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

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Gupta Pathology of HEV hepatitis

• Reports on histological features
• Early reports mainly on epidemics
• Etiology assumed to be due to HEV (waterborne
  NANB)
• Changes similar to HAV
• Prominent cholestasis and portal inflammation
  (Gupta Smetana 1957, Morrow et al. 1968, Dienes
  et al. 1986, De Cock et al. 1987, Ramalingaswamy
  Purcell 1988, Song et al 1992, Kobayashi et al.
  1993, Asher et al. 1990, Sallie et al. 1994)
• Cholestatic rosettes in upto 50
• Extensive necrosis and collapse in fatal cases
  (Asher et al 1990, Sallie et al 1994)
• Prominent phlebitis (Asher et al., 1990)
• Recovery associated with normal etiology (Khuroo
  et al 1980)
• Monkeys do not show cholestasis

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Gupta Pathology of HEV hepatitis
Histological features of AIIMS cases Sporadic
Acute Hepatitis (AH) 25 cases Acute Liver
Failure (ALF/FHF) 91 cases Sub Acute Liver
Failure (SAHF) 92 cases Cholestatic Hepatitis
(Chol H) 44 cases Sporadic acute hepatitis
includes only HEV alone or in combination with
HAV and HBV Other cases include single and
multiple infections with hepatitis viruses Only
those cases with adequate liver biopsies are
included This is an ongoing study
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Gupta Pathology of HEV hepatitis
HEV sporadic hepatitis Biopsy during hepatitis /
post-mortem Histological features HEV HEVHAV HEV
HBV Total Acute Hepatitis (spotty and confluent)
4 1 - 5 AH with bridging necrosis 3 1 1 5 AH
with panlobular necrosis 4 2 1 7 AH with
periportal necrosis - - - - All Cases 11 4 2 17
Biopsies at Recovery Histological
features lt15d 15d-1m 1m-3m Total Acute
hepatitis 2 1 1 4 Minimal/non-specific
changes - - 1 1 Recovery phase/near-normal - 1 2 3
Total 2 2 4 8
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Gupta Pathology of HEV hepatitis
Histopathology of Sporadic HEV Hepatitis Necrosis
Severe in fatal cases Ballooning
change Histological Cholestasis Prominent in
50 Cholestatic rosettes Portal
inflammation Plasma cells, Eosinophils inclu
ded Bile ductular changes fatty change not
common
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Gupta Pathology of HEV hepatitis
Viral markers of cases of ALF and SAHF Viral
Markers ALF SAHF HAV 1 - HBV 13 25 HCV
2 7 HEV 23 5 HAVHEV 3 - HBVHEV
5 6 HBVHCVHEV - 1 HBVHCV 1 3 No
Markers 21 7 Not Available 22 38 TOTAL 91 92
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Gupta Pathology of HEV hepatitis
Histological features of acute liver failure
(ALF/ FHF) Cases of ALF generally show severer
forms of hepatocellular necrosis (Panlobular and
bridging) 68 / 91 (74.7) Combination of
Panlobular and Bridging Necrosis also found 8 /
91 (8.8) Cholestasis in some form identified in
80. This is partly due to sepsis Chronicity and
cirrhosis not documented No feature to identify
specific etiology
Feature A AE B BC C BE E NIL NA Total PLMN - -
3 - - - 5 2 7 17 PLMN AHBN - - 2 1 1 1 - 2 1 8 AH
BN - - 7 - - 3 10 12 11 43 AH 1 - 1 - - 1 2 2 1 8
REC PH - - - - - - 6 1 1 8 NON SP - 2 - - 1 - - 2
1 6 NORM - 1 - - - - - - - 1 Total 1 3 13 1 2 5 23
21 22 91
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Gupta Pathology of HEV hepatitis
Histological features of subacute liver failure
(SAHF) Viral Markers (Total 92) HBV 25 HBV
HCV 3 HEV 5 HBV HEV 6 HCV 7 HBV HCV
HEV 1 No Markers 7 Not Available
38 Histological Features(Total 92) Panlobular
massive necrosis Acute Hepatitis Bridging
Necrosis 2 Acute hepatitis bridging necrosis
61 Acute hepatitis 6 Acute on chronic liver
disease 3 Resolving hepatitis 4 Chronic
hepatitis 3 Near normal / non specific changes
13 Bridging necrosis common (around 70) rapid
progression to cirrhosis documented in survivors
with HBV etiology predominantly cases due to
pure HEV etiology who survive are not documented
to progress to cirrhosis no feature to identify
specific etiology
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Gupta Pathology of HEV hepatitis
Cholestatic hepatitis retrospective and
prospective study Group I (CH) Hepatitis with
icterus gt 6 weeks, clinical features of
cholestasis either Serum Bililirubin gt 10 mg/dl
with conjugated unconjugated gt 41, OR Serum
alkaline phosphatase gt twice normal, no IHBR
dilatation (lt 4 mm) CBD ( lt 8 mm) Group II
(NCH) Acute hepatitis without above
features Group III (EHBO) Biliary obstruction on
US, clinical cholestasis Work-up of
cases Detailed clinical history including drug
exposure Biochemical estimations LFT,
Prothrombin time Viral markers Anti HAV IgM,
Anti HEV IgM, HBsAg , Anti HBc IgM, Anti HDV, HCV
IgG, HBV DNA, HCV RNA Autoimmune markers ANA,
ASMA Histopathology HE, PAS-D, Reticulin,
Masson trichrome, Orcein, Rhodanine
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Gupta Pathology of HEV hepatitis
Cholestatic hepatitis histological
Evaluation Histological features graded 0-3 (29
features) No. of portal tracts Kupffer
cell Portal inflammation Bile duct
damage Overall Bile duct inflammation Lymphoc
yte Bile duct proliferation Plasma
cell Fibrosis (Reticulin) Eosinophil Fibrosis
(Trichrome) Portal edema Ballooning Bridging
necrosis Acidophil body Spotty
necrosis Steatosis Confluent
necrosis Rosette Panlobular necrosis Giant
Hepatocyte Copper Associated Proteins Cholestasis
Copper Cellular Ground glass
hepatocyte Canalicular Ductular Zona
l
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Gupta Pathology of HEV hepatitis
Cholestatic hepatitis major clinical
features Feature Group I (CH) Group II
(NCH) Group III (EHBO) p Number 44 27 21
Age 35.7014.92 29.636.7 45.3316.0 I vs. III
0.02 Gender MF 359 1512 1110 Illness
(wks) 28.8628.45 29.639.70 44.7695.21 I vs.
II 0.00001 Jaundice (wks) 18.1422.18 4.674.67 21
.6719.79 I vs. II 0.00001 Cholestasis
(wks) 6.3612.81 ___ 19.3319.79 I vs. III
0.00001 Drug intake 43.18 18.52 22.83 I vs. II
vs. III 0.019 Drug ATT- 22.73 ATT- 7.11 ___
___ OHA- 6.82 Digox- 7.41 ___ ___
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Major biochemical features
Gupta Pathology of HEV hepatitis
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Etiological Diagnosis
Gupta Pathology of HEV hepatitis
UNKNOWN 13 (29.4)
HBV 6 HEV 1 HBV HEV 2
VIRAL 10 (22.7)
Group I (CH)
ATT 7 /11
HBV 5 HEV 1 HBV HEV 2 ATT 3
DRUGS 11 (25.0)
VIRALDRUGS 8 (18.18)
AUTO-IMMUNE 2 (4.5)
GroupII (NCH)
HBV 5 HEV 4 HBV HEV 1
ATT 2 / 4
VIRAL 13 (48.4)
DRUGS 4 (14.8)
UNKNOWN 10 (37.0)
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Gupta Pathology of HEV hepatitis
Major histological features in cholestatic
hepatitis Feature GI CH GII NCH III EHBO
(44) (27) (21) Portal inflammation
Lymphocytic infilt.
Eosinophils Plasma Cells Histiocytes
- - Portal - - Piecemeal necrosis
Necrosis - Bile duct damage
- Bile duct inflammation - - Cellular
cholestasis Canalicular cholestasis
Ductular cholestasis -
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Gupta Pathology of HEV hepatitis
Cholestatic hepatitis Logistic multinomial
regression analysis to discriminate CH from NCH
EHBO Differential Histology Specificity Sensitivit
y Pos pred Neg pred Diagnosis value value CH
vs NCH Zone 2 Cholestasis 86.36 88.89 80.00
92.68 (CH lt NCH) Bile duct damage (CH gt
NCH) CH vs EHBO Bile duct damage (CH gt
EHBO) Bile duct proliferation (EHBO gt
CH) 94.74 76.19 88.89 87.80 Canalicular
Cholestasis (EHBO gt CH) Cellular
Cholestasis (CH gt EHBO) Kupffer cell
proliferation (EHBO gt CH)
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Gupta Pathology of HEV hepatitis
Summary Histopathological features of HEV
hepatitis Associated with histological
cholestasis Histological cholestasis not
exclusive to HEV Hepatitis HEV does not appear to
be the commonest cause for clinical cholestatic
hepatitis Histological overlap with other
etiology of hepatitis No specific
histopathological feature identified as
yet Chronic hepatitis/Cirrhosis not documented