Sub Acute Hepatic Failure

SUB ACUTE HEPATIC FAILUREGUIDE- DR.ATUL SHENDE

CANDITATE-DR.SARATH MENON.R

DIVISION OF GASTROENTEROLOGY

MGM MEDICAL COLLEGE ,INDORE

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

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

DEFINITION & TERMINOLOGY

Gimson et al( King’s college )- term LOHF - evidence of hepatic

decompensation - 8 – 24 weeks from onset of icterusO’ Grady et al - encephalopathy occurs after 4

weeks of jaundiceBernau et al – term Sub fulminant hepatic

failure -encephalopathy 2wk-3 month

after onset of jaundice

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

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

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

AETIOLOGY

Most common cause is viral hepatitis

Herbal medicines

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%

PATHOLOGY

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

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

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%

ENCEPHALOPATHY

40 % 60% 80% 30% 27%

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%

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

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 /sensitivityRx : INJ. Cefotaxime 1 gm 8 th hrly or 10-

14 d Tab. Ofloxacin 400mg bd

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

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

Minor criteria Urine volune <500ml/d Urine Na < 10 meq/l Urine osmolality greater than plasma

osmolaliy Serum Na < 130 meq/l

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

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

MANAGEMENT

Supportive therapy Specific therapy - control of liver cell necrosis - acceleration of liver cell

regeneration - replacement of necrosed liver

tissue

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

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

REPLACEMENT OF NECROSED LIVER CELLS

LIVER SUPPORT SYSTEM & BIO ARTIFICIAL LIVER

1.Hepatassist liver support system2 . Extra-corporeal liver assist device (ELAD)

Advantages: less cost - shortage of donor livers - avoid immunosupressent agents - bridging time to liver

transplantation

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

HEPATASSIST LIVER SUPPORT SYSTEM

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

EALD

ELAD

LIVER TRANSPLANTATION

Curative treatment in FHF with survival rate @ 50-70%

Useful in SAHF but limitation

Chance of viral replication in transplant

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

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

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

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