basics about chronic liver disease for a pediatrician. fast and easy guide to common causes of chronic liver diseases in children Please leave a comment if you like it..

1. Speaker:
Abhinav Agarwal
Moderator:
Prof B.K.Das

2.  No standard definition
 Progressive destruction + regeneration of
liver parenchyma
 Hepatocellular necrosis, inflammation and
fibrosis
 For hepatitis B and C = >6 month
 Often misleading in children for other diseases
 Autoimmune hepatitis and metabolic
disorders = CLD @ 1st contact

3.  Pathological:
 Protracted necroinflammatory liver disease,
irrespective of etiology that may be complicated
by cirrhosis.
*Digestive and Liver Disease 43S (2011) S331–S343

4.  Radiology: defines cirrhosis as
 Volume redistribution
 Coarsened echotexture
 Nodular/irregular surface
 Nodules regenerative/dysplastic
 F/S/O Portal hypertension

5. Inflammation of
liver
Severe disease
Continue
unchanged
Subside
spontaneously or
with treatment

6.  Infective –
 Viral Hepatitis B
 Viral Hepatitis C
 Autoimmune –
 Autoimmune hepatitis
 Primary Sclerosing
Cholangitis
 Primary biliary cirrhosis
 Metabolic Liver Disease –
 Wilson Disease
 Hemochromatosis
 Indian childhood cirrhosis
 Cystic fibrosis
 Galactosemia
 Gaucher and niemann pick
disease
 Glycogen storage
disorders
 Hepatic Venous Outflow
Tract Obstruction –
 Budd chiari syndrome
 Veno occlusive disorders
 Drug induced
 Biliary malfomations –
 Choledochal cyst
 Congenital hepatic
fibrosis
 Caroli’s disease
 Cryptogenic

7.  Insidious onset:-
 Prolonged/ repeated episodes of jaundice
 Portal hypertension
 Upper G.I. bleed
 Abdominal distension
 Failure to thrive
 Hepatosplenomegaly +/-
 Ascitis
 Cutaneous portosystemic shunt
 Acute onset:-
 Wilson disease, cystic fibrosis, autoimmune hepatitis
 Asymptomatic:-
 Hepatosplenomegaly with failure to thrive

8.  Features of Portal Hypertension:
 Increased portal pressure >12mm Hg or 30cm
saline (normal 7-10mm Hg or 10-15cm saline)
 Hematemesis
 Hematochezia
 Malena
 Caput medusa
 Ascitis
 Altered sensorium
 Cruveilheir-Baumgarten syndrome
 Splenomegaly
 Hepatomegaly

9. History
• Previous episode of jaundice
• Family History
• Meconium ileus: Cystic fibrosis
• Umbilical vein catheterisation: budd chiari
• H/o Drug intake
Signs &
symptoms
• Hemolytic DCT negative anemia, CNS, KF ring:-
Wilsons disease
• Cataract:- Galactosemia
• Associated Autoimmune Diseases, female: AIH
• Pruritus: Cholestatic jaundice

10. Investigations
•ALP /5’NT/GGT > SGOT/SGPT : Obstructive disease
•Conjugated bilirubin > unconjugated : Obstructive
•SGOT & PT 1000x : acute viral hepatitis, toxic injury, hypoxia,
hypoperfusion
•SGOT > SGPT : Alcohol induced, fulminant echovirus
•High antibodies, raised IgG : AIH
•Isolated increase of ALP- not from liver
•A:G Reversal - CL
Radiology
•M R Cholangiography: biliary tract lesions
•99m Tc-iminodiacetic acid: intrahepatic v/s extrahepatic
cholestasis
•99m Tc-sulphur colloid: focal lesion >2-3cm
•PTC/ERCP
•Angigraphy: Portal Hypertension

11.  Severity of
necroinflammatory
activity (severity of
underlying disease
process)
 Acceleration
 Longitudinal data
 Measure of fibrosis and
architectural alteration
(level of scarring)
 Distance
 Point data

12.  Supportive:
Condition Drug Dose
Cholestasis Phenobarbitone 3-10mg/kg/day
Cholestyramine 250-500 mg/kg/day
Steatorrhoea Formula containing medium chain TG
Pruritus Ursodeoxycholic acid 10-15mg/kg/day
Vitamin Deficiency Vitamin A 10,000-25,000
I.U./day
Vitamin D 3-5 µg/kg/day
Vitamin E 0.05-2 µg/kg/day
Vitamin K 25-200 I.U./kg/day
Micronutrient Calcium 25-100mg/kg/day
Phosphorus 25-50 mg/kg/day
Zinc 1 mg/kg/day

13.  Portal Hypertension:-
 Supportive:
 Management of shock
 Oxygen
 NG aspiration
 Medical:
 Beta blocker- propanolol , nadolol, timolol
 Vasoconstrictors- vasopressin, terlipressin
 Antisecretory- somatostatin, octreotide
 Vasodilators- nitroglycerine, isosorbides
 Hematemesis:
1.Ballon tamponade
2.Endoscopic sclerotherapy
3.Variceal ligation or banding

14.  Surgical:
 Recurrent variceal bleed
 Hypersplenism
 Extrahepatic or intrahepatic presinusoidal type of
portal hypertension
 Radiological:
 PTE (Percutaneous transhepatic embolisation)
 TIPSS (Transjugular intrahepatic portosystemic shunt)
 Treatment of causative factors

15.  Hepadnavirideae
 Ongoing hepatic injury >6m
 Risk of developing chronic infection is
inversely related to age of acquisition
 90% in<1yr of age
 30% in 1-5 yrs of age
 2% for older

16.  Natural History:

17. *AASLD Practice Guidelines 2009

18. *AASLD Practice Guidelines 2009

19. *AASLD Practice Guidelines 2009

20.  Phases:-
 Treatment:-
Phases HBeAg HBV DNA ALT Symptoms
Immunotolerant Positive High Normal No
Immunoactive Positive (wild)
Negative (mutant)
High elevated +/-
Non replicative Negative Low Normal -
HBeAg HBV DNA
(10^5 copies/ml)
ALT Management
+ + ≤ 2 x normal Observe
+ + >2 x normal Observe 6m.
Treat If no
seroconversion
- + >2 x normal Treat
- - ≤2 x normal Observe
+/- + Cirrhosis Treat
+/- - cirrhosis Observe
*AASLD Practice Guidelines 2009

21. *AASLD Practice Guidelines 2009

22.  Antivirals:-
 Peginterferon-α2 and nucleotide/nucleoside
analogs (telbivudine, tenofevir, entecavir) used
in adults
Agent Advantages Disadvantages
Interferon HBsAg loss
Short duration (24 wks)
No resistance
Subcutaneous
Poor tolerance
Lamivudine Oral
Excellent tolerance
Used in ESLD
Use in ADV failure
Drug resistance
common
Adefovir Oral
Excellent tolerance
Use in ESLD
Use in LAM failure
Approved in >12 yrs
Drug resistance rare

23. *AASLD Practice Guidelines 2009

24.  Natural History

25.  Diagnosis:
ANTI HCV HCV RNA INTERPRETATION
Positive Positive Acute on chronic
Positive Negative Resolution of HCV, acute HCV during
period of low viremia
Negative Positive Early acute HCV infection, chronic
HCV in immunosuppresed state, false
positive HCV RNA test
Negative Negative No infection
 Treatment: in >3 yrs age
 IFN-α2B
 Ribavirin
 Interferon and ribavirin for 48 wks
 Peginterferon
 Telaprevir
 Studies are pending in pediatrics
*Nelson Textbook of Pediatrics 19th Edition

26.  Non resolving inflammation of unknown
origin
 Characterstics:
 Histology:
 interface hepatitis
 portal plasma cell infiltration
 piecemeal necrosis of hepatocytes
 Hypergammaglobulinemia
 Circulating organ non specific antibodies
 Females > males
 4 – 6% of chronic liver disease in childhood

27.  Asociation:-
 Autoimmune thyroiditis
 Arthritis, vasculitis
 Hemolytic anemia (Coombs positive)
 Vitiligo
 Nephrotic syndrome
 Ulcerative colitis
 IDDM

28.  Clinical Presentation:-
 Acute viral hepatitis like onset- 25-30%
 Chronic insidious onset- 30-40%
 Rapid acute liver failure- 10-15%
 Asymptomatic
 Triggered by- infections, drugs, environment
 Overlap syndrome:-
 autoimmune hepatitis with sclerosing cholangitis

29.  Diagnosis:-
 Elevated liver enzymes (not ALP)
 Raised GGT levels
 Presence of autoantibodies
 Histologic findings
 Absent viral markers, negative history of drug,
and negligible alcohol exposure
 USG: rule out structural disorder

30. *AASLD Practice Guidelines 2010

31. AIH Type 1 Type 2
Autoantibodies ANA, Anti actin
antibodies, auto
antibodies against liver
antigen and liver
pancreas antigen,
atypical pANCA, anti
smooth-muscle antibody
Against liver-kidney
microsome 1, antibody
against liver cytosol
Age at presentation Any age Childhood and young
adulthood
Sex Female in 75% cases Female in 95% cases
Other autoimmune
disorders
Common Common, autoimmune
polyendocrinopathy-
candidiasis-ectodermal
dystrophy
Severity Broad range Severe
Treatment failure Infrequent Frequent
Relapse Variable common
* Nelson Textbook of Pediatrics 19th Edition

32.  Treatment:-
*AASLD Practice Guidelines 2010

33.  Inborn error of metabolism
 Toxic accumulation of copper in liver, brain,
cornea and other tissue.
 Abnormal gene ATP7B (metal transporting
ATPase)

34. *AASLD Practice Guidelines 2008

35. *AASLD Practice Guidelines 2008

36.  Avoid food and water with high concentration of copper
 Definitive treatment- liver transplant
*AASLD Practice Guidelines 2008

37.  Increased inappropriate absorption of oral
iron (in genetically predisposed and those
with ineffective erythropoiesis)
*AASLD Practice guidelines 2011

38.  Treatment:-
*AASLD Practice guidelines 2011

39.  Mutation of CFTR gene (cystic fibrosis
transmembrane conductance regulator)
 Less than 1/3rd patients develop clinically
significant liver disease
 Pathognomic lesion: focal biliary cirrhosis
 Risk factors:
 Older age
 Pancreatic insufficiency
 Male gender
 h/o meconium ileus
Viscid
secretions
Blockage of
biliary
ductules
Periductal
inflammation
Fibrosis
Multilobular
cirrhosis
• Portal
Hypertension
Liver Failure

40.  Treatment
 Symptomatic
 Liver transplant
 Enzyme replacement: no role in liver disease

41.  Obstruction of hepatic veins
 Efferent hepatic veins to entry of IVC into the
right atrium
 No specific cause found
 Thrombosis can result from hypercoagulable
states
 Clinical Features:
 Progressive abdominal distension
 Hepatomegaly and ascitis
 Portal hypertension
 Progressive derangement of liver function
*Liver International ISSN 1478-3223

42.  Diagnosis:-
 USG color doppler
 Coagulation profile
 CT scan
 MRI
 Infra- and suprahepatic caval pressures
 hepatic venography
 Liver biopsy
 Management:-
 Anticoagulation – warfarin
 Sodium restriction
 Diuretics
 Paracentesis
 Transjugular intrahepatic portosystemic shunt
 Angioplasty and stenting
 Liver transplantation
*Liver International ISSN 1478-3223