test result Serum aspartate amino transferase level > 70U/L Lactate dehydrogenase level >600 U/L Low platelet count(Most reliable indicator) Platelet count < 150 000/mm3 • Requires at least 2 of above mentioned abnormalities

More Related