Liver Disease and PregnancyDr.Harsh SaxenaJ.R 1 medicine
Challenging disease to manage• Because of physiology of pregnancy certain disorders take more ominous course in pregnancy than in non pregnant state and some are unique to pregnancy• May have severe maternal & fetal effectsTherefore it is important to have accurate diagnosis
Physiological changes in hepaticparametersNO CHANGE WITH CHANGE• Hepatic blood flow • Albumin - ↓ 20%-50%• Hepatic & splenic size • Globulin -↑• Liver histopathology • Fibrinogen - ↑50%↑• Bilirubin- direct or • ALP - ↑2-4 fold indirect, AST, ALT, • LDH - ↑slight• PT,APTT • Cholesterol & TGL - ↑2fold↑ AST, ALT,S Bb, duringpregnancy indicate liver disease
ClassificationUnique to pregnancy• Hyperemesis Gravidarum• Intrahepatic cholestasis of pregnancy• HELLP• Acute fatty liver of pregnancyconcurrent with pregnancy• Viral hepatitis A,B,C,EPregnancy on Preexisting ch liver disease• Cirrhosis & Portal HT
Hypermesis Gravidarum• Hyperemesis Gravidarum occurs in 1 in 20 pts per 1,000,in the first trimester usually between 4 to 10 weeks of gestation.• Hormones levels seem to play a role ,having peak of human chorionic gonadotrophin and oestradiol levels high.• Risk factors are :hyperthyroidism,molar pregnancy ,pre existing diabetes,multiple gestataion,multiparity.
• Symptoms: severe nausea and vomiting,patient may often present dehydrated and shows evidence of malnutrition and poor weight gain.• Upto half patients have abnormal liver enzymes,aminotransferase levels may rise up to 200IU/L,alkaline phosphatase may rise to twice the normal values.both direct and indirect bilirubin values may rise to 4mg/dl.
• Serum amylase and lipase may rise to 5 times normal.• Non pharmacological interventions are avoiding nausea triggers odours from perfumes,smoke,cooking,foods.low fat,small frequent diets.
• Vitamin B6 in a dose of 10 to 25 mg QID is the initial treatmet of choice,in conjuncton with doxylamine12.5 mg qid• Promethazine 12.5 mg orally or rectally every 4 hrs.• Diphenhydramine 50 to 100 mg orally or rectally every 4 to 6 hours can be used in unresponsive patients.
• In absence of dehydration, metoclopramide 5 to 10 mg im orally thrice a day or promethazine 12.5 or 25 mg IM/ orally/ rectally every 4 hours can be added.• If all these agents fails then methylprednisolone 16 mg thrice a day per orally or iv for 3 days followed by 2 weeks taper.
• Minor complication acid base,electrolyte disturbances,serious complication are oesophageal rupture,retinal haemorrhage,renal damage.
Intra hepatic cholestasis• Intra-hepatic cholestais of pregnancy is common disorder in the third trimester , and resolve after delivery.• Having multifactorial aetiology genetic, hormonal , exogenous factor.• Intra hepatic cholestasis of pregnancy is due to abnormal bililary transport resulting in saturation of hepatic transport system
It is associated with intrauterine growthretardation and premature birth.Recurrent familial intra hepatic cholestasis ofpregnancy as heritable defect in the multidrugresistance MDR3 gene,encoded for canalicularphospholipid translocator involved in bile ductsecretion of phospholipids.
symptomsGeneralised pruritis that begins in the periphery,often worse on the palms and soles that moves to the trunks.Pruritis progress as pregnancy continues and resolves within 48 hours of deliverySome patients have diarehoea and steatorrhoea.
• Diagnosis:serum bilirubin usually <6mg/dl and transaminses are elevated from a minimal rise to 20 times normal.bile acids levels are > 10 umol/L and may be 100 folds normal all these resolves within 2 to 8 weeks of delivery.
treatment• Patients should be treated at centres capable of treating premature infants.• Medical treatment of choice is ursodeoxycholic acid UDCA, dose of 1 g per day.• Cholestyramine also reduces pruritus in total divided doses of 10 to 12 g per day.• Maternal outcome is good with symptom resolution after delivery.
Acute Fatty Liver of Pregnancy• Prevalence is 1 per 10,000 to 15,000 pregnancies and mostly in the 2 half of pregnancy.• AFLP is in the family of microvesicular fat diseases.• Risk factors: older maternal age,primiparity,multiplegestations,pre- eclampsia,male foetus.
• Genetic mutation that affects their mitochondrial fatty acid oxidation pathway• A foetus with long chain 3 hydroxyacl-coenzyme A dehydrogenase LCHAD deficiency.
Symptoms• Patient will have nausea,anorexia,lethargy,abdominal pain,ascitis,and progressive jaundice.• Acute renal failure occurs in 50% ,HE in 60% and 50% have hypertension,proteinuria and oedema, suggestive of pre-eclampsia.
Diagnosis• Serum aminotransferase levels are moderately elevated around 300-500 U/L,bilirubin < 5 mg/dl other abnormalities includes hypoglycemia, elevated ammonia levels,thrombocytopaenia,renal dysfunction.• Liver biopsy shows microvesicular steatosis.
Treatment• Continuous foetal monitoring should be initiated.• Supportive measures are required in the form of glucose infusion,adequate hydration and blood products .• Primary treatment is prompt delivery of the foetus, recovery before delivery is not seen.•
• Liver functions normalises within a week.• Maternal complication include post partum haemorrhage, renal failure,hypogycaemia,DIC,pancreatitis and pulmonary oedema.
HELLP syndrome• Its presents as complication of pre- eclampsia.HELLP syndrome affects 1 to 6 per 1000 pregnancies.• Pre-eclampsia is characterised by hypertension, proteinuria, oedema with onset in the second or third trimester and affects 5 -7 % of pregnancies.
• Risk factors:mutliparous.• Initial source of the insult is unknown but all patients have evidence of endothelial injury with fibrin deposit that causes a microangiopathic haemolytic anaemia and platelet activation and consumption, leading to thrombocytopaenia . fibrin deposits cause obstruction in the hepatic sinusoids which leads to areas of haemorrhage and eventual necrosis I the liver.
symptoms• Right upper quadrant or epigastric pain, nausea,vomiting,malaise, and non specific flu like symptoms.• Physical examination includes right upper quadrant or epigastrium tenderness and generalised oedema.hypertension and proteinuria are common.• Lab findings includes platelet count of less than then 100,000,serum aspartate aminotransferase greater than 70U/L,serum lactic dehydrogenase greater than 600U/L
• Peripheral blood smear may shows schistocytes,burr cells and echinocytes.
Treatment• HELLP syndrome is progressive, can sometimes have sudden, severe advancement compromising maternal and foetal outcome.• A good blood pressure control should be maintained IV hydralazine or labetalol may be used to maintain SBP pressure less than 160 mm Hg and DBP less than 105 mm Hg.
• In patients at less than 34 wks gestation with a reassuring foetal and maternal status, delivery may be delayed for a steroid course of betamethasone 12 mg every 24 hours for 2 doses with delivery 24 hours after the last dose.• During labour and 24 hours post partum pts should receive IV Mgso4 for seizures prophylaxis with 4 g loading dose follwed by 2 g per hour, with delivery 24 hours after the last dose.
• If patients is already in labour, a vaginal delivery may proceed, as long as no evidence exists of foetal distress or DIC .• Platelets are generally transfused when the platelet count is less than 20,000/mm3,delivery eventually leads to improvement in thrombocytopenia.• Patients should be monitored for 48 hrs at least in post partum period for evidence of pulmonary oedema due to fluid shifts or renal or hepatic dysfunction.
Viral hepatitis• The incidence of viral hepatitis A,B,C is the same in pregnancy as it is for general population, but incidence of hepatitis E is much higher.• In hepatitis A which is fecal orally transmitted,signs and symptoms are nonspecific and majority of cases are anicteric and usually mild.• There is no evidence that hepatitis A virus is teratogenic and transmission to the fetus negligible.
• Active immunization using formalin inactivated viral vaccine is more than 90 % effective.
• Hepatitis B is endemic in Asia and Africa.• Occurs often among intravenous drug abusers , homosexuals, health care personnel , sexually transmitted by saliva , vaginal secretion and semen.• All pregnant women should be screened for hepatitis B in the first trimester.• Most neonatal infection is vertically transmitted by peripartum ingestion of infected maternal fluids including breast milk.
• The risk perinatal transmission is greatest during the third trimester , to decrease this risk lamivudine 100 mg per day can be given from the start of the third trimester.• Infants born to HBsAg positive mothers should receive both HBIG and HB vaccine IM at seprate sites within 12 hours followed by second and third dose of vaccine at 1 and 6 months.
• Hepatitis C infection does not seem to alter the course of pregnancy and does not place the mother at risk of pre-term labour ,• pre-eclampsia , or gestational diabetes.• Risk factors included intravenous drug users, history of transfusion , multiple sex partners,• No vaccine for hepatitis C exists and primary prevention is necessary to avoid infection
• Treatmemt of hepatitis C with ribavirin and alpha interferon is contraindicated in pregnancy,as ribavirin is teratogenic and alpha interferon causes severe neurotoxicity under age of 2 years.• Breastfeeding is not contraindicated.
• Hepatitis E has a higher incidence rate and higher rate of fulminant hepatitis versus general population.• Incresed rates of abortion stillbirths,neonatal deaths are reported.• Post exposure or pre exposure anti HEV immunoglobulins have no benefit,breast feeding is not contraindicated.
Cirrhosis• Hepatic cirrhosis is characterized by irreversible chronic liver with extensive fibrosis and regenerative nodules.• Having clinical manifestation of jaundice,edema,coagulopathy,metabolic abnormalities and portal hypertension.
• Usually patients with cirrhosis are infertile woman,and who do became pregent have poor prognosis.• Comman complication are transient hepatic failure, variceal hemorrhage, preterm delivery and fetal growth restriction.
Varices in pregnancy• In pregnant women,as in young nonpregnent women,esophageal varies are caused equally by either cirrhosis or extrahepatic portal hypertension.• Bleeding during pregnancy from varices occurs in third to half and a major cause of maternal mortality.
Treatment• Beta blocking drugs such as propranolol are given to reduce portal pressure and to reduce risk of bleeding.• Endoscopic band ligation done for acute bleeding.banding can also be done prophylactically.• Transjugular intrahepatic portosystemic stent shunting TIPSS is done in emergency.