LIVER DISEASE IN PREGNANCY

SAUMYA JAYAKUMAR. MD, FRCP(C)

SEPT.29, 2023

OBJECTIVES

• DISCUSS THE NORMAL CHANGES TO LIVER LABS THAT OCCUR IN PREGNANCY
• APPRECIATE THE EFFECT OF PREGNANCY ON CHRONIC LIVER DISEASE, AND THE LIVER DISEASES UNIQUE TO PREGNANCY
• UNDERSTAND THE MANAGEMENT OF CHRONIC LIVER DISEASE IN PREGNANCY

PHYSIOLOGIC CHANGES IN PREGNANCY

INVESTIGATIONS IN PREGNANCY

Adapted from Brady, C. Hep Comm Rev 2020; 4(2)

APPROACH TO LIVER DISEASE IN PREGNANCY

• DISEASES UNIQUE TO PREGNANCY
• HYPEREMESIS GRAVIDARUM
• IHCP (INTRAHEPATIC CHOLESTASIS OF PREGNANCY)
• AFLP (ACUTE FATTY LIVER OF PREGNANCY)
• PRE-ECLAMPSIA/ECLAMPSIA/ HELLP
• DISEASES EXACERBATED BY PREGNANCY
• HYPERCOAGULABLE DISORDERS (HVT, PVT)
• HEPATITIS E
• HSV HEPATITIS
• GALLSTONE/GB DISEASE AND PANCREATITIS
• CIRRHOSIS/PORTAL HTN
• AIH*
• LIVER MASSES IN PREGNANCY*
• DISEASE COURSE INDEPENDENT OF PREGNANCY
• VIRAL (HEP A/B/C)
• DRUG TOXICITY, ETOH
• INFLAMMATORY/PBC/PSC
• METABOLIC

Tan, T. AJG 2016

CONSIDERATIONS IN PREGNANCY

• EFFECT OF PREGNANCY ON LIVER DISEASE
• WORSENING/IMPROVING/NO CHANGE DURING PREGNANCY AND IMMEDIATELY POST-PARTUM
• EFFECT OF LIVER DISEASE ON PREGNANCY
• EFFECT ON MOTHER – MORBIDITY AND MORTALITY
• EFFECT ON FETUS
• EFFECT OF MEDICATIONS – TERATOGENICITY
• MORBIDITY AND MORTALITY
• NEED FOR EARLY DELIVERY
• CONSIDERATION RE: MODE OF DELIVERY (VAGINAL VS C/S)
• PROCEDURES TO AVOID IN PREGNANCY
• EFFECTS POST-PARTUM:
• SAFETY OF TREATMENT MEDICATIONS DURING BREAST-FEEDING
• RISK OF TRANSMISSION OF INFECTIOUS HEPATITIS WITH BREAST-FEEDING

COMMON LIVER DISEASES AND PREGNANCY

Shaheen, A. Liver Int 2010;30

FDA DRUG CLASSIFICATION

LIVER DISEASES UNIQUE TO PREGNANCY

HYPEREMESIS GRAVIDARUM

• INTRACTABLE N/V, REQUIRING HOSPITALIZATION IN 50% 🡪 OFTEN SEE DEHYDRATION, WEIGHT LOSS, AND ELECTROLYTE ABNORMALITIES 🡪 WEIGHT LOSS >5% PREPREGNANT BODY WEIGHT
• PUQE – PREGNANCY UNIQUE QUANTIFICATION OF EMESIS AND NAUSEA
• ACCOUNTS FOR DAILY NUMBER OF EPISODES OF VOMITING
• LENGTH OF NAUSEA IN HOURS/D
• NUMBER OF RETCHING EPISODES PER DAY
• LIVER INVOLVEMENT IN 50%

​

OUTCOMES

MATERNAL

• NUTRITIONAL DEFICIENCIES (B1 🡪 WERNICKE’S; THIAMINE DEFICIENCY; VIT K DEFICIENCY)
• ELECTROLYTE DEFICIENCIES
• HYPOKALEMIA ASSOCIATED WITH INCREASED MORTALITY
• ESOPHAGEAL INJURY
• MALLORY-WEISS, BOERHAAVE, HAMMAN’S
• PSYCHOSOCIAL
• PTSD, DEPRESSION
• RESUSCITATION
• IV, TPN

FETAL

• PRETERM BIRTH
• LOW BIRTH WEIGHT
• DOUBLE RISK OF PRETERM DELIVERY (<37WEEKS)
• RISK OF PRE-ECLAMPSIA
• 3FOLD INCREASED RISK OF PLACENTAL ABRUPTION
• POSSIBLE INCREASED RISK OF PSYCHIATRIC DISORDERS IN CHILDREN EXPOSED TO HEG IN UTERO

TREATMENT OF HYPEREMESIS GRAVIDARUM

• FETAL U/S
• LIFESTYLE MODIFICATION:
• SMALL, MORE FREQUENT MEALS (HIGH IN PROTEIN AND CHO, LOW FAT)
• AVOID GREASY/SPICY/ACIDIC FOODS, CAFFEINE 🡪 BRAT DIET
• DRINK BETWEEN MEALS – FLUIDS BETTER TOLERATED IF COLD, CLEAR, CARBONATED OR SOUR, AND IF DRUNK THROUGH STRAW;
• SUCK ON POPSICLES OR LOLLIPOPS
• AVOID ENVIRONMENTAL TRIGGERS

​

MEDICAL TREATMENT OF HG

• ENTERAL/PARENTERAL NUTRITION , IV RESUSCITATION (WITH D5 DEXTROSE)
• VITAMIN B6 25MG Q6-8H (EFFECTIVE IN MILD-MOD NAUSEA, NOT FOR HG)
• ACID REDUCTION – PREFER ALUMINUM OR CA SALTS
• ANTIHISTAMINES– DOXYLAMINE (+VIT B6); DIMENHYDRINATE; DIPHENHYDRAMINE 🡪 RR 0.34
• DOPAMINE ANTAGONISTS (MAXERAN) 🡪 NO EFFECT ON INFANT, BUT MOMS DEVELOP MOVEMENT DISORDERS; CLASS B
• DICLEGIS (10MG DOXYLAMINE AND10MG PYRIDOXINE)
• SEROTONIN ANTAGONISTS (ONDANSETRON, GRANISETRON) –CLASS B
• PROMETHAZINE – CNS BLOCKADE OF DOPAMINE AND SEROTONIN RECEPTORS (USED AS SECOND LINE AGENT)
• CLONIDINE: CENTRALLY ACTING ALFA AGONIST
• MIRTAZIPINE: 15MG/DAY - USE WHEN HEG COMPLICATED BY PSYCH ISSUES
• GLUCOCORTICOIDS (RESERVED FOR SEVERE AND REFRACTORY HYPEREMESIS)
• 🡪 METHYLPREDNISOLONE 16MG IV Q8H X 48-72H, THEN PRED 40MG OF X 1D, THEN 20MG/D X3D, THEN 10MG/D X 3 D, THEN 5MG/D X 7D (REGIMEN CAN BE REPEATED UP TO 3 TIMES OVER 6 WK PERIOD)
• INCREASED INCIDENCE OF CLEFT PALATES IF USED BEFORE 10 WEEKS GA, THEREFORE AVOID BEFORE THEN

​

INTRAHEPATIC CHOLESTASIS OF PREGNANCY

• MOST COMMON LIVER DISEASE IN PREGNANCY (UNIQUE TO PREGNANCY)
• PREVALENCE IN EUROPE 0.3-0.7%, BUT WORLDWIDE PREVALENCE IS 0.1-15% OF ALL PREGNANCIES (UP TO 22% IN CHILE)
• INCREASED PREVALENCE IN AMERICAN INDIGENOUS AND SOUTH ASIAN
• GENETIC ABNORMALITY IN BILE ACID TRANSPORT, RESULTING IN RETENTION OF SUBSTANCES NORMALLY EXCRETED WITH BILE
• T3>T2, RARELY SEE BEFORE 26 WEEKS
• DEFINED AS ELEVATED SERUM BILE ACIDS 🡪 REVERSAL OF DIRECTION OF FLOW OF BA (USUALLY FROM FETUS TO MOTHER, NOW FROM MOTHER TO FETUS)

INTRAHEPATIC CHOLESTASIS OF PREGNANCY

Hagenbeck, C Recommendations of Working Group on Obstetrics and Pediatric Medicine – Maternal Disorders; 2021 Aug

• SX:
• PRURITUS (PERIPHERY 🡪TO TRUNK AND FACE), NO PRIMARY SKIN LESIONS
• OCC RUQ PAIN
• JAUNDICE IN 20-60% OF PATIENTS WITH IHCP, USUALLY APPEARS 1-4 WEEKS AFTER ONSET OF PRURITUS
• SX USUALLY RESOLVE 2-8 DAYS AFTER DELIVERY
• LAB RESULTS TAKE 2-4 WEEKS TO NORMALIZE

​

• LABS:
• 🡹BILI; NORMAL INR (IF 🡹 , THEN DUE TO VIT K DEFICIENCY)
• ALP: NORMAL TO 🡹(UP TO 4X ULN); NORMAL OR ONLY SLIGHTLY 🡹 GGT
• AST, ALT – ELEVATED TO 10X ULN, CAN REACH UP TO 1000
• DEFINING LAB: 🡹FASTING SERUM BILE ACIDS (ELEVATED 10-100 FOLD)
• ? ROLE IN ELEVATED RATIO OF CHOLIC:CHENODEOXYCHOLIC ACID; DECREASED RATIO OF GLYCINE:TAURINE CONJUGATES
• BX: CHOLESTASIS, NO INFLAMMATION (NOT RECOMMENDED)

​

IHCP - OUTCOMES

• FETAL:
• INTRAUTERINE DEATH (USUALLY ~38 WEEKS)
• PRETERM DELIVERY (NO LATER THAN 37WKS)
• MECONIUM STAINING
• INCREASED NEONATAL RESPIRATORY DISTRESS
• MOST FETAL COMPLICATIONS OCCUR WITH HIGHER BA LEVEL (≥40ΜMOL/L)
• BA>100ΜMOL/L ASSOCIATED WITH PERINATAL DEATH (OR 1.26)

• MATERNAL:
• PRURITUS
• NO HEPATIC DAMAGE
• SMALL SUBSET MAY HAVE UNDERLYING HEPATIC DISEASE (HCV, NAFLD)
• RECURRENCE - 40-70% OF PREGNANCIES
• ADMINISTRATION OF COMBO OCPS CAN RESULT IN RECURRENT CHOLESTASIS
• INCREASED RISK OF GALLSTONES IN FUTURE
• INCREASED HEMORRHAGE RISK (DUE TO VIT K MALABSORPTION)

Hillman, S. BMJ 2016

MANAGEMENT OF PRURITUS

• STANDARD THERAPY:
• UDCA
• HYDROXYZINE 25-50 MG/D
• CHOLESTYRAMINE 8-16MG/D (CAN CAUSE STEATORRHEA, EXACERBATE VIT K DEFICIENCY)
• RIFAMPICIN – CAN RESULT IN A 50% DECREASE IN BA
• RESCUE THERAPY:
• SAM-E (GLUTATHIONE PRECURSOR)
• QUESTRAN
• RIFAMPIN – LIMITED EXPERIENCE IN PREGNANCY, BUT NO EVIDENCE FOR HARM
• DEXAMETHASONE 12MG/D FOR PRURITUS – EVEN LESS EFFECTIVE THAN UDCA

​

Marshall, H et-al. Gastro 2005; 129:476

Geenes V et-al. Eur J Obstet Gynecol Reprod Biol 2015; 189:59

IHCP – PREGNANCY MANAGEMENT

• TX: UDCA 10-15MG/KG (~300- 500MG BID) UNTIL DELIVERY
• RECENT META-ANALYSIS SHOWED IMPROVED PRURITUS, LIVER ENZYMES, AND FETAL OUTCOMES
• RIFAMPICIN??
• CHECK BA WEEKLY; WEEKLY BIOPHYSICAL PROFILES
• EARLY DELIVERY – TIMING GUIDED BY MOM’S SX, PREVIOUS OBSTETRICAL HX, AND RISK/BENEFIT RATIO FOR FETUS (CAN DELIVER AT 40 WEEKS IF PEAK BA <39, AND NO OTHER RF)
• TRY TO DO AROUND 37/38 WEEKS GA; EARLIER IF CHOLESTASIS IS SEVERE/JAUNDICED, OR IF LUNG MATURITY IS ACHIEVED
• IF SERUM BA 40-99, DELIVER AT 36-37WKS GA; IF BA >100, DELIVERY AT 36 WEEKS GA (OR EVEN EARLIER, DEPENDING ON SX) OR PRIOR HX OF IHCP WITH FETAL DEMISE)
• STEROIDS FOR LUNG MATURATION
• ↑ INR BEFORE DELIVERY – GIVE VIT K; NOT NEEDED ROUTINELY

Ghosh, S. Ind J Derm 2013;58

IHCP POST-PARTUM MANAGEMENT

• DELIVERY:
• NO ADVANTAGE TO CESARIAN OVER VAGINAL
• NO CONCERNS WITH BREASTFEEDING WITH IHCP OR WITH URSO
• SWEDISH REGISTRY STUDY SHOWED THAT WOMEN WITH IHCP HAD HIGHER RATES OF HCC & CCA (HR 3.6 AND 2.6, RESPECTIVELY), DMII, THYROID DISEASE, PSORIASIS, INFLAMMATORY ARTHROPATHIES, CROHN’S, AND CAD (CAD SEEN ONLY IN PATIENTS WHO ALSO HAD HYPERTENSIVE ISSUES IN PREGNANCY).

Wilkstrom Shemer EA et-al. JHep 2015; 63

PRE-ECLAMPSIA/ECLAMPSIA/HELLP

• LIVER INJURY IN ALL THREE DUE TO VASOCONSTRICTION AND FIBRIN PRECIPITATION IN LIVER
• PREECLAMPSIA:
• 5-7% OF WOMEN
• T3>T2
• HTN + PROTEINURIA (≥300MG/D; OR PROTEIN:CR RATIO ≥ 30MG/MMOL) + PERIPHERAL EDEMA
• RF: PRIOR HTN; EXTREMES OF AGE; G1P0; MULTIPLE FETAL PREGNANCIES
• ECLAMPSIA
• PROGRESSION OF PREECLAMPSIA TO SEIZURES
• HELLP
• 0.1-0.6% OF ALL PREGNANCIES; 4-20% OF WOMEN WITH SEVERE PRE-ECLAMPSIA BUT 15-20% OF PATIENTS DO NOT HAVE HTN OR PROTEINURIA
• HEMOLYSIS + ELEVATED LIVER ENZYMES + LOW PLT
• T3/POSTPARTUM (70% 28-36WKS GA, REMAINING 30% DEVELOP AFTER DELIVERY) 🡪 DIFFERENTIATES HELLP FROM HUS-TTP
• RF: WHITE, MULTIPAROUS

​

HELLP - OUTCOMES

• MATERNAL:
• MORTALITY – 1-3%
• DIC:1/5
• ABRUPTIO PLACENTAE:16%
• AKI
• PULMONARY EDEMA
• SUBCAPSULAR LIVER HEMORRHAGE/HEMATOMA
• HEPATIC RUPTURE – 30% MORTALITY
• RETINAL DETACHMENT
• RECURRENCE : ~1/4
• HIGH RISK FOR DEVELOPING PREECLAMPSIA IN SUBSEQUENT PREGNANCIES (20-75%)

• FETAL:
• PREMATURITY (70%)
• INTRAUTERINE GROWTH RESTRICTION (IUGR)
• PERINATAL MORTALITY (7-35%) 🡪 MORTALITY DEPENDS ON GA

​

​

Tan,T. AJG 2016

MANAGEMENT OF HELLP

• GLUCOCORTICOIDS:
• MISSISSIPPI PROTOCOL – STEROIDS, MG SULFATE AND CONTROL OF SYSTOLIC BP 🡪 COCHRANE REVIEW FOUND THAT ALTHOUGH PLATELETS INCREASED, THERE WAS NO DIFFERENCE IN MATERNAL MORTALITY/MORBIDITY, OR IN PERINATAL/INFANT DEATH
• STEROIDS USED IN GA<34 WEEKS TO ACCELERATE LUNG MATURITY
• DELIVERY:
• IF ≥34WKS GA
• IF THERE IS SEVERE MATERNAL DISEASE (MOF, DIC, LIVER INFARCT/HEMORRHAGE, AKI, ABRUPTIO PLACENTA) OR FETAL DISTRESS/NON-REASSURING FETAL STATUS
• IF <34 WKS GA, DELIVER AFTER GIVING STEROIDS (TO ACCELERATE FETAL LUNG MATURITY)
• IF <30-32 WITH “UNFAVOURABLE CERVIX”, DO C/S

HELLP

• SX:
• ABDO PAIN 🡪 MIDEPIGASTRIUM, RUQ OR BELOW STERNUM
• HEPATOMEGALY
• N/V
• MALAISE
• JAUNDICE
• ASCITES
• BLEEDING (FROM 🡻PLT) IS UNCOMMON

​

• LABS:
• ANEMIA AND THROMBOCYTOPENIA (PLT<50 - 100)
• SMEAR – EVIDENCE OF MICROANGIOPATHIC HEMOLYSIS; SCHISTOCYTES
• INCREASED AST, BILI AND LDH; LOW HAPTOGLOBIN
• NORMAL INR, UNLESS HAVE DEVELOPED DIC
• IMAGING – USEFUL ONLY IF SUSPECT INFARCTION/HEMATOMA/RUPTURE

​

ACUTE FATTY LIVER OF PREGNANCY (AFLP)

• RF:
• TWIN/MULTIPLE PREGNANCIES
• MALE FETUS
• NULLIPAROUS
• PREECLAMPSIA/HELLP PRESENT IN 50% OF CASES
• FETAL LCHAD DEFICIENCY
• LOW BMI (<20)
• PRIOR AFLP
• SX:
• N/V
• ABDO PAIN (EPIGASTRIC, RUQ)
• FEVER
• ANOREXIA
• JAUNDICE, OTHER SIGNS OF LIVER FAILURE (INCL HE) 🡪 ALF
• PREECLAMPSIA (50%)
• NORMAL/SMALL SIZED LIVER

​

​

​

• LABS:
• AST, ALT>1000
• 🡹BILI, INR, PTT
• HYPOGLYCEMIA
• 🡻PLT
• DIC IN UP TO 70%
• AKI
• CENTRAL DI
• HYPERURICEMIA
• BX:
• MICROVESICULAR STEATOSIS

​

​

-Incidence – 1:7,000-20,000

-T3 (GA 30-38wk)

DIAGNOSIS OF AFLP

Tran, T. AJG 2016

AFLP OUTCOMES

• MATERNAL:
• MORTALITY: <5%
• CENTRAL DIABETES INSIPIDUS
• PANCREATITIS
• RECURRENCE IS POSSIBLE, BUT RISK NOT KNOWN

• FETAL:
• FATAL NONKETOTIC HYPOGLYCEMIA (IMITATE REYE’S OR UREA CYCLE DEFECTS)
• NEONATAL CARDIOMYOPATHY (POSSIBLY FATAL)
• PROGRESSIVE NEUROMYOPATHY

​

AFLP - MANAGEMENT

• MFM REFERRAL/INVOLVEMENT
• DELIVERY
• MATERNAL STABILIZATION – GLC INFUSION (D10/50W), REVERSAL OF COAGULOPATHY (FFP, CRYO, PRBC, PLT)
• MAY REQUIRE ICU ADMISSION (DIALYSIS/VENT/INTUBATION)
• PATIENTS EASILY FLUID OVERLOADED – JUDICIOUS USE OF FLUIDS
• NUTRITIONAL SUPPORT AS NEEDED
• TRANSFUSIONS (FOR ONGOING HEMOLYSIS)
• MAY SEE TRANSIENT WORSENING OF LIVER AND RENAL FUNCTION AFTER DELIVERY FOR A FEW DAYS.
• IF NO IMPROVEMENT AFTER DELIVERY, OR IF SX START AFTER DELIVERY, MAY NEED LIVER TRANSPLANT
• ALL CHILDREN BORN FROM AFLP PREG SHOULD BE TESTED FOR LCHAD MUTATION (ESP G1528C MUTATION)
• -MAY RECUR WITH SUBSEQUENT PREGNANCIES, EVEN IF GENETIC TESTING IN MOTHER AND CHILD ARE NEGATIVE

SUMMARY OF LIVER DISEASES UNIQUE TO PREGNANCY

DISEASES EXACERBATED BY PREGNANCY

• ACUTE HEV
• HSV HEPATITIS
• GALLSTONE DISEASE
• THROMBOPHILIC CONDITIONS

HSV HEPATITIS

• CAN OCCUR ANYTIME DURING THE PREGNANCY, BUT MORTALITY IS HIGHEST IN T3, ESPECIALLY IF DEVELOP FULMINANT HEPATITIS
• >80% MORTALITY IF LEFT UNTREATED
• SX:
• PRODROME OF FEVER AND URTI SX; ANOREXIA, N/V; ABDO PAIN
• USUALLY ANICTERIC AT PRESENTATION
• MAY HAVE ORAL/GENITAL VESICULAR ERUPTION (30-57%)
• 🡪 NEED CX OF VESICULAR FLUID,
• LABS/DX:
• 🡹🡹TRANSAMINASES (3000-6000)
• LEUKOPENIA
• INCREASED INR; NORMAL BILI
• HSV SEROLOGY
• BX:
• VIRAL, INTRANUCLEAR LESIONS (“GROUND GLASS” AND “COWDRY” INCLUSIONS)
• MULTINUCLEAR CELLS
• IF – VIRAL AG
• TX:
• ACYCLOVIR
• C/S PREFERRED IF THERE IS ANY POSSIBILITY OF GENITAL INVOLVEMENT

​

HEV

• ENDEMIC AREAS/TRAVEL – PAKISTAN, NORTHERN AFRICA, MEXICO
• PREGNANT WOMEN IN T3 PREDISPOSED TO DEVELOP SEVERE DISEASE, AND CAN DEVELOP FULMINANT HEPATITIS (MORTALITY 20%)
• FECAL-ORAL TRANSMISSION, OCCASIONALLY VIA TRANSFUSION
• OCCASIONALLY SPREAD THROUGH UNDERCOOKED DEER/BOAR/PIG MEAT
• WORSE OUTCOMES WITH HEV JAUNDICE/HEPATITIS THAN WITH JAUNDICE AND HEPATITIS OF OTHER VIRAL ETIOLOGY
• CAN RESEMBLE AFLP, HEPATIC INFARCT, HELLP, OR HSV
• SX: ACUTE VIRAL HEP (N/V, ABDO PAIN, FEVER, HM; RARELY SEE DIARRHEA, ARTHRALGIAS, PRURITUS, AND URTICARIAL RASH)
• LABS:
• INCREASED BILI, ALT, AST
• DX: SEROLOGY + HEV IN SERUM/STOOL BY PCR
• TX: CURRENTLY NO VACCINE (IG PROPHYLAXIS NOT SHOWN TO BE OF BENEFIT)
• SUPPORTIVE TX
• ?BENEFIT FROM RIBAVIRIN (CASE REPORTS ONLY)

GALLSTONE DISEASE

• INCREASED ESTROGEN AND PROGESTERONE RESULT IN SM RELAXATION AND DECREASED GB MOTILITY, PREDISPOSING PREGNANT WOMEN TO THE FORMATION OF STONES, BILIARY SLUDGE, AND ACUTE CHOLECYSTITIS.
• ALSO SEE CHOLESTEROL SUPERSATURATION IN BILE, AND RELATIVE OVERPRODUCTION OF HYDROPHOBIC BA, REDUCING THE ABILITY TO SOLUBILIZE CHOLESTEROL.
• PREVALENCE BILIARY SLUDGE – 5-36%; GALLSTONE PREVALENCE – 2-11% 🡪 THOSE WITH SLUDGE ARE MORE LIKELY TO REMAIN ASX, BUT 1/3 OF THOSE WITH STONES EXPERIENCED BILIARY COLIC

MANAGEMENT

• ADMISSION
• SUPPORTIVE CARE (IVF, ABX, ANALGESIA, BOWEL REST)
• ABX: AMP-SULBATACM 3G IVQ6H/TAZOCIN 3.375G IVQ6H / TICARCILLIN-CLAV 3.1G IV Q4H/CEFTRIAZONE 1GIVQ24H+FLAGYL 500IVQ8H
• IF POSSIBLE, DELAY SURGERY UNTIL T2/EARLYT3 (RISK OF SA/PREMATURE DELIVERY HIGHEST IN T1/T3, RESPECTIVELY).
• LAPAROSCOPIC SURGERY HAS BETTER OUTCOME (MATERNAL AND FETAL MORTALITY) THAN OPEN
• PROCEED WITH SURGERY IN PATIENTS WITH RECURRENT SX, HAS PASSED CBD STONE OR HAD PANCREATITIS
• ACUTE CHOLECYSTITIS
• IF HAVE CHOLEDOCHOLITHIASIS, THEN CAN DO ERCP (LEAD SHIELD FOR ABDOMEN)
• PAIN CONTROL 🡪 DEMEROL VS MORPHINE

​

​

HYPERCOAGULABLE DISORDERS

• BUDD-CHIARI/PVT:
• 20% OF HVT CASES OCCUR IN WOMEN WHO WERE EITHER ON OCPS OR WERE PREGNANT AT THE TIME OF THE CLOT, OR POST-PARTUM 🡪 INCREASED HORMONES LEAD TO A HEIGHTENED PROCOAGULANT STATE
• PREG ALSO EXACERBATES OTHER HYPERCOAGULABLE D/O (APL, FVL, PROTEIN S DEFICIENCY)
• HIGHER RATES OF EARLY PREGNANCY LOSS
• TX: LIVER TRANSPLANT IF SEVERE?; ANTICOAGULATION

​

LIVER DISEASES COINCIDENTAL WITH PREGNANCY

• VIRAL
• METABOLIC
• INHERITED
• CIRRHOSIS

​

VIRAL HEPATITIS AND PREGNANCY

• HBV:
• MATERNAL VL HIGHEST RISK FOR VERTICAL TRANSMISSION
• DNA LEVELS OF 10⁶ ASSOC WITH 3% RISK OF TRANSMISSION, INCREASED TO 8% 10⁸ 🡪 START ANTIVIRAL THERAPY IN T3 IF VL >10⁶ (IE >200,000COPIES)
• NO DIFFERENCE IN RATES OF TRANSMISSION BETWEEN VAGINAL OR C/S, BUT ACG GUIDELINES RECOMMEND AGAINST ELECTIVE C/S (VERY LOW LEVEL EVIDENCE)
• POSSIBILITY OF FLARE POST-PARTUM, SO CAN EITHER CONTINUE TX FOR 3 MONTHS, OR DO CAREFUL MONITORING OF LIVER ENZYMES
• POST-DELIVERY HBV VACCINE AT HBIG

​

• HCV:
• AVOID INVASIVE TESTING (AMNIO, FETAL SCALP ELECTRODE MONITORING)
• RISK OF TRANSMISSION INCREASED WITH PPROM (>6H)
• RATE OF VERTICAL TRANSMISSION 3-10% (INCREASES IF COINFECTED WITH HIV OR HBV)
• NO DIFFERENCE IN RATES OF TRANSMISSION WITH MODE OF DELIVERY, BUT 2016 GUIDELINES DO NOT RECOMMEND ELECTIVE C/S (VERY LOW LEVEL EVIDENCE)

METABOLIC

• NAFLD: INCREASED RISK OF IUGR, MACROSOMIA, PRE-TERM DELIVERY, SPONTANEOUS ABORTION, RISK OF C/S, AND LONG TERM RISKS FOR CHILD FOR RISKS OF OBESITY AND DMII IN CHILDHOOD 🡪 MAINSTAY OF TREATMENT IS CONTROLLING GDM AND WEIGHT GAIN
• AIH: INCREASED RISK OF PREMATURITY, LOW BIRTH WEIGHT, AND FETAL LOSS 🡪 PRESENCE OF SLA/LP AND RO/SSA ASSOCIATED WITH WORSE PREGNANCY OUTCOMES;
• POSSIBLE RISK OF FLARE EITHER DURING PREGNANCY OR POST-PARTUM
• PBC: RULE OF 1/3S IN PREGNANCY; HOWEVER, PREGNANCY MAY BE COMPLICATED BY PRURITUS, DEVELOPMENT OF DOMINANT STRICTURES, OR CHOLEDOCHOLITHIASIS

​

​

• WILSON’S: MAINTAIN CHELATION THERAPY, AS IF DEVELOP HEMOLYSIS, CAN RESULT IN HEPATIC INSUFFICIENCY AND MATERNAL DEATH;
• INCREASED RISK OF IUGR AND PREECLAMPSIA
• ADENOMAS: GROW DURING PREGNANCY 🡪 INCREASED RISK OF RUPTURE (INCREASED MATERNAL AND FETAL MORTALITY)
• MONITOR FOR SIGNS OF BLEEDING 🡪 SURGERY IF PRESENT OR IF LESIONS ARE LARGER THAN 5CM (WAIT FOR T2 FOR SURGERY)

​

CIRRHOSIS AND PREGNANCY

• PREGNANCY IN CIRRHOSIS – INCREASED RISK OF PREMATURE DELIVERY, SPONTANEOUS ABORTIONS AND INCREASED MATERNAL-FETAL MORTALITY
• MATERNAL MORTALITY IN PATIENTS WITH MELD>10: 7.8%
• INCREASED RISK OF DECOMPENSATION DURING PREGNANCY AND DELIVERY 🡪 PREGNANCY INDUCED INCREASE IN PORTAL PRESSURES
• VARICEAL BLEEDING – LEADING CAUSE OF MORTALITY
• RATE OF BLEEDING: 30% (UP TO 50-80% IF PRE-EXISTING VARICES)
• EACH EPISODE OF VARICEAL BLEEDING ASSOC WITH MATERNAL MORTALITY 20-50%, RATE OF FETAL LOSS HIGHER 🡪 LOWER RATES AND BETTER MORTALITY IF NON-CIRRHOTIC PHTN (MORTALITY 2-6%)
• BANDING IS PREFERRED FOR PRIMARY PROPH, ALTHOUGH ROLE OF PROPHYLAXIS IS STILL CONTROVERSIAL
• CAN USE OCTREOTIDE WITH BLEEDING (CLASS B)
• PROPANOLOL – CLASS C, BUT HAS BEEN USED TO CONTROL FETAL ARRHYTHMIAS 🡪 ASSOC WITH IUGR, NEONATAL BRADYCARDIA, AND HYPOGLYCEMIA
• SALVAGE THERAPY WITH TIPS ONLY IN LIFE-THREATENING CASES
• ENDOSCOPY WARRANTED IN ALL CIRRHOTIC PATIENTS WHO BECOME PREGNANT
• TIMING: T2 (IDEALLY 28WK GA)
• AVOID FENTANYL/VERSED

Shaheen, A. Liver Int 2010;30

DELIVERY IN CIRRHOSIS

• TRADITIONALLY- VAGINAL DELIVERY WITH SHORT SECOND PHASE OF LABOUR AND USE OF FORCEPS/VACUUM
• PROLONGED VAGINAL DELIVERY – INCREASED RISK OF VARICEAL BLEEDING
• IN PATIENTS WITH CIRRHOSIS WITH DOCUMENTED VARICES, DELIVERY CAN BE VAGINALLY ONLY IF PATIENT DOES NOT PUSH (USE GRAVITY, AND THEN FORCEPS/VACUUM) 🡪 CONSIDER C/S IN THESE CASES
• IN PATIENTS WHO HAVE NOT HAD AN EGD, THE C/S IS ADVISED

​

PREGNANCY AND CIRRHOSIS MEDICATIONS

Shaheen, A. Liver Int 2010;30

SUMMARY OF MANAGEMENT

• WHEN THINKING OF DIAGNOSIS, CONSIDER APPROACH IN TERMS OF TRIMESTER, OR DISEASES UNIQUE TO PREGNANCY VS EXACERBATED BY PREGNANCY VS UNRELATED TO PREGNANCY
• WHEN CONSIDERING MANAGEMENT, APPROACH I PREFER IS
• HOW DOES PREGNANCY AFFECT THE DISEASE (IMPROVE VS WORSEN VS NO CHANGE)
• HOW DOES DISEASE AFFECT PREGNANCY
• MATERNAL MORTALITY AND MORBIDITY
• FETAL MORBIDITY AND MORTALITY
• PERI-PARTUM MANAGEMENT (C/S VS VAGINAL DELIVERY, ROLE OF MONITORING OF BOTH MOTHER AND FETUS)
• POST-PARTUM MANAGEMENT (BREAST FEEDING IMPLICATIONS FOR BOTH VIRAL INFECTIONS AND MEDICATIONS; TESTING FOR NEONATE)
• ACG 2016 GUIDELINES GOOD SOURCE

QUESTIONS?