dr.

Muhammad Ilham Aldika Akbar SpOG

• Pendidikan Spesialis Kebidanan & Kandungan Fakultas Kedokteran Universitas

Airlangga (2007-2011)
• Dosen dan Staf Pengajar SMF/Departemen Obstetri Ginekologi Fakultas
Kedokteran Universitas Airlangga (2010-sekarang)
• Peserta Kongres Dunia ke 18 International Society for The Study of
Hypertension in Pregnancy (ISSHP), Geneva-Swiss, 9-12 Juli 2012. Menjadi
pembicara dalam sesi oral presentasi, membawakan 1 poster penelitian, dan
menjadi moderator dalam salah satu sesi diskusi.
• Peserta Seminar “New Direction in The Management of Metabolic Syndrome”,
Surabaya, 2 September 2012.
Acute Fatty Liver in Pregnancy
Muhammad Ilham Aldika Akbar, dr., SpOG(K)
Maternal Fetal Medicine, Department Obsgyn
Dr. Soetomo Hospital - UNAIR Hospital
Faculty of Medicine Universitas Airlangga
 LIVER DISEASE COMPLICATING PREGNANCY

RELATED TO ACUTE DISEASE THAT ARE CHRONIC DISEASE THAT

PREGNANCY COINCIDENTAL TO PREGNACY PREDATE PREGNANCY

Hyperemesis Gravidarum Acute viral Hepatitis Chronic Hepatitis

Intrahepatic Cholestasis Cirrhosis
AFLP Esophageal varices
HELLP syndrome
Physiological changes in pregnancy

Liver physiological changes

Protein synthesis
Carbohydrate Metabolism
Amino Acid Metabolism
Detoxification and excretion

Liver’s workload increasing

ACUTE FATTY LIVER OF PREGNANCY
• Acute fatty metamorphosis or Acute
yellow atrophy
• 1 in 10.000 pregnancies
• Soetomo Hospital: 18 cases (Jan 2011-
Des 2015)
• 3rd Trimester
• 30 -38 weeks

Two swollen hepatocytes containing numerous

microvesicular fat deposition (Cunningham et al,
2014)
Risk Factors
• Primigravida
• Preeclampsia
• Multiple Pregnancy (increased production of fatty acid metabolites by fetus)
• Male Fetus (?)
• Drugs (NSAID)
Pathogenesis

Recessively
inherited
mitochondrial
abnormalities of
fatty acid oxidation
Pathogenesis Mother Father
Heterozygous LCHAD Heterozygous LCHAD
Deficiency Deficiency
FFA accumulation Fatty degeneration
in Liver and infiltration
Genetics

Homozygous LCHAD
FFA ↑ ↑ >
Deficiency
Hepatic Capacity
AFLP Fetal Liver
DRUGS Abnormal FFA
Hepatic Activity ↑
Pregnancy oxydation
↑
Multiple
Pregnancy
Maternal Liver
Unmetabolized FFA Unmetabolized FFA
↑↑
PLACENTA ↑↑

Akbar MIA et al, 2017

Clinical Findings
Severe Liver
Dysfunction
Nausea AKI
Vomitting Pulmonary
Malaise Edema
Anorexia DIC
Jaundice Fetal Death
Hemolysis
Preeclampsia
Maternal Death

Cunningham et al, 2014 Ko HH et al, 2006

 Clinical Findings AFLP Patients in Soetomo Hospital 2011-2015
20
18
18
16
14
14
12
12 11 11
10
10
8
8 7 7
6
6
4
4
2
0
0
Jaundice Hypoglicemia Vomitting Hypertension Ascites Encephalopathy
Yes No

Akbar MIA et al, 2017

Jaundice (100%), hypoglicemia (77.78%), and nausea-
vomitting (61%) late in pregnancy is an ALARM of AFLP
 AFLP almost always manifest late in Pregnancy
<12 13-27
Postpartum 0% 6%
11%
Mean: 33,93 +
4,43 weeks

<12
13-27
28-36
37-40
37-40
22% Postpartum
28-36
61%

Akbar MIA et al, 2017

Laboratory Findings

Ko HH et al, 2006
Laboratory Parameter Mean + SD Normal Change Laboratory findings was
consistent with literature
Albumin (g/dL) 2,59 + 0,60 3,4-4,8 ↓
review
Direct Bil (mg/dL) 10,08 + 5,59 <0,2 ↑↑
Total Bil (mg/dL) 14,38 + 7,87 0,1-1 ↑↑ Hipoalbumin
AST (IU/L) 948,72 + 2114,77 <35 ↑↑ Hiperbilirubin
ALT (IU/L) 395,61 + 726,43 <35 ↑↑ Increased Liver Function Test
Increased Renal Function
Glucose (mg/dL) 53,28 + 23,98 70,27-100 ↓↓
test
PT (second) 28,44 + 26,68 10-14 ↑↑ Increased Hemostatic
APTT (second) 82,28 + 157,53 26-38 ↑↑ function
Creatinine (mg/dL) 2,9 + 1,64 0,5-0,9 ↑↑ Hipoglycemia
Platelet (x103/µL) 175,33 + 127,72 150-400 =
Leucosyte (x103/µL) 21,99 + 11, 26 3,6-11 ↑↑

Akbar MIA et al, 2017

DIAGNOSIS AFLP
• Difficult  non spesific clinical presentation
• Rule out other cause/disease:
• Preeclampsia – HELLP syndrome
• Intrahepatic Cholestasis of Pregnancy (ICP)
• Acute Viral Hepatitis
• Drug induced Hepatitis
• Serological marker
• Ultrasound & CT  low sensitivity and spesificity
• Liver Biopsy
 Parameter AFLP HELLP Synd ICP Viral Hepatitis
Onset (TM) Late 2nd or 3rd 2nd – 3rd 2nd or 3rd Any
Sign & Symptoms Jaundice, nausea- Preeclampsia, Intense pruritus, Fever, nausea
vomitting, abdominal epigastric or right jaundice, vomitting,
pain, malaise upper quadrant steatorrhea
pain, nausea,
vomitting
Laboratory ALT < 500 U/L, ALT < 500 IU/L ALT < 500 IU/L ALT > 500 IU/L
hypoglicemia, Platelets <150x109/L Markedly elevated Elevated bilirubin
hyperbilirubinemia, LDH > 600 ALP & GGT, Positive serology
leukocytosis, DIC, increased bile acids, test
thrombocytopenia, bilirubin (<103
prolonged PT, umol/L)
hypofibrinogenemia
Ko HH et al, 2006
Liu J et al, 2017
 Abdominal Pain
Vomitting
Polydipsi/ Poliuria
Ascites/bright liver
(USG) Leucocytosis

High Ammonia Encephalopathy

SWANSEA
Hyperbilirubinemia
Coagulopathy CRITERIA
Minimum 6 from 14
High AST-ALT Hypoglycemia
Sign/Symptoms

Renal Impairment High Uric Acid

Microvesicular steatosis
(liver biopsy)
 SWANSEA CRITERIA

100% Sensitivity
57% Spesifisity Goel A et al, 2011
85% Positive Predictive Value
100% Negative Predictive Value

The use of this criteria has not been standarized

No study demonstrated this criteria result in earlier time to diagnosis

Liu J et al, 2017
 LIVER IMAGING FOR AFLP
Focal fatty liver with multiple hyperechoic lesion that
mimic hemangiomas or metastases
POOR SENSITIVITY in all
imaging
USG: 3/11, CT- SCAN: 5/11, MRI: 0/11
Castro et al, 1996

POOR SENSITIVITY in
Ultrasound
Only 25% had sonographic findings
(ascites, echogenic liver)
Knight et al, 2008
http://www.ultrasoundcases.info/Slide-View.aspx?cat=131&case=5659
MANAGEMENT
Management AFLP
• Delivery of the fetus is paramount!
• Treatment is largerly supportive
• Life threatening condition postpartum: acute liver failure with
encephalopathy, DIC, acute renal failure & gastrointestinal bleeding.
• Admission to ICU:
• Frequent monitoring for coagulopathy and blood products
• Aggressive correction of hypoglicemia
• Mechanical ventilation for ARDS
• Dialysis
• Plasmapheresis
Liu J et al, 2017
 Early Diagnosis AFLP

• Airway management • Maintenance IV

• Treatment Hypertension Fluid and Blood
• Correction hypoglycemia, product
electrolyte imbalance,
Maternal Stabilization • Frequent Vital sign
and caogulation assesment
abnormalities • Mental status

Delivery
• Vaginal delivery preffered
• CS often performed because deteriorating
maternal fetal condition • Carefull risk of
• Hemodynamic pancreatitis
monitoring • Serial screening
• Glucose infusion serum lipase &
• Transfusion blood Postpartum Intensive
amylase
products Care • Imaging
The definitive management of AFLP is prompt termination of
pregnancy and supportive care

Prompt delivery rapidly stops the overload on the mother’s hepatic

fatty acid oxydation system, which then returns to normal and
improves liver tests and function

Benjaminov, 2004

If delivery delayed, complications such as acute liver failure with

encephalophaty and IUFD may develop
MODE OF DELIVERY
Vaginal delivery is preferred

CS is recommended for severe AFLP, after coagulation disorder is

resolved

The surgery was postponed when obtained coagulopathy, and after

delivery, should be the installation of condom balloon catheter to
prevent hemorrhage postpartum
 Mode of Delivery AFLP Cases
10
9
9
8 SC Rate
7
6 50 % vs 28.57%
6
5
4
4
3
2 2
2
1 1
1
0
0
Vaginal Delivery Muzeaux Forceps SC Unborn
Soetomo Hospital Hasan Sadikin Hospital
Akbar MIA et al, 2017 Pribadhi A. et al, 2015
MATERNAL FETAL
OUTCOME
SHORT & LONG TERM FETAL MATERNAL OUTCOMES IN AFLP
• Maternal Mortality Rates in US: 85% (1980) to 10-15 % (2000)
• Worlwide mortality < 10%
• Women who receive prompt treatment have improvement over 1-3 weeks
• Hepatic improvement 1-2 days of delivery
• AKI resolve in 7-10 days
• Long term outcome?
• 25 women, 54 month post delivery, no major adverse event (Xiong et al, 2015)
• USG: 40% increased echogenicity, 40% normal
FETAL OUTCOMES
• Fetal mortality as high as 20%, due to maternal acidosis
• FAOD (Fatty Acid Oxidation Defect)
• Follow up 50 children with LCHAD Deficiency: 38% Mortality Rate within 3 month,
chronic issues: retinopathy, metabolic crises, muscle pain, hypotonia (Den Boer
ME et al, 2002)
• In USA: Fetal/newborn screening for FAOD, including MCAD and VLCAD
 MATERNAL-FETAL OUTCOMES IN INDONESIA
Bandung, 2010-2013 90.00% 85.70%
7 AFLP Cases  Maternal Mortality 85.7% 80.00%
71.40%
7 Fetal  1 IUFD, 4 perinatal death, 2 live baby 70.00% 66.67%
57.90%
Fetal Mortality 71.4% 60.00%
Pribadhi A. et al, 2015 50.00%
40.00%
30.00%
Surabaya, 2011-2016 20.00%
18 AFLP Cases  Maternal Mortality 66.67% 10.00%
58% Septic Shock, 42% Encephalopathy 0.00%
19 Fetal  Fetal Mortality 57.9%, Maternal Mortality Fetal Mortality
100% Early onset sepsis Soetomo Hospital Hasan Sadikin Hospital
Akbar MIA. et al, 2017
 MATERNAL COMPLICATION
Complication N (%)
Maternal Death 12 (66.67 %)
Septic 13 (72.22 %)
Encephalopathy 11 (61.11 %)
Pulmonary Edema 2 (11.11 %)
Coagulopathy 13 (72.22 %)
Acute Kidney Injury 15 (83.33 %)
Hypoglycemia 14 (77.78 %)
The number of complications was correlated
with maternal death (p=0.04). Pribadhi A. et al, 2015

The only parameter clearly correlated with maternal

death in AFLP was the presence of hypertension
Akbar MIA et al, 2017
 FETAL OUTCOMES
mild
asphyxia 10%
16% 21%

16% <2000
2000-2500
moderate 2500-3000
asphyxia 3000-3500
21% IUFD
58% unknown
16%
37%
severe Akbar MIA et al, 2017
asphyxia
5%
The incidence of IUFD in AFLP patients was negatively correlated with
gestational age at labor and birth weight (p=0.001 and 0.004)
CASE REPORT
 Ny. A/30 y.o
Second pregnancy

Until 7 month
ANC Midwife: Normal

37 week
Midwife
Complain: ikterus, tea like urine
Refer to Rural Secondary Hospital
Refer to Our
Hospital
Ikteric, BP: 130/90, VT: (-)
Albumin: 2.32; SGOT/SGPT: 148/62
Direct – Indirect Bilirubin: 8.42/8.03
SOETOMO HOSPITAL

PHYSICAL EXAMINATION:
Ikteric, BP: 120/80 HR: 88 t: 36.8’C
Heart-Lung: normal
BMI: 22.2 m/kg2

OBSTETRICS EXAMINATION:
Fundal Height: 32 cm, HIS (-), FHR: 150 bpm ABDOMINAL ULTRASOUND:
VT: 3 cm/50%/transverse SS/Hodge 1/Amniotic Sheat (+) • Liver: no abnormality
FETAL ULTRASOUND: • Spleen: No Abnormality
~ 38/39 weeks ~ 3103 g
NST: Category 1

LABORATORY EXAMINATION:
Random Blood Glucose: 48, BUN/SK: 25/2.96, Albumin: 2.26, SGOT/PT: 158/66
PPT/APTT: 27.8 (11)/ 53.7 (25)
Uric Acid: 8.3, AFP: 402, Bilirubin Direct/Total: 6.74/9.31
Cholesterol: 155, TG: 200
 Swansea Score
Vomiting (-)
Abdominal Pain (-)
Poliuria (-)
Ensefalopati (-)
Peningkatan bilirubin (+)
Coagulopathy (+)
Hipoglycemia (+)
7
Increased Uric Acid (+) Positive
Leukositosis >16.000 (+) SIGN
Asites or bright liver on USG (-)
Increased LFT (+)
Increased Amonia level > 47чmol (?)
Increased Serum Creatinin (+)
Microvesicular steatosis pada biopsi liver (?) 36
Diagnosis :
GII P1001 38/39 wk SLIU + Head pres + Laten Phase + Secondary Elderly Primi + AFLP + AKI
+ Hipoalbuminemia + Abnormal Hemostatic function + EFW 3100 g

Maternal Stabilization
Termination per vagina ~ progression

Secondary Arrest of Dilatation

Cito LSCS  ♀/ 2650 g/ 48 cm/ AS 1-1-3

Atonia Uteri  Supravaginal Hysterectomy

POSTPARTUM CARE 01-10-2017
02-10-2017
03-10-2017 04-10-2017

Hb 8,2 9,5 9,5 10,1

Ventilator Support WBC 25.410 19.150 15.830 `17.800
Multi spesialist approach PLT 156.000 154.000 115.000 88.000
Hct 22,2 29,6 29 31,5
DRUGS: GDA 82 56124 77 52
-Diet sonde Hepar 6x150 cc Albumin 2,25 2,69 2,49
-Inf. Clinimix 20E 1500 cc/24 hour Na/K/Cl
138/4,5/108 143/4,9/115 143/4,3/116 146/4,1/117
-Inj. Ceftriaxone 1 g every 12 hour
-Drip Metronidazole 3x500 mg iv PPT 16,1 (10) 17,1 (10,5) 14,1 (9,6)
-Inj. Vit K 1 amp every 8 hour
-Inj. Omeprazole 160 mg SP every 24 APTT 37,3 (23,4) 48,20 (24,4) 46,6 (26,3)
hour
LDH
-Inj. Metoclopramid 1 amp every 8 hour
BUN/SK 49/2,47 39/1,48
-UDCA 250 mg every 8 hour
-Curcuma 1 tab every 8 hour OT/PT 86/30 73/30 51/19
-Sucralfat syr C II every 8 hour Ca
-Balans cairan CM=CK + 500 cc Bil D/T 5,33/7,15
The Patient is still in ICU care until now
With Multiple Organ Damage:
Acute Kidney Injury
AFLP
Septic
Encephalopathy
Hypoalbumin
Acute Liver Failure

PROGNOSIS POOR
Conclusion
• AFLP is obstetric emergency condition that must be diagnosed as
quickly as possible
• Icteric, with excessive nausea-vomitting during 3rd trimester should
raise awareness the possibility of AFLP
• Swansea Criteria can be used as a clinical tools to diagnose AFLP
• Termination of Pregnancy is the only best treatment for AFLP