Chronic Liver Disease

Presentor : Dr. Kanakaseshu KalanadhabhattaDesignation : Fellow, RCOG Accredited Fellowship Programme in Maternal Medicine

Hospital : Fernandez Hospital, Hyderabad

Date of Presentation : 10.06.2017

28 year old, primi with 33+ weeks gestational age

LMP-07/09/2016

EDD-14/06/2017

Referred to Fernandez Hospital in view of pancytopenia

with severe anemia and generalized weakness.

Raised BP readings since 2 days, not on medication

1st trimester

Had regular ANC at local hospital

Had no ultrasound evaluation

Screen positive hypothyroid- started on thyronorm

75 mcg once daily

Generalised weakness-cbc- pancytopenia-evaluated

at Care Hospital in Sept 2016

Care Hospital Evaluation details

Bone marrow biopsy :

Tear drop cells with leuco erythroblastic picture

Erythroid hyperplasia with focal megaloblastic maturation

Depleted iron stores

(Dimorphic anaemia)? Myelodysplastic Syndrome

ANA-positive, rest of ANA profile negative

DCT negative

Received 3 units PRBC transfusions, followed by iron and vitamin

B12 supplementation

Serial Investigation in later pregnancy

Date Hb WBC Platelets Bilirubin(D/I)

Serum Creatinine

27/9/16 3.7 1290 65000 4.5(0.3/4.2) 0.5

23/11/16 7.8 5.2(1.1/4.1)

9/12/16 8.4 4.5(1.7/2.8)

24/12/16 5.8 5.5(1.8/3.4)

22/2/17 6.8 6.0(0.7/5.3)

27/3/17 5.9 4600 49000 4.3

26/4/17 5.2 8900 82000 4.6(1.2/3.4) 0.8

10/3/17: evaluated for persistent anemia and

elevated bilirubin (4.5-6, predominently

unconjugated), showed following results

SGOT-99,SGPT-30

Serum proteins: 5.8, Alb:3.2, Globulin:2.6, A/Gratio:1.2

Serum iron:193.10micro gram/dl

Serum B12:906.6 pg/ml( received supplements)

Serum LDH: 2919U/L

DCT-negative

ANA positive with remaining profile negative

Fetal Evaluation Details

Scan at 15 weeks: normal;

Quadruple screen-low risk

TIFFA at 27wks: normal

Incidental finding of maternal moderate

hepatosplenomegaly

Growth scan at 33.1 weeks: normal

SLIUG, cephalic; EFW 1469g ( 1.6C), AFI11; normal

dopplers, CPR-1.07

At FH on 27.4.17 @ 31.1 wks

H/o blood pressure readings (130/90) since 2 days

Received 3units of packed cells (Hb-3.7%) elsewhere

Referred to FH for further management

We referred her to Century multispecialty hospital

on same day for further evaluation in view of

bicytopenia with unconjugated hyperbilirubinemia

requiring specialists inputs

Past Medical History

Generalized weakness pre pregnancy, gradually

increased, requiring blood transfusion before

marriage once (confidential from husband),not

evaluated..no documents available.

No h/0 jaundice, fever, joint pains, drug use,

indegenous medicine use

Menstrual history

Regular cycles

POG-34.2weeks

Past surgical history-Nil particular

Family history- Nil particular

O/E @ Century Hospital

Thin built, Moderately nourished; conscious ,coherent, afebrile

Pallor +++,icterus++, grade2 pedaledema+

No cyanosis/clubbing / lymphadenopathy

PR : 117/min, regular , BP : 140/90 mm Hg,urine alb-negative,

RR : 20/min, Spo2:96% on room air

CVS: NAD

RS: NAD

CNS: NAD

P/A: Distended,fluid thrill present, liver and spleen could not be

assessed due to ascites

Uterus-30-32wks, cephalic ,LOT ,FHS-144/min,regular

Investigations @ Century Hospital

DATE Hb WBC Platelets Serum

creatinine

Blood urea LDH

27/4/17 7.3 10,580 55,000 5647

28/4/17 6.9 6,730 47,000 0.8 5204

29/4/17 5.5 7,990 38,000 0.9 34 4647

30/4/17 6.4 9,020 39,000 0.8 37 4063

1/5/17 7.3 8,160 31,000 0.7 33 3754

2/5/17 9.5 9,540 35,000 1.0

3/5/17 9.7 10430 30,000 2882

5/5/17 9.5 9260 27,000

6/5/17 8.0 6510 18,000 0.7 3614

LFT

DATE SGPT A/G ALP Bilirubin PT-INR APTT

27/4/17 20 2.1/2.1(1.0)

124 5.5(1.2/4.3)

1.16 43.4

28/4/17 4.3(0.9/3.4)

29/4/17 19

30/4/17 1.14 34.5

1/5/17 1.15 36.9

6/5/17 13 1.3 148 1.4(0.4/1.0)

Other Investigations

USG on 28/4/17

Minimal bilateral pleural effusion

Minimal to moderate ascites

Moderate splenomegaly

Coarse increased echotexture of liver-S/O liver parenchymal

changes

HIV, HCV , HbsAg - negative

RBS-68 mg%

Serum electrolytes- normal

Parasight F and V -negative

On 30.04.217

Sudden onset shortness of breath;

BP 220/120 mm hg

Findings suggestive of pulmonary edema

ABG: Metabolic acidosis with type 1 respiratory failure

She received IV Furosemide 40 mg stat , Nifedepine SR 10 mgTID,Labetalol 200 mg TID,transferred to ICU ,started on noninvasive ventilation,continued fconservative management

Antenatal steroids given after stabilisation

Working Diagnosis : ?CLD + partial HELLP with pulmonary edema; with background of pancytopenia? EVANS syndrome

Delivery Details

LSCS under General anaesthesia on 2/5/17 in view of maternal medical disease and FGR

One unit SDP was transfused pre-surgery

LSCS was uneventful

Baby -1.46kg girl baby, normal APGAR, shifted to NICU for further care

Received 2 units PRBC

Intra abdominal drain was kept in view of thrombocytopenia and gross ascites

Post operative

Elective ventilation for 24 hours postoperatively in

view of congested lungs

Evaluated by hepatologist in view of ascites,

jaundice, pancytopenia and splenomegaly

Diagnosis of CLD ? AUTOIMMUNE HEPATITIS was

made

Drain was removed on postoperative day 4

Post operative

Colostomy bag kept insitu at drain site in view of persistent

ooze from drain site

Discharged on 4th POD in stable condition on

Tab.Spironolactone twice daily, labetalol 100mg twice daily

She was advised

upper GI endoscopy

Fibroscan of liver/ MR elastography of liver

Post discharged review on 14th POD

Symptomatically improved

Ascites , pedal edema and icterus reduced

upper GI endoscopy done- normal

Colostomy bag removed

Spironolactone continued

MR Elastrography & Hepatogram -16.5.17

Morphological changes in liver and spleen suggestive of

CLD with portal hypertension likely secondary to –

chronic EHPVO

Splenomegaly, Severe ascites

Mean hepatic parenchymal stiffness of 5.5 Kpa

suggesting stage 4 fibrosis or cirrhosis

Marked T2 hypointense signal of renal cortices

suggestive of ?hemosiderosis

Readmission 18.05.2017

On 16th POD admitted with fever, vomitings, severe

abdominal pain radiating to back and abdominal

distension of 2 days duration

Investigations revealed worsened pancytopenia and

jaundice (bilirubin of 11 gm%)

Repeat ultasound: Hepatosplenomegaly, ascites, bulky

pancreas with altered parenchymal echopattern –?early

pancreatitis

Serum lipase, amylase, ferritin normal

CT Abdomen

Hepatosplenomegaly, with multiple collaterals at

perisplenic and splenoportal axis,splenic hilum- S/O

portal hypertension

Partial thrombosis of inferior mesentric vein and

extra hepatic inferior vena cava

Diagnostic paracentesis done and ascitic fluid sent

for analysis- results suggestive of SBP

Ascitic Fluid Analysis

Gross:Reddish Colour,slighty turbid

Microscopy :400 cells/mm3,100% lymphocytes

Culture :E.Coli,Enterococcus fecalis :heavy growth

Glucose 101 mg/dl

Protein 2.0 gm/dl

Amylase 15 u/lit

Investigations

DATE Hb WBC PLT BILIRTotal(D/I)

SGPT T. PRTEIN

S CR

18/5/17 6.6 3,420 1,50,000 0.6

19/5/17

20/5/17 7.2 55,000 0.6

21/5/17 8.0 4,310 74,000 8.4(5.1/3.3)

23 5.2

22/5/17 7.5 4,830 83,000

23/5/17 6.4 2,890 67,000 0.4

Other Investigations & Management

Serum electrolytes , PT,APTT normal

Rx: NBM, NG tube, iv fluids, Inj Meropenam1 gm IV

TID, inj.Metrogyl 400 mg IV TID, inj.Fondaparinux

7.5 mg SC OD

She improved after 48 hours, started on soft diet

Discharged after 4 days in stable condition

Final Diagnosis

Final diagnosis:Chronic liver disease(?Autoimmune

hepatitis) ,pancytopenia presented in pregnancy

with preeclampsia -->acute pulmonary edema

Postoperative partial decompensation of liver

function and spontaneous bacterial peritonitis,

partial thrombosis of inferior mesentric vein and

extrahepatic IVC

Summary

28 year old primi with probable acquired hematological

disorder prior to pregnancy with severe anaemia

requiring blood transfusion once,conceived

spontaneously presented with pancytopenia in 1st

trimester before pregnancy confirmation ,partially

evaluated outside , bonemarrow biopsy suggestive of

erythroid hyperplasia with focal megaloblastic

maturation with depleted iron suggestive of dimorphic

anaemia?MYELO DYSPLASTIC SYNDROME

Summary

Temporary improvement in hemoglobin with PRBC

transfusion ,but fall in 2nd trimester,persistent anemia and

thrombocytopenia despite iron,B12 supplementation with

hyperbilirubinemia predominantly unconjugated

DCT was negative, ANA positive,other ANA profile normal.

Re-evaluated at 28 weeks gestation;raised LDH (2900U/L)

with normal iron, B12 levels and mildly raised SGPT,SGOT.

Severe FGR noted at 33 weeks gestation

Summary

At 33 weeks gestation developed gestational

hypertension; again received 3units PRBC in view of

severe anaemia and thrombocytopenia

Evaluation at century hospital at 33 weeks gestation

revealed labs suggestive of ? Partial HELLP(normal

SGPT,increased LDH, low platelet count)

Ultrasound showed mild splenomegaly with moderate

ascites ,increased echotexture of liver suggestive of

CHRONIC LIVER DISEASE with Portal hypertension

Viral hepatitis screen was negative, patient developed

acute pulmonary edema, accelerated hypertension,

metabolic acidosis, required LSCS under general

anaesthesia with SDP and PRBC transfusion

Baby though FGR (1.6KG) was healthy

Persistent anaemia , thrombocytopenia even after

delivery makes diagnosis of HELLP doubtful.

Postoperative day 5 bilirubin became almost normal. No

hypoglycemia, hepatic encephalopathy, coagulopathy or

esophageal varices.

Fibroscan done on postoperative day 14 showed

features suggestive of cirrhosis (stage 4 fibrosis)

On POD 16, developed bacterial peritonitis with

worsening of bilirubin levels which improved after

antibiotic cover

Also there was incidental finding of partial

thrombosis of inferior mesenteric vein and

extrahepatic IVC.

Discussion

1. What is the underlying hematological disorder?initial

pancytopenia ,later bicytopenia(anaemia,

thrombocytopenia) which persisted beyond delivery.

2. Can we consider PNH as a possibility in view of inferior

mesenteric vein thrombosis ,thrombocytopenia and

hemolytic anaemia(Raised LDH , low Hb%,

unconjugated hyperbilirubinemia)patient requires

further evaluation with flow cytometry studies and

hematologist's follow up.

Discussion

3. Diagnosis of chronic liver disease inview of

ultrasound,CT abdomen and MR elastography findings

is appropriate . However since LFT except bilirubin are

normal and there are no other complications like

varices,hepatic encephalopathy probably it is in early

stages, though fibroscan shows grade IV changes.

Cause of liver disease needs to be evaluated.

(autoimmune hepatitis markers,serum ceruloplasmin,

urine copper, KF ring test, alpha1 antitrypsin levels,

AFP levels and +/- liver biopsy)

Discussion

4. Development of peritonitis in the background of

ascites following LSCS despite all aseptic measures

after 2 weeks of LSCS should be considered as

SPONTANEOUS BACTERIAL PERITONITIS , but in this

patient since she had drain insitu followed by

colostomy bag which was removed on postoperative

day14,(following which she developed peritonitis)

secondary bacterial peritonitis should be considered.

Discussion

5. Postpartum thromboprophylaxis in view of severe

preeclampsia and LSCS in patient of chronic liver

disease with severe thrombocytopenia is risky

and needs hematologist inputs and followup.

6. Ascites in this patient can be accounted for by

severe preeclampsia +/-decompensated liver

disease.

Discussion

7. Contraceptive advice is very important in these patients

until maternal diagnosis is established, disease stabilized ,

prognosis ascertained . OC pills to be avoided in view of

thrombosis, IUCD to be avoided in view of infection and

bleeding risk; Barrier can be used.

8. Pre-pregnancy evaluation with aCL, LAC, beta 2

glycoprotein also indicated in view of history of

thrombosis and severe preeclampsia needing early

delivery.

Take Home Message

Any patient with bicytopenia or pancytopenia needs USG

abdomen to rule out hypersplenism, portal hypertension,

before labeling as hematological disorder

Preeclampsia needs to be aggressively managed in already

decompensated liver disease

Peritonitis is a post op complication we need to anticipate

in cases of CLD with ascites

All CLD cases need to be evaluated for the etiology

PNH should be considered in DD in patients with persistent

anemia and thrombocytopenia