Jaundice with Pregnancy

Peculiar to pregnancy Acute Fatty Liver of pregnancy Intra-hepatic cholestasis of pregnancy Jaundice complicating pre- eclampsia HELLP syndrome Hepatic rupture and infarction ( 2nd and 3rd trimester) Hyperemesis gravidarum ( Ist trimester)

Intercurrent jaundice affecting pregnant female: Viral hepatitis Gall stones Hepatotoxic drugs Budd Chiari syndrome

Effect of pregnancy on pre existing liver disease: Liver Cirrhosis post viral, Wilson’s disease Autoimmune PBC Liver masses Alcoholic liver disease

Acute Fatty Liver of pregnancy: Rare ( 5/100.000 pregnancies) Risk factors: Ist pregnancy Twins Male fetus Preeclampsia Pathogenesis: Mutant gene causing a defect in mitochondrial fatty oxidation and caused by deficiency in long chain hydroxy acetyl Co-A dehydrogenase leading to increased deposition of triglycerides in hepatocytes leading to micro and macrovesicular steatosis

Pathogenesis cont. Clinical picture: suggestive host factors : Increased urinary organic acids Increased plasma carnitine and ethyl carnitine ( detected by overnight fasting) . Clinical picture: 3rd trimester May be earlier or immediately after delivery Acute onset of Headache, abdominal pain, nausea , vomiting ,pruritis, fever, ascites in 50% Jaundice appears soon after the onset Fulminant liver failure may follow

Investigations: Increased serum bilirubin ++ AST, ALT +++ serum Ammonia +++ TLC with neutrophilia --- platelets Coagulopathy --- fibrinogen ( DIC in 10%) Hypoglycemia Proteinuria, ++ serum uric acid

Invest. Cont. Abdominal ultrasound ( bright liver) Liver biopsy ( contraindicated).

Treatment: Mild cases: Advanced disease: Early delivery is considered ICU admission Dexamethasone 8mg/kg/12hours High doses of FFP Termination of pregnancy if the condition is life threatening

Complications: DIC GIT bleeding Hepatic coma renal failure Pancreatitis Hypoglycemia Fetal mortality ( 85%) if associated with eclampsia

Intrahepatic cholestasis of pregnancy: Pathogenesis Inherited senitivity to estrogens Lower plasma level of selenium Decreased hepatocyte membrane fluidity Alteration of Na- K adenosine triphosphatase activity in hepatocyte membrane Production of cholestatic metabolites

Intra-hepatic cholestasis of pregnancy: Clinical picture second and third trimester The onset of ICP is typically heralded by the development of pruritus, which may be intolerable. Pruritus predominates on the palms and the soles of the feet, and is worse at night The diagnosis of ICP is based upon the presence of pruritus associated with elevated levels of serum bile acids and/or aminotransferases, and the absence of diseases that may produce similar symptoms.

Treatment for ICP focuses on reducing symptoms and preventing maternal and fetal complications. ursodeoxycholic acid at a dose of 500 mg twice a day (or 15 mg/kg per day) until delivery Cholestyramine 8 g/day for 15 days ( binds bile acids and improves pruritis) Vitamin K may help and avoids the risk of hemorrhage at delivery Early delivery because of the risks to the fetus

The timing of delivery the patients' symptoms (jaundice if present), potential risks associated with prematurity whether the cervix is favorable. In most patients not treated with UDCA, delivery should be accomplished by 38 weeks. However, when cholestasis is severe , delivery should be considered at 36 weeks gestation if lung maturity is achieved or as soon thereafter as fetal lung maturity is established

The maternal prognosis in ICP is good. Severe cholestasis leading to deficiencies of fat soluble vitamins is uncommon. The maternal prognosis in ICP is good. Recurrent ICP 60-70% Gall stones ICP carries significant risk for the fetus prematurity Neonatal respiratory distress syndrome IUFD

HEV in pregnancy: Acute viral hepatitis can complicate pregnancy. The course of hepatitis A, B and C is similar to that of non-pregnant patients. By contrast, Hepatitis E is more severe during pregnancy. Several other viral infections have been reported in pregnancy. Rare condition in developed countries Higher incidence in developing countries Fulminant hepatic failure and mortality in pregnant females 16% maternal mortality in the 3rd trimester and 50% fetal mortality DD : acute fatty liver pregnancy, other viral hepatitis in pregnancy Diagnosed by serum IgM anti HEV antibody

Effect of pregnancy on pre existing liver disease: Pregnancy is unusual in women with severe chronic liver disease Old age Anovulatory state Those with milder form of disease may get pregnant Cirrhosis and portal hypertension Worsening of jaundice Progression of LCF Increased incidence of still birth and prematurity All medications should be reviewed for potential teratogenicity Early Termination of pregnancy in case of hepatic decompensation Successful liver transplantation has been described during pregnancy

Autoimmune hepatitis: affects women in the child bearing period The course of the disease is unpredictable Although spontaneous remission may occur, exacerbation of the disease and maternal mortality has been reported during pregnancy. Pregnancy induces a state of immune tolerance accomodating the fetus and causing a shift of T- helper 1 to T- helper 2 immune response causing an ammeloration of disease activity( TH1 dependent)

Exacerbation of the disease post partum occurs due to T hepler 1 predomination The high hormone level in pregnancy also plays a part in immune tolerance Treatment : Low dose prednisolone seems to be the preferred treatment Treatment of pruritis ( cholestyramine) Use of azthioprine must be individualized

Primary biliary cirrhosis: May be exacerbated during pregnancy Spontaneous improvement during pregnancy may occur UDCA ( 15 mg/kg) is the treatment of choice Cholestyramine and vit. K may be needed Treatment may be continued during pregnancy and breast feeding Increased incidence of abortion, still births

Wilson’s disease: Ceruloplasmin and copper concentrations in sera may double in the third trimester of pregnancy May develop neuropsychiatric stigmata of the disease Interruption of treatment ( d- penicillamine, trientine, zinc ) during pregnancy has resulted in fulminant hepatic failure However the dose of treatment should be reduced to the minimum necesssary dose ( 25-50% original dose) especially in the last trimester.

D penicillamine: teratogenic in 5 % of cases ( doses > 500mg/day) Oral supplementation with pyridoxine is recommended Zinc is the treatment of choice during pregnancy ( safe to fetus), 50 mg/8 hours

Enlarge and rupture during pregnancy due to high level of estrogen Liver masses: Adenomas FNH Haemangiomas Enlarge and rupture during pregnancy due to high level of estrogen Tumors greater than 5 cm---- surgical resection before becoming pregnant

Liver Abscess: Amebic liver abscess: Pyogenic abscess: Rare Preterm labor Jaundice and peritonitis are rare Ultasound and serology Aspiration for imminent rupture Pyogenic abscess: Life threatening condition Fever , jaundice, tender hepatomegaly Polymicrobial Ttt combination of antibiotics and percutaneous aspiration

Evaluation of liver disease in pregnancy History and review of systems: History of pruritus during previous pregnancies or while using oral contraceptives. abdominal pain, nausea or vomiting. polyuria and polydipsia. Drugs. Travel. exposure to viral hepatitis. history of gallstones. Note trimester of pregnancy.

Physical examination Blood tests Temperature, blood pressure. Proteinuria. liver examination (difficult during late pregnancy) Blood tests Complete blood count including platelets Routine liver function tests including prothrombin time Serum creatinine, electrolytes, glucose and uric acid levels Serology for viral hepatitis (A, B, C) and cytomegalovirus Test for hepatitis E if suspected (especially in endemic countries less commonly in non-endemic countries)

Measure serum total bile acids if cholestasis is suspected and not otherwise apparent (not a routine test) Urinalysis and culture Ultrasonography of the liver and bile ducts Monitor evolution of symptoms and liver function tests before and after delivery

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