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Hepatic Problems in Maternity HDU
Cathy Nelson-Piercy
Consultant Obstetric Physician
Professor of Obstetric Medicine
KCL Division of Women’s Health
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Deranged liver enzymes ? Cause
HELLP syndrome
AFLP
Hepatic Problems Page 1
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Liver disease in pregnancy
Due to pregnancy
Hyperemesis
Obstetric Cholestasis
Pre-eclampsia
HELLP syndrome
Acute Fatty Liver of Pregnancy
Incidental to pregnancy
Viral Hepatitis
Drug hepatotoxicity
Cholelithiasis
Exacerbation of CAH, PBC, sclerosing cholangitis
Liver Transplant
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Causes of liver dysfunction in pregnancy
142/4377 (3.2%) in 15 months prospective study Most due to pregnancy specific causes Pre-eclampsia 68 1.6% HELLP 30 0.7% OC 23 0.5% Hyperemesis 11 0.35% AFLP 5 0.1% Sepsis, post-op 51 1.2% Hepatobiliary disease 17 0.39%
Ch’ng CL et al. Gut 2003; 52: 315
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HELLP Syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets)
Incidence
4-20% of PET
21% of early-onset <30 /40
Murphy & Stirrat. Hypertension in pregnancy 2000; 19: 221-231
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Deaths from HELLP Syndrome in UK
HELLP Pre-eclampsia
2006-2008 8 19 2003-2005 8 14 2000-2002 8 14 1997-1999 5 15 Maternal mortality < 1% Perinatal mortality 9.4-16.2%
Rath & Bartz. Zentralb Gynakol 2004; 126: 294 Maternal mortality = 4.7%
Romero Arauz. Ginecol Obstet Mex 2001; 69: 189
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HELLP - Clinical Features
Epigastric / RUQ pain (65%) N & V (35%) RUQ tenderness (may precede LFTs) Hypertension and proteinuria (mild) Low grade haemolysis (no anaemia) Abnormal LFTs
Raised transaminases Raised LDH Raised unconjugated bilirubin
Low / falling platelets (< 100,000) DIC (20%)
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Clinical Diagnosis
Platelet count < 100 x 109
AST ≥ 70 U/L LDH > 600 U/L
Sibai AJOG 1990 Mississippi classification Class 1 platelets ≤ 50 x 109 Class 2 platelets 50-100 x 109 Class 3 platelets 101-150 x 109
Sullivan AJOG 1994
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Gestation
Romero Arauz et al. Ginecol Obstet Mex 2001; 69: 189 n = 170 92% antepartum
9% < 27 weeks 66% 28-36 weeks 25% term
8% postpartum
Postpartum worsening well described 30% arise postpartum Liver enzymes recover before platelets
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HELLP syndrome - CRISES
Acute renal failure – 7%
Abruption – 16%
Liver haematoma
Liver rupture
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Maternal morbidity in HELLP
Romero Arauz et al. Ginecol Obstet Mex 2001; 69: 189 N = 170 AKI 13.5% Abruption 6.6% Pneumonia 3% Liver haematoma 2.3% Pulmonary oedema 2.3% DIC 1.7% Cerebral haemorrhage 1.2% Morbidity increased with lower platelet counts
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Renal failure complicating Pre-eclampsia
Cohort study; 1995-1998 Groote Schuur, Cape Town; 28,000 deliveries/yr 588 admitted to obstetric HDU 89 severe PET + renal failure (Cr>100+ oliguria) 1:1500; 73 cases reviewed Median max Cr = 341 umol/l
Drakeley et al. AJOG 2002; 186: 253.
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AKI
57% multips, 43% primips Mean gestation at delivery = 32 weeks 16% Hx chronic renal disease / hypertension 48% HELLP 30% abruption 16% eclampsia Perinatal mortality = 45%; maternal mortality = 0% 10% required short term dialysis None required long term dialysis / transplant
(0.55% (n = 6)Yorkshire required dialysis)
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RCT Steroids for HELLP syndrome
Fonseca JE et al. Am JOG 2005; 193: 1587
N = 132, dexamethasone 10 mg 12hrly + 3 doses postpartum
Non significant shortening of hospitalization 6.5 vs 8.2 days
No difference in time to recovery of platelet counts lactate dehydrogenase aspartate aminotransferase development of complications
Results were found in both pregnant and puerperal women.
No indication for steroids
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As for pre-eclampsia
Stabilize and Deliver
Platelet transfusion only if active bleeding or to allow regional techniques / central venous access
HELLP syndrome: management Page 14
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Acute fatty liver of pregnancy (AFLP)
Very rare (1/7000-1/16,000)
Microvesicular fatty infiltration due to defective beta oxidation of fat
?Variant of pre-eclampsia
Always third trimester (mean = 35 weeks)
Potentially lethal Maternal mortality 10% Fetal mortality 20-50%
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AFLP - Clinical features
nausea, vomiting, malaise (100%) abdominal pain (43%) associated pre-eclampsia (50-70%)
mild hypertension and proteinuria
Jaundice (37%) Pruritus (10%) fulminant liver failure / hepatic encephalopathy /
coagulopathy / hypoglycaemia AKI (90%) Diabetes insipidus
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AFLP: Swansea Criteria
Any six of the following:
Vomiting Abdominal pain Polydipsia/polyuria Encephalopathy Elevated bilirubin levels Hypoglycaemia Elevated urate Elevated white cell count OR Confirmed by Post Mortem
Elevated transaminases Elevated Ammonia levels Renal impairment Coagulopathy Ascites or bright liver on
scan Microvesicular steatosis on
liver biopsy
Ch’ng et al (2002). Gut 51: 876-880
Metabolic acidosis / raised lactate
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Associated Diabetes Insipidus
Xs vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-D: -arginine vasopressin (dDAVP), [synthetic form].
Impaired liver function means vasopressinase is not degraded, leading to further breakdown of AVP / ADH
Polyuria / polydipsia affect up to 80%
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AFLP
Biochemistry 3 to 10 fold elevation in transaminases Raised creatinine profound hypoglycaemia marked hyperuricaemia
Haematology Abnormal clotting with normal platelets raised WBC
Diagnosis Clinical Radiology; CT / MRI liver biopsy; fat stain
Blood gases, lactate, amylase
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Microvesicular fatty infiltration without necrosis.
LEFT. Centrizonal hepatocytes ballooned, distended with vacuoles that are typical of microvesicular fat.
RIGHT. Oil red O stain markedly positive for fat
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AFLP – Management; HDU / Critical care
Treat hypoglycaemia 10 / 50% dextrose
Treat coagulopathy 10mg Vit K IV X 3 days FFP
Deliver close fetal surveillance
N acetyl cysteine (as for paracetemol OD) 150mg/kg over 15 mins in 200mls 5% dextrose 50mg/kg over 4 hours in 500mls 100mg/kg over 16hours in 1000mls and continue
Supportive Rx of liver failure / Transplantation
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Complications
ARDS Pulmonary oedema 43% Pancreatitis 43% AKI 56% Encephalopathy 50% Ascites 30% Wound seroma 40%
Broad spectrum antibiotics and antifungal agents
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Gut 2008; 57:951-6
N = 57; 5/100,000 Feb 05-Aug 06
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Estimated Incidence
• 52 confirmed cases in 18 months • Incidence 1 in 21,000 deliveries
(95% CI 1/16,000-1/28,100)
• Incidence in SE Thames 1997-8 1 in 16,300 (95% CI 1/5,600-1/78,700)†
• Incidence in SW Wales 1999-2000 1 in 880 (95% CI 1/380-1/2,700)††
† Waterstone M, Bewley S, Wolfe C (2001). BMJ 322:1089-93 †† Ch’ng et al (2002). Gut 51: 876-880
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Characteristics of Affected Women n (%)
Primigravid 32 (62)
White 31 (60)
Age <20 ≥35
0 (0) 14 (27)
Twin pregnancy 10 (19)
Pre-eclampsia 9 (17)
Previous AFLP 1 (2)
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Gestation at diagnosis
0
1
2
3
4
5
6
7
8
9
10
21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Gestation at diagnosis/delivery (weeks)
Num
ber o
f wom
en
PostnatalAntenatal
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Features at Diagnosis n (%)
Vomiting 32 (62) Abdominal pain 30 (58) Polydipsia/polyuria 7 (13) Encephalopathy 5 (10)
USS performed 40 (77)
Ascites/bright liver seen 10 (25*)
Liver biopsy performed 0 (0)
*Percentage of those scanned
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Postpartum
Worsening of liver, renal dysfunction and coagulopathy for 48hrs
? Screen for LCHAD (long chain 3-hydroxyacyl-coenzyme A dehydrogenase) deficiency - Disorder of mitochondrial fatty acid oxidation. Variety of mutations
If LCHAD deficiency, 25% fetuses affected
Recurrence of maternal liver disease 15-25%
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Pathophysiology
Pre-eclampsia ELLP HELLP AFLP Pre-eclampsia HELLP HUS
TTP
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Differential Diagnosis of HELLP syndrome and AFLP
HELLP AFLP Epigastric Pain ++ + Hypertension ++ + Proteinuria ++ + Elevated liver enzymes + ++ Hypoglycaemia +/- +++ Hyperuricaemia + ++ DIC/Coagulopathy + ++ Thrombocytopenia (without DIC) ++ +/- WBC raised + ++ Multiple pregnancy + Primiparous ++ + Male fetus 50% 70% (M:F = 3: 1)
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Learning Points - Liver
n AFLP n liaise with liver unit / Nacetyl cysteine n Monitor: Prothrombin time, glucose, albumin, lactate n Correct coagulopathy / hypoglycaemia n Broad spectrum antibiotics and antifungals n Watch for encephalopathy n Intracerebral pressure monitoring
n HELLP syndrome n Scan if severe RUQ (CT / US) n ‘Hepatic angina’ n Chest pain / acidosis
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Thank you for your attention!