Sub acute hepatic failure (SAHF) is a condition seen predominantly in India characterized by persistent jaundice for more than 8 weeks, ascites, and submassive or bridging liver necrosis on biopsy without pre-existing liver disease. The most common causes are viral hepatitis B and C. SAHF has a protracted course compared to fulminant hepatic failure and often leads to complications like renal failure and infections. Currently, the best treatment option is liver transplantation, though supportive care and newer bioartificial liver devices can help manage the condition. Without transplantation, mortality from medically treated SAHF is as high as 70%.

1. SUB ACUTE HEPATIC FAILURE
DR.SARATH MENON.R
DIVISION OF GASTROENTEROLOGY
MGM MEDICAL COLLEGE ,INDORE

2. INTRODUCTION
 severe devastating medical conditon with high
mortality even in medically treated
 Difference between fulminant hepatic failure
 Clinical entity seen in Indian subcontinent
 Revised criteria for diagnosis
 Clinical symptoms & lab.evaluation
 Management

3. HISTORY OF SAHF
 reported from India in 1982
 Series of similar cases reported by Tandon et al
 Coined the term SAHF
-Persistent jaundice 10 weeks after onset of icterus
-development of ascites with/without
encephalopathy
- absence of pre-existing liver disease
-Biochemical evidence of hepatocellular necrosis
- Sub massive or bridging necrosis on liver biopsy

4. DEFINITION & TERMINOLOGY
 Gimson et al( King’s college )- term LOHF
- evidence of hepatic decompensation
- 8 – 24 weeks from onset of icterus
O’ Grady et al
- encephalopathy occurs after 4 weeks of
jaundice
Bernau et al – term Sub fulminant hepatic failure
-encephalopathy 2wk-3 month after
onset of jaundice

5. REVISED CRITERIA FOR SAHF
(INT.SYMPOSIUM-’93)
 INCLUSION CRITERIA
- jaundice persisting > 8 weeks after its onset with
ascites with/without encephalopathy
- SGPT level TWICE upper limit of normal

6.  EXCLUSION CRITERIA-
- presence of dilated biliary radicals on USG
- evidence of varices larger than grade 1 on
endoscopy
- alcoholism
- chronic renal failure
- KF ring or low ceruloplasmin level
- liver biopsy- established histology evidence of
cirrhosis

7. SAHF- A CLINICAL ENTITY OR NOT?
 After 8 weeks
 Protracted course
 Ascites- cardinal
 Cerbral edema –
unusual
 Enceph- preterminal
and gradual
 Renal failure & SBP
 Infections- 10-15%
 Renal failure- mc.death
 Within 8 weeks
 Rapid & explosive
 Cerberal edema &
encephalopathy-
determinent
 Infection -80% cases
 Cerebral edema
,septicemia –mc death
SAHF
FULMINANT HEPATIC
FAILURE

8. AETIOLOGY
 Most common cause is viral hepatitis
 Herbal medicines

9. DIST. OF VIRUSES IN CASES OF SAHF
Name of virus Shah et al Amarapurkar et
al
Zachariah et al
HEP A virus 00 % 04% 03%
HEP B virus 18 % 34% 19%
HEP C virus 17% 58% 00%
HEP D virus 00% 04% 00%
HEP E virus 00% 00% 16%

10. PATHOLOGY
 Sub massive or bridging necrosis
 Portal- portal,central – central,portal –central
 Ballooning degeneration of hepatocytes
 Lobular inflammation
 Proliferation of bile duct

11. CLINICAL PROFILE
 Age – 4th – 5 th decade
 Jaundice & ascites – cardinal
 Encephalopathy – terminal event
 Cerebral edema uncommon
 Hepatomegaly – 40- 60%
 Splenomegaly – 10- 30%
 Renal failure & SBP –common
 Renal failure- 50% death
 GI bleed & infection- 30% death
 Medically treated cases 70% -90% mortality
 Survivors- c/c.liver disease within 1 to 2 yr

12. DISTRIBUTION OF CLINICAL FEATURES IN SAHF
IN VARIOUS STUDIES
Shah et al Tandon et
al
Gimson et
al
Zachariah
et al
Pruti H S et
al
JAUNDICE 100% 100% 100 100 100
ASCITES 80% 80% 60% 100% 100%
ENCEPHAL
OPATHY
40 % 60% 80% 30% 27%

13. COMPLICATION OF SAHF IN VARIOUS STUDIES
Shah et al Tandon et al Gimson et al
GI bleed 10% 20% 30%
Renal failure 30% 40% 50%
Infections 10% 10% 15%

14. LAB INVESTIGATIONS
 Serum. Bilirubin –elevated
 SGPT- elevated ( not more than 6 times normal)
 S.Albumin-mildly decreased
 Ascitic fluid- transudative
 Coag .factors-2,5,7,9.10-decreased 50%
-diagnostic,prognostic,therapeutic
 serum fibronectin - decreased
 Liver biopsy-sub massive or bridging fibrosis

15. COMPLICATIONS
 Spontaneous bacterial peritonitis
- infection of ascitic fluid
- bacterial translocation
- E.coli, S.viridans,S.aureus, Enterococcus
 Diagnosis
- PMN>250 cells /cu.mm in ascitic fluid
- ascitic fluid culture /sensitivity
Rx :
INJ. Cefotaxime 1 gm 8 th hrly
or 10-14 d
Tab. Ofloxacin 400mg bd

16. HEPATO RENAL SYNDROME
 Major cause of mortality (50%) in SAHF
 Functional renal failure without renal pathology
 Arterial renal circulation disturbances
 Diagnosis – ascitis with step wise increase in
s.creatinine
 Type 1 HRS- prog. impairment in renal failure
- s.creatinine > 2.5 mg%
- 24hr creat.clearance <20ml/mt in 2weeks
 Type 2 HRS-fairly stable dec. GFR& incr. creat.
 Prognosis of HRS- poor
 Defn.Rx
liver transplantation

17. CRITERIA FOR HRS
 Major criteria
 Low GFR- s.creat >1.5mg/dl or 24 hr
creat.clearance <40ml/mt
 Absence of shock,ongoing infection,fluid
loss,nephrotoxic drugs
 No sustained improvement in renal function on
diuretic withdrawl or plasma expansion 0f 1.5L
 proteinuria,< 500 mg/dl
 No usg evidence of obstructive uropathy or renal
parenchymal disease

18.  Minor criteria
 Urine volune <500ml/d
 Urine Na < 10 meq/l
 Urine osmolality greater than plasma osmolaliy
 Serum Na < 130 meq/l

19. COAGULOPATHY
 GI bleed & IC bleed
 GI bleeding causes death in 20-30%
 Several causes
- dec. factor II,V,VII,IX,X
- dec. anti-thrombinIII & protein C
- thrombocytopenia

20. HEPATIC ENCEPHALOPATHY
 Gradual and terminal in contrary to FHF- rapid and
determinant for diagnosis
 Accumulation gut derived ammonia get to brain by
vascular shunting
 False neurotransmitters and mercaptans
 Cerebral edema uncommon

21. MANAGEMENT
 Supportive therapy
 Specific therapy
- control of liver cell necrosis
- acceleration of liver cell regeneration
- replacement of necrosed liver tissue

22. SUPPORTIVE THERAPY
 Management in ICU
 Adequate nutrition by oral or parentral route
 Fluid and electolyte balance
 Identify and treat the complications like infections,
hepatorenal syndrome, GI bleed

23. SPECIFIC THERAPY
 CONTROL OF LIVER CELL NECROSIS
- no standard drug available today
- corticosteroids not useful as in FHF
- antiviral drugs are tried in various trials
do not show good results
 ACCELERATION OF LIVER CELLS
- prostaglandlins (PGE-1) @ 0.2-0.6 micro
gm/kg/hr. for 28 days (sinclair et al)
hepatocyte growth factors – hepatotrophin
- induces DNA synthesis in hepatocytes

24. REPLACEMENT OF NECROSED LIVER CELLS
 LIVER SUPPORT SYSTEM & BIO ARTIFICIAL
LIVER
1.Hepatassist liver support system
2 . Extra-corporeal liver assist device (ELAD)
Advantages: less cost
- shortage of donor livers
- avoid immunosupressent agents
- bridging time to liver transplantation

25. HEPATASSIST LIVER SUPPORT SYSTEM
 Use of pig liver
 Bioreactor- heart of system
- hollow container with semipermeable membrane (0.2)
micron porous fibres
- allow hepatocytes to contact with plasma
 Venous blood taken from superfecial femoral vein
 Treatment last for 6 hrs

26. HEPATASSIST LIVER SUPPORT SYSTEM

27. ELAD
 Early stages of development
 Uses hepatoblastoma cells grown in hollow fibre
cartridges
 Blood passes through the porous channels in cell
chamber = removal of bilirubin & synthesis of
albumin and clotting factor
 Uses 200gm hepatocytes
 No kuppfer cells,bile duct epithelial cells

28. EALD

29. ELAD

30. LIVER TRANSPLANTATION
 Curative treatment in FHF with survival rate @ 50-
70%
 Useful in SAHF but limitation
 Chance of viral replication in transplant

31. SELECTION CRITERIA
Kings college criteria
 PT > 100 sec or INR .6.5
or
any 3 of follow. variables
 Age <10 or >40 yr
 Etiology non A ,non B hepatitis,idiosyncrytic drug
reaction
 PT> 50 sec
 S.bilirubin >18 mg/dl

32. TYPES OF LIVER TRANSPLANTATION
 Most common
 Permanent
 Native liver removed
 New liver in same
anatomic position
 Long term immuno
suppression
 Split graft can be used
 Temporary
 Heterotopic position
 Native liver in situ
 Immunosuppresents
weaned off
 Donor graft can be
removed
orthotopic auxillary

33. HEPATOCYTE TRANSPLANTATION
 New development in hepatology
 Researches ongoing
 Hepatocytes transplanted in spleen
 Native liver in situ
 Advantages:
- replacement to complex liver
transplantation
- avoid surgical complications
- avoid long term immuno-suppression

34. CONCLUSION
 Condition seen in indian subcontinent
 Viral etiology
 Persistent jaundice > 8 weeks from onset
 Ascitis cardinal symptom
 Liver biopsy-sub massive or bridging fibrosis
 Renal failure- bad prognosis
 Mortality upto 70% in medically treated
 Best available option- liver transplantation