What is the relative frequency of E etiology in AVH What is the age and sex distribution What is the

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Acharya Acute and subacute liver failure
Acute and subacute liver failure due to HEV
Issues to be addressed 1. What are the
characteristics of ALF SLF in India? 2. How
common is HEV as the cause of these liver
failures? 3. What associated diseases are high
risk for liver failure? 4. What is the
association of pregnancy with HEV infection and
liver failure?
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Acharya Acute and subacute liver failure
Characteristics of HEV-associated ALF SLF in
India Definition subclassification AIIMS data,
n800 (Hepatology 1996, JGH 2000, J hepatology
2004) Time Symptoms Icterus lt 1 wk 81 72 lt 2
wk 94 89 lt 4 wk All All Beyond 4 wks liver
failure manifests as ascites SHF Demographic
characteristics - Criteria Survivors Non-Survivo
rs Total Number 336 (42) 464 (58) 800
(100) Age (Yrs.) 25.30.7 320.8 290.7 MF 1
1.2 11.3 11.26 Pregnancy 25 30 27.5 P-E
Period (d) 5.90.6 (0-28) 6.30.4 (0-28) 5.70.2
(0-25) I-E interval (d) 4.30.5 (0-21) 4.90.3
(0-21) 4.70.3 (0-28) plt0.001 Liver bx - AVH
BN / SMN
Homogeneous presentation Subclassification
based on rapidity of encephalopathy?
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Acharya Acute and subacute liver failure
Causes of death prognosis
Causes of Death CE 72 Sepsis 24 RF 3 GI
bleed 1
Prognosis Age gt 40 Yrs, CE, S.bil gt 15mg,
Pro. T gt 25 secs Blood Ammonia - 124
µmol/ - 80 Sens/specific
- RR for death 14
75 death lt 3 days Etiology ? Survival
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Acharya Acute and subacute liver failure

• Subacute liver failure
• Definition IASL subcommittee J Gastroenterol
  Hepatol 199914403-4
• Distinct form of liver failure
• Ascites/ encephalopathy after 4 weeks and before
  24 weeks of acute hepatitis without h/o
  pre-existing liver disease
• Mortality 70
• Liver biopsy acute hepatitis with bridging
  necrosis
• Death renal failure, sepsis

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Acharya Acute and subacute liver failure

• Comparison of ALF, SHF Liver Failure due to CLD
  - I
• Criterion ALF SHF LF-CLD
• Number 423 200 683
• Age (yrs) 29.50.6 40.14.7 55.34.6
• Sex MF 200233 14555 420263
• Dur. of illness before LF lt 4 wk 4 -12 wk gt 6 m
• Clinical presentation
• HE All (100) 32 (17) 410 (60)
• CE 245 (58) 11 (7.5) 32 (4.7)
• Ascites Nil All All
• Liver Size Small Large (55) PMN (35)
• Mortality 280 (66) 146 (73) 273 (40)
• p lt 0.01

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Acharya Acute and subacute liver failure

• Comparison of ALF, SHF Liver Failure due to CLD
  - II
• Criterion ALF SHF LF-CLD
• Cause of death
• HE 201 (72) 25 (17) 19 (7)
• RF 8 (3) 64 (44) 90 (33)
• Sepsis 67 (24) 31 (21) 80 (28)
• GI bleed 4 (1.4) 26 (18) 84 (31)
• Time (onset ? death) 1.90.1days 4.42.8days 4.6
  3.0days
• S.bil (mg/dl) 14.16.3 20.16.84 6.22.8
• ALT (KU/dl) 605.3296.1 12788.15 6214
• S.Alb (g/dl) 3.70.5 2.70.49 2.40.4
• Proth time (gtcontrol) 21.97.2
  18.410.7 8.23.4
• Varices ND lt Gr II - 25 Gr II-IV - 90
• Course Explosive Protracted Smouldering
• Liver biopsy SMN /BN BN Piecemeal Necrosis
• p lt 0.01

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Acharya Acute and subacute liver failure
How common is HEV as the cause of ALF?
Percentage aetiologies Authors Cases HAV HBV HCV H
DV HEV Mixed Non A-E Drugs Acharya et al,
1999 458 4 11 4 0 23 6 47 5 Khuroo et al,
1997 119 3 15 3 3 38 NR 39 1 Jaiswal et al,
1996 95 4 27 2 5 41 4 15 0
NR, Not reported HAV, hepatitis A virus HBV,
hepatitis B virus HCV, hepatitis C virus HDV,
hepatitis D virus HEV, hepatitis E virus Non
A-E, non-A, non-E viruses
Cause (n458) ALF No. cases () Hepatotropic
viruses 190 (42) Isolated viral infection HAV 18
(4) HBV 48 (10.5) HCV 20 (4.4) HDV 0 HEV 104
(23) Mixed viral infections 29 (6.3) Hepatitis
(AE) 7 Hepatitis (BE) 13
Cause (n458) ALF No. cases () Hepatitis
(CE) 4 Hepatitis (BC) 1 Hepatitis
(BA) 1 Hepatitis (CA) 1 Hepatitis
(BAE) 1 Hepatitis (BCE) 1 No identifiable
viral markers but presentation like viral
hepatitis (non A-E) 216 (47) Antitubercular
drugs 21 (4.6) Mushroom poisoning 2 (0.4)
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Acharya Acute and subacute liver failure
How common is HEV SLF? N128
How common is HEV ALF? N44, survival 16.36
Isolated viral infection 76 (60)
Mixed viral infection 26(20)
No markers 26 (20)
HEVHBV 12 HEVHAV - 1 HEVHCV -
4 HEVHBVHCV 2 HBVHCV 6 HBVHAV - 1

• HBV 62 ( 82)
• HEV 11 ( 15)
• HAV - 1 (1.3)
• HCV - 2 (2.6)

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Acharya Acute and subacute liver failure
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Acharya Acute and subacute liver failure
Associated disease at high risk for liver failure

• Pregnant females (2nd/3rd Trimester)
• Compensated CLD - GE 2003 (n4), JGH 2003 (n12)
• Other candidates (? evidence) NAFLD, ALD, Other
  CLD

AIIMS (Jan 03 - Dec 03) I - S.bil gt 2.5 mg ALT
gt 2,5 x N, OR child score deterioration
by 3 in 30d. n107 Cirrhosis Liver II-Chronic
decompensation (gt 1 Yr) III-Stable
compensated cirrhosis
Criteria Group I Group II Group
III Number 42 32 33 HEV RNA 50 19 10 Childs
at inclusion 11.12.5 9.92.3 5.71.5 Childs
At 4 wk 11.52.7 7.93.9 5.71.5 Mortality (4
wk) 50 13 0 Mortality (6 M) 76 (Surv.
N10) 31(Surv. N22) 0 Gr. I vs II, plt 0.001
I vs III plt0.001
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Acharya Acute and subacute liver failure

• Acute viral hepatitis in pregnancy
• Karnad et al Crit care Med 2004321418
• 1997-2001 n453 pregnant patients in ICU
• Death - 98 (22)
• Multivariate analysis for mortality
• Disease OR
• CVS 5.8
• AVH 5.8
• Resp. fail 12.9
• CNS 4.73
• DIC 2.4
• IC Haem. 5.4
• Lack of perinatal care 1.94

Centre Year HEV Srinagar (n76) 2003 65
(85.5) MAMC (n62) 2004 28 (45) AIIMS
(n60) 2003 22 (37) Total (n198) 115
(58) 60 AVH HEV 10-15 - HBV 20-30 -
NANE HEV ALF 62, 33, 64 Non-HEV ALF 10
, NR, 9 Mortality HEV Vs Non HEV ALF
- Well known from epidemics of HEV infection
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Acharya Acute and subacute liver failure
HEV in pregnancy Sporadic setup - AVH ( AIIMS
1989) Subjects No. HAV HBV() (HEV) Pregnant 169
1.7 16.6 82 Nonpregnant 70 5.7 45 49 Men 287 5.
6 36 57 p lt 0.001 HEV is most common
cause of hepatitis and incidence is highest in
pregnancy. Sporadic ALF (AIIMS - 1989) Aetiology
Men Non pregn. Pregn. HBV 1/103
1/45 4/21(19) NANB 1/164 0/34 10/107
(9.3) (HEV) HAV 0/16 0/4 0/3
(0) Total 2/283 (lt1) 1/83 (lt1) 14/131
(11) lt 0.01 p gt 0.1 Irrespective of etiology,
AVH causes severe liver disease during pregnancy
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Acharya Acute and subacute liver failure
Epidemics and mortality due to ALF Epidemic Autho
r Total() Men () Nonpreg.() Pregn.() Kashmir
Khuroo Frequency 2.9 2.8 2.1 17.3 (1981) Mortali
ty 14 2.8 0 22 Delhi Visnathan Frequency 2 2.
8 1.5 5.33 (1956) Mortality 4.7 2 3 10 Azamg
arh Tandon Frequency 2.1 2.6 2.3 10.3
(1982) Mortality 12 8.4 13.4 39 Higher
susceptibility of pregnant females
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Acharya Acute and subacute liver failure
HEV RNA quantitation in different groups of
patients
Group Mean viral titre (IgM HEV ve)
(Million copies per ml. of serum) FHF (Pregnant
females) (n10) 6.5 0.7 FHF Males
(n10) 6.3 0.6 AVH (Male and female)
(n10) 6.9 1.2
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Acharya Acute and subacute liver failure

• Summary
• ALF in India invariably presents with
  encephalopathy within 4 weeks of onset of
  hepatitis illness and beyond 4 weeks. Liver
  failure subsequent to acute hepatitis
  predominantly manifests in the form of ascites -
  SLF. Natural course, cause of death, sequelae and
  etiology in both the forms of liver failure are
  distinct.
• While HEV is the commonest cause of ALF in India,
  HBV followed by HEV superinfection over Chr.
  HBV/HCV disease are major causes of SLF.
• HEV co-infection with HAV may be a risk factor
  for ALF in children.
• HEV superinfection in patients with CLD may cause
  rapid deterioration in liver function and death.
• Pregnant females in India are more prone to
  develop HEV-AVH and AVH in pregnant female
  irrespective of etiology causes severe liver
  disease and higher mortality.