JURNAL Gastro Liver Dis.pregnancy

8/10/2019 JURNAL Gastro Liver Dis.pregnancy

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Deepak Joshi, Andra James, Alberto Quaglia, Rachel H Westbrook, Michael A Heneghan

LANC ET 2 1

Liver isease in Pregnancy

Yusdeny lanasakti

Department of Internal Medicine

dr Soetomo Teaching Hospital- Airlangga University School of Medicine

SURABAYA


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Severe liver disease, although rare, can occur and

leads to increased morbidity and mortality for both

mother and newborn infant

up to 3% of all pregnancies are complicated by

liver disorders

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ntroduction

Alterations in normal physiological and hormonal

profi les occur throughout pregnancy

LANC ET 2 1

liver disease in pregnancy can be related or

unrelated to pregnancy


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serum albumin concentration falls due to the

expansion in plasma volume, and the alkaline

phosphatase activity increases due to added

placental secretion

Blood volume increases by about 50%, peaking in

the second trimester.

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Normal Physiological Changes in

Pregnancy

Pregnancy rise in maternal heart rate, cardiac

output, together with a fall in blood pressure and

systemic vascular resistance

LANC ET 2 1

Telangiectasia or spider angiomas and palmar

erythema are normal fi ndings in pregnancy and are

caused by the hyperoestrogenic state


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Hyperemesis gravidarum

Intrahepatic cholestasis of pregnancy

Pre-eclampsia and eclampsia

HELLP syndrome

Acute fatty liver of pregnancy

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Pregnancy-related

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Pre-existing liver diseases

Cirrhosis and portal hypertension Hepatitis B and C

Autoimmune liver disease

Wilsons disease

Liver diseases co-incident with pregnancy

Viral hepatitis

Biliary disease Budd-Chiari syndrome

Liver transplantation

Drug-induced hepatotoxicity

Pregnancy-unrelated

Liver isease in Pregnancy


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Classification of Liver Diseases in Pregnancy


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Abnormalities : serum urea and creatinine hypophosphataemia,

hypomagnesiumia, and hypokalaemia

Serum aminotransferases can be raised by as much as 20 times the upper limit ofnormal,jaundice is rare

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Hyperemesis Gravidarum

Hyperemesis gravidarum occurs in 0.32.0% of all pregnancies usually within the

first trimester.

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Biochemical abnormalities resolve on resolution of vomiting


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The key symptom is pruritus, especially of the palms and soles followed by

generalised symptoms, usually occurs from week 25 of gestation

Intrahepatic cholestasis can lead to chronic placental insufficiency, resulting in fetalcomplications that include anoxia, prematurity, perinatal death, fetal distress, and

stillbirth

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Intrahepatic Cholestasis of

PregnancyDefined as pruritus with serum bile acids occurring in the second half of

pregnancyresolves after delivery.

LANC ET 2 1

Aminotransferase activity can be increased by 20 times the normal level. The key

diagnostic test is a fasting serum bile acid concentration of greater than 10 mol/L


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Intrahepatic cholestasis of pregnancy normally resolves after delivery but, in rare

can persist after delivery, leading to fibrosis and even cirrhosis

UDCA (1015 mg/kg bodyweight) provides relief against pruritus, improve liverfunction tests, and is well tolerated both by mother and fetus

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UDCA : plasma bile acid and sulphated progesterone metabolite concentrations

LANC ET 2 1

Intrahepatic cholestasis of pregnancy might therefore be a predictor for the

development of liver and biliary disease in the future


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Characteristic microscopic changes , involve periportal areas with identifiable

sinusoidal fibrin thrombi, haemorrhage, and hepatocellular necrosis.

Clinical features: right upper abdominal pain, headache, nausea, and vomiting.Abnormal liver function tests occur in 2030% of patients

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Pre-eclampsia and Eclampsia

Preeclampsia is characterised by hypertension and proteinuria (greater than 300 mg

in 24 h) after 20 weeks of gestation and/or within 48 h after delivery

LANC ET 2 1

Complications include maternal hypertensive crises, renal dysfunction, hepatic

rupture or infarction, seizures, and increased perinatal morbidity and mortality.

Liver biochemical profile usually normalises within 2 weeks of delivery


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Figure 2: Liver biops y from a young woman with eclampsia

Haematoxylin and eosin staining. Liver biopsy shows an area of coagulative

necrosis (marked by the arrows), which involves perivenular and midzonalhepatocytes. The arrowhead indicates a portal tract.


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HELLP shows symptoms similar to pre-eclampsia and is one of the criteria that can

define severe pre-eclampsia, it can develop in women who might not have any

other signs or symptoms of pre-eclampsia

510% of women with pre-eclampsia develop HELLP

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HELLP Syndrome

The combination of haemolysis with a micro-angiopathic blood smear, increased

liver enzymes, and low platelets (HELLP) in pregnancy was first described in 1982

LANC ET 2 1

HELLP usually arises in the second or third trimester, but can also develop after

delivery. Risk factors include advanced maternal age, multiparity, and white ethnic

origin


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Liver injury is precipitated by intravascular fibrin deposition, hypovolaemia, and

increased sinusoidal pressure resulting in mild-to-moderate increase of aminotrans

ferases and mild elevation of bilirubin

Hypertension and proteinuria is evident in up to 85% of cases

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HELLP Syndrome

HELLP syndrome might be asymptomatic or present with right upper quadrant

and epigastric pain, nausea, vomiting, and malaise

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The prothrombin time or INR remains normal unless there is evidence of DIC or

severe liver injury


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typically present in the third trimester with severe right upper quadrant pain and

pyrexia Increased aminotransferase concentrations in excess of 3000 U/L,

leucocytosis, pyrexia, and anaemia are frequently seen

DD : acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, andhaemolytic uraemic syndrome

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Hepatic Haematoma, Infarct ion, and

Rupture

Occur in a minority of women with established pre-eclampsia or HELLP syndrome

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Acute complications include acute respiratory distress syndrome, acute kidney

injury, and hypovolaemic shock


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Intravenous magnesium sulphate with platelet, coagulation support, or both, are

recommended especially in the presence of bleeding.

Prompt delivery : over 34 weeks of gestation, if fetal distress or if maternal end-organ disease + (ie, DIC, renal failure, or abruptia placenta)

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The cornerstone of management is delivery

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Indications for liver transplantation include persistent bleeding from haematoma,

hepatic rupture, or liver failure

Hepatic Haematoma, Infarction, and Rupture


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Prompt delivery is essential After delivery, women can develop a long cholestatic

phase, taking up to 4 weeks for resolution

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Acute Fatty Liver of Pregnancy

Clinical presentation varies from nausea and abdominal pain to hepatic

encephalopathy and jaundice

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DIC can occur with normal hepatic laboratory findings, but common abnormalities

include raised aminotransferase concentrations, prothrombin time, and serum uric

acid and bilirubin concentrations Hypoglycaemia is a poor prognostic sign.

The newborn infant should be assessed for signs of hypoglycaemia, hepatic failure,

myopathy, and other features associated with defects in fatty acid oxidation.


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Figure 5: Acu te fat ty l iver of pregnanc y

Haematoxylin and eosin staining. Hepatocytes show a clear cytoplasm (arrow) or many

minute vacuoles


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LANC ET 2 1

Pre-existing Liver Diseases

and Pregnancy


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When pregnancy is successful in a cirrhotic woman, spontaneous abortion rate, riskof prematurity, and perinatal death rate are all increased.

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Cirrhos is w ith Portal Hypertens ion

Pregnancy in cirrhotic women is rare anovulation and amenorrhoea

LANC ET 2 1

Portal hypertension worsens blood volume and flow , vascular resistance

due to external compression of the inferior vena cava

25% of pts with varices bleeding during pregnancy. The greatest risk is seen in the

second trimester, when portal pressures peak, and during delivery


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Banding before pregnancy, although not proven, is

appropriate for high-risk varices

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Cirrhosis with Portal Hypertension

All cirrhotic patients should undergo variceal screening.

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Propranolol has also been used safely inpregnancy but side-eff ects include fetal

growth retardation, neonatal bradycardia,

and hypoglycaemia


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Women who are not cirrhotic but HBV-positive are at risk of transmitting the

virus to the fetus

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Hepati t is B and Hepati t is C Infect ion s

HBV vaccine can be given safely during

pregnancy if needed

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HBV viral load is a key factor in transmission,

with high viral load being associated with 80

90% risk of transmission

Transmission can occur directly via the

placenta (intrauterine), during

breastfeeding, or during delivery


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Pregnancy in patients with hepatitis C virus (HCV) is usually uneventful. Risk of

vertical transmission of HCV remains low, except when the fetus is exposed to

large volumes of mothers blood and vaginal fl uid during delivery or if the motheris co-infected with HIV.

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Hepatitis B and Hepatitis C Infections

Mode of delivery does not affect the risk of transmission, with similar rates seen

with normal vaginal delivery and caesarean section

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Use of lamivudine and other antiviral drugs during the third trimester to reduce

HBV viral load and thus decrease the risk of transmission to the fetus, is a sourceof debate.

Ribavirin is teratogenic and the use of pegylated interferon in combination with

ribavirin is contra-indicated during pregnancy, but not during breastfeeding.


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Women with autoimmune hepatitis need stable immunosuppressionthroughout pregnancy

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Au to immune Liver Disease

Successful pregnancies are achievable in women with autoimmune

hepatitis

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Although azathioprine is teratogenic in animal models, teratogenic effects

in human beings have not been described.

If flares occur administrationof steroids or increase in steroid dose. If an

immunosuppressant is needed, azathioprine remains the safest choice


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present with hyperbilirubinaemia, aminotransferases, Coombes-negativehaemolytic anaemia, and low serum alkaline phosphatase

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Wilsons Disease

Rare autosomal recessive disease of defective biliary copper excretion

deposition in the liver, brain, and kidneys.

LANC ET 2 1

In pregnant women with undiagnosed Wilsonsdisease, evidence of acute

liver failure and haemolysis could be misinterpreted as HELLP syndrome.

In women with known Wilsons disease, serum copper levels and

caeruloplasmin can rise during pregnancy without treatment, leading to a

flare in patient symptoms.


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LANC ET 2 1

Liver Diseases Co-incident

with Pregnancy


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Increased severity of disease is associated with advanced maternal age,with severe infection in the third trimester associated with an increased

risk of prematurity.

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Acu te Viral Hepati t is

A recent study has identified the presence of ascites and hypertension as

factors that help to differentiate liver disease specific to pregnancy from

viral hepatitis

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Pregnant women are more vulnerable to hepatitis E virus (HEV) infection

than to HAV, HBV, and HCV.

HEV remains the most prevalent viral cause of acute liver failure in

pregnancy


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Reported maternal mortality from fulminant hepatic failure secondary toHEV in pregnancy is 4154%, with a fetal mortality rate of 69%.

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Acute Viral Hepatitis.

Pregnant women are more likely to acquire HEV in the second or

third trimester, with a median gestational age of 28 weeks

LANC ET 2 1

Poor outcomes are associated with the development of grade III or IV

hepatic encephalopathy

Management is supportive, delivery does not affect maternal outcome.


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10% of pregnant women develop either gallstones or viscus biliary sludge

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B il iary Disease

Gallstones are more common in pregnancy : cholesterol secretion in the

second and third trimester, lithogenicity of the bile, and gallbladder

motility.

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Open or laparoscopic cholecystectomy can be done safely and successfully

during the second trimester

ERCP and sphincterotomy can be done if needed, with little added risk

compared with that in non-pregnant women.


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20% of cases of Budd-Chiari syndrome occur in women who are on the

oral contraceptive pill, are pregnant, or have delivered in the previous 2

months

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Budd-Chiar i Synd rome

Budd-Chiari syndrome is defined as outflow obstruction of the hepatic

veinscommonly associated with myeloproliferative disorders.

LANC ET 2 1

Patients with known Budd-Chiari syndrome are at risk of developing an

exacerbation during pregnancy because of concentrationsof

female sex hormones.

Clinical features include right upper quadrant pain, jaundice, and ascites.

Doppler ultrasound is very important in diagnosis.


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Pregnancy should be deferred for 1 year after liver transplantation, whichallows lower doses of immunosuppression and more stable graft function

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Liver Transplantat ion

Young patients who have been successfully grafted can become pregnant.

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Caesarean deliveries are also more likely in this group

Commonly used drugs such as tacrolimus, mycophenalate mofetil,

prednisolone, azathioprine, and ciclosporin all carry a risk of teratogenicity


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JURNAL Gastro Liver Dis.pregnancy