VIRAL HEPATITIS IN

PREGNANCY
Presentor- Maj Kirit Pandey
Moderator- Lt col Bidhan Roy
 VIRAL HEPATITIS

• 6 types- A, B,D,C,E & G

• All are RNA viruses except Hep B
• Vertical transmission – Hep B & C
• Hep D is a defective RNA virus that requires co-Infection with Hep B
• Hep E is similar to Hep A but more serious , with significant mortality in pregnant ladies
 CLINICAL FEATURES

Symptoms Signs
• Anorexia • Dehydration
• Fatigue • Hepatomegaly (firm enlarged palpable liver
• Nausea or Vomiting edge)

• Right upper Quadrant Abdominal Pain • Jaundice

• Dark urine
• Pale stool
 DIFFERENTIAL DIAGNOSIS
(IN PREGNANCY)
• 1) Hyperemesis Gravidarum

• 2) HELLP Syndrome

• 3) Acute Fatty Liver of Pregnancy

• 4) Intrahepatic Cholestasis of Pregnancy

 HEPATITIS A
synonym Infectious Hepatitis

Type of Virus SsRNA (27 nm)

Incubation Period 28 days ( 15-28 days)

transmission Feco-oral route

Carrier state No

Severity of Hepatitis +-

Immunity
Passive immunisation Hyperimmune Globulin

Active immunisation Vaccine (Hepatitis A)

 HEPATITIS A

• HAV replicates in liver & excreted in Bile.

• Poor hygiene & poor sanitation- common source outbreaks of HAV
• Post cooking food contamination by unhygienic food handlers
• Imp prevention strategies

1) Heating food to > 185 degree F for 1 min (ACOG PB 86)

2) Disinfecting surface with household solution of bleach

• Case fatality ratio < 1% (ACOG PB 86)

 HEPATITIS A

• Non specific signs & symptoms

• Majority – Asymptomatic
• Non teratogenic
• No evidence of Vertical transmission
• Diagnosis- specific Anti-hepatitis A virus IgM
• T/t- supportive, adequate nutrition & rest
 VACCINE- INDICATIONS

• Indicated for persons with increased risk of Hep A

• Chronic liver d/s
• Receiver of clotting factor concentrates
• Persons working with HAV infected primates and research lab setting
• 2 types:
type content dosing
Single antigen Inactivated HAV 2 doses- 6 to 12 months
apart
combination Inactivated HAV + 3 doses – 0, 1,6 months
HBV antigen

• Immunoglobulin is available for post exposure prophylaxis @ 0.1ml/kg (CDC revised guideline for post
exposure prophylaxis 2010)
 HEPATITIS B
synonym Serum Hepatitis

Type of Virus ds DNA

Incubation Period 30-180 days

transmission Predominantly Parenteral

Carrier state yes

Severity of Hepatitis ++

Immunity
Passive immunisation Hyperimmune Globulin

Active immunisation Vaccine (Hepatitis B)

 HEPATITIS B

• Intact virus- Dane particle, has 3 major antigens

• HBsAg – marker of ongoing infection, disappears during convalescent phase of disease and its
persistence indicates chronic infection
• HBcAg – middle portion of Dane particle, only in hepatocytes
• HBeAg – marker of infectivity & viral replication
• HBV – highly infectious and can be transmitted by infected blood/ blood products, saliva or
sexual intercourse
• 10% acute cases- becomes chronic (ACOG PB 86)
 HEPATITIS B
(RISK FACTORS)
1) Individuals with multiple sexual partners
2) IV drug users
3) Have sexual partners with high risk behaviours

• Sexual contact is efficient mechanism for spread~25% of frequent sexual contacts of infected
individuals become infected (ACOG PB 86)
• All blood donors are routinely screened, hence transmission by transfusion of blood products is
decreasing
 HEPATITIS B- SPECTRUM
• Acute infection – flu like symptoms (25% pt) , asymptomatic in rest
• Majority- do not develop Jaundice , fever is less common
• Course: resolves Chronic carriers Lethal Fulminant Hepatitis
90% 5-10% < 1%

10 chronic carriers Chronic persistent hepatitis Chronic Active Hepatitis

07 03
Liver Enzymes – Normal frequently develops cirrhosis,
D/s - Do not progress hepatic failure and primary
HCC

50% develops Delta virus Co-

infection

Source: ACOG PRACTICE BULLETIN 86

 IMPORTANCE

• Vertical transmission- mostly d/t contact with infected maternal Blood & vaginal secretions
during parturition & acquired during breastfeeding
First/ second trimester 10% chance
Third Trimester 80-90 % chance

• This rate is higher in HBeAg + mothers

• USG- not a teratogen, hence cannot be detected on USG
• Increased incidence of LBW & prematurity
(ACOG Practice Bulletin-86)
 VACCINATION

1) All individuals with high risk behaviour

2) Health care workers, hemo-dialysis patient
3) International travellers

• 2 single antigen vaccine and one recombinant vaccine available

• HBIG is available for passive immunisation
 INSTITUTIONAL POLICY
(SINGLE VACCINE)
Single Vaccine (Engerix –B)
Dose 3 doses (0.5 ml/ 1 ml each)
Schedule 0,1,6 months
Route Anterolateral aspect of thigh (< 1 yr)
Deltoid in older children
Not to be given in Gluteal region
Cost 115/-

• No adequate data available in pregnant women

• Available data do not suggest an increased risk of major birth defects and miscarriage in women
(CDC site & Gsk Engerix B vaccine leaflet)
• Combination vaccine – TWINRIX contains recombinant HBsAg and inactivated HAV

• 3 doses at 0,1,6 months

• When a rapid immune response is needed for an occupational /travel requirement- accelerated schedule of 0,7,21-30 days followed by a
booster dose at 12 months can be given.

• Vaccine is to be administered in Deltoid region only, other sites results in lower rates of seroconversion

• Pregnancy is not a contra-indication

 LAB INVESTIGATIONS
( WILLIAMS OBSTETRICS 25 E, FIG 55-2, PG 1064)
 MANAGEMENT

• Universal routine screening in first trimester

• If mother + : status of d/s is established, whether active/passive
Active Disease High Viral Load Initiate Therapy
Elevated ALT
Non Active Disease Low Viral load & Low Repeat HBV DNA in late
ALT 2nd Trimester

If Viral Load> 10^6

copies/ml, antiviral
prophylaxis to be started in
3rd trimester

• Lamivudine is an effective drug ( ACOG PB 86)

 RECOMMENDATION

• If viral load >2,00,000 IU/ml indicates a level where the combination of birth dose of vaccine
and HBIG may fail.
• First line Antiviral therapy with Tenofovir May be recommended
• Second line antivirals include treatment with Telbivudine or lamivudine
• Antiviral therapy begins at 28-32 weeks and continues 3 months postpartum
(ACOG Practice bulletin 86)
• Cesarean delivery for prevention of neonatal infection is controversial, but generally not
recommended.
• Some studies show no advantage but some show reduction in neonatal infection from 24.9% in
vaginal delivery to 10% in CS
• Vaccination can be given during pregnancy and is advisable in seronegative women during high
risk of infection.
 ANTIVIRALS
Tenofovir Lamivudine
• Analogue of Cytidine, inhibits HIV 1&2 Reverse
• Nucleotide analogue HIV & HBV reverse
transcriptase and HBV Reverse transcriptase
transcriptase inhibitor
• Category C drug
• 300 mg daily dose PO
• 100 mg/day PO
• from 32 week POG to 4 weeks post partum • From 28-32 weeks
• Sharp decline in viral load • In pt with HBV DNA > 10^8 copies/ml
• No viral resistance to the drug • Decreased transmission from 28.0% to 12.5%

• Dose reduction in renal impairment • No adverse effects

• No complete prevention of transmission, even in
case of successful LAM t/t
 POSTNATAL MANAGEMENT

• Infected newborns – usually asymptomatic, but approx 85% will develop chronic infection if left
untreated
• Isolation from mother – not needed
• Mother’s secretions- potentiality infective ,mange with universal precautions
• Recommendation:
HBV immune globulin (0.5 ml Im) within 12 h of birth followed by first dose of Hepatitis B
vaccine (0.5 ml Im) within 12 h of birth and then at 1& 6 months
Efficacy – 85-95% (ACOG practice bulletin –86)
• Without immunisation, 10-20% +ve pt transmits viral infection to infant
• This increases to 90% if mother is HBsAg and HBeAg +ve
• Immune prophylaxis and Hep B vaccine given to infants born to HBV infected mothers has decreased transmission dramatically
and prevented approximately 90 percent of infections (Smith, 2012)
• Women with high HBV viral loads—106 to 108copies/mL,or those who are HBeAg positive, still have a least at 10% vertical
transmission rate, regardless of immune prophylaxis
PREVENTION OF VERTICAL TRANSMISSION
 HEPATITIS C
synonym Hepatitis C
Type of Virus ssRNA

Incubation Period 30-60 days

transmission Parenteral

Carrier state yes

Severity of Hepatitis +

Immunity
Passive immunisation None

Active immunisation None

 HEPATITIS C

• more frequent in women with HIV infection

• Route of transmission- blood/ blood products, sexual contact & vertical transmission
• chronic infection following hepatitis C is > 50% (ACOG PB 86)
• Incidental finding of Increased ALT on deeper evaluation demonstrates seropositivity for anti-
HCV antibodies
• Vertical transmission by contact with infected maternal blood and vaginal secretion
• Rate of transmission is 3-6% (ACOG PB 86)
• But , if the mother is HIV +, this rate further increases
• Risk of vertical transmission correlates with HCV RNA viral load of mother
• Rarely transmitted by Breastfeeding
• Risk factors- transfusion of blood products , use of intra- venous drug, hemophiliacs & high risk
behaviour
• Mass screening of blood products reduced the risk of transmission
• Majority- Asymptomatic
• 50% progress to chronic infection
• 20% chronic HCV infections leads to chronic active hepatitis or cirrhosis
• CO-infection with HIV accelarate the progression & severity of hepatic injury
• recent reports have shown modestly increased fetal risks for low birthweight, NICU admission,
preterm delivery, and mechanical ventilation (Berkley, 2008; Pergam, 2008; Reddick, 2011)

• Invasive prenatal diagnostic procedures have not been reported to increase transmission to the
fetus. However, Rac and Sheffield (2014) note that few studies have addressed this possibility,
and they recommend avoiding traversing the placenta during amniocentesis.

• HCV genotype, invasive prenatal procedures, breastfeeding, and delivery mode are not
associated with mother-to-child transmission

• HCV is not contraindicated for breast feeding

 IMPORTANCE

• Diagnosis is by detection of antibody to Hepatitis C virus by ELISA

• No licensed vaccine for prevention
• alpha interferon (standard and pegylated), alone or in combination with ribavirin is contraindicated in
pregnancy because of the teratogenic potential
• Non-availability of prenatal or postnatal pharmacologic or immunologic measures to decrease the risk
of vertical transmission
• Further studies going on regarding the use of Antiretroviral drugs in mother for prevention and
peginterferon-a,2a, a modification of interferon a,2a which has prolonged absorption, slower clearance
and a longer half life
 RECOMMENDATION

• Routine prenatal HCV screening is not recommended, however, women with significant risk
factors for infection should be offered antibody screening
• Route of delivery has not been shown to influence the risk of vertical HCV transmission, and
cesarean delivery should be reserved for obstetric indications in women with HCV infection.
• Present recommendations do not advise against breast- feeding for HCV-positive mothers
• There is no effective treatment available to treat HCV infections in mothers and newborns. For
this reason, routine HCV screening is not recommended at the present time.
 HEPATITIS D
synonym Delta Hepatitis
Type of Virus ssRNA

Incubation Period 15- 80 days

transmission Parenteral

Carrier state yes

Severity of Hepatitis +

Immunity
Passive immunisation Hyperimmune Globulin

Active immunisation Vaccine (HBV)

 HEPATITIS D

• Delta hepatitis, this is a defective RNA virus that is a hybrid particle with an HBsAg coat and a
delta core
• The virus must co-infect with hepatitis B either simultaneously or secondarily
• It cannot persist in serum longer than hepatitis B virus
• Transmission is similar to hepatitis B
• Chronic co-infection with B and D hepatitis is more severe and accelerated than with HBV
alone, and up to 75 percent of affected patients develop cirrhosis
• Once Cirrhosis ensues, pt have typical signs of end stage liver d/s, such as Jaundice, muscle
wasting, ascites, spider hemangioma, Palmer erythema and encephalopathy
• Disease follows a BIPHASIC CURVE
• HDV infection is detected by the presence of anti-HDV and HDV DNA
• Neonatal transmission is unusual, as neonatal HBV vaccination usually prevents delta hepatitis.
 HEPATITIS E
• Enterically transmitted by contaminated water supplies & ingestion of raw/undercooked shellfish
• It causes epidemic outbreaks in third-world countries with substantial morbidity and mortality
rates
• Pregnant women have a higher case- fatality rate than non pregnant individuals
• Fulminant hepatitis, although rare overall, is more common in gravidas and contributes to the
increased mortality rates
• Jin & Coworkers (2016) reported maternal and fetal case-fatality rates of 21 and 34 percent,
respectively
• In one report, HEV infection in women coinfected with HIV resulted in a 100% mortality rate
• A recombinant HEV vaccine has been developed and licensed in China
• It is >95 percent effective for 12 months after vaccination
• Long-term efficacy is 87 percent, and protective titers are maintained for up to 4.5 years (Zhang,
2015)
• Genotype 4 predominates in China.
• US- FDA approved vaccine is not available
 HEPATITIS G

• Hepatitis G is the former name of an RNA flavivirus now known as HPvG or human pegivirus
• This blood-borne infection of the liver, spleen, bone marrow, and mononuclear cells of the
peripheral blood does not actually cause hepatitis (Chivero, 2015)
• It may modulate the immune response, particularly during co-infection with HIV
• Currently, no treatment aside from basic blood and body fluid precautions is recommended.
• Vertical transmission (to the fetus/infant) and horizontal transmission (to peers) has been
described (Trinks, 2014).
 RECOMMENDATIONS

• Routine prenatal screening of all pregnant women by HBsAg testing

• Newborns born to hepatitis B carriers should receive combined immuno-prophylaxis consisting
of HBIG and hepatitis B vaccine within 12 hours of birth
• Hepatitis B infection is a preventable disease, and all at-risk individuals, particularly health care
workers, should be vaccinated
• All infants should receive the hepatitis B vaccine series as part of the recommended childhood
immunization schedule
 RECOMMENDATIONS

• Breastfeeding is not contraindicated in women with HAV infection with appropriate hygienic
precautions, in those chronically infected with hepatitis B if the infant receives HBIG passive
prophylaxis and vaccine active prophylaxis, or in women with HCV infection
• Routine prenatal HCV screening is not recommended; however, women with significant risk
factors for infection should be offered antibody screening
• Route of delivery has not been shown to influence the risk of vertical HCV transmission, and
cesarean delivery should be reserved for obstetric indications in women with HCV infection.
 GALLBLADDER DISEASE DURING
PREGNANCY
• After the I trimester, the gallbladder fasting volume and the residual volume after postprandial
emptying are doubled
• Incomplete emptying may result in retention of cholesterol crystals, a prerequisite for cholesterol
gallstones
• Acute cholecystitis during pregnancy & peurperium is common
• Symptomatic cholecystitis is initially managed in a manner similar to that for non-pregnant
women
• operative and endoscopic interventions are increasingly favored over conservative measures
• Othman and coworkers (2012) showed that women managed conservatively had more pain,
more recurrent visits to the emergency department, more hospitalizations, and a higher rate of
cesarean delivery.
• Recommendation- more aggressive surgical approach, Lap cholecystectomy and it can be
performed safely in all trimesters
(Williams obstetrics 25 e)
 CHOLELITHIASIS & CHOLECYSTITIS

• Acute cholecystitis -cystic duct is obstructed.

• Bacterial infection plays imp role.
• Clinical features : Right upper quadrant pain is accompanied by anorexia, nausea and vomiting, low-
grade fever, and mild leukocytosis
• USG can help visualize stones, and both false-positive and false- negative rates range from 2 to 4
percent (Greenberger, 2015)
• In acute cases, medical therapy consists of IV fluids, antimicrobials, analgesics, and in some instances,
nasogastric suction, before surgical therapy
• Laparoscopic cholecystectomy is the preferred treatment for most patients.
 AUTOIMMUNE HEPATITIS

• Reduced fertility rate secondary to Amenorrhoea & anovulation

• Can occur de-novo during pregnancy or post partum
• Pregnancy can ameliorate autoimmune hepatitis, whereas delivery can exacerbate it
• Clinically- Asymptomatic to an acute presentation with liver failure
• Steroids and azathioprine are safe during pregnancy but birth defects have been described
• Need careful monitoring during pregnancy and several months postpartum
 WILSON DISEASE

• Pregnancy do not seem to have an adverse effect on the clinical course of Wilson disease
• Recurrent abortions are common in untreated patients ~ upto 26%
• Untreated symptomatic women tend to suffer amenorrhea, oligomenorrohea, irregular menses
and multiple miscarriages
• However pregnancy is safe and successful when treatment with a chealating drug is continued
uninterrupted
• Zinc sulphate can be used
 BUDD CHIARI SYNDROME

• Usually presents in last trimester

• Treatment is no different from that used in non pregnant person except warfarin (FDA CAT X)
• LMWH as a curative dose should be started as soon as the diagnosis is established
• Pharmacological and endoscopic therapy for portal hypertension can be applied
 CIRRHOSIS AND PORTAL HYPERTENSION

• Worsening jaundice with progressive liver failure, ascites and hepatic coma during the course of
pregnancy in women with cirrhosis
• Increased incidence of stillbirths, premature delivery, hypertension and peripartum infection in
women with cirrhosis specially when ascites is present
• Sclerotherapy or endoscopic band ligation are successful in pregnant women with variceal
hemorrhage
• Prevention of variceal bleed in known cirrhotics who desires pregnancy is based on classic
treatment with B blockers and/ or endoscopic ligature
• Prophylaxis with B-blockers May be continued during pregnancy