reiview Liver diseases in pregnancy

1. Liver Diseases
in Pregnancy
Mohammed El-besh

2. Liver disease is a rare complication of
pregnancy, but when it occurs it may do
so in a dramatic and tragic fashion for
both mother and infant. Diseases such
as acute fatty liver of pregnancy (AFLP)
may begin innocuously with mild
symptoms and liver enzyme
abnormalities but, if left untreated, can
progress to jaundice, liver failure, and
death.

3. Spectrum of liver
diseases in pregnancy

4. Preexistent liver diseases
 Portal hypertension, cirrhosis, primary biliary
cirrhosis
 Autoimmune hepatitis
 Wilson disease
 Chronic infection with hepatitis B or hepatitis C virus
 Alcoholic liver disease

5. Liver diseases coincidental
with but not induced by
pregnancy
 Acute viral hepatitis and other viral infections
 Alcohol-related diseases
 Gallstone disease
 Budd-Chiari syndrome

6. liver diseases unique to
pregnancy
 Hyperemesis gravidarum,
 intrahepatic cholestasis of pregnancy,
 Preeclampsia and eclampsia
 hemolysis and elevated liver enzymes and low platelets
(HELLP) syndrome
 acute fatty liver of pregnancy,

8. Hyperemesis Gravidarum
Presentation and assessment
 The FIRST trimester
 persistent vomiting with no other cause,
 Severe dehydration
 evidence of acute starvation (usually with ketonuria), and evidence
of acute weight loss, of 5% or greater.
Investigations
 Up 50 % of the hospitalized patients have abnormal liver enzymes.
Aminotransferase levels may rise up to 200 IU/L but are generally
less than 300 IU/L, and alkaline phosphatase may rise to twice the
normal value.
 Both direct and indirect bilirubin values may rise to 4 mg/dL, and
serum amylase and lipase may rise up to 5 times normal values.
 Electrolyte imbalance e.g. hypokalemia

9. Etiology : unknown
Risk factors :
 multiple gestations
 molar pregnancies
 fetal anomalies such as hydrops fetalis and trisomy

10. Intrahepatic cholestasis of
pregnancy
Presentation and assessment
 The second and third trimesters
 The most common symptom is pruritus.
 steatorrhea, malabsorption of fat-soluble vitamins, and
weight loss.
 Clinical jaundice is detected in 10%-15% of the cases
Investigations
 Elevated fasting serum bile acids level (> 10 μmol/L)
confirms the diagnosis.
 Aminotransferases can be elevated as well up to 2-10 folds
 Alkaline phosphatase levels might not be helpful due to
higher physiological levels in late pregnancy.

11.  The cause of IHCP is unknown
 but is thought to be multifactorial
 genetic, hormonal, and environmental
involvement.
 Family clustering and varying incidence in different
geographic regions speaks strongly for a genetic
etiology of ICP

12. Severe pre-
eclampsia/eclampsia &HELLP
syndrome
 Pre-eclampsia (or pre-eclamptic toxaemia, PET) occurs after
the 20 th week of pregnancy, and can occur into the
postpartum period.
 It is defined as pregnancy-induced hypertension (PIH) with
a systolic BP >140 mmHg and/ or diastolic BP >90 mmHg
(on 2 separate occasions); with proteinuria of 0.3 g in a 24-
hour period.
 Severe pre-eclampsia is defined as pre-eclampsia with a
systolic BP >160 mmHg or diastolic BP >110 mmHg and/or
symptoms

13. Up to 10% of women with
severe pre-eclampsia, and
25–50% of
women with eclampsia are
affected by the HELLP
syndrome.

14. HELLP
is a multisystem disease consisting of generalized vasospasm
and coagulation defects.
No common precipitating factor has been identified.
• H aemolysis is due to a microangiopathic haemolytic
anaemia (MAHA).
• E levated L iver enzymes are due to hepatic necrosis (in
severe cases intra-hepatic haemorrhage, subcapsular
haematoma or hepatic rupture may occur).
• L ow P latelets/thrombocytopaenia is due to consumption
Some authors consider it as a varient form of Pre-
eclampsi

15. Risk factors for Pre-eclampsia :
 First pregnancy.
 Pre-eclampsia in a previous pregnancy.
 A family history of PIH or PET.
 Diastolic BP >80 mmHg at booking.
 Obesity.
 Increasing maternal age.
 Multiple pregnancies or polyhydramnios.
 Underlying medical conditions:
 Previous hypertension
 Diabetes mellitus
 Renal disease
 Autoimmune disease such as SLE or antiphospholipid
antibodies

16.  Pre-eclampsia Presentation and assessment
may be asymptomatic and only discovered by routine blood
pressure screening, or when complications such as eclampsia
occur.
Signs and symptoms:
Neurological:
• Headache and/or visual disturbance (cerebral oedema)
• Hyperreflexia/clonus • Seizures. eclampsia
• Papilloedema
Respiratory:
• Dyspnoea on exertion
• Pulmonary oedema • ALI, ARDS

17. Cardiovascular: hypertension (>140/90 mmHg).
GI:
• Nausea and vomiting;
• Epigastric discomfort (hepatic
engorgement/ischaemia)
Renal: proteinuria, marked oliguria (often <0.25
ml/kg/hour).
General:
• Peripheral oedema
• Facial and laryngeal oedema (this may result in
difficulty in endotracheal intubation)

18. Investigations
• FBC (thrombocytopenia may be seen, platelets
<100 x 10 9 /L).
• Blood film (if TTP suspected).
• Coagulation studies, including fibrinogen (DIC may
occur with raised PT and APTT, thrombocytopenia,
hypofibrinogenaemia).
• U&Es (may be deranged as AKI can occur, a
creatinine >80 μmol/L is likely to be abnormal,
depending on maternal size).
• LFTs (may be deranged with i ALT and/or i AST;
hypoproteinaemia may occur).
• Serum glucose (hypo/hyperglycaemia may be
present).

19. • Urinalysis, options include:
• Urine dipstick (proteinuria: > ++seen; severe
proteinuria:>+++seen); >+ proteinuria seen
requires further investigation
24-hour collection (proteinuria: > 0.3 g/24 hours;
severe proteinuria:>1 g/24 hours)
• Blood, urine, and sputum cultures (if infection is
suspected).
• US of the fetus, to examine for fetal well-being.

20. HELLP Presentation and assessment
 May be asymptomatic
 signs and symptoms overlap with those of pre-eclampsia
 Right upper quadrant and epigastric pain, nausea,
vomiting, malaise, headache, edema, and weight gain
are common complaints.
 Hypertension and proteinuria should be expected,
occurring in up to 80% of cases.
 Jaundice is rare, occurring in only 5% of patients.
•

21. Liver affection in HELLP
 Hepatic consequences include :
 Hepatic infarction,
 Subcapsular Hematomas
 Intraparenchymal Hemorrhage.
 When the ALT or AST is >1,000 U/l or abdominal pain
radiates into the right shoulder, cross-sectional imaging
can assist in excluding hepatic complications with more
accuracy than ultrasound.
 Hepatic infarction should be suspected with right upper
quadrant pain with fever, whereas abdominal swelling or
shock presentation can occur with hepatic rupture

24. Management of Pre-clamsia
,Eclampsia &HELLP
 The definitive treatment for severe
preclampsia/eclampsia is delivery of the baby:
• The decision to deliver must weigh up the needs of the
mother against the maturity of the baby
• Seizures and other symptoms should be controlled prior
to proceeding to delivery/Caesarean section if possible
• Consider IV steroids for fetal lung development
• Patients may be transferred to critical care for enhanced
monitoring and vital organ support pre- or post-delivery

25. Immediate management
 Give O 2 and support airway, breathing, and
circulation as required.
 Hypertension treatment
• The aim should be to reduce diastolic BP to around 90–100 mmHg,
precipitous drops in BP should be avoided.
• There is no consensus as to what constitutes first- or second-line
therapy, a reasonable approach might be:
First-line treatment: labetalol 200 mg PO, repeated after 30 minutes if
required; if oral labetalol is ineffective consider labetalol 50 mg IV
repeated every 5 minutes to a maximum of 200 mg, followed by
infusion at 5–50 mg/hour
• Second-line: if labetalol is not tolerated or contraindicated (e.g. in
asthmatics) give nifedipine 10 mg PO, which can be repeated after 30
minutes if required ( nifedipine should not be given sublingually )

26. • Third-line: hydralazine 5–10 mg by slow IV bolus,
repeated after 15 minutes, followed by an infusion at 5–15
mg/hour (consider a bolus of 􀁤 500 ml crystalloid before,
or at the same time as hydralazine given in the antenatal
period)
• Atenolol, ACE inhibitors, ARBs, and diuretics should be
avoided

27. Treatment and/or prevention of eclamptic seizures
• Magnesium sulphate IV 4 g (16 mmol MgSO 4 ) over 5–10
minutes, followed by an infusion of 1 g/hour (4 mmol/hour) for
at least 24 hours:
• A further dose of magnesium sulphate 2 g (8 mmol MgSO 4 )
over 15–20 minutes can be given if further seizures occur; or the
infusion rate i to 2 g/hour
• Close observation for evidence of magnesium toxicity is
essential
• Second-line eclampsia treatments are only rarely required if BP
control and magnesium have been used, but may include:
• IV phenytoin or benzodiazepines
• Induction of anaesthesia with endotracheal intubation and
ventilation

28. Correction of thrombocytopaenia may be required:
• Patients with a platelet count >40 x 10 9 /L are unlikely to
bleed
• Transfusion is generally only required if the platelet count drops
to less than 20 x 10 9 /L
• Patients who undergo Caesarean section should be transfused
to a platelet count >50 x 10 9 /L
• Patients with DIC should be given FFP and
fl uid restriction regimen is associated with good maternal
outcome
• Limit maintenance fluids to 80 ml/hour unless there are other
ongoing fluid losses, such as haemorrhage packed RBCs.

29. Further management in
HELLP
• Consider plasmapheresis after delivery.
• Epoprostenol and ketanserin have also been used as
’treatments.
Messepi Protocol : ????
 The University of Mississippi developed a treatment
protocol that is often applied as standard of care in the
management of women with HELLP.
 Known as “The Mississippi Protocol”, it includes
corticosteroids, magnesium sulfate, and systolic blood
pressure control
 It improve platelets counts no affection on morbidity nor
mortality

31. Acute fatty liver of pregnancy
 Acute fatty liver of pregnancy (AFLP) is a rare but
a serious condition that is unique to pregnancy
and happens in the third trimester.
 rare, incidence of 1 per 7270 to 13000 deliveries
 outcomes can be grave with acute liver failure and
death

32. Pathogenesis
 The pathogenesis of AFLP was unknown
 However, molecular advances over the past decade suggest
that AFLP may result from mitochondrial dysfunction.
 Defects in fetal mitochondrial fatty acid β-oxidation have
been linked to development of maternal AFLP, particularly
fetal defects in long-chain 3-hydroxy-acylcoenzyme
dehydrogenase (LCHAD) , which is part of the mitochondrial
trifunctional protein (MTP) complex
 Studies provided further evidence that carrying a fetus with
LCHAD deficiency is associated with a high risk for developing
AFLP.
 The precise mechanism by which an LCHAD deficient fetus
causes AFLP in a heterozygote mother is still unclear
 The mechanism of hepatocellular damage may involve the
affected fetus producing abnormal fatty acid metabolites

33. Clinical presentation
 it usually presents in the third trimester
 It is more frequent in primiparous women and can return in
subsequent pregnancies
Usually presents after 30 w, and often near term (35–36 w)
With nonspecific symptoms
 Gradual onset of nausea, anorexia and malaise.
 Severe vomiting (60%)
 Abdominal pain (60%) should alert the clinician to the diagnosis.
Co-existing features
 mild pre-eclampsia,
 but hypertension and proteinuria are usually mild.

34. Jaundice usually appears within 2w of the onset of symptoms
early jaundice may indicate severe disease
±Ascites.
Liver function
3- to 10-fold elevation in transaminase levels
raised alkaline phosphatase.
DIC
90%
often the presenting feature postpartum
± severe.
Renal impairment.
± fulminant liver failure with hepatic encephalopathy.
Hypoglycaemia 70% ± severe
± Polyuria and features of diabetes insipidus (DI)

36.  To meet the criteria the patient should
have 6 or more of these clinical Findings
 Swansea criteria had a sensitivity of 100%
(95%CI: 77-100) and specificity of 57%
(95%CI: 20-88), with positive and
negative predictive values of 85% and
100% in one report

37. AFLP vs HELLP
 Profound hypoglycaemia (70%)
 Marked hyperuricaemia (which is out of
proportion to the other features of
preeclampsia (90%)
 Coagulopathy (90%) in the absence of
thrombocytopenia.

39. Radiological evaluation
MRI,CT or US: ± hepatic steatosis,
but the liver may appear normal {fat
is microvesicular}
CT: decreased attenuation {fatty
infiltration}.

40. Liver biopsy
Liver biopsy with special stains for fatty change or electron
microscopy: gold standard for diagnosis.
microvesicular fatty infiltration (steatosis) of hepatocytes,
most prominent in the central zone, with periportal sparing
little or no inflammation or hepatocellular necrosis.
not always necessary or practical in the presence of
coagulopathy

41. The best markers of
severity: –
 Prothrombin time
 Glucose
 Acidosis
 Raised lactate
 Encephalopathy.

42. Management
 Stabilization of the mother and early recognition and
delivery are the keys for successful management.
 Close monitoring and management of associated
complications is necessary to improve outcomes.
 Plasmapheresis was used in few series in severe cases
with reported success
 N-acetylcysteine (NAC)
an antioxidant and glutathione precursor, promotes
selective inactivation of free radicals
logical tt in hepatic failure

43.  Orthotopic liver transplantation
1.fulminant hepatic failure
2.irreversible liver failure despite delivery of the fetus and
aggressive supportive care.