1. Acute Hepatitis and prolonged fever –
How far do we go?
Presenter:
Anita Dhanrajani - Jaslok Hospital, Mumbai
Moderator:
Ujjal Poddar – Pediatric Gastroenterologist, SGPGI, Lucknow
Panelists:
Gaurav Narula - Pediatric Oncologist, Tata Hospital, Mumbai
Prakash Vaidya – Pediatrician, Fortis Hospital, Mumbai
Geeta Billa – Hepatologist, Hiranandani Hospital, Mumbai

2. Acute hepatitis with prolonged
fever – how far do we go?
Dr Anita Dhanrajani
Under guidance of Dr Aabha Nagral
Jaslok Hospital And Research Centre

3. HISTORY
• 17 y, M
• BONCM
• Presenting complaints of fever for 10 days and
jaundice for 15 days.
• Right upper quadrant pain
• Anorexia, vomiting, malaise and fatigue
• Fever low grade, intermittent

4. HISTORY
• No h/o drug intake
• No history of blood transfusions, sexual
contact
• No previous history of jaundice
• No history of alcohol intake

5. EXAMINATION
•
•
•
•
•
Tachycardia
Icterus
Liver palpable: 4 cm, tender, firm, sharp edge
Spleen palpable: 2 cm BLCM
Enlarged submandibular lymph nodes: 2.5 cm

6. COURSE
•
•
•
•
Rapidly progressed to altered sensorium
Grade 3 encephalopathy – needing ventilation
Developed haematemesis and malena
Abdominal distension with presence of free
fluid
• Fever subsided

7. INVESTIGATIONS
CBC
Hb – 10.2gm%
WBC:
4500/mm3
P 28, L70
PC – 1.1 lacs
LFTs
T Bili – 13.8
ALP – 40 IU
SGPT –
1740
SGOT –
1028
TSP/Alb: 4.8
gm%, 1.9 gm
%
Viral
markers
IgM anti HAV –
positive
IgM anti
HEV –
Positive
HBV, HCV,
HIV negative
USG
abdomen
Mild ascites,
hepatomegaly,
splenomegaly
Coagulatio PT – 28/12
n profile
INR – 2.3
Others
S ammonia
– 110
RBS – 44 mg%
S
Blood culture
creatinine – - negative

8. PRIMARY DIAGNOSIS
Acute viral hepatitis (A+E) with fulminant
hepatic failure (FHF)
• Prodrome followed by jaundice and then
encephalophathy
• High bilirubin with high ALT
• Prolonged PT
• High ammonia
• IgM anti HAV plus HEV positive

9. FURTHER COURSE
• Encephalopathy recovered – patient
extubated
• Fever reappeared – high grade
• Tachycardia, tachypnea
• Hepatomegaly, splenomegaly and
lymphadenopathy persisted
• Continuing coagulopathy
Any thoughts?

10. Cause of fever?
•
•
•
•
Peritonitis (SBP)
Urinary tract infection
Ventilator induced pneumonia
Septicemia
What next?

11. FURTHER INVESTIGATIONS
CULTURES
BLOOD negative
URINE –
negative
ASCITIC
FLUID –
negative
SPUTUM negative
RADIOLOGY USG –
CT brain –
ascites,
normal
hepatospleno
megaly
PET CT
whole body –
adenopathy
XRAY CHEST
– normal
IMMUNOLO
GY
IgG – 1839
(N:664-1401)
IgM – 385
(N:55-141)
IgA – 200
(N:103-404)
C3 : 64 (73135)
C4 : 9.9 (1272)
VIRAL
MARKERS
CMV –
negative
EBV negative
INVASIVE
Lymph node
biopsy –
reactive
hyperplasia
with atypical
Bone marrow
biopsy - ?
myelodysplas
ia

12. What next?

13. BONE MARROW REVIEWED

14. Other investigations
•
•
•
•
Ferritin: 18,080 ug/L [N:15-200 ug/L]
Triglycerides: 642 mg/dl [N:150 mg/dl]
Fibrinogen: 150 mg/dl [N: 200 – 400 mg/dl]
NK cell activity and perforin levels sent – could
not be assessed due to low number of
lymphocytes

15. FINAL DIAGNOSIS
Secondary Haemophagocytic
Lymphohistiocytosis (HLH) – secondary to
viral hepatitis

16. FURTHER COURSE AND TREATMENT
•
•
•
•
•
Started on treatment as per HLH 2004 protocol
Dexamethasone - 10mg/m2 daily
Etoposide - 150 mg/m2 twice weekly
Cyclosporine - 6 mg/kg daily
Prophylactic co trimoxazole – 5 mg/kg thrice
weekly
• Continued antibiotics and antifungals –
Cefoperazone, Teicoplanin, Amphotericin B ,
Colistin

17. FURTHER COURSE AND TREATMENT
• Child developed severe neutropenia after 3
doses of etoposide (ANC <500)
• Discontinued etoposide
• Hypotension, hypoxia – required mechanical
ventilation and inotropic support
• Succumbed to illness

18. When to suspect HLH
CLINICAL CLUES
Unremitting , undiagnosed
prolonged fever
LABORATORY CLUES
Rapidly progressive
cytopenias
Organomegaly –
splenomegaly,
lymphadenopathy
Hyperferritinemia
Hypertriglyceridemia
Hypofibrinogenemia
Bleeding manifestations
BM or Organ biopsy with
hemophagocytosis

19. DIAGNOSIS OF HLH
• The diagnosis of HLH can be established if one of either 1 or 2
below is fulfilled:
1. A molecular diagnosis consistent with HLH is made.
2. Diagnostic criteria for HLH are fulfilled (5 of the 8 criteria)
• Fever
• Splenomegaly
• Cytopenias (affecting 2-3 lineages in the peripheral
blood):hemoglobin 9 g/dL, platelets 1 lac, neutrophils 10
• Hypertriglyceridemia and/or hypofibrinogenemia: fasting
triglycerides 3.0 mmol/L (ie, 265 mg/dL), fibrinogen 1.5 g/L
• Hemophagocytosis in BM, spleen, or lymph nodes
• Low or absent NK-cell activity.

20. TAKE HOME MESSAGE
• Secondary HLH high index of suspicion – can
complicate any viral illness.
• Investigations for primary HLH should form
part of initial work up in any given HLH case
• Initial treatment of primary and secondary
HLH – same.