Liver diseases in pregnancy Lisa McKnight, MD, FRCPC Hin Hin Ko, MD, FRCPC CDDW 2013 • Both speakers have no relevant financial disclosures CDDW/CASL Meeting Session: CanMEDS Roles Covered in this Session:  Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles, applying medical knowledge, clinical skills, and professional attitudes in their provision of patient-centered care. Medical Expert is the central physician Role in the CanMEDS framework.) Communicator (as Communicators, physicians effectively facilitate the doctor-patient relationship and the dynamic exchanges that occur before, during, and after the medical encounter.)  Collaborator (as Collaborators, physicians effectively work within a healthcare team to achieve optimal patient care.) Manager (as Managers, physicians are integral participants in healthcare organizations, organizing sustainable practices, making decisions about allocating resources, and contributing to the effectiveness of the healthcare system.) Health Advocate (as Health Advocates, physicians responsibly use their expertise and influence to advance the health and well-being of individual patients, communities, and populations.)  Scholar (as Scholars, physicians demonstrate a lifelong commitment to reflective learning, as well as the creation, dissemination, application and translation of medical knowledge.) Professional (as Professionals, physicians are committed to the health and well-being of individuals and society through ethical practice, profession-led regulation, and high personal standards of behaviour.) At the end of this session, participants should be able: • To recognize normal physiologic changes associated with pregnancy. • To have a systematic approach to liver diseases in pregnancy. • To recognize and manage intrahepatic cholestasis of pregnancy. • To recognize acute fatty liver of pregnancy and HELLP syndrome. Liver Disease in Pregnancy • Normal physiologic changes • Liver disease specific to pregnancy – ICP, AFLP • Multisystem dx unique to pregnancy • Intercurrent liver disease in pregnancy (Viral hep) • Chronic liver diseases • Pregnancy as predisposing factor Liver during normal pregnancy • Size and appearance of liver unchanged • Blood flow to liver unchanged despite increased maternal blood flow    Hct Albumin Bilirubin GGT (late) transferrin AST/ALT PT Bile Acids ALP (2nd/3rd) Cholesterol (Total Chol + TGs ) Hepatol 1996;23(5):1030 Physical Examination • Spider angiomata 60-70% • Palmar erythema (63% white, 39% black women) • Liver is not palpable • Jaundice is NOT normal Cardinal Features of Disease • • • • • Jaundice Pruritus Abdominal pain Nausea/Vomiting Liver biochemical abnormalities Case • 25 yo medical student, G2P1, 35 weeks GA, singleton with intractable itching. • Primarily palms and soles, prevents sleep • Elevated ALT/AST, ALP, Bili • Will Urso help with the itch? • What is optimal timing of delivery? Intrahepatic Cholestasis of Pregnancy Prevalence: • Geographic variation • 1-2% pregnancies in US/Europe; 5% Latinos Timing: • Late 2nd to 3rd trimester (between 28-30 wk gestation) • Recurs in 2/3 of subsequent pregnancies • 5x more frequent with multiple gestations ICP Pathogenesis • Genetic • More common if family history • Assn with MDR-3 gene defect • Hormonal • Sensitivity to cholestatic effect of estrogen • Administration of estrogen may precipitate • Environmental • More common in colder months • Selenium exposure ICP Clinical Presentation • Intense pruritus in palms and soles • Pruritus worse at night • Excoriations due to scratching • Jaundice (10%) starts 1-4 wks after pruritus • Nausea and vomiting 575% • Abdominal pain 9-24% ICP Laboratory findings • Cholestatic picture • Total bilirubin rarely > 85umol/L • GGT either normal or only modestly elevated • AST/ALT elevated 2-10x; normal in 20-60% • PT can be elevated – Vit K deficiency • Elevated bile acids – do not correlate with severity ICP Management • Vitamin K before delivery • Ursodeoxycholic acid (500mg BID until delivery or 15mg/kg/d) • Cholestyramine (8-16g per day) • Hydroxyzine (25-50mg per day) • Fetal Complications: – – – – Premature labor – 30-40% Meconium-stained amniotic fluid 27% Fetal distress 18% Stillbirth 3% World J Gastro 2009 15(17):2049 ICP Management ICP Management ICP Management • Urso: – Reduced itching by -16mm on visual scale – Statistically significant – Did not meet clinically significant threshold (-30 mm) – 32% women met clinically significant criteria (NNT=6) – RR meconium in fluid 0.39 • Early delivery vs. expectant – 88% maternity units in UK induce at 37-38 wks GA – Expectant: 63% had early intervention – Early not assn with ↑C-section Conclusions • First trial to report quantified reduction in itching • Urso significantly reduces pruritus but size of benefit may be too small for doctors/women to agree to it. • Pregnancy risk B • Unclear benefit to early delivery, but most women/physicians currently practice Hyperemesis Gravidarum Prevalence: •“morning sickness” in > 50% •hyperemesis gravidarum complicates 0.35% - 0.8% of pregnancies Timing: •1st trimester (4-10wk); resolves by 20 wk GA Hyperemesis Gravidarum Presentation: • Severe, persistent nausea and vomiting, wt loss > 5% or pre-preg BW or vomiting >3x/d with wt loss >3kg + ketonuria • Mild jaundice, pruritus Hyperemesis Gravidarum Blood work: • 50% have  LFTs (2-3x normal) seen 1-3 wk after onset • ALT > AST; usually 100s, rarely as high as 1000s • Hyperbilirubinemia can occur, but rarely >4mg/dL • Electrolyte imbalances Treatment: • Gut rest, IV fluids • Resolves rapidly with cessation of emesis • Negligible mortality HELLP Syndrome • Severe, life-threatening complication of preeclampsia Incidence: • 1-2/1,000 pregnancies • 10-20% of women with preeclampsia/eclampsia Timing: • Mostly in 3rd trimester (28 -36 wk GA) • 2nd trimester and post-partum are possible Etiology: • ? Imbalance between vasoconstrictive and vasodilative forces causing endothelial dysfunction and platelet aggregation HELLP Syndrome • Clinical Presentation: – Mean age: 25 years – Abdo pain (RUQ; mid-epigastrium) 70-90% – Nausea, vomiting & malaise common – Headache 25% – Visual changes 15-30% HELLP Syndrome • Physical exam: – Hypertension (>140/90 mmHg) 85% – Proteinuria 85% – Generalized edema 50-67% – Ascites 8-10% – Jaundice 5% H EL LP • Lab Abnormalities – emolysis, ( AST/ALT), (low platelets) – Blood smear - schistocytes – Low haptoglobin level in 95% – Bilirubin elevation 47-62% – Low platelets (<100) 50% – AST/ALT elevation (3x above normal) HELLP Syndrome • Maternal complications – – – – – – – – – DIC 4-38% Placental abruption 10-16% Acute renal failure 1-8% Severe ascites 5-8% Pulmonary edema 2-10% ARDS 1% Hepatic infarction / rupture/hematoma 1% 1.1%; stroke, cardiac arrest Mortality 8% HELLP Syndrome • Management – Stabilize mother; assess fetal condition; decide whether prompt delivery is needed – Consult MFM – Glucocorticosteroids; anti-hypertensive; IV Mg sulphate – Prompt delivery is indicated: • >34 wk GA • Non-reassuring fetal status • Presence of severe maternal disease Acute Fatty Liver of Pregnancy Epidemiology: •Rare; 1/7000 – 1/20,000 deliveries •More common with primiparas, male & multiple gestations Time: •Typically in 3rd trimester •Can recur in subsequent pregnancies Etiology: •? Decreased mitochondrial oxidation of fatty acids with elevated estrogen levels •LCHAD deficiency identified in 20% Acute Fatty Liver of Pregnancy Presentation: • Nausea, vomiting 75% • Abdominal pain (epigastric) 50% • Anorexia • Jaundice • Preeclampsia (HTN, proteinuria) seen in > 50% • Other: asterixis, encephalopathy, ascites • Rare: transient polyuria & polydipsia due to central diabetes insipidus; pancreatitis AFLP Laboratory findings • • • • • • AST / ALT elevated (up to 1000 IU/L) Elevated Bili PT may be prolonged Leukocytosis with neutrophilic left shift Thrombocytopenia in 90% Renal failure, hypoglycemia, hyperuricemia Liver Biopsy • NOT indicated – Overall architecture is not altered – Microvesicular fatty infiltration of hepatocytes – Droplets are minute, surround central nuclei Acute Fatty Liver of Pregnancy • Maternal Complications – Upper GI bleed 30-40% – Renal dysfunction 70% – DIC 56% – Pancreatitis 30% – Severe hypoglycemia 25-50% – Mortality > 90% before 1970; now < 10% for mother, baby 36% Acute Fatty Liver of Pregnancy Management: •Medical and obstetric emergency!! •Treatment – deliver baby ASAP after maternal stabilization At the end of this session, participants should be able: • To recognize normal physiologic changes associated with pregnancy. • To have a systematic approach to liver diseases in pregnancy. • To recognize and manage intrahepatic cholestasis of pregnancy. • To recognize acute fatty liver of pregnancy and HELLP syndrome.