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LIVER DIORDERS OF PREGNANCY detailed PPT.pptx

Liver disorder in PREGNANCY

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LIVER DISORDERS IN PREGNANCY
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Hepatobiliary changes Physiological Changes  Impaired gallbladder (GB) motility: Sex hormones → increased smooth muscle relaxation in the biliary tree gallbladder volume and decreased contractility.  Impaired motility of the gastrointestinal tract: Pregnancy induces hypomotility throughout the gastrointestinal tract, probably via high progesterone levels. Lower esophageal sphincter pressure also decreases progressively to very low levels during pregnancy. Impaired small bowel and large bowel transit occurs in preg-nancy.  Lithogenic changes in the composition of bile: Bile lithogenicity is increased because of the effects of sex hormones on the relative concentrations of cholesterol, phospholipids and bile acids with an increase in choles-terol synthesis and excretion into bile.
ANATOMIC CHANGES Anatomic Changes  On liver USG, the biliary tract is usually normal though GB volume may be increased.  On hepatic Doppler USG, there are some changes in the hepatic venous flow pattern and portal flow veloc-ity, due to haemodynamic changes during pregnancy. The absolute hepatic blood flow is unchanged even after a 40% increase in blood volume and cardiac output.
Changes in serum liver function tests  Bilirubin- unchanged  ALT- UNCHANGED  AST- UNCHANGED  GGT- UNCHANGED OR SLIGHTLY DECREASED  ALP- 2-3 FOLD INCREASE  TRIGLYCERIDE- 2-3 FOLD INCREASE  GLOBULINS- INVREASE IN ALPHA AND BETA GLOBULIN
CAUSES OF JAUNDICE IN PREGNANCY Unrelated to pregnancy Hepatic causes  Acute viral hepatitis  Drug-induced hepatitis  Chronic viral and autoimmune  hepatitis Wilson's disease  Cirrhosis  Budd-Chiari syndrome Pre-hepatic causes  Haemolytic anaemia Post-hepatic causes  Common bile duct stone/stricture  Biliary parasitosis
Pregnancy related Pregnancy specific  Hyperemesis gravidarum  Intrahepatic cholestasis of pregnancy  Pre-eclampsia/eclampsia  HELLP syndrome  Acute fatty liver of pregnancy
INTRA HEPATIC CHOLESTASIS OF PREGNANCY
Definition- intrahepatic cholestasis of pregnancy is a reversible type of hormonally influenced cholestasis developing in late pregnancy characterized by generalized itching , and total bile acid >= 19 micromole/l ( RCOG AUGUST 2022) Incidence - 2/ 10000 in US  1.24% in India  prevalence - 0.3 and 5.6%  In 2nd and 3rd trimester
RISK FACTORS  Advanced maternal age,  GENETIC ETIOLOGY  History of cholestasis secondary to oral contraceptives,  Personal or family history of IHCP  Multiple pregnancy  ENVIRONMENTAL factors like selenium deficiency
PATHOGENESIS  Mutations of ABCB4 gene ( Adenosine triphosphate binding casette subfamily B membrane 4)  It encodes for multi drug resistance protein 3 (MDR 3) ,  Which further encodes for canalicular phospholipid pump transport  MDR3 associated mutations associated with progressive familial intrahepatic cholestasis
 Bile acids are cleared incompletely  Accumulate in plasma
SYMPTOMS PRURITUS  It is the cardinal symptom  Usually persistent and generalized  Palms and soles  Worse at night leading to sleep disturbances  Due to Cholestasis  Bile salts in dermis
 It usually precede icterus and laboratory findings  Usually resolves within 1-2days postnataly  On examination- scratch marks , excoriations  Jaundice develops in 14 to 25% after 1- 4 weeks of onset of pruritis.
CAUSES OF PRURITUS IN PREGNANCY Pregnancy specific  Pruritic urticarial papules and plaques of pregnancy  ICP  Pemphigoid gestationis  Atopic eruption of pregnancy  Pruritus folliculitis of pregnancy  Prurigo of pregnancy Pregnancy nonspecific  Xerosis  Atopic dermatitis  Allergic contact dermatitis  Scabies or lice
COMPLICATIONS MATERNAL  Vitamin K deficiency  PPH  There is association with Preeclampsia and GDM
FETAL  Fetal distress,  Preterm labour,  Prematurity,  Meconium stained amniotic fluid  RISK OF SUDDEN FETAL DEMISE-bile salts acts on AV NODE of fetus leading to sudden arrythmias
INVESTIGATION  Rasied Sr.total bilirubin  Sr.ALT and AST are raised in 60% of cases  Direct bilirubin exceeds 6mg /dl  Raised Bile Acids.  COAGULATION PROFILE  GDM AND PRE ECLAMPSIA SCREENING  LIVER USG- to exclude other causes of cholestasis .gallstones are reported in upto 13% of women with icp
Management  If patient has pruritis but lab tests are normal, to repeat bile acids and AST AND ALT after 1 week  2 GOALS: TO REDUCE SYMPTOMS  PERINATAL MORTALITY AND MORBIDITY
Non specific treatment  Topical emollients – safe in pregnancy , eg. Lactocalamine lotion  Antihistamines- like fexofenadine , chlorphenamnine
Ursodeoxycholic acid (UDCA) a) Mechanism of action: Displacement of more hydro-phobic endogenous bile salts from the bile acid pool. Taurocholic and taurodeoxycholic acids are signifi-cantly decreased by UCDA. It thus protects the hepa-tocyte membrane from the damaging toxicity of bile salts, enhances bile acid clearance across the placenta from the fetus. b) Dose: UDCA 500 mg twice daily as the starting dose. It may be increased by 250-500 mg/week, if there is no improvement in symptoms or biochemistry, to a dose of 2 g/day in divided doses. Side effects: Mild to moderate gastrointestinal disturbance. It is not teratogenic. It has no effect in reduction in adverse perinatal outcomes (RCOG August 2022). Specific treatment
Other drugs  S ADENOSYL METHIONINE  RIFAMPICIN  Cholestyramine  Dexamethasone
DELIVERY According to RCOG August 2022 guidelines: Mild ICP (peak bile acids 19-39 µmol/L) and no other risk factors: Consider options of planned birth by 40 weeks' gestation with ongoing antenatal care. Moderate ICP with peak bile acids 40-99 µmol/L and no other risk factors: Consider planned birth at 38-39 weeks' gestation. Severe ICP with peak bile acids 100 µmol/L or more: Consider planned birth at 35-36 weeks' gestation.
OUTCOME  Usually improves after delivery  No residual hepatic defect is left  60-70% recur in subsequent pregnancy  Long term association:  Gall stones  Hep c  Cholestasis, fibrosis, pancreatitis
Postnatal Follow Up  LFT not to be repeated before 10 days after birth.  All women diagnosed with ICP should have their liver function and serum bile acid level checked 6 weeks. postpartum to ensure resolution (RCOG August 2022).  Contraception: Oral contraceptives containing estro-gen should be used with caution and at the lowest possible dose.  Recurrence Rate: High recurrence rate of 45-90%. At booking in subsequent pregnancies, baseline measurement of liver function tests and bile acid concentrations should be performed in order to establish that these are normal. They should only be repeated, if clinically indicated (RCOG August 2022).
ACUTE FATTY LIVER OF PREGNANCY
 Micro vesicular fatty infiltration  It is rare and life threatening  Leads to hepatic failure and encephalopathy  Incidence 1 /7000 TO 12000  Occurs at (30-38wks)  Third trimester
RISK FACTOR  LCHAD DEF( long chain hydroxy acyl co enzyme A dehydrogenase)  Nulliparity  Male fetus  Twin pregnancy  Low body mass index  Primigravida
PATHOPHYSIOLOGY  LCHAD, found on the mitochondrial membrane is involved in the beta oxidation of long chain fatty acids. LCHAD deficiency is in 20% of the women suffering from AFLP. It is autosomal recessive in inheritance and mothers are often found to be heterozygous for the affected mutation.  Heterozygous parents may carry a homozygous fetus for LCHAD deficiency → accumulation of medium and long chain fatty acids in the fetus → unmetabolized fatty acids will re-enter the maternal circulation through the placenta → overwhelms the beta-oxidation enzymes of the heterozygous mother → hepatic strain → AFLP.  These fatty acids are:  Toxic to pancreas → AFLP associated pancreatitis.  Cause placental dysfunction → hypoxaemic injury to the fetus.  Predisposes patients to the hepatotoxic effects of fatty acids → microvesicular fatty steatosis of the liver → impairing downstream production of coagulation factors, fibrinogen, and cholesterol and impairing detoxifying function of the
SYMPTOMS  Most common presenation is usally in 3rd trimester (30-38th week)  Non specific  Nausea, vomiting , headache, anorexia  HTN without pre eclampsia  20% have co existing HELLP  Encephalopathy  Hypoglycemia  Features of pancreatitis  Right upper quadrant pain and epigastric pain
COMPLICATIONS MATERNAL  Acute renal failure 60%  Hypoglycemia 53%  Hepatic encephalopathy  Ascites  Jaundice  HELLP
DERANGED PARAMETERS  Increase levels of AST ALT 5 to 10 times / > 2 times of upper limits  Raised bilirubin  Rasied creatinine, urea, uric acid  Raised WBC  Raised levels of ammonia  Raised PT/INR.  Raises thrombin time  Decrease blood sugar
 HISTOLOGIC FINDINGS:  Microvesicular fatty infiltration  Swollen hepatocytes  Foamy cytoplasm  SPECIAL STAINS : OIL RED O  ELECTRON MICORSCOPY.
DIAGNOSIS SWANSEA CRITERIA - 6 or more THEN AFLP.  Clinical  Laboratory  Liver biopsy (gold standard)
SWANSEA CRITERIA
AFLP
MANAGEMENT  Early diagnosis  Intensive supportive care  Prompt delivery
 Critical care support: Fluid status (aggressive fluid re-placement in a setting of low plasma osmotic pressure can lead to pulmonary edema).  Monitor hypoglycaemia: Monitor glucose every 6-8 hrs, maintain plasma glucose >65 mg/dL.  Monitor coagulopathy: PT, APTT every 6-8 hrs.  Avoid invasive haemodynamic monitoring as increased risk of coagulation defects.  Continuous FHR monitoring.  MgSO if <32 weeks gestation for neuroprotection ₄ Prompt delivery of the fetus irrespective of gestational age:  a) IOL if vaginal birth anticipated within 24 hrs and disease not rapidly progressing in that time frame. Cervical ripening agents may be used.  b) If unlikely that vaginal delivery will occur in 24 hrs, think about CS.  c) Prior to CS, stabilize the patient and correct coagulopathy.  d) Regional anaesthesia may be given, if no coagulopathy.  e) If coagulopathy, prefer GA, but avoid hepatotoxic drugs like halothane.  f) Isoflurane has no hepatotoxicity, and it improves hepatic blood flow
DELIVERY  MODE OF DELIVERY depends on maternal and fetal condition  Labour induction can be done if tests for fetal well being are reassuring  If not LSCS.
Postpartum management a) Careful inspection of genital tract after vaginal birth b) In most cases, AFLP resolves completely after de-livery and LFT may return to normal in 7-10 days Patient may show signs of improvement after 2 days. In some, there is a transient worsening followed by recovery. c) Do LFT, creatinine every 6 hrs till a downward trend is observed. d) Plasmapheresis, following delivery in patients who fail to improve with delivery and supportive care within 2-8 days. e) Genetic testing of newborns: Molecular testing for LCHAD as early diagnosis in a newborn can be life-saving (test for G1528C mutation). If negative for this mutation, do medium chain, short chain acyl. CoA dehydrogenase testing. Long-term prognosis depends on the defect in fatty acid oxidation in the offspring.
OUTCOME  Maternal mortality - 7%  Perinatal mortality - 15% (Sibai study 2007)  Hepatic dysfunction resolves within 1wk postpartum  If persists after 6wk, consider alternative pathologies  OC pills can be used  Rarely recur in subsequent pregnancy, recuurence rate is 25%
VIRAL HEPATITIS
 It is the most common cause of hepatic dysfunction in pregnancy  I-8.8%  II-19.4%  III-18.6% (Harrison)
HEP A B C D E TYPE RNA DNA RNA RNA RNA TRANSMISSION Feco- oral Parenter al,sexual parenteral parenteral., sexual Feco oral IP 15-50d 30-180 14-180 42-180 21-56 CHRONIC INFECTION no yes yes yes rare VERTICAL TRANSMISSION yes yes yes VACCINE AVAILABLE yes yes No no yes
HEPATITIS A  Pregnancy doesn't alter course of acute HAV infection  It is not teratogenic  Preterm birth, prom, neonatal Cholestasis
MANAGEMENT  MOTHER Immunoglobulins – 0.02 ml/kg HAV vaccine single dose  NEONATE Ig given if mother is infected within 2wks of delivery
HEPATITIS B  Most common cause of morbidity and mortality related to Cirrhosis and hepatocellular carcinoma  risk for development of chronic HBV infection is strongly linked to the age of exposure. 90% in infants, 50% in toddlers and young children 5% in adults
Vertical transmission  MTCT rates also vary significantly according to the mother’s HBsAg status (70–90% transmission rate for HBsAg+ mothers  TRIMESTER  II -10%  III- 90%
DIAGNOSIS
MANAGEMENT  Symptomatic and supportive  Monitor hydration  Vaccination of family members
Pathogenesis of mother to child transmission  Happens in two different mechanisms Intrauterine- uncommon Intrapartum or perinatal- it is the most frequent route (95%)  Infection in 2nd and 3rd trimester carries transmission risk of 10% and 90%  Maternal HBV replicative status determines the mother’s infectivity.
 C-section should not be performed electively in HBV- positive mothers to prevent fetal infection  Women chronically infected with HBV should be allowed to breastfeed as recommended for infant health  Breastfeeding is avoided if there is cracked or bleeding nipple
 Discontinuation of therapy at any point during or after pregnancy requires careful monitoring because of the potential for HBV flares upon antiviral therapy withdrawal.
VACCINATION  Neonate – 0(within 12hrs), 1, 6  Mother – 0, 4 , 24 wks  causes of immuno prophylaxis failure(8-30%) (ACG) include high levels of maternal viraemia, intrauterine infection, or mutations of the HBV surface protein
CDC recommendations
HEPATITIS C  Hepatitis C has little impact on pregnancy  Unlike HBV, postpartum flares of HCV have not been described.  This risk is highest in pregnant women co- infected with HIV
Prevalence in pregnancy is 2.3-17%  Parenteral transmission, mother to child transmission is most common route of infection among infants and children.  Vertical transmission 3-6%  Risk of transmission include HCV viremia, maternal HIV HCV co infection(3 times more).
 All pregnant women with risk factors for HCV should be screened with anti-HCV antibody.  Screening should not be performed in women without risk factors for HCV acquisition  Invasive procedures (e.g., amniocentesis, invasive fetal monitoring) should be minimized in infected mothers and their fetus to prevent vertical transmission of hepatitis C
 C-section should not be performed electively in HCV-positive mothers to prevent fetal infection  Women chronically infected with HCV should be allowed to breastfeed as indicated for infant health  Hepatitis C therapy (ribavarin and interferon ) should not be offered to pregnant women to either treat HCV or decrease the risk for vertical transmission
 Infants – anti HCV IgG is present due to passive transmission  If detectable after 18mnths or HCV RNA is positive , it indicates MTCT
Hepatitis D  DELTA VIRUS, Defective RNA virus  Single stranded circular RNA virus  Must co-infect with HBV  Transmission similar to HBV  Chronic co-infection with HBV and HDV is more severe  Neonatal transmission is unusual
HEPATITIS E  Cause epidemic  Case fatality rate - 20%  Cause - fulminant hepatitis and acute hepatic failure  Reason - higher hep E viral load in pregnant women increased cytokine secretion in pregnant women  Complications – abortions , stillbirth
HYPEREMESIS GRAVIDARUM
 Definition – nausea and vomiting of pregnancy severe enough to produce weight loss, dehydration, ketosis, alkalosis and hypokalemia
Incidence - 0.3-2%(ACG)  Associated with 5% pre gravid weight loss with dehydration and ketosis  It is the diagnosis of exclusion  It is most common in 1st trimester  Usually resolves by 16wks
RISK FACTORS  Primigravida  Molar pregnancy,  Multiple pregnancies,  Trophoblastic disease,  Fetal abnormalities(triploidy, trisomy 21, and hydrops fetalis)  Hyperthyroidism, h pylori , female fetus  Psychological
CLINICAL FEATURES  Symptoms – nausea , vomiting jaundice, Pruritis  About 15% of patients experience liver dysfunction  Serum amino transferase levels increased, but rarely exceed above 200 U/l  Usually mild and resolves with cessation of vomiting
COMPLICATIONS MATERNAL  Dehydration  Electrolyte imbalance  Starvation  Weight loss  Ketosis  Malory weiss tear  Boerhaave syndrome(GE rupture)  Wernickes encephalopathy(thiamine)  Vitamin K deficiency
COMPLICATIONS FETAL Low birth weight (LBW) babies,  Small for gestational age babies,  Preterm birth, and  Poor 5-min Apgar scores  If WE supervens , risk of fetal death is 40%
INVESTIGATIONS  Hyponatremia  Hypokalemia  Hypochloremic metabolic alkolosis  Raised hematocrit  Raised TC  urea/creat ratio is elevated  LFT changes is the marker of severity  Urine – ketonuria  Liver biopsy – bile sludges
MANAGEMENT
SUMMARY Acute hepatitis ICP HELLP AFLP Hyperemesi s gravidarum TRIMESTER any III III III I PRESENTATION Fever ,jaun dice pruritis HTN, N/V, pain N/V, pain N/V AST 2000+ N - 300 N - 300 200-800 N-300 Bilirubin 5-20 1-5 1-4 4-10 N -4 PLATELETS N/< N << << N creatinine N N > >>> > FIBRINOGEN N N N <<< N FETAL COMPLICATIO N Vertical transmissio n Prematuri ty, Fetal distress, IUGR IUGR, prematuri ty prematurit y LBW Preterm
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