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Diseases of liver in pregnancy (Pregnancy-specific conditions (HELLP…
Diseases of liver in pregnancy
Basic functions
Metabolism of carbohydrates
Metabolism of lipids: fatty acids, bile acids
Metabolism of proteins
Transamination, deamination, decarboxylation
Synthesis of urea (ornithine cycle)
Synthesis of plasma proteins (albumins, globulins)
Synthesis of coagulation factors
Synthesis of heme
Metabolism of bilirubin
Phagocytosis of bacteria and bacterial endotoxins
Metabolism of drugs and other xenobiotics (cytochrome P 450)
Physiological changes in pregnancy
Perfusion of the liver remains unchanged
Increased metabolic activity
Inactivation and biotransformation of steroid hormones that are synthesized at larger amount
Increase in total metabolic rate
Taking over the function of the immature fetal liver
Biochemical indicators of the liver function during normal pregnancy
Concentration of total protein -
Albumin concentration -
Aminotransferases (AspAT, AlAT) =
Alkaline phosphatase +
GGTP, 5‘Nu =
Total bilirubin, Free bilirubin -/=
Urea, uric acid -
Liver diseases in pregnancy
Pregnancy-specific conditions
Liver diseases that are not specific to pregnancy but complicate its outcome
Pregnancy in a woman with chronic liver disease
Pregnancy-specific conditions
Hyperemesis gravidarum
Preeclampsia and eclampsia
Spontaneous hepatic rupture
Intrahepatic cholestasis of pregnancy
Usually in the 3rd trimester (rarely before 26 weeks)
Risk factors:
older age multiparity, multiple gestation family history, cholestasis associated with the use of OC
Symptoms
good general status!
Skin itching (mostly palms and feet) can be severe and causes sleeplessness, irritation, scratching
moderate jaundice (20-60%)
rarer malabsorption (steatorrhea)
dark color of urine
Effect of cholestasis on a fetus
impairment of fetal wellbeing
preterm expulsion meconium to amniotic fluid
preterm labor
perinatal mortality (more often after 37 weeks, following an increase in bile acid concentration)
Laboratory tests
BIL (rarely above 6 mg/dl) +
AspAT, AlAT normal (=) or +
Alkaline phosphatase +
Bile acids(the most sensitive marker!) +
GGTP normal or +
Etiology
unexplained
impaired metabolism of progesterone, estrogens and bile acids
genetic factors: mutation of MDR3 (multiple drug resistance 3) gene (92% - recurrence, 22% - more frequent cholelithiasis in pregnancy)
altered composition of hepatocyte and biliary epithelial cell membranes
Management
Cholestasis constitutes indication to hospitalization
Monitoring of fetal wellbeing
counting of fetal movements, NST, CTG, Manning’s score
Control of liver function (AspAT, AlAT, prothrombin time)
Earlier termination of pregnancy at 36-38 weeks (induction of labor) in the case of:
suspected fetal hypoxia
progressive itching and laboratory evidence for deterioration of liver function despite treatment
Termination of pregnancy before the 40th week!
treatment aimed at attenuation of maternal symptoms:
Ursodeoxycholic acid
Cholestyramine (decreases vit. K, bleeding)
Phenobarbital, Antihistaminic agents (hydroxyzine), Vitamin K, Short-term corticosteroid therapy
Prognosis for pregnant women - good
Clinical signs of the cholestasis resolve within 2 days after birth
Laboratory parameters normalize up to 6 weeks after birth
A history of intrahepatic cholestasis constitutes contraindication to OC
Acute fatty liver of pregnancy
In the 3rd trimester (after the 30th week)
Mortality: maternal 10%, fetal 45%
Associated with obesity, twin pregnancy, male fetus, primiparity after 30 years of age
Etiology
unknown, mutation of 3-hydroksy-CoA dehydrogenase gene (with resultant accumulation of TG in hepatocytes)
Symptoms
nausea, severe vomiting (!), abdominal pain,
lack of appetite, swelling, hypertension, proteinuria, jaundice,
poor general status (!)
may result in hepatic encephalopathy with fulminant liver failure, kidney injury, DIC, acute cardiovascular failure
Laboratory findings
TYPICAL: severe hypoglycemia, hyperuricemia
Thrombocytopenia, leukocytosis
Elevated concentration of urea, creatinine,
Elevated concentration of bilirubin
Moderate increase in ASPAT and ALAT activities
Marked increase in alkaline phosphatase activity
Hypoalbuminemia, Prolonged prothrombin time
Imaging
USG,
Normal size of the liver
Diffuse hyperechogeneicity
Collections of fluid in the abdominal cavity
Management
Intensive surveillance of mother and fetus
Prompt termination of pregnancy upon normalization of complete blood count and glycemia, water-electrolyte balance, coagulation disorders
Treatment at the Intensive Care Unit!
Vaginal delivery – increased risk for bleeding during cesarean section
HELLP syndrome
H emolysis E levated L iver enzymes L ow P latelets
Multi organ disorders associated with severe preeclampsia or eclampsia
Symptoms
right epigastric pain (90%)
pain on palpation of the right subcostal area (90%)
general weakness and poor condition (90%)
nausea, severe vomiting (80%)
arterial hypertension, proteinuria, headache, petechiae, mucosal pallor
Differential diagnosis of pain in the upper right abdominal quadrant
Obstetrical causes: labor, costal pain caused by fetal movements, uterine rupture, ectopic pregnancy
Gynecological causes: ovarian torsion, ovarian cyst rupture
Gastrointestinal conditions: cholelithiasis, cholecystitis, appendicitis, hepatitis, pancreatitis, peptic ulcer, liver hematoma, liver rupture
Cardiac diseases: myocardial infarction, pericarditis
Lung diseases: pulmonary embolism, pneumonia
Urogenital diseases: pyelonephritis, urolithiasis
Pathogenesis (unclear)
Microangiopathic hemolytic anemia
Structural changes of erythrocyte membrane
Intravascular activation of platelets
80% in pregnancy, especially in the 3rd trimester:
placental abruption, fetal death, DIC, shock, sepsis, liver hematoma
20% in puerperium: pulmonary edema, renal failure
Laboratory findings
Hemolysis – fragmented erythrocytes, spherocytosis on the differential
Characteristic color of urine
LDH > 600 U/L, BIL > 1.2 mg%
AspAT, AlAT > 70 U/L
Thrombocytopenia < 100 000 per mm3
Management
Careful monitoring of maternal status: normalization of blood pressure, prevention of tonic-clonic seizures, imaging of the liver
Monitoring of a fetus (CTG, USG)
Therapy - corticosteroids
Transfusion of blood/blood preparations
Hospitalization at a tertiary center
Treatment should be oriented at pregnancy termination
HELLP after 34 weeks – immediate induction of labor
HELLP and DIC, irrespective of gestational age – immediate induction of labor
HELLP w/o DIC before 34 weeks – corticosteroids and referral to a tertiary center
Labor
Vaginal labor: whenever early termination of pregnancy is feasible (multiparas)
Cesarean section:
General anesthesia (due to thrombocytopenia)
Longitudinal midline incision (control of the liver)
Abdominal drainage
Maternal mortality 2.5%, fetal mortality 35%
Careful postoperative monitoring of maternal status – early deterioration of general status and exacerbation of biochemical disorders
Risk for recurrent HELLP syndrome in subsequent pregnancies (3-27%)
Liver hematoma and liver rupture
Very rare complication of HELLP syndrome
Right lobe of liver
Prodromal period: poor condition, headache, dyspeptic symptoms
Signs of preeclampsia
Acute cardiovascular collapse
Mortality ca. 70-80%
Liver diseases that are not specific to pregnancy but complicate its outcome
Viral hepatitis
The most common cause of jaundice during pregnancy
Rapidly progressing inflammation and necrosis of the liver
Caused by:
95% - primary hepatotropic viruses (hepatitis viruses A-E and G),
5% - secondary hepatotropic viruses (EBV, CMV, HSV type 1 and 2, rubella virus, varicella zoster virus, measles virus, adenoviruses, yellow fever virus)
Hepatitis A
HAV (RNA virus of the family Picornaviriae)
Alimentary transmission (possible transmission during sexual contact)
In a lay language referred to as the „alimentary jaundice” or the „disease of dirty hands”
Only acute form; there is NO conversion to a chronic hepatitis
Infection does not influence the pregnancy outcome
There is no vertical transmission
Perinatal infection is very rare, most likely results from intrapartum transmission
Vaccines containing inactivated virus and prophylactic immunoglobulins can be safely used in pregnant women
Hepatitis B and D
Hepatitis B is caused by HBV and hepatitis D by HDV, but solely in presence of HBV (co-infection or superinfection of a HBV carrier)
HBV is a DNA virus of the family Hepadnaviridae
HBV is highly contagious!
Incubation 8-24 weeks
Hepatitis B
ROUTE OF INFECTION – PARENTERAL
Loss of tissue integrity
Sexual contact
Vertical transmission
Perinatal infection
Acute and CHRONIC hepatitis
RISK FACTORS AND RISK GROUPS
Close contact with an infected person
Invasive diagnostic or therapeutic procedures
Many sexual partners
Addiction to intravenous illicit drugs
Occupational exposure
HBV does not exert a teratogenic effect
If maternal acute infection took place in the 1st trimester and resulted in recovery, the risk of neonatal infection is likely reduced to a minimum
In the case of maternal infection in the 2nd trimester the risk transmission onto a fetus amounts 10%
The risk of maternal-fetal transmission in the 3rd trimester equals 90%
Most (95%) perinatal infections take place during labor
Risk of neonatal infection from a HBeAg(+) mother approximates 90%
The risk of transmission from a HBeAg(-), HbsAg(+) mother equals to 10%
Intrauterine infections are rare
Breast feeding – if neonate was subjected to immunoprevention
Hepatitis C
RNA virus from the family Flaviviridae
Incubation 6-60 days
In 80% of the cases conversion to a chronic condition!
20% of the patients develop liver cirrhosis within 10 years of infection
HCV is a carcinogenic virus (primary carcinoma of the liver)
80% of the cases are asymptomatic (!!!) prior to development of liver failure or carcinoma of the liver
The prevalence of hepatitis C in Poland is estimated at ca. 1.4% of the population
Usually infection with HCV is detected accidentally
ROUTES OF INFECTION
Parenteral (!)
Via injured skin, BLOOD
Sexual transmission (???)
Maternal-fetal route
VERTICAL ROUTE: Increasing number of children with hepatitis C
Usually transmission during minor medical procedures
injection, blood sampling, nevus removal
The most „invasive” procedures associated with the risk of HCV infection include SUTURING OF THE PERINEUM and dental procedures
Unknown route of infection in 40-60% of the cases
Chronic hepatitis C does not exert a negative effect on the pregnancy outcome
Ca. 4.3% of maternal-fetal transmissions of HCV(+)
Co-infection with HIV is reflected by marked increase in the HCV transmission rate
Neonates of HCV(+) positive mothers show the presence of maternal IgG for up to 18-24 months
Screening for HCV is recommended in women from high-risk group
Current guidelines do not emphasize the role of cesarean section in the management of HCV (+) HIV (-) patients
Maternal infection with HCV does not constitute contraindication to breastfeeding
Hepatitis E
RNA virus
Alimentary transmission
Endemic in some developing countries
In pregnant women may manifest as a fulminant form
Infection takes place at birth or during perinatal period
Cholelithiasis
Changes in the biliary tree and composition of the bile in pregnancy:
impaired gallbladder motility
oversaturation of bile with cholesterol
formation of gallbladder sludge
all will lead to Formation of gallstones
Increased risk for cholelithiasis in multiparas:
Many pregnancies,
Repeated episodes of increased biliary concentration of cholesterol
Manifestation mostly in the second half of pregnancy and after birth
Sudden acute pain in the right subcostal region
Diagnosis hindered due to elevated uterine fundus
Incidence of calculous cholecystitis 0.05-0.3%
Diagnosis – ultrasonography
Treatment of acute colic – spasmolytic agents
Surgical treatment – of choice after birth
Pregnancy in a woman with chronic liver disease
Autoimmune hepatitis
Chronic liver disease of unknown etiology
Progressive parenchymal injury
Usually diagnosed at the stage of liver cirrhosis – when pregnancy is unlikely
May initially manifest as oligomenorrhea and infertility
Reduced activity of the disease in response to an appropriate immunosuppressive treatment may result in resuming menses and pregnancy
Decreased severity of the disease during pregnancy
Recurrence after birth
Treatment prior to and during pregnancy: corticosteroids, azathioprine
LIVER CIRRHOSIS
Decompensated cirrhosis – very low chances for becoming pregnant
Compensated cirrhosis does not constitute contraindication to pregnancy
Complications
Bleeding from esophageal varices – 50% mortality
(prophylactic ligation, β-blockers)
Liver failure with encephalopathy
Itching of the skin
Miscarriage, preterm births, intrauterine deaths
Pregnancy after liver transplant
The first pregnancy after liver transplant was reported in 1978
Due to administration of immunosuppressive agents, pregnancy should be planned at least 6 months after the transplantation
In none of the cases reported to date pregnancy did not exert unfavorable effect on the liver function
Perinatal outcomes and prognosis for a neonate are good
Pregnant women after liver transplant are at increased risk of:
arterial hypertension, preeclampsia
premature rupture of membranes, infection