Chapter 58. Hepatic, Biliary, and Pancreatic Disorders. Will Obs

 Hepatic, Biliary, and Pancreatic Disorders

BS. Nguyễn Hồng Anh

Disorers o the liver, gallblaer, an pancreas together constitute a ormiable list o complications that may arise in pregnancy. Some stem rom preexisting conitions, an some are

unique to gestation. Te relationships o several o these with

pregnancy can be intriguing an challenging.

HEPATIC DISORDERS

Liver iseases complicating pregnancy are place into three

general categories. Te rst inclues those specic to pregnancy an resolve either spontaneously or ollowing elivery.

Hyperemesis graviarum, intrahepatic cholestasis, acute atty

liver, an HELLP syndrome—which is characterize by hemolysis, elevate liver enzyme levels, an low platelet counts, are

examples. Te secon category involves acute hepatic isorers

that are coinciental to pregnancy, such as acute viral hepatitis.

Last are chronic liver iseases that preate pregnancy, such as

chronic viral or autoimmune hepatitis, cirrhosis, or esophageal

varices.

Laboratory testing can ai ierentiation o these isorers.

Hepatic ysunction rom hyperemesis graviarum may mani-

est as milly elevate serum bilirubin an transaminase levels

(Chap. 57, p. 1014). Others liste in Table 58-1 can show

more marke nings. One example, severe preeclampsia syn-

rome, iscusse in Chapter 40 (p. 689), can be urther com

plicate by the HELLP synrome, which can rarely cause liver

ailure (Casey, 2020).

Importantly, several normal pregnancy-inuce physiological changes inuce appreciable liver-relate clinical an laboratory maniestations (Chap. 4, p. 70 an Appenix, p. 1229).

Abnormalities such as increase serum alkaline phosphatase

levels, palmar erythema, an spier angiomas are common uring normal pregnancy. In aition, higher levels o estrogen,

progesterone, an other pregnancy hormones alter expression

o the cytochrome P450 system. For example, hepatic CYP1A2

expression eclines, but that o CYP2D6 an CYP3A4 rises.

Te latter pair possibly aects metabolism o commonly use

therapeutic agents in pregnancy (Dallmann, 2018; Ornoy,

2019). Cytochrome enzymes are also expresse in the placenta.

Te net eect is complex an likely inuence by gestational

age an organ o expression (Isoherranen, 2013). Despite these

unctional changes, no major hepatic histological changes are

inuce by normal pregnancy.

■ Acute Liver Failure in Pregnancy

Fortunately, liver ailure is uncommon uring pregnancy. O

the various causes, rug-inuce liver injury (DILI) is probably

the most requent non-pregnancy-relate etiology (Hoonagle,

2019). Acetaminophen toxicity is the most prevalent cause in

the Unite States (Lee, 2018). Other sources o liver ailure

inclue acute atty liver o pregnancy (AFLP), ulminant viral

hepatitis, environmental toxins, autoimmune hepatitis, shock

liver, an alternative meicines. In a highly selective stuy o

70 reerre women with a hepatic encephalopathy, hal were

cause by AFLP an hal were associate with HELLP syn-

rome (Casey, 2020).

Te treatment o acute liver ailure in pregnancy mirrors that

or nonpregnant iniviuals. Terapy targets the unerlying etiology, an a team o obstetricians, maternal-etal meicine an

critical care specialists, hepatologists, an transplant surgeons is

TABLE 58-1. Clinical Findings with Liver Diseases in Pregnancy

Diagnosis Onset Symptoms AST (U/L)

Bili

(mg%) Cr (mg%) Hematological Comments

Hyperemesis

gravidarum

Early N&V <300 1–4 NL or

elevated

(prerenal)

NL Common, infant

vitamin K

deficiency,

Wernicke

encephalopathy,

Boerhaave

syndrome

ICP Late Pruritus ±

jaundice

<200 1–5 NL NL Common (0.5–2%),

bile acids (>10

μmol/L), normal

hepatic function

AFLP Late N&V (70%), HTN/

preeclampsia,

RUQ pain

145–565 2–8 >0.9 Thrombocyto penia,

coagulopathy ±

DIC, nucleated

red cells,

hemolysis,

echinocytosis

Low glucose,

cholesterol

<220 mg/dL,

fibrinogen <300

mg/dL

HELLP Late Preeclampsia,

RUQ pain

75–250

(initial)

1–2 <1.0 Thrombocytopenia,

mild hemolysis

Common (7–10%

of preeclampsia),

normal hepatic

function

Hepatitis

Viral Variable,

chronic,

episodic

Jaundice, RUQ

pain, fatigue

400–5000 20 NL Coagulopathy

if cirrhotic,

thrombocyto penia

Common (1–3%),

serological tests

for hepatitis A,

B, C, E

Autoimmune Variable,

chronic,

episodic

Jaundice, RUQ

pain, fatigue

100–1000 3–10 NL Coagulopathy

if cirrhotic,

thrombocyto penia

Uncommon,

ANA+, antiLKM1, anti–

smooth muscle

NAFLD Variable,

chronic,

episodic

Obese,

diabetes, ±

RUQ pain

NL to

slightly

elevated

NL NL NL Common (6–8%),

sonographic

findings, MR

imaging/

CT findings,

± metabolic

syndrome, NASH,

cirrhosis

AFLP = acute fatty liver of pregnancy; ANA = antinuclear antibodies; AST = aspartate transaminase; Bili = bilirubin;

BP = blood pressure; Cr = creatinine; CT = computed tomography; DIC = disseminated intravascular coagulation;

HELLP = hemolysis, elevated liver enzymes, low platelets; HTN = hypertension; ICP = intrahepatic cholestasis of pregnancy;

LKM1 = liver, kidney microsome 1; MR = magnetic resonance; NAFLD = nonalcoholic fatty liver disease;

NASH = nonalcoholic steatohepatitis; NL = normal; N&V = nausea and vomiting; RUQ = right upper quadrant.

to investigate hepatic structure. For a pregnancy-relate etiology, elivery is unertaken. Because o comorbi coagulopathy,

vaginal elivery is preerable i it can be achieve expeitiously

an etal conition allows. Hepatotoxic agents are avoie, coagulopathy is correcte, an monitoring or cerebral eema an

increase intracranial pressure is necessary (Brown, 2018). Liver

transplantation is problematic uring pregnancy, but elivery

beore transplantation is consiere i necessary (Bacak, 2016).

assemble. Laboratory stuies initially inclue serum levels o

transaminases, bilirubin, amylase, lipase, electrolytes, creatinine,

albumin, brinogen, lactate, an total cholesterol; complete

bloo count; an coagulation stuies (Bacak, 2016). Etiologytargete testing is escribe ully in later sections but broaly

inclues viral an autoimmune serological assays an testing or

acetaminophen, iron, an copper toxicity. Compute tomography (C) an magnetic resonance (MR) imaging may be neee1032

Section 12

Medical and Surgical Complications

■ Intrahepatic Cholestasis of Pregnancy

Characterize by pruritus, jaunice, or both, this conition has

been calle recurrent jaunice o pregnancy, cholestatic hepatosis, an icterus graviarum. Intrahepatic cholestasis o pregnancy

(ICP) is more common in multietal pregnancy, an genetic

inuences are signicant (Sticova, 2018). Because o this, its

incience varies by population. In North America, the overall

incience approximates 1 case in 500 to 1000 pregnancies, but

its rate nears 5.6 percent among pregnant Latina women in

Los Angeles (Lee, 2006). Historically, inigenous women rom

Chile an Bolivia also have a relatively high incience o ICP.

For unknown reasons, this incience has ecrease since the

1970s an is now less than 2 percent (Reyes, 2016). In Sween,

China, an Israel, the incience varies rom 0.25 to 1.5 percent

(Luo, 2015).

Pathogenesis

Te cause o ICP is unclear, but changes in various sex steroi hormone levels are implicate. In one stuy, women

treate with vaginal progesterone or preterm labor prophylaxis showe a ourol increase in the ICP rate (Zipori, 2020).

Current research ocuses on the numerous mutations in the

many genes that control hepatocellular transport systems. One

example is mutations o the ABCB4 gene, which encoes multirug resistance protein 3 (MDR3) associate with progressive

amilial intrahepatic cholestasis. Another is error in the ABCB11

gene, which encoes a bile-salt export pump (Reichert, 2018).

Other potential gene proucts are the arnesoi X receptor

an transporting APase encoe by ATP8B1 (Abu-Hayyeh,

2016; Sticova, 2018). Te latter preisposes to rug-inuce

cholestasis. In this regar, we have encountere impressive cholestatic jaunice in gravias taking azathioprine ollowing renal

transplantation.

Following the inciting cause(s), bile acis are incompletely

cleare an accumulate in plasma. Hyperbilirubinemia results

rom retention o conjugate pigment, but total plasma concentrations rarely excee 4 to 5 mg/L. Alkaline phosphatase

levels are usually elevate even more than or normal pregnancy. Serum transaminase levels are normal to moerately

elevate but selom excee 200 U/L (see able 58-1). Liver

biopsy shows mil cholestasis with bile plugs in the hepatocytes an canaliculi o the centrilobular regions. Inammation

or necrosis is absent. Tese changes isappear ater elivery

but oten recur in subsequent pregnancies or with estrogencontaining contraceptives.

Clinical Presentation

Generalize pruritus that shows preilection or the palms an

soles usually evelops in late pregnancy or occasionally earlier.

Constitutional symptoms are absent, an skin changes are limite to excoriations rom scratching.

Serum transaminase an bile aci levels are measure in

women with suspecte ICP. As a threshol or comparison, total

serum bile aci levels typically remain <10 μmol/L throughout

normal pregnancy (Egan, 2012). Elevate total serum bile aci

or transaminase levels plus pruritus supports an ICP iagnosis. Biochemical tests may be abnormal at presentation or may

ollow initial pruritus ater several weeks. Moreover, a rise in

transaminase levels may precee an increase in serum bile aci

levels (Woo, 2018b). Approximately 10 percent o women

have concurrent jaunice.

With normal liver enzyme levels or with specic skin n-

ings, pruritus may instea reect other ermatological isorers

(Chap. 65, p. 1155). Sonography may be warrante to exclue

cholelithiasis an biliary obstruction (p. 1042). Moreover, acute

viral hepatitis is an unlikely iagnosis because o the usually low

serum transaminase levels seen with ICP. Conversely, unerlying chronic hepatitis C is associate with a signicantly greater

risk o eveloping ICP, which may be as much as 20-ol

higher (Marschall, 2013).

Management

Pruritus may be troublesome an is thought to result rom

elevate serum bile salt concentrations. Antihistamines an

topical emollients usually provie some relie. Cholestyramine

is reporte to be eective, but this compoun also lowers

absorption o at-soluble vitamins. Tis may lea to vitamin K

eciency an etal coagulopathy. Subsequent etal intracranial

hemorrhage an stillbirth have been reporte (Matos, 1997).

Currently, the most popular treatment is with ursoeoxycholic aci (Actigall), which relieves pruritus an reuces serum

levels o bile salts an liver enzymes (Bacq, 2012; Parízek,

2016). It is available as 300-mg capsules. Oral osing is 10 to

15 mg/kg maternal boy weight aily, which is ivie into

two or three oses (ran, 2016). In a large ranomize trial,

the maternal “itch score” was not signicantly lower with urso-

eoxycholic aci compare with placebo (Chappell, 2019).

From our experiences at Parklan Hospital, however, pruritus

typically improves ater 2 to 3 weeks o ursoeoxycholic aci

therapy (Yule, 2021). Such treatment has also been reporte

to lower risks or stillbirth an etal istress an is iscusse

subsequently.

Other escribe treatments inclue therapeutic plasma

exchange an riampin (Liu, 2018; Ovaia, 2018). A ranomize

trial comparing ursoeoxycholic aci an riampicin is unerway

(Australian New Zealan Clinical rials Registry, 2019).

Perinatal Outcomes

Early reports escribe excessive averse etal outcomes in

women with ICP. However, ata rom the past two ecaes

are ambiguous concerning increase perinatal mortality rates

an whether close etal surveillance is preventive. Sheiner an

coworkers (2006) escribe no ierences in perinatal outcomes in 376 aecte pregnancies compare with their overall obstetrical population. However, rates o labor inuction

an cesarean elivery in aecte women were signicantly

higher. In a stuy o 5477 women with ICP rom a atabase o

1.2 million births, neonates ha a lower 5-minute Apgar score,

but the stillbirth rate was not greater (Wikström Shemer, 2013).

Te latter rate was thought to reect a higher labor inuction

rate, which at the time o the stuy was recommene to avoi

stillbirth.

In some stuies, complications evelope more requently

in women with higher total bile aci levels (Di Mascio, 2019;

Herrera, 2018; Ovaia, 2019). Tese stuies escribe stillbirthsHepatic, Biliary, and Pancreatic Disorders 1033

CHAPTER 58

abnormalities o atty aci oxiation. Several mutations or the

mitochonrial triunctional protein enzyme complex that catalyzes the last oxiative steps in the pathway are implicate. Te

most common are the G1528C an E474Q missense mutations o the gene on chromosome 2 that coes or long-chain-

3-hyroxyacyl-CoA ehyrogenase (LCHAD) (Liu, 2017a).

Mutations or meium-chain acyl-CoA ehyrogenase (MCAD)

an or carnitine palmitoyltranserase 1 (CP1) eciency are

others. Tese are similar to mutations in chilren with Reye-like

synromes.

Sims an colleagues (1995) observe that some homozygous LCHAD-ecient chilren with Reye-like synromes ha

heterozygous mothers with AFLP. Tis was also seen in women

with a compoun heterozygous etus. Although some conclue

that only heterozygous LCHAD-ecient mothers are at risk or

ALFP when their etus is homozygous, this is not always true (Liu,

2017a). An association between atty aci β-oxiation enzyme

eects an severe preeclampsia, especially in women with HELLP

synrome, is also controversial (Chap. 40, p. 693). Most observations erive rom retrospective stuy o mothers with a chil

who later evelope Reye-like synrome. One case-control stuy

compare 50 mothers o chilren with a atty aci oxiation

eect an 1250 mothers o matche control inants (Browning,

2006). During their pregnancy, 12 percent o mothers with an

aecte chil evelope HELLP synrome an 4 percent evelope AFLP. Comparatively, only 0.9 percent o control women

evelope liver problems. Despite these nings, the clinical, biochemical, an histopathological nings are sufciently isparate

an support that severe preeclampsia, with or without HELLP

synrome, an AFLP are istinct synromes (American College

o Obstetricians an Gynecologists, 2012; Byrne, 2020).

Clinical Findings

AFLP almost always maniests in the last trimester an rarely

mipregnancy (Wong, 2020). From Parklan Hospital,

espite normal nings uring antenatal testing. One stuy o

693 Sweish women oun a greater perinatal mortality rate in

women with bile acis levels >40 μmol/L (Glantz, 2004). In

others, an increase stillbirth risk was note in women whose

serum bile aci levels were >100 μmol/L (Brouwers, 2015;

Chappell, 2019, Kawakita, 2015). Chappell an associates

(2019) also oun that ursoeoxycholic aci treatment i not

lower perinatal eath rates. Te use o antenatal etal testing

was not escribe. In a metaanalysis o 5557 women with ICP,

Ovaia an colleagues (2019) conclue that serum bile aci

levels >100 μmol/L were associate with stillbirth.

Other averse perinatal outcomes also have been escribe.

Brouwers an colleagues (2015) oun higher rates o spontaneous preterm birth (19 percent) an meconium-staine amnionic ui (48 percent), espite active management leaing to

earlier elivery. Novel associations o ICP with preeclampsia, gestational iabetes, an large or gestational age also are

reporte (Wikström Shemer, 2013).

In summary, management is irecte at early elivery to

mitigate the relatively uncommon incience o etal eath.

reatment with ursoeoxycholic aci oes not always improve

maternal symptoms or protect against stillbirth. It is problematic that antenatal testing oes not reliably orecast impening

etal eath. We o not routinely employ these or uncomplicate ICP. Te precise gestational age or labor inuction is

uncertain, but many authors recommen 37 weeks’ gestation

(Woo, 2018b). At Parklan Hospital, we routinely inuce

labor at 38 weeks i symptoms worsen or i serum bile aci

levels excee 40 μmol/L.

Fetal Effects of Bile Acids

As note, evience supports that maternal serum bile aci levels

>100 μmol/L contribute to etal eath an meconium passage. Fetal eath may be relate to the cariotoxicity o bile

acis, which causes cariac ysunction an presumably cariac

arrest. In an ex-vivo preparation o cariac myocytes, cholic

aci lowere beating rates in a ose-epenent ashion, while

elevating intracellular calcium concentration (Gao, 2014).

Prolongation o the etal cariac PR interval an successul

reversal with ursoeoxycholic aci has been escribe (Rorí-

guez, 2018; Strehlow, 2010). Last, Ozel an coworkers (2018)

emonstrate impaire global ventricular unction in etuses o

pregnancies complicate by ICP.

■ Acute Fatty Liver of Pregnancy

Te most requent cause o acute liver ailure uring pregnancy

is acute atty liver—also calle acute atty metamorphosis or acute

yellow atrophy. It is characterize by accumulation o microvesicular at that literally “crows out” normal hepatocytic unction (Fig. 58-1). Grossly, the liver is small, sot, yellow, an

greasy. In its worst orm, the incience approximates 1 case per

10,000 births (Nelson, 2013). AFLP recurring in subsequent

pregnancy is rare (Usta, 1994).

Etiopathogenesis

Although the unerlying cause remains unclear, many cases o

AFLP are associate with recessively inherite mitochonrial

FIGURE 58-1 Acute fatty liver of pregnancy. Cross section of the

liver from a woman who died as the result of pulmonary aspiration and respiratory failure. The liver has a greasy yellow appearance. Inset: Electron photomicrograph of a swollen hepatocyte

containing numerous microvesicular fat droplets (*). The nucleus

(N) remains centered within the cell in contrast to the case with

macrovesicular fat deposition. (Reproduced with permission from

Dr. Don Wheeler.)1034

Section 12

Medical and Surgical Complications

Nelson an colleagues (2013) escribe 51 women with

AFLP at a mean gestational age o 37 weeks (range 31.7 to

40.9 weeks). Approximately 41 percent were nulliparous an

20 percent were elivere at 34 weeks’ gestation or earlier.

Women with a multietal gestation account or 20 percent o

cases (Vigil-De Gracia, 2011).

AFLP has a broa spectrum o clinical eatures an severity, an symptoms usually avance over several ays. Persistent

nausea an vomiting are major complaints. Degrees o malaise, anorexia, epigastric pain, an progressive jaunice vary.

In almost all severe cases, acute liver injury causes prooun

enothelial cell activation, capillary leakage, an hemoconcentration; acute kiney injury; ascites; an sometimes pulmonary

permeability eema (Bernal, 2013). Hal o aecte women

have hypertension, proteinuria, an eema, alone or in combination. Notably, these signs also suggest preeclampsia.

As shown in Tables 58-1 an 58-2, egrees o moerate to

severe liver ysunction are maniest by hypobrinogenemia,

hypocholesterolemia, an prolonge clotting times. Serum

bilirubin levels usually are <10 mg/L, an serum transaminase levels are moestly elevate an usually <1000 U/L. An

AFLP iagnosis is arrive at by clinical an laboratory n-

ings. Biopsy is unnecessary. Te Swansea criteria propose by

Ch’ng an associates (2002) as a screening tool an preictor o

severity shows suitable sensitivity (Table 58-3) (Morton, 2018;

Wang, 2017).

Hemolysis can be severe an is thought to stem rom eects

o hypocholesterolemia on erythrocyte membranes (Cunningham, 1985). Laboratory evience inclues leukocytosis,

nucleate re cells, mil to moerate thrombocytopenia, an

increase serum levels o lactic aci ehyrogenase (LDH) or

ecrease haptoglobin levels. Te peripheral bloo smear emonstrates echinocytosis. However, the hematocrit is oten high

or within the normal range because o hemoconcentration.

TABLE 58-3. Swansea Criteria for AFLP Diagnosisa

Clinical features

Vomiting

Abdominal pain

Encephalopathy

Polydipsia/polyuria

Laboratory features

Bilirubin >0.8 mg/dL AKI or Cr >1.7 mg/dL

Glucose <72 mg/dL Ammonia >47 μmol/L

WBC >11,000/μL Coagulopathy or PT >14 s

AST or ALT >42U/L Urea >340 μmol/L

Ultrasound features

Ascites or echogenic liver

Histologic features

Microvesicular steatosis

aThe presence of six or more features without another

explanation for them supports a diagnosis of AFLP.

AFLP = acute fatty liver of pregnancy; AKI = acute kidney

injury; ALT = alanine transaminase; AST = aspartate transaminase; PT = protime; WBC = white blood cell count.

With severe hemoconcentration, uteroplacental perusion is

reuce an this, along with maternal aciosis, can cause etal

eath. Likewise, maternal an etal aciemia are associate with

a high incience o etal jeopary an a concorantly high cesarean elivery rate.

Te egree o clotting ysunction varies an can be

potentially lie threatening, especially i cesarean elivery is

unertaken. Coagulopathy is cause by iminishe hepatic

procoagulant synthesis, although some evience supports

TABLE 58-2. Comparison of Clinical Findings at the Time of Admission in

67 Women with Acute Fatty Liver of Pregnancy and 67 with

HELLP Syndrome

Factor AFLP HELLP p Value

Clinical findings (%)

Hypertension

Abdominal pain

Nausea/vomiting

62

34

63

94

46

19

<0.001

0.18

<0.001

Laboratory values

AST (u/L)

Creatinine (mg/dL)

Fibrinogen (mg/dL)

Bilirubin (mg/dL)

Platelets (per μL)

LDH (u/L)

Glucose (mg/dL)

278 [146, 564]

1.6 [1, 2]

200 [95, 298]

2.9 [1, 6]

163,000 [121, 205]

464 [361, 749]

88 [68, 102]

135 [77, 250]

0.6 [1, 1]

455 [367, 519]

0.6 [0, 1]

115,000 [78, 150]

552 [439, 759]

98 [83, 114]

<0.001

<0.001

<0.001

<0.001

<0.001

0.19

0.011

AFLP = acute fatty liver of pregnancy; AST = aspartate transaminase;

HELLP = hemolysis, elevated liver enzymes, and low platelets; LDH = lactic

acid dehydrogenase.

Data from Byrne, 2020; Nelson, 2020.Hepatic, Biliary, and Pancreatic Disorders 1035

CHAPTER 58

increase consumption rom isseminate intravascular coagulopathy. As shown in able 58-2, hypobrinogenemia can be

prooun. O 51 women care or at Parklan Hospital, almost

one thir ha a plasma brinogen level nair below 100 mg/

L (Nelson, 2014). Elevate levels o serum d-imers or brinsplit proucts also inicate an element o consumptive coagulopathy (Lisman, 2017). Although usually moest, occasionally

thrombocytopenia is marke. Among the women rom Parklan Hospital, 20 percent ha platelet counts <100,000/μL,

an 10 percent ha platelet counts <50,000/μL (Byrne, 2020).

Because liver ysunction an kiney injury are central to

AFLP, Byrne an colleagues (2020) have propose the acronym FaCC to ierentiate AFLP rom HELLP synrome

using levels o commonly available laboratory analytes: brinogen (<300 mg/L) an cholesterol (<220 mg/L), creatinine

(>0.9 mg/L), an total bilirubin (>1 mg/L). o emphasize, the clinical eatures an sequelae o AFLP are attribute

to liver ysunction, whereas in HELLP synrome the procoagulant prouction an unction o the liver appears relatively

preserve.

AFLP typically continues to worsen ater iagnosis. Hypoglycemia is common, an hepatic encephalopathy, severe

coagulopathy, an some egree o renal ailure each evelop in

approximately hal o women. Delivery ortunately arrests liver

unction eterioration, but recovery may require substantial

supportive care.

Various liver imaging techniques can help conrm the

iagnosis, but none is particularly reliable (Liu, 2017a). In a

prospective evaluation o the Swansea criteria, only a quarter

o women with AFLP ha classic sonographic nings that

inclue maternal ascites or an echogenic hepatic appearance (Knight, 2008). Although Châtel an coworkers (2016)

escribe greater liver at etecte by MR imaging, this has not

been our experience.

We have encountere several women with an unerevelope orm o AFLP. Clinical involvement is relatively minor

an laboratory aberrations—usually only hemolysis an a

ecrease plasma brinogen level—heral the synrome. Tus,

the spectrum o liver involvement can inclue unnotice miler

cases, nings that are instea attribute to preeclampsia, or

a severe orm isplaying overt hepatic ailure an associate

encephalopathy.

Management

Intensive supportive measures an soun obstetrical care are

essential. Delivery o the etus is necessary in the treatment o

AFLP, an signicant procrastination increases maternal an

etal risks. We preer a trial o labor inuction with close etal

surveillance. Although some recommen cesarean elivery to

hasten hepatic healing, this raises maternal bleeing complication risks when coagulopathy is severe. Nonetheless, cesarean elivery is common ue to etal intolerance o labor, an

rates approach 90 percent. In some cases, the etus has alreay

ie when AFLP is iagnose, an the elivery route is less

problematic. o correct coagulopathy, transusions with whole

bloo or packe re cells, along with resh-rozen plasma, cryoprecipitate, an platelets, are usually necessary or surgery or

vaginal laceration repair (Chap. 44, p. 772).

Hepatic unction usually returns to normal within a week

postpartum, but in the interim, intensive meical support may

be require. wo associate conitions can be seen uring this

time. Perhaps a ourth o women have evience or transient

diabetes insipidus. Tis presumably stems rom elevate vasopressinase concentrations cause by iminishe hepatic pro-

uction o its inactivating enzyme. Secon, acute pancreatitis

evelops in approximately 20 percent.

With supportive care, recovery usually is complete. Maternal eaths are cause by liver ailure, sepsis, hemorrhage, aspiration, renal ailure, pancreatitis, an gastrointestinal bleeing.

wo women ie in the series rom Parklan Hospital. One

ha associate encephalopathy an aspirate beore intubation uring transer to our care. Te other was a woman

with prooun liver ailure an nonresponsive hypotension

(Nelson, 2013). Other treatment measures have inclue plasma

exchange an liver transplantation (Ringers, 2016; Wu, 2018).

Maternal and Perinatal Outcomes

Maternal mortality rates with AFLP approache 75 percent

in the past, but the contemporaneous outlook is much better.

From his review, Sibai (2007) cites an average mortality rate

o 7 percent. He also cite a 70-percent preterm elivery rate

an a 15-percent perinatal mortality rate, which in the past was

nearly 90 percent. During the past our ecaes at Parklan

Hospital, the maternal an perinatal mortality rates have been

4 percent an 12 percent, respectively (Byrne, 2020).

■ Viral Hepatitis

Most viral hepatitis synromes are asymptomatic, an acute

symptomatic inections are becoming less common in the

Unite States. Tere are at least ve istinct types o viruses

causing hepatitis: A (HAV), B (HBV), D (HDV) cause by

the hepatitis B–associate elta agent, C (HCV), an E (HEV).

Te clinical presentation o acute inection is similar in all, an

although the viruses themselves probably are not hepatotoxic,

the immunological response to them causes hepatocellular

necrosis (Dienstag, 2018a,b). Several other viral agents can

inect the liver, an two examples are cytomegalovirus an herpes simplex virus (Calix, 2020; McCormack, 2019).

Acute inections are most oten subclinical an anicteric.

When they are clinically apparent, nausea an vomiting, hea-

ache, an malaise may precee jaunice by 1 to 2 weeks. By the

time jaunice evelops, symptoms usually are improving. Lowgrae ever is more common with hepatitis A. Serum transaminase levels vary, an their peaks o not correspon with isease

severity. Peak levels that range rom 400 to 4000 U/L are usually reache by the time jaunice evelops (see able 58-1).

Serum bilirubin values typically continue to rise, an peak at 5

to 20 mg/L, espite alling serum transaminase levels.

Severe eatures shoul prompt hospitalization. Tese inclue

persistent nausea an vomiting, prolonge prothrombin time,

low serum albumin level, hypoglycemia, high serum bilirubin

level, or central nervous system symptoms. In most cases, clinical an biochemical recovery is complete within 1 to 2 months

in all cases o hepatitis A, in most cases o hepatitis B, but in

only a small proportion o those cause by hepatitis C.1036

Section 12

Medical and Surgical Complications

Patient’s eces, secretions, bepans, an other articles in contact

with the intestinal tract shoul be hanle with glove-protecte

hans. In hospitals, extra precautions, such as ouble gloving uring elivery an surgical proceures, are recommene. Due to

signicant exposure o health-care personnel to hepatitis B, the

Centers or Disease Control an Prevention (CDC) recommen

active an passive vaccination, as escribe later (p. 1037) (Schillie, 2018). For hepatitis C, although irect antiviral regimens have

been evelope, there is no vaccine. Guielines instea recommen postexposure serosurveillance only.

Acute hepatitis has a case-atality rate o 0.1 percent. For those

requiring hospitalization, it may reach 1 percent. Most atalities

are ue to ulminant hepatic necrosis, which in later pregnancy

may resemble AFLP. In these cases, hepatic encephalopathy is the

usual presentation, an the mortality rate is 80 percent. Approximately hal o patients with ulminant isease have hepatitis B

inection, an co-inection with the elta agent is common.

Chronic hepatitis is more prevalent than acute inection. Te

CDC (2019) estimates that almost 3.5 million persons in the

Unite States are living with chronic viral hepatitis. Although

most are asymptomatic, approximately 20 percent evelop cirrhosis within 10 to 20 years (Dienstag, 2018a). When present,

symptoms are nonspecic an usually inclue atigue. In some

patients, cirrhosis with liver ailure or bleeing varices may be

the initial ning. Also, asymptomatic chronic viral hepatitis

remains the leaing cause o liver cancer an the most requent

reason or liver transplantation.

Chronic viral hepatitis is usually iagnose serologically

(Table 58-4). With persistently abnormal biochemical tests,

liver biopsy usually iscloses active inammation, continuing

necrosis, an brosis that may lea to cirrhosis. Chronic hepatitis is classie by cause; grae, ene by histological activity;

an stage, which is the egree o progression (Dienstag, 2018a).

Most young women with chronic viral hepatitis either are

asymptomatic or have only mil liver isease. For asymptomatic women, pregnancies are usually uncomplicate. With symptomatic chronic active hepatitis, pregnancy outcome epens

primarily on isease severity, an especially on the presence o

portal hypertension (p. 1040). Te ew women whom we have

manage have one well, but their long-term prognosis is poor.

Accoringly, they shoul be counsele regaring possible liver

transplantation as well as contraceptive an sterilization options.

Hepatitis A

Vaccination has reuce the incience o hepatitis A by 95

percent. In 2019, the rate was 6 cases per 100,000 iniviuals

in the Unite States (Centers or Disease Control an Prevention, 2021). HAV is an RNA picornavirus an is transmitte

by the ecal–oral route an usually by contaminate oo or

water ingestion. Te incubation perio approximates 4 weeks.

Iniviuals she virus in their eces, an uring the relatively

brie perio o viremia, their bloo also is inectious. Signs an

symptoms are oten nonspecic an usually mil, although

jaunice evelops in most patients. Symptoms usually last less

than 2 months, but 10 to 15 percent o patients may remain

symptomatic or relapse or up to 6 months (Dienstag, 2018b).

Early serological testing ienties immunoglobulin M (IgM)

anti-HAV antiboy, which may persist or several months.

During convalescence, IgG antiboy preominates, an it provies subsequent immunity. Hepatitis A lacks a chronic stage.

Vaccination uring chilhoo with inactivate hepatitis

viral vaccine is more than 90-percent eective. Te American

College o Obstetricians an Gynecologists (2018) an the

Avisory Committee on Immunization Practices recommens

HAV vaccination or high-risk aults (Freeman, 2020). Tis

inclues pregnant women at risk (Nelson, 2020). Caniates

are persons with chronic liver isease, human immunoe-

ciency virus (HIV) inection, homelessness, or illegal rug use.

Tose working in group acilities with at-risk persons, con-

ucting research with HAV, or traveling to or aopting rom

enemic areas also are inclue. High-risk countries are liste

in the CDC (2020b) “Yellow Book”—Health Inormation or

International ravel.

For an unvaccinate gravia who is recently expose by

close personal or sexual contact with a person with hepatitis

A, passive immunization is provie by a 0.1-mL/kg ose o

immune globulin. Concurrently, the rst ose o the hepatitis

A vaccine series is given in a separate arm (Nelson, 2020).

Pregnancy and Hepatitis A. Management o hepatitis A in

pregnancy inclues a balance iet an iminishe physical

activity. Women with mil illness may be manage as outpatients. In evelope countries, the eects o hepatitis A on

pregnancy outcomes are not ramatic (American College o

Obstetricians an Gynecologists, 2012, 2018). However, in

resource-poor countries, both perinatal an maternal mortality rates are substantively higher. HAV is not teratogenic,

an transmission to the etus is negligible. Te risk o preterm

birth may be higher, an neonatal cholestasis has been reporte

(Urganci, 2003). Although HAV RNA has been isolate in

breast milk, no cases o neonatal hepatitis A have been reporte

seconary to breasteeing (Daui, 2012).

Hepatitis B

Tis inection stems rom a ouble-strane DNA virus that

is oun worlwie. HBV is enemic in Arica, Central an

TABLE 58-4. Laboratory Features of Chronic Hepatitis

Disorders Tests Autoantibodies

Hepatitis B HBsAg, IgG anti-HBc,

HBeAg, HBV DNA

Uncommon

Hepatitis C Anti-HCV, HCV RNA Anti-LKM1

Hepatitis D Anti-HDV, HDV RNA,

HBsAg, IgG anti-HBc

Anti-LKM3

Autoimmune ANA, anti-LKM1, anti-SLA,

hyperglobulinemia

ANA, anti-LKM1,

anti-SLA

Cryptogenic All negative None

HBc = hepatitis core; HBeAg = hepatitis B e antigen;

HBsAg = hepatitis B surface antigen; LKM = liver, kidney

microsome; SLA = soluble liver antigen.

Modified with permission from Jameson JL, Fauci AS,

Kasper DL, et al: Harrison’s Principles of Internal Medicine,

20th ed. New York, NY: McGraw Hill; 2018.Hepatic, Biliary, and Pancreatic Disorders 1037

CHAPTER 58

Southeast Asia, China, Eastern Europe, the Mile East, an

certain areas o South America. In all these, inection prevalence reaches 5 to 20 percent. An estimate 1.6 million people

in the Unite States have chronic hepatitis B (Lim, 2020).

HBV is carcinogenic, an chronic inection is a known risk or

hepatocellular carcinoma. For others, cirrhosis can be a longterm sequela.

HBV is transmitte by exposure to bloo or other boy

uis rom inecte iniviuals. In enemic countries, vertical

transmission, that is rom mother to etus or newborn, accounts

or at least 35 to 50 percent o chronic HBV inections. In

low-prevalence countries such as the Unite States, which has

a prevalence below 2 percent, the more requent transmission

moe is sexual contact or share contaminate neeles.

Acute hepatitis B evelops ater an incubation perio that

ranges rom 40 to 150 ays (Schillie, 2018). At least hal o

acute inections are asymptomatic. Symptoms completely

resolve within 3 to 4 months in most. However, acute hepatitis

B accounts or hal o ulminant hepatitis cases.

Figure 58-2 etails the sequence o the various HBV antigens an antiboies in acute inection. Te rst serological

marker is hepatitis B surace antigen (HBsAg), which oten

precees the rise in transaminase levels. As HBsAg isappears, antiboies to the surace antigen evelop (anti-HBs),

an this marks complete isease resolution. Hepatitis B core

antigen (HBcAg) is an intracellular antigen an not etectable in serum. However, antiboies against this core antigen

(anti-HBc) are etectable an oun within weeks o HBsAg

appearance. Te hepatitis B e antigen (HBeAg) is present uring times o high viral replication an oten correlates with

etectable HBV DNA. Ater acute hepatitis, at least 90 percent o aults recover completely, an the remainer are consiere to have chronic hepatitis B.

0 4 8 12

HBeAg

HBsAg

IgM Anti-HBc

IgG Anti-HBc

Anti-HBs

Anti-HBe

ALT

Jaundice

16 20 24 28 32

Weeks after exposure

36 52 100

FIGURE 58-2 Sequence of various antigens and antibodies in

acute hepatitis B. ALT = alanine transaminase; anti-HBc = antibody

to hepatitis B core antigen; anti-HBe = antibody to hepatitis B e

antigen; anti-HBs = antibody to hepatitis B surface antigen; HBeAg =

hepatitis B e antigen; HBsAg = hepatitis B surface antigen. (Redrawn

from Dienstag JL: Acute viral hepatitis. In Jameson JL, Fauci AS,

Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine,

20th ed. New York, NY: McGraw Hill; 2018b, p 2347.)

Chronic HBV inection is oten asymptomatic but may cause

persistent anorexia, weight loss, atigue, an hepatosplenomegaly.

Extrahepatic maniestations inclue arthritis, generalize vasculitis, glomerulonephritis, pericaritis, myocaritis, transverse

myelitis, an peripheral neuropathy. One risk actor or chronic

isease is age at acquisition. Pertinent to the obstetrician, this

risk excees 90 percent in newborns. Te risk is 50 percent in

young chilren an is less than 10 percent in immunocompetent aults (Schillie, 2018). An immunocompromise state such

as with HIV inection, organ transplantation, or chemotherapy

creates vulnerability.

Tose with chronic HBV inection have serum test results

that show HBsAg persistence. Tese inecte persons may be

asymptomatic carriers or may have chronic liver isease with or

without cirrhosis or hepatocellular cancer. Te presence o HPV

DNA in serum tests is a marker o HBV replication. Tose with

high HBV replication, which is reecte in high HBV DNA

levels with or without HBeAg, have the greatest likelihoo o

eveloping cirrhosis an hepatocellular carcinoma.

Pregnancy and Hepatitis B. Te US Preventive Services

ask Force (2019) recommens that all pregnant women be

screene or HBV. Tis practice ienties asymptomatic cases

an later allows neonatal intervention. At the rst prenatal care

visit, a serologic HBsAg level is obtaine, an this is repeate

in high-risk women again at the time o elivery. All states

require cases o HBV inection to be reporte, an 26 manate

that pregnant women be screene (Culp, 2016). HBV inection oes not cause excessive rates o maternal morbiity or

mortality (Stewart, 2013). In one regional stuy in the Unite

States, 14 percent o women with HBV inection ha a worsening o isease, sometimes terme a fare, either antepartum

or in the 6 months postpartum (Kushner, 2018). A review o

ata rom the National Inpatient Sample reporte a moest

rise in preterm birth rates in HBV-positive mothers but no

eect on etal-growth restriction or preeclampsia rates (Re-

ick, 2011). Others have shown similar results (Cui, 2017;

Liu, 2017b).

ransplacental HBV inection is uncommon, an owers

an associates (2001) reporte that viral DNA is rarely oun

in amnionic ui or cor bloo. Te highest HBV DNA levels

are oun in women who transmitte the virus to their etuses

(Dunkelberg, 2014; Society or Maternal-Fetal Meicine, 2016).

o curb vertical transmission, newborns o seropositive

mothers are given hepatitis B immune globulin (HBIG) plus

the rst o a three-ose hepatitis B recombinant vaccine series

very soon ater birth. In the absence o HBV immunoprophylaxis, 10 to 20 percent o women positive or HBsAg transmit

viral inection to their inant. Tis rate rises to almost 90 percent i the mother is HBsAg an HBeAg positive. Aministration o immunoprophylaxis an hepatitis B vaccine shortly

ater birth has lowere transmission ramatically an prevente

approximately 90 percent o inections (Smith, 2012). But,

women with high HBV viral loas—106 to 108 copies/mL—or

those who are HBeAg positive still have at least a 10-percent

vertical transmission rate, regarless o immunoprophylaxis

(Rogan, 2019; Yi, 2016). Hill an colleagues (2002) reporte1038

Section 12

Medical and Surgical Complications

HCV screening or all aults at least once in a lietime, an

more regularly or those with risk actors (Schillie 2020). Tese

are injection rug use, hemoialysis, or exposure to bloo-

contaminate items. Te CDC also recommene prenatal

HCV screening or all women regarless o risk actors. Te

US Preventive Services ask Force (2020) has publishe similar

recommenations.

Chronic hepatitis C is iagnose by ientication o

anti-HCV antiboies etecte with a serum immunoassay.

Acute HCV inection is usually asymptomatic or yiels mil

symptoms. Only 10 to 15 percent o patients evelop jaun-

ice. Te incubation perio ranges rom 15 to 160 ays,

with a mean o 7 weeks. ransaminase levels are elevate

episoically uring the acute inection. HCV RNA testing

conrms clinical suspicion o active or acute HCV inection.

RNA levels may be oun even beore rises in transaminase

an anti-HCV levels. Anti-HCV antiboy is not etecte

or an average o 15 weeks an in some cases up to 1 year

(Dienstag, 2018b).

Nearly 80 to 90 percent o patients with acute HCV will

be chronically inecte. Although most remain asymptomatic,

approximately 20 to 30 percent progress to cirrhosis within 20

to 30 years. ransaminase an HCV RNA values uctuate over

time. Liver biopsy reveals chronic isease an brosis in up to

50 percent, however, these nings are oten mil. Overall, the

long-term prognosis or most patients is goo.

Pregnancy and Hepatitis C. As expecte, most pregnant

women iagnose with HCV have chronic isease. Aggregate

reports have chronicle moestly greater etal risks o low birthweight, neonatal intensive-care amission, preterm elivery, an

mechanical ventilation (Rossi, 2020; Society or Maternal-Fetal

Meicine, 2017). In some women, these averse outcomes may

have been inuence by concurrent high-risk behaviors associate with HCV inection.

Te primary averse perinatal outcome is vertical transmission o HCV inection to the etus-neonate. Tis is higher in

mothers with viremia (Inol, 2014). Airoli an Berghella

(2006) cite a rate o 1 to 3 percent in HCV-positive, RNAnegative women compare with 4 to 6 percent in those who

were RNA-positive. In a report rom Dublin, the vertical transmission rate in 545 women with HCV inection was 7 percent

in RNA-positive women compare with none in those who

were RNA-negative (McMenamin, 2008). Some have oun

an even higher risk when the mother is co-inecte with HIV

(Snijewin, 2015; ovo, 2016). Approximately two thirs o

prenatal transmission cases occur peripartum. HCV genotype,

invasive prenatal proceures, breasteeing, an elivery moe

are not associate with vertical transmission. Tat sai, invasive

proceures such as scalp-electroe etal heart rate monitoring

are avoie. HCV inection is not a contrainication to breast-

eeing (Post, 2017).

No license vaccine is available or HCV prevention. In

2011, the rst irect-acting antiviral rugs against HCV

became available. Since then, secon-generation prototypes

with ewer averse eects have been evelope an are given as

combinations to nonpregnant iniviuals. Tey are currently

that the 2.4-percent transmission rate was not increase with

breasteeing i neonatal vaccination was complete. Although

virus is present in breast milk, the incience o transmission is

not iminishe by ormula eeing (Shi, 2011). Te American

Acaemy o Peiatrics an the American College o Obstetricians an Gynecologists (2018) o not consier maternal HBV

inection a contrainication to breasteeing.

As a secon transmission-prevention practice, the CDC an

numerous societies now recommen antiviral therapy to ecrease

viral levels in gravias whose viral loa excees 106 to 108 copies/

mL (Schillie, 2018). Newer rugs inclue tenoovir, an aenosine nucleosie analogue, an telbivuine, a thymiine analogue.

enoovir is the rst-line agent uring pregnancy, an no ose

ajustments are necessary (Cressey, 2018). Tese antiviral meications appear sae in pregnancy an are not associate with

greater rates o congenital malormations or averse obstetrical

outcomes (Sylvester-Armstrong, 2019). Follow-up o chilren at

age 6 to 7 years oun no relate problems (Wen, 2020).

Regaring efcacy, one ranomize trial in Tailan showe

that tenoovir compare with placebo beginning at 28 weeks’ gestation i not reuce the low rate o vertical transmission i both

active an passive immunoprophylaxis were given at birth to the

neonate (Jourain, 2018). In another similar ranomize trial,

vertical transmission rates were signicantly lowere (Pan, 2016).

For high-risk mothers who are seronegative, HBV vaccine

can be given uring pregnancy. Caniates are persons with

chronic liver isease, iabetes, HIV or HCV inection, injection rug use, occupational exposure risk, househol contacts,

or long-term travel to enemic areas. Tose requiring ialysis,

living in a long-term-care or correctional acility, or engaging

in sex with multiple or HBV-inecte partners also are inclue

(Schillie, 2018).

Vaccine efcacy is similar to that or nonpregnant aults,

an overall seroconversion rates approach 95 percent ater three

oses (Stewart, 2013). Te traitional vaccination scheule o

0, 1, an 6 months may be ifcult to complete uring pregnancy, an compliance rates ecline postpartum. Shefel an

coworkers (2006) reporte that an accelerate three-ose regimen—given initially an at 1 an 4 months—resulte in seroconversion rates o 56, 77, an 90 percent, respectively. Tis

regimen was usually easily complete uring prenatal care.

Hepatitis D

Also calle delta hepatitis, this is a eective RNA virus that is a

hybri particle with an HBsAg coat an a elta core. Te HDV

must co-inect with HBV either simultaneously or seconarily,

an transmission is similar to HBV.

Hepatitis C

Tis inection stems rom a single-strane RNA virus. ransmission is via bloo an other boy uis, although sexual

transmission is inefcient. In the Unite States, ault prevalence o HCV was reporte to be 2 to 5 cases per 1000 births

(Prasa, 2020; Rossi, 2020). Up to a thir o anti-HCV positive persons have no ientiable risk actors (Dienstag, 2018b).

Until recently, screening or HCV was encourage only or

high-risk iniviuals. But in 2020, the CDC recommeneHepatic, Biliary, and Pancreatic Disorders 1039

CHAPTER 58

not recommene or use in pregnancy except in clinical trials

(Society or Maternal-Fetal Meicine, 2017). Te combination

o leipasvir plus soosbuvir shows efcacy an reassuring saety

ata in early clinical trials.

Hepatitis E

Tis inection stems rom a water-borne RNA virus, which usually is enterically transmitte by contaminate water supplies.

Hepatitis E is oun worlwie, but the Centers or Disease

Control (2020a) lists Mexico, Asia, an Arica as enemic

areas. In these regions, seroprevalence rates vary by age an

geography, but overall rates o 10 percent have been reporte.

In Mexico, Durango State has the highest rate—37 percent

(Fierro, 2016).

Hepatitis E is the most common cause o acute hepatitis

worlwie but rarely causes liver ailure in the Unite States

(Fontana, 2016). Epiemic outbreaks in thir-worl countries

result in substantial morbiity an mortality rates. Pregnant

women have a greater case-atality rate than nonpregnant iniviuals (Li, 2020). In a metaanalysis o nearly 4000 women

rom Asia an Arica, maternal an etal case-atality rates were

21 an 34 percent, respectively (Jin, 2016a). Fulminant hepatitis, although rare, is more common in gravias an contributes

to the increase mortality rates.

A recombinant HEV vaccine has been evelope an

license in China (Zaman, 2020). It is >95 percent eective or

12 months ater vaccination. Long-term efcacy is 87 percent,

an protective titers are maintaine or up to 4.5 years (Zhang,

2015). Preliminary ata rom inavertently vaccinate pregnant

women show no averse maternal or etal events (Wu, 2012).

■ Autoimmune Hepatitis

Tis generally progressive chronic hepatitis is more common

in women an western countries. Autoimmune hepatitis requently coexists with other types o autoimmune isease, particularly autoimmune thyroi isease an Sjögren synrome.

It is characterize by multiple autoimmune antiboies such as

antinuclear (ANA), anti-smooth muscle, an anti-liver, kiney

microsome 1 (LKM1) antiboies (see able 58-1). Rates o

subsequent cirrhosis vary worlwie. Te less common type 2

autoimmune hepatitis has an even higher prevalence in emales

an typically a more aggressive presentation. Te incience

peaks in chilhoo an aolescence.

Symptoms are typical o acute an chronic hepatitis, but a

ourth o patients may be asymptomatic. reatment employs

corticosterois, alone or combine with azathioprine (Dienstag, 2018a). Failure to respon to these two agents is more

requent in those with type 2 isease. Nearly all women with

type 2 isease require long-term intensive therapy. In some

patients with progressive isease an cirrhosis, hepatocellular

carcinoma evelops.

In general, autoimmune hepatitis—especially when severe—

increases the risk o averse pregnancy outcomes. Westbrook

an coworkers (2012) reporte the outcomes o 81 pregnancies in 53 women. A thir ha a are, an these were more

common in those not taking meication an those with active

isease in the year beore conception. Women with cirrhosis

ha more maternal an etal complications. From a Sweish

national atabase o 171 births, the requencies o preterm

birth, low birthweight, an iabetes were elevate, but not

those o preeclampsia or cesarean elivery (Stokkelan, 2016).

Another stuy reporte elivery beore 38 weeks’ gestation in

25 percent o cases an evelopment o a postpartum are in a

thir (Danielsson Borssén, 2016). However, averse outcomes

were not greater in women with cirrhosis. Given the important

role o procoagulant prouction, surveillance o coagulation

inices is avise to minimize obstetrical hemorrhage complications. Also, the usual vaccines, along with pneumococcal vaccine, shoul be given (Furer, 2020).

■ Iron and Copper Overload

Chronic hepatitis an cirrhosis can result rom iron an copper

overloa. Iron overloa may stem rom a primary cause, such as

hereitary hemochromatosis, or rom seconary complications

o erythrocyte isorers (Chap. 56 p. 1052). Many gene mutations unerlying hereitary hemochromatosis involve hepciin

an result in ysregulate iron transport. Some o these mutations are more common in certain populations rom northern

Europe (Pietrangelo, 2016; Salgia, 2015). Cariomyopathy,

iabetes, joint isease, an skin changes can coexist with liver

isease. Diagnosis is mae by ientiying an HFE gene mutation an elevate serum erritin an transerrin saturation levels. An abnormal HFE gene alone is not iagnostic because the

mutation has low penetrance. Pregnancy outcomes are riven

by the egree o liver ysunction, although higher iron levels

may aect birthweight (Dorak, 2009).

A orm o neonatal hemochromatosis that oes not aect

the mother is now thought to be alloimmune an is calle

gestational alloimmune liver disease (Anastasio, 2016; Ibrahim, 2020). With this, maternal autoantiboies cross to the

etus an meiate ysunction o iron homeostasis, although

the antigenic target o these alloantiboies remains unclear. It

is associate with signicant neonatal morbiity an mortality an requently recurs in subsequent pregnancies. In these

cases, antepartum treatment with intravenous immunoglobulin

(IVIG) may improve outcomes (Felman, 2013; Roumiantsev,

2015).

Wilson disease is cause by copper overloa leaing to

chronic hepatitis an cirrhosis. Autosomal recessive mutations

o the ATP7B gene unerlie this isorer. Tis gene coes or

the P-type APase involve in copper transport to ceruloplasmin an bile (Banman, 2015). Tis systemic conition can

also maniest with cariomyopathy, renal isease, neuropsychiatric symptoms, an certain enocrine abnormalities. Serum

ceruloplasmin, slit-lamp examination, an 24-hour urinary

copper excretion are use to ientiy this isease. A KayserFleischer ring surrouning the iris is highly specic, but a suspecte iagnosis generally requires subsequent genetic analysis

conrmation.

With Wilson isease, inertility may be present, but pregnancy outcomes among aecte women are inuence by isease severity (Malik, 2013). In one multicenter stuy o 282

pregnancies, the miscarriage rate was 26 percent, an 6 percent

o the women ha worsening liver isease (Peienberger, 2018).1040

Section 12

Medical and Surgical Complications

Birth eects were not increase with chelation treatment.

Maternal an neonatal outcomes were goo. Te American

College o Gastroenterology states that ew ata guie which o

the various chelating agents is best (ran, 2016). Tese inclue

penicillamine, zinc, an trientine, an any theoretical risks are

outweighe by the risks o iscontinuing therapy. Te latter

inclue not only hepatic ecompensation, but also injury to

the placenta an etal liver. Accoringly, the American College

o Gastroenterology recommens that pregnant women shoul

continue their chelation therapy, although a ose reuction o

25 to 50 percent shoul be consiere to promote woun healing in the event o a surgical elivery.

■ Nonalcoholic Fatty Liver Disease

Tis is the most common chronic liver isease in the Unite

States. Unsurprisingly, because it is requently comorbi with

obesity, it is emonstrable in 25 percent o American aults

(Abelmalek, 2018). Nonalcoholic atty liver isease (NAFLD)

is a macrovesicular atty liver conition that resembles alcohol-inuce liver injury but is seen without ethanol abuse. Its

most severe orm—nonalcoholic steatohepatitis (NASH)—is an

increasingly recognize conition that may occasionally progress to hepatic cirrhosis. Currently, this is the thir most common inication or liver transplantation in the Unite States

(Diehl, 2017).

Obesity, type 2 iabetes, an hyperlipiemia—syndrome X

—requently coexist with NAFLD (Chap. 51, p. 904). Te current hypothesis suggests that these conitions may interact with

other unknown etiological agents to cause multiple insults that

lea to hepatic injury (Buzzetti, 2016). In one stuy o inivi-

uals with type 2 iabetes an normal liver enzyme levels, hal

ha NAFLD, an those with NAFLD showe greater insulin

resistance (Portillo-Sanchex, 2015). In a stuy o obese aolescents unergoing bariatric surgery an intraoperative core

liver biopsy, more than a thir ha atty liver without hepatitis.

An aitional 20 percent ha borerline or enite NASH

(Xanthakos, 2015).

Liver amage ollows a progressive continuum rom NAFLD

to NASH an then to hepatic brosis that may progress to cirrhosis (Goh, 2016). Te isease is usually asymptomatic, an it

is a requent explanation or elevate serum transaminase levels oun uring routine screening. When other liver isease is

exclue, NAFLD is the cause o elevate asymptomatic transaminase levels in up to 90 percent o cases. Currently, weight

loss along with control o iabetes an yslipiemia is the only

recommene treatment.

Pregnancy

During the past ecae, we have encountere an increasing

number o obese an iabetic gravias with atty liver inltration. Tese women appear to have no greater rates o averse

outcomes relative to liver involvement compare with pregnant

women o similar weight. However, some emerging ata inicate

potential concerns. In one patient registry, risks o gestational

iabetes, preeclampsia, preterm birth, an low-birthweight

newborns were two- to threeol higher than in unaecte

women (Hagström, 2016). Yarrington an colleagues (2016)

reporte a high rate o gestational iabetes among nonobese

women who ha elevate alanine transaminase levels in the rst

trimester. Somewhat relate, in another stuy, almost a ourth

o women with prior gestational iabetes ha NAFLD (Foghsgaar, 2017). Last, some evience suggests that the etus o an

aecte mother is at increase risk or NAFLD in aulthoo

(Baker, 2018).

■ Cirrhosis

Irreversible chronic liver injury with extensive brosis an

regenerative noules is the nal common pathway or several

isorers. Laënnec cirrhosis rom chronic alcohol exposure is the

most requent cause in the general population. However, in

young women, most cases are cause by postnecrotic cirrhosis

rom chronic hepatitis B or C. As iscusse, many cases o cryptogenic cirrhosis are now known to be cause by NAFLD (Ge,

2016; Goh, 2016). Clinical maniestations o cirrhosis inclue

jaunice, eema, coagulopathy, an metabolic abnormalities.

O associate conitions, portal hypertension can lea to gastroesophageal varices, an splenomegaly may cause thrombocytopenia. Also, the incience o venous thromboembolism is

increase. Te prognosis is poor, an 75 percent have progressive isease that leas to eath in 1 to 5 years.

Te incience in pregnancy was reporte to be 1 case in

3300 births (Palatnik, 2017). Common complications inclue

transient hepatic ailure, variceal hemorrhage, preterm elivery, etal-growth restriction, spontaneous bacterial peritonitis,

an maternal eath (an, 2008). Outcomes generally are poor,

especially i esophageal varices coexist. Another potentially

atal cirrhosis complication arises rom associate splenic artery

aneurysms. Up to 20 percent o aneurysm ruptures occur uring pregnancy, an 70 percent o these rupture in the thir

trimester (an, 2008). Te 20-percent maternal mortality rate

is likely relate to the emergent iagnosis o these aneurysms

(Ha, 2009).

■ Portal Hypertension and Esophageal Varices

In pregnant women, the causes o esophageal varices are

equally ivie between cirrhosis an extrahepatic portal vein

obstruction (Anrae, 2018). O the extrahepatic cases, some

evelop ollowing portal vein thrombosis associate with one

o the thrombophilia syndromes (Chap. 55, p. 976). Others ollow thrombosis relate to umbilical vein catheterization when

the woman was a neonate, especially i she was born preterm.

Last, the rare Budd-Chiari syndrome results rom hepatic vein

thrombosis that causes extrahepatic portal hypertension. O 16

pregnancies complicate by this synrome, one observational

stuy reporte avorable outcomes (Khan, 2017).

With either intrahepatic or extrahepatic resistance to ow,

portal vein pressure rises rom its normal range o 5 to 10 mm

Hg, an values may excee 30 mm Hg. Collateral circulation

evelops that carries portal bloo to the systemic circulation.

Bloo rains into the gastric, intercostal, an other veins to

reach the esophageal system, where varices evelop. In rare

cases, abominal wall varices evelop (Woo, 2018a). Bleeing

is usually rom varices near the gastroesophageal junction, anHepatic, Biliary, and Pancreatic Disorders 1041

CHAPTER 58

hemorrhage can be severe. Bleeing uring pregnancy rom

varices occurs in a thir to hal o aecte women an is the

major cause o maternal mortality in this group (an, 2008).

Maternal prognosis with esophageal varices largely epens

on whether these rupture. Te mortality rate is 18 percent i

varices are associate with cirrhosis compare with 2 percent

or varices without cirrhosis. Similarly, perinatal mortality rates

are high in women with varices an are worse i cirrhosis cause

the varices. Increase rates o neonatal emise, preterm birth,

low birthweight, preeclampsia, an postpartum hemorrhage

have been reporte (Puljic, 2016).

reatment is the same as or nonpregnant patients. Preventively, all patients with cirrhosis, incluing pregnant women,

shoul unergo enoscopic screening or variceal ilation

(Bacon, 2015). Beta-blocking rugs such as propranolol are

given to ecrease portal pressure an bleeing risk (Ge, 2016;

ran, 2016).

For acute bleeing an or prophylaxis, enoscopic ban

ligation is preerre to sclerotherapy because it avois any

potential risk o injecting sclerotherapeutic chemicals. Acute

meical management or bleeing varices verie enoscopically inclues the intravenous vasoconstrictors octreotie or

somatostatin along with enoscopic baning. Vasopressin is

less oten use. I enoscopy is not available, balloon tamponade using a triple-lumen Sengstaken-Blakemore tube, which is

place into the esophagus an stomach to compress bleeing

varices, can be liesaving. An interventional raiology proce-

ure—transjugular intrahepatic portosystemic stent shunting

(TIPSS)—also can control bleeing rom gastric varices that

is unresponsive to other measures (Ge, 2016; an, 2008). We

have ha goo outcomes with this proceure one electively

uring pregnancy in women with prior variceal hemorrhage

(Chanramouli, 2020).

■ Acetaminophen Hepatotoxicity

As iscusse earlier (p. 1030), acetaminophen is the most requent cause o acute liver ailure in the Unite States (Lee,

2018). Tis commonly use meication can be associate with

hepatotoxicity at oses above 4 g/, an even less in certain

populations (Clark, 2012). Te rug is oten use uring pregnancy, an overose–either accientally or by attempte suicie–may lea to hepatocellular necrosis an acute liver ailure

(aney, 2017). Massive necrosis causes a cytokine storm an

multiorgan ysunction. Early overose symptoms are nausea,

vomiting, iaphoresis, malaise, an pallor. Ater a latent perio

o 24 to 48 hours, liver ailure ensues, an it usually begins to

resolve in 5 ays. In a prospective Danish stuy, only 35 percent o patients who were treate or ulminant hepatic ailure

spontaneously recovere beore being liste or liver transplantation (Schmit, 2007).

Te antiote is N-acetylcysteine (NAC), which must be given

promptly. Te rug is thought to raise glutathione levels, which

ai metabolism o the toxic metabolite, N-acetyl-p-benzoquinoneimine. Te Rumack-Matthew nomogram uses serum acetaminophen levels to preict subsequent plasma hepatotoxic

levels as a unction o the time rom acute ingestion (Rumack,

1975). Te nee or treatment is base on these projections, an

online nomograms an calculators are available. I the plasma

level excees 150 μg/mL 4 hours ater ingestion, treatment is

given. When plasma eterminations are not available, empirical treatment is initiate i the ingeste amount is >7.5 g.

An oral loaing ose o 140 mg/kg is given ollowe by 70 mg/kg

every 4 hours or a total treatment uration o 72 hours (Hear,

2008). Both the oral an an equally efcacious intravenous

osing regimen have been reviewe by Hogman an Garrar

(2012). Although the rug reaches therapeutic concentrations

in the etus, any protective eects o NAC uring acetaminophen overose are unknown (Wiest, 2014).

Ater 14 weeks’ gestation, the etus has some cytochrome

P450 activity necessary or metabolism o acetaminophen to

the toxic metabolite. Riggs an associates (1989) reporte ollow-up ata rom the Rocky Mountain Poison an Drug Center in 60 women suering overose. Te likelihoo o maternal

an etal survival was better i the antiote was given soon ater

overose. At least one 33-week etus appears to have ie as

a irect result o hepatotoxicity 2 ays ater maternal ingestion. In another case, Wang an coworkers (1997) conrme

acetaminophen placental transer an oun maternal an cor

bloo levels measuring 41 μg/mL. Both the mother an the

emergently elivere neonate ie rom hepatorenal ailure.

■ Focal Nodular Hyperplasia

Tis benign lesion o the liver is characterize in most cases

by a well-elineate accumulation o normal but isorere

hepatocytes surrouning a central stellate scar. Tese usually

can be ierentiate rom hepatic aenomas by MR an C

imaging. Except in rare situations o unremitting pain, surgery

is rarely inicate, an most women remain asymptomatic uring pregnancy. In one review o 20 cases, no woman ha relate

complications uring pregnancy (Riai, 2013). Tree women

showe 20-percent tumor growth; in hal, the tumor iminishe in size; an the remaining seven tumors were unchange

across pregnancy. In another surveillance o 44 lesions with

MR imaging in 30 gravias, tumor size was unchange in 80

percent an ecrease in most o the remainer (RamírezFuentes, 2013). Investigators conclue that size changes were

unrelate to pregnancy, combination oral contraceptive use, or

menopause. Tis lesion is not a contrainication to estrogencontaining contraceptives (Chap. 38, p. 673).

■ Hepatocellular Adenoma

Tis rare benign neoplasm evelops most oten in young

women. Lesions are more common in iniviuals taking

combination oral contraceptives or other steroi meications

(Renzulli, 2019). Hepatic aenomas have a 5-percent risk o

malignant transormation an a signicant risk o ruptureassociate hemorrhage, particularly in pregnancy. Te rupture

risk progresses with lesion size, an surgery is generally recommene or tumors measuring >5 cm (Agrawal, 2015). Tus,

ierentiation rom ocal noular hyperplasia is important an

can be achieve by MR or C imaging.

ran an associates (2016) recommen sonographic surveillance o hepatic aenomas uring pregnancy. In a stuy o1042

Section 12

Medical and Surgical Complications

51 pregnancies in women with an aenoma <5 cm, 25 percent o the lesions expane approximately 14 mm (Gaspersz,

2020). In one review o 27 cases in pregnancy, 23 became apparent in the thir trimester an puerperium (Cobey, 2004). No

bleeing complications ollowe tumors measuring <6.5 cm.

However, 60 percent presente with tumor rupture that

resulte in seven maternal eaths an six etal eaths. O note,

13 o 27 women presente within 2 months postpartum, an

in hal, hemorrhage herale rupture. Bleeing aenomas can

be manage by angiographic embolization ollowe by resection (silimigras, 2019).

■ Liver Transplantation

Accoring to the Organ Procurement an ransplantation

Network (2020) more than 177,000 liver transplantations

have been perorme in the Unite States. Analysis o the

National Inpatient Sample atabase oun 2 liver transplantations per 100,000 eliveries (Ghazali, 2017). In most stuies,

the 80-percent live-birth rate compares avorably with that o

the general population. However, risks o preeclampsia, cesarean elivery, etal-growth restriction, an preterm birth are signicantly elevate (Coscia, 2010; Deshpane, 2012; Kanzaki,

2016). Although cesarean elivery is common, vaginal elivery

is not contrainicate (Maej, 2018). Mattila an colleagues

(2017) oun that hal o the women they care or ha maternal complications, incluing acute grat rejection. Importantly,

4 percent o mothers ha ie within a year ater elivery, but

this rate is comparable to that in nonpregnant liver transplantation patients.

GALLBLADDER DISORDERS

■ Cholelithiasis and Cholecystitis

In the Unite States, 17 percent o women have gallstones.

Most stones contain cholesterol, an its oversecretion into bile

is thought to be a major actor in stone ormation. Te cumulative risk o all patients with gallstones to become symptomatic

is 20 percent (Lammert, 2016). For this reason, prophylactic

cholecystectomy is not warrante or asymptomatic stones.

Symptomatic cholelithiasis typically presents with right upper

or epigastric abominal pain, bloating, belching, nausea, an

atty oo intolerance. Pain stems rom gallblaer contraction, which orces a stone up into the sac’s neck. With subsequent gallblaer relaxation, the stone alls back to relieve the

obstruction. Laboratory values are normal, an leukocytosis or

elevate liver an pancreatic enzymes shoul warn or acute

cholecystitis or pancreatitis. Stanar care or symptomatic

cholelithiasis is laparoscopic cholecystectomy (Caasso, 2014).

Less oten, oral ursoeoxycholic aci therapy or extracorporeal

shock wave lithotripsy are use, but experience with these uring pregnancy is lacking.

Acute cholecystitis usually evelops when a stone obstructs

the cystic uct, which connects the gallblaer to the common

bile uct. Bacterial inection plays a role in 50 to 85 percent o

cases. In more than hal o patients with acute cholecystitis, a

history o prior right upper quarant pain rom biliary colic is

elicite. With acute isease, pain is accompanie by anorexia,

nausea an vomiting, low-grae ever, an mil leukocytosis.

As shown in Figure 58-3, sonography will isplay stones, an

both alse-positive an alse-negative rates range rom 2 to 4

percent (Greenberger, 2018). In acute cases, meical therapy

consists o intravenous uis, antibiotics, analgesics, an in

some instances, nasogastric suction. Surgical therapy ollows,

an laparoscopic cholecystectomy is the preerre route or

most.

■ Gallbladder Disease During Pregnancy

Ater the rst trimester, the gallblaer asting volume an

the resiual volume ater postpranial emptying are ouble.

Incomplete emptying may result in retention o cholesterol

crystals, a prerequisite or cholesterol gallstones. From stuies,

the combine incience o biliary sluge an gallstones is 5 to

8 percent (Ko, 2005, 2014).

Postpartum, sluge requently regresses, an occasionally

gallstones will resorb. Still, gallblaer iseases are the most

common cause o nonobstetrical amissions in the rst year

ollowing elivery (Lyon-Rochelle, 2011). Tis is particularly

true or women manage conservatively uring pregnancy.

Jorge an coworkers (2015) reporte that hal o 53 women

with symptomatic cholelithiasis in pregnancy unerwent later

postpartum cholecystectomy. In 80 percent o these women,

recurrent symptoms ha evelope prior to surgery.

■ Medical versus Surgical Management

Symptomatic cholelithiasis is common in pregnancy. Othman an colleagues (2012) showe that gravias manage

conservatively ha greater pain, more recurrent emergency

epartment visits, more hospitalizations, an higher cesarean

elivery rate. Dhupar an associates (2010) reporte more

complications with conservative management o gallblaer

isease compare with laparoscopic cholecystectomy in pregnancy. Tese inclue multiple amissions, prolonge total

parenteral nutrition (PN), an unplanne labor inuction

or worsening gallblaer symptoms. Tereore, operative an

FIGURE 58-3 Sonogram shows multiple, hyperechoic gallstones

collecting along the inferior wall of an anechoic gallbladder.Hepatic, Biliary, and Pancreatic Disorders 1043

CHAPTER 58

enoscopic interventions are increasingly avore over conservative measures.

Acute cholecystitis uring pregnancy or the puerperium is

also common. Acute isease in pregnancy may be complicate

by sepsis, pancreatitis, venous thromboembolism, an bowel

obstruction (El-Messii, 2018). Cholecystitis is initially manage similarly to that or nonpregnant women. In the istant

past, most avore meical therapy. However, the recurrence

rate uring the same pregnancy is high, an 25 to 50 percent o

women ultimately require cholecystectomy or persistent symptoms (Dhupar, 2010). Moreover, i cholecystitis recurs later in

gestation, preterm labor is more likely an cholecystectomy is

technically more ifcult.

Cholecystectomy can be perorme saely in all trimesters

(Kwon, 2018). A metaanalysis oun that cholecystectomy

oes not raise the risk o preterm labor or o maternal or etal

mortality (Athwal, 2016). O surgical routes, laparoscopic

cholecystectomy has evolve as the avore approach (Pearl,

2017; Shigemi, 2019). Tis is iscusse urther in Chapter 49

(p. 867). Management at Parklan Hospital avors a surgical

approach, especially i biliary pancreatitis, as subsequently iscusse, is comorbi (Juo, 2018).

■ Endoscopic Retrograde

Cholangiopancreatography

Approximately 10 percent o patients with symptomatic stone

isease have common uct stones (Stinton, 2012). Symptomatic biliary uct gallstones uring pregnancy can be retrieve

by enoscopic retrograe cholangiopancreatography (ERCP)

(Fogel, 2014; Greenberger, 2018). Te proceure is perorme

i common uct obstruction is suspecte or proven. ERCP

can be moie in many cases so that raiation exposure rom

uoroscopy is avoie (Sethi, 2015). I stanar uoroscopy is

use, a lea apron shiel is place between the raiation source

an the etus.

In 68 ERCP proceures perorme in pregnant women at

Parklan Hospital, all but two women ha gallstones, an common uct stones were ientie in hal o 65 women (ang,

2009). Stones were successully remove in all but one woman.

A biliary stent was place in 22 percent o cases an remove

ater elivery. Complications were minimal, but post-ERCP

pancreatitis evelope in 16 percent. Pregnancy outcomes were

not ierent rom those in the general obstetrical population.

As a less invasive approach, MR cholangiopancreatography

(MRCP) in pregnancy has been reporte (Oto, 2009).

Ascending cholangitis can complicate acute biliary obstruction. Nearly 70 percent o aecte patients evelop Charcot

triad—jaunice, abominal pain, an ever. Te iagnosis is

aie by sonography, an treatment is broa-spectrum antibiotics an biliary rainage by ERCP (Greenberger, 2018).

PANCREATIC DISORDERS

■ Pancreatitis

Acute pancreatic inammation is triggere by actors that cause

activation o pancreatic trypsinogen ollowe by autoigestion.

It is characterize by cell-membrane isruption an proteolysis,

eema, hemorrhage, an necrosis (Conwell, 2018). Up to 10

percent o patients evelop necrotizing pancreatitis, which carries a mortality risk o 15 percent. Tis rate rises i inection

evelops (Cain, 2015).

Te incience o pancreatitis varies with the population

stuie. At Parklan Hospital, with a preominant MexicanAmerican population, acute pancreatitis complicate approximately 1 in 3300 pregnancies (Ramin, 1995). From other

reviews, the incience is 1 case in 3500 to 6000 pregnancies

(Ey, 2008; Hacker, 2015; Hernanez, 2007).

In nonpregnant patients, acute pancreatitis is almost

equally associate with gallstones an alcohol abuse. During

pregnancy, however, cholelithiasis is almost always the preisposing conition. Other causes are hyperlipiemias, usually

hypertriglyceriemia; hyperparathyroiism; congenital uctal

anomalies; recent ERCP; some rugs; an rarely autoimmune

pancreatitis (Conwell, 2018; ang, 2018). Nonbiliary pancreatitis occasionally evelops postoperatively, or it is associate

with trauma, rugs, or some viral inections. Certain metabolic

conitions, incluing acute AFLP an amilial hypertriglyceri-

emia, also preispose to pancreatitis (Nelson, 2013). Cases o

acute an chronic pancreatitis have been linke to numerous

mutations o the cystic brosis transmembrane conuctance

regulator gene (Chang, 2015).

Diagnosis

Acute pancreatitis incites incapacitating epigastric pain, nausea

an vomiting, an abominal istention. Patients are usually

istresse an have low-grae ever, tachycaria, hypotension,

an abominal tenerness. As many as 10 percent have sepsis,

which causes enothelial activation an can lea to acute respiratory istress synrome (Chap. 50, p. 887).

Serum lipase measurements are preerre or iagnosis,

however, amylase levels also can be use. In 173 pregnant

women with pancreatitis, the mean amylase value approximate 2000 IU/L, an the mean lipase value approache

3000 IU/L (Table 58-5). Importantly, the degree o enzyme

elevation and disease severity do not reliably correlate. By 48 to

72 hours amylase levels may return to normal espite other

evience or continuing pancreatitis. Serum lipase activity

typically remains increase with continue inammation.

Leukocytosis is usually oun, an 25 percent o patients have

hypocalcemia. Elevate serum bilirubin an aspartate transaminase levels may signiy concomitant gallstone isease.

TABLE 58-5. Laboratory Values in 173 Pregnant Women

with Acute Pancreatitis

Analyte Mean Range Normal

Serum amylase (IU/L) 1980 111–8917 28–100

Serum lipase (IU/L) 3076 36–41,824 7–59

Total bilirubin (mg/dL) 1.7 0.1–8.71 0.2–1.3

Aspartate transaminase

(U/L)

115 11–1113 10–35

Leukocytes (per μL) 10,700 1000–27,200 3900–10,700

From Ramin, 1995; Tang, 2010; Turhan, 2010.1044

Section 12

Medical and Surgical Complications

Several prognostic scoring systems are use to classiy pancreatitis severity. However, the Ranson criteria an the Apache

II scoring system may be less relevant or pregnancy. In contrast, the Atlanta Classication incorporates the egree o organ

ailure as a measure o severity an may be more applicable in

pregnancy (Cain, 2015; Conwell, 2018). With this last tool,

mild disease lacks organ ailure or systemic complications. Moderately severe disease shows organ ailure lasting <48 h, with or

without local or systemic complications. Severe disease is ene

by persistent single- or multi-organ ailure (Banks, 2013).

Management

Meical treatment mirrors that or nonpregnant patients.

Tis inclues analgesics, intravenous hyration, an measures to ecrease pancreatic secretion by interiction o oral

intake. Nasogastric suction oes not improve outcomes o

mil to moerate isease. In a series by Ramin an colleagues

(1995), all 43 aecte pregnant women respone to conservative treatment an were hospitalize or a mean o 8.5

ays. I bacterial superinection, necrotizing pancreatitis, sepsis, or cholangitis is oun, broa-spectrum antimicrobials

are aministere. I common uct stones are oun, ERCP

is inicate.

Enteral eeing may be helpul once pain improves an associate ileus resolves. For women with more severe pancreatitis an prolonge isease course, total enteral nutrition using

nasojejunal eeing is superior to PN (Cain, 2015; Conwell,

2018). Cholecystectomy is consiere ater inammation subsies because women with gallstone pancreatitis carry a greater

risk o recurrent inammation (Cain, 2015). Juo an coworkers (2018) reporte that a thir o women with biliary pancreatitis not treate with cholecystectomy were reamitte, an

30 percent o these ha recurrent pancreatitis. O the initial

group, those who instea i unergo cholecystectomy ha

only a 5-percent reamission rate.

Pregnancy Outcomes

Increasing severity o pancreatitis is associate with averse

maternal an etal outcomes (ang, 2018). In one review o

101 pancreatitis cases, Ey an coworkers (2008) oun a

30-percent preterm elivery rate, an 11 percent were elivere

beore 35 weeks’ gestation. Tere were also 4 percent stillbirths.

Tere were two pancreatitis-relate maternal eaths. Importantly, almost a thir o women ha recurrent pancreatitis

uring pregnancy. In another stuy o 342 pregnancies complicate by pancreatitis, preterm elivery an etal mortality

rates were comparable to the ata rom Ey (Hacker, 2015).

■ Pancreatic Transplantation

Few reports escribe pregnancy ollowing pancreas transplantation. O 44 pregnancies in 73 women ollowing pancreas-kiney

transplantation, outcomes are encouraging, an vaginal elivery has been escribe (Mastrobattista, 2008). Although the

incience o hypertension, preeclampsia, preterm elivery, an

etal-growth restriction are high, there was only one perinatal

eath. Four rejection episoes evelope uring pregnancy an

were treate successully. Pancreatic islet autotransplantation

an at least three subsequent successul pregnancies have been

reporte (Jung, 2007).

Nhận xét